Open Access Others

Stability of an Aspirin in the Aspirin+Curcumin Admixture at Different Storage Conditions

Hyun-Jin Kim, Min-A Kang, Yoo-Sin Park, Shin-Hee Kim, Ju-Seop Kang

Journal of Pharmaceutical Research International, Page 830-838
DOI: 10.9734/BJPR/2013/4083

Aims: The pure stability of aspirin in the aspirin (100 μg/mL) only and aspirin (100 μg/mL) +curcumin (600 μg/mL) admixture without any ingredient under two solvents (distilled water, DW and normal saline, NS), three storage temperatures (25ºC, 4ºC and -20ºC) and periods (1st, 3rd and 7th days) was evaluated.
Study Design: The injectable DW- and NS-aspirin containing solutions in the laboratory cap polyethylene bottle were stored and evaluated at controlled temperature (25ºC, 4ºC and -20ºC) during 7 days.
Methodology: Effects of admixture compounds, periods of storage and temperature of storage on the concentrations of active compound (aspirin) were analyzed. The concentration of aspirin in each solution was determined by stability-indicating high-performance liquid chromatography (HPLC)-ultraviolet (UV) detection. A 1.0 mL volume of each sample was withdrawn and reconstituted with 3.0 mL of ethanol and directly injected into HPLC system immediately after filtration at 1st, 3rd and 7th days for analysis. The stability of the solutions was determined by calculating the percentage of the initial aspirin concentrations remaining at each test condition and periods. Stability was defined as the retention of at least 90% of the initial aspirin concentration.
Results: The concentration of aspirin of the aspirin only and aspirin+curcumin admixture solutions remained at least 90% of original without any color change or precipitation in the DW and NS solution at 4ºC and -20ºC throughout 7 day period and showed instability that decreased gradually below 90% of original concentrations after 1 day at 25ºC in the two solutions.
Conclusion: Two kinds of solutions of only aspirin and aspirin+curcumin admixture, in DW and NS, showed different stability dependence on temperature of storage that means maintained stability at 4ºC and -20ºC and did not show effect of admixture of curcumin on aspirin stability during 7 days except 25ºC.

Open Access Case Study

A Study on the Incidence of Infections and Infestations among the Malnourished Children of the Slum Area

Md. Sabir Hossain, Nayla Binte Iqbal, Md. Hafizur Rahman, Md. Tanvir Sarwar, Asad Ud- Daula, Md. Fuad Hossain, Md. Ibrahim Khalil

Journal of Pharmaceutical Research International, Page 929-939
DOI: 10.9734/BJPR/2013/4812

Aims: To make approaches to data collection and analysis for reviewing the impact of malnourishment upon the high incidence of infections and infestations among children in slum.
Study Design: This prospective study was carried out among the total of 110 slum children and incidence of infections and infestations among them was observed. Data were collected by survey of dwelling condition, face to face interviews with the mother and examination of physical condition of children aged less than 12 years. To calculate the incidence rate for infections and infestation among the malnourished children and their association with aspects of demographic, socioeconomic, health and community factors Gomez's original classification and Waterlow classification was used and statistical analysis was done.
Place and Duration of Study: The study was conducted from July 2011 to June 2012 in Kushtia Districts of Bangladesh.
Methodology: The survey form was prepared in two sections. The first part was conducted in order to assess the nutritional status by taking anthropometric measurement and dietary history of the child and the second part was prepared for examining presence of any disease. Children were eligible for inclusion in the study if they were less than 12 years of age. For all dwellings with at least one eligible child data on socioeconomic and demographic variables were collected through structured face-to-face interviews. Where the main householder or career or mother was not available the interview was conducted with a secondary householder or career.
Results: Of the total 110 slum children 67.27% were found moderately malnourished, 12.72% were severely malnourished and 11.81% were mild malnourished. It also found that a greater part of the children were wasted (52.72%) and 15.45% of the children were both wasted and stunted. In this study 45 children (40.9%) out of 110 were found to be infected with one or more of the infections. Among these infections the most prevalent are - cough (17.27%), skin abscess (14.54%), diarrhea (13.63%), tonsillitis (8.18%) and respiratory distress (15.45%) are also very common. Among the malnourished boys 43.24% were infected and the infestation rate among the malnourished boys was 45.94%. Among the malnourished girls the infection and infestation rate was 45.31% and 37.5% respectively. By sexes combined 44.5% malnourished children were infected and 40.6% were infested.
Conclusion: The analysis proved that the factors which predispose the host to malnutrition also predispose to infection, thus establishing the vicious circle of infection-malnutrition-infection. The analysis also revealed that intestinal parasitic infestations contribute significantly to poor growth and malnutrition in children.

Open Access Original Research Article

Block Copolymer Crosslinked Nanoassemblies Co-Entrapping Acridine Yellow and Doxorubicin for Cancer Theranostics

Pengxiao Cao, Andrei Ponta, JiAe Kim, Younsoo Bae

Journal of Pharmaceutical Research International, Page 523-535
DOI: 10.9734/BJPR/2013/4574

Aims: To develop block copolymer crosslinked nanoassemblies (CNAs) that co-entrap an imaging dye (Acridine Yellow: AY) and therapeutic agent (doxorubicin: DOX) as novel nanoparticle drug carriers for a combined application of drug delivery-based therapy and diagnostic imaging technologies (theranostics).
Study Design: Physicochemical properties of AY-CNAs, such as molecular weight, particle size, surface charge, drug entrapment yield, and drug release profiles, were characterized prior to determining intracellular uptake profile, in vitro cytotoxicity, and in vivo tissue distribution patterns of the particles.
Place and Duration of Study: Department of Pharmaceutical Sciences (University of Kentucky), between June 2012 and January 2013.
Methodology: The AY-crosslinked CNAs (CNAs) were synthesized from biocompatible poly(ethylene glycol)-poly(aspartate) block copolymers by using AY as a crosslinker while DOX was physically entrapped in the particle through an ionic interaction. AY-CNAs and AY-CNAs with DOX were characterized to determine their particle properties (molecular weight, size, and optical properties), intracellular uptake and cytotoxicity in an in vitro cell culture system using human colon HT29 and lung A549 cancer cell lines, and tissue accumulation and tumor-preferential drug delivery efficiency ex vivo with a xenograft mouse tumor model.
Results: AY-CNAs maintained nanoscale particle sizes (< 20 nm), fluorescence optical properties, and negative surface charge before and after drug entrapment. AY-CNAs with DOX were confirmed to kill cancer cells as effectively as free drug formulations, and to enhance intracellular uptake in vitro and tumor accumulation ex vivo.
Conclusion: These results demonstrate that block copolymer nanoassemblies crosslinked with an imaging dye are promising platforms for the development of theranostic nanoparticle drug carriers.

Open Access Original Research Article

Free Radical Scavenging Activities of Nyctanthes arbor-tristis. L on Adjuvant Induced Arthritis in Rats

Smeera Thomas, J. Grace Nirmala, R. T. Narendhirakannan

Journal of Pharmaceutical Research International, Page 536-547
DOI: 10.9734/BJPR/2013/3295

Aims: The present study was undertaken to explore in vivo antioxidant potential of ethanol extracts of Nyctanthes arbor-tristis leaf and stem in adjuvant induced arthritic rats.
Methodology: Arthritis induced rats were administered with extract of Nyctanthes arbor-tristis leaf and stem. (150 mg/kg body Weight/rat/day for 30 days.
Results: A significant decrease in paw edema was observed following oral administration of the leaf and stem extracts. A significant (p<0.05) increase in the level of tissue TBARS, GPx and catalase was seen in arthritis induced rats (group II) and NAT treated rats (group III and group IV) showed a significant decrease in lipid peroxides, GPx and catalase level to near normalcy. The activity of total tissue SOD was found significantly (p<0.05) low in arthritis induced rats (group II) while a substantial increase in the activity to near normal level was noticed in NAT administered rats. The alterations in hematological and other biochemical parameters were restored to near normal levels after a treatment period of 30 days. The structural changes of the tissues shows the therapeutic ability of Nyctanthes arbor-tristis stem and leaf in experimental animals which were further evidenced by histological observations made on the hind limb tissue.
Conclusion: As Nyctanthes arbor-tristis is of natural origin, it is a safe and effective intervention for free radical mediated diseases.

Open Access Original Research Article

Antimicrobial Resistance Evaluation of Organisms Isolated from Liquid Herbal Products Manufactured and Marketed in South Eastern Nigeria

N. T. Ujam, A. N. Oli, M. N. Ikegbunam, M. U. Adikwu, C. O. Esimone

Journal of Pharmaceutical Research International, Page 548-562
DOI: 10.9734/BJPR/2013/3554

Objective: To determine the susceptibility and resistance pattern of bacteria and fungi isolates obtained from herbal anti-infective liquid preparations manufactured and marketed in South-East Nigeria to conventional antibiotics.
Study Design: Experimental
Place and Duration of the study: Pharmaceutical Microbiology and biotechnology Laboratory, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe University, Agulu Campus between October 2011 and March 2012.
Methodology: Isolation and characterization of contaminating microorganisms were carried out using standard procedures. A total of forty-nine (49) bacteria and forty (40) fungi isolated from the herbal products were examined for susceptibility to conventional antibiotics using the disc diffusion method. The bacterial isolates were tested against ciprofloxacin, ofloxacin, amoxicillin-clavulanic acid, gentamicin, cefotaxime, ceftazidime, ceftriazone, sulphamethoxazole, tetracycline and ampicillin were employed while fungi isolates were tested against five common antifungal-griseofulvin, nystatin, ketoconazole, fluconazole and clotrimazole. The Multiple Antibiotic Resistance Index (MARI) of each of the isolated bacteria was obtained following the standard method.
Result: The antimicrobial susceptibility-resistance profile of the bacteria isolates revealed that most of the bacteria were sensitive to ciprofloxacin, ofloxacin, gentamicin, and ceftriaxone, On the other hand, a good number of the isolates demonstrated high level of resistance to common antibiotics like Ampicillin, amoxycillin-clavulanic acid, trimethoprim-sulphamethoxazole, and moderate level of resistance to Tetracycline, and some of the third generation cephalosporins - ceftazidime and cefotazime. Multiple Antibiotic Resistance Index (MARI) evaluation revealed that most of the isolates were resistance to more than fifty percent (50%) of the number of antibiotics used. The fungal isolates were susceptible to nystatin, ketoconazole and clotrimazole, resistance to fluconazole and high resistance recorded against griseofulvin.
Conclusion: The results of this study revealed that the herbal medications can serve as a trail of spread of antibiotic-resistance genes.

Open Access Original Research Article

Hepatoprotective Effect of Drynaria quercifolia Fronds Hydroalcoholic Extract and Isolated Constituent against CCl4-Induced Hepatocellular Damage

Pradeep Kamboj, Ajudhia Nath Kalia

Journal of Pharmaceutical Research International, Page 563-578
DOI: 10.9734/BJPR/2013/3620

Aims: The present study was conducted to evaluate the hepatoprotective effect of hydroalcoholic extract of Drynaria quercifolia fronds (Dq), its fractions and isolated compound (Dq-4) from ethyl acetate (EA) fraction.
Place and Duration of Study: Department of Pharmacognosy and Department of Herbal Drug Research, ISF College of Pharmacy, Moga, between June 2010 and May 2012.
Methodology: The toxicant CCl4 (1ml/kg) was administered on 4th and 5th day to induce hepatotoxicity in Wistar rats (in-vivo) and the in-vitro hepatoprotection was evaluated against CCl4 (1%) induced toxicity in HepG2 cellines.
Results: The pre-treatment of rats with Dq extract, EA fraction and Dq-4 for 7 days produced a significant dose dependent hepatoprotective action by decreased levels of hepatic enzymes, total bilirubin and TBARS and increased levels of total proteins, albumin, and reduced glutathione. The histological examination provided the supportive evidences. Additionally, Dq extract, EA fraction and Dq-4 significantly decreased the CCl4-induced in-vitro toxicity in HepG2 cellines evident by MTT reduction assay and trypan blue method.
Conclusion: The study scientifically validated the traditional use of D. quercifolia for liver disorders and strongly demonstrates antioxidative effect on hepatocytes in restoring their normal architecture and functional ability.

Open Access Original Research Article

Chronic Anti-Inflammatory Activity of Ethanolic Extract of Leaves of Clerodendrum viscosum by Carrageenin Induced Paw Oedema in Wistar Albino Rats

Chandrashekar R., S. N. Rao

Journal of Pharmaceutical Research International, Page 579-586
DOI: 10.9734/BJPR/2013/3505

Aims: The aim of the study was to investigate chronic anti-inflammatory activity of ethanolic extract of the leaves of Clerodendrum viscosum (EELCV) by carrageenin induced paw oedema in Wistar albino rats.
Study Design: Prospective.
Place and Duration of Study: Dept of Pharmacology, Yenepoya Medical College, Yenepoya University, Derlakatte, Mangalore 575018, Karnataka, India. June 2010-August 2010.
Methodology: Dried powdered leaves of Clerodendrum viscosum were subjected to Soxhlet extraction by using 90 % ethanol. Based on acute oral toxicity study according to Organization for Economic Cooperation and Development (OECD) guidelines no. 423, three doses of the test drug was selected (75, 150 & 300 mg/kg) for rats, and were subjected to screening for anti-inflammatory activity.
Results: Oral administration of EELCV at doses of 150 mg/kg (P = .01) and 300mg/kg (P = .05) has shown significant anti-inflammatory activity by carrageenin induced paw oedema in Wistar albino rats compared to control. A significant inhibition of oedema formation was also observed at 4th hour.
Conclusion: Administration of EELCV orally at the doses of 150 mg/kg (P = .01) and 300mg/kg (P = .05) showed significant anti-inflammatory activity by carrageenin induced paw oedema in Wistar Albino rats. The percentage inhibition of the oedema at 3rd hour was 63.75 % for the dose of 150 mg/kg and 46.30 % for the dose of 300 mg/kg. A significant inhibition was also observed at 4th hour.

Open Access Original Research Article

Susceptibility Profile of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates to Antibiotics and Methanolic Extracts of Parkia biglobosa (Jacq) Benth

A. F. Obajuluwa, J. A. Onaolapo, A. R. Oyi, B. O. Olayinka

Journal of Pharmaceutical Research International, Page 587-596
DOI: 10.9734/BJPR/2013/2080

Aims: To study the susceptibility profile of methicillin-resistant Staphylococcus aureus (MRSA) isolates from orthopaedic patients to antibiotics and methanolic extracts of Parkia biglobosa.
Background: Antimicrobial resistance in Staphylococcus aureus has attained alarming proportions worldwide; with methicillin resistant Staphylococcus aureus (MRSA) becoming a major pathogen of public health importance associated with community and hospital acquired infections. Wound infections in orthopaedic patients with multidrug resistant pathogens significantly delay or prevent the union of fractured bones. The increasing prevalence of multidrug resistance in Staphylococcus aureus isolates calls for the search for alternative anti-staphylococcal agents.
Methodology: Suspected staphylococcal isolates from wound, skin and bed swab samples from orthopaedic patients in a tertiary hospital in Zaria, Nigeria were characterized by established microbiological procedures and their antibiotic susceptibility pattern determined by the Kirby-Bauer-CLSI modified disc agar diffusion (DAD) technique. The activity of crude methanolic extract of the root, stem bark and leaf of Parkia biglobosa on the isolates determined.
Results: A total of 179 isolates were confirmed S. aureus: wounds (24.6%), skin (39.1%) and bed (36.3%). The isolation rates for MRSA from the various sites were: wound (75%), skin (51.4%) and bed (73.8%). Antibiotic susceptibility testing revealed that the isolates were generally resistant to ampicillin (100% for all sites); ceftriazone (wound 69.7%, skin 72.2%, bed 70.8%); gentamicin (wound 54.5%, skin 52.8%, bed 37.5%) and ciprofloxacin (wound 51.5%, skin 47.2%, bed 35.4%). The phytochemical screening of the methanolic extract of the leaf, root and stem bark of Parkia biglobosa showed the presence of saponin, tannin, flavonoids and cardiac glycosides. The stem bark of Parkia biglobosa showed the greatest activity against all the multidrug resistant MRSA isolates at the 10mg/ml-25mg/ml concentration range used. In the search for alternative antistaphylococcal agents from natural sources, Parkia biglobosa will be a possible candidate for further investigation.
Conclusion: There was high prevalence of multidrug resistant Staphylococcus aureus isolates from the clinical and surveillance samples from the orthopaedic patients.

Open Access Original Research Article

Optimization of Gabapentin Release and Targeting Absorption, Through Incorporation into Alginate Beads

Pierre A. Hanna, Shadeed Gad, Hassan M. Ghonaim, Mamdouh M. Ghorab

Journal of Pharmaceutical Research International, Page 597-616
DOI: 10.9734/BJPR/2013/3020

Aims: 1) To study the effect of some formulation variables on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release. 2) Optimize the mucoadhesion capabilities for targeting drug absorption and release-controlling capabilities of alginate beads.
Methodology: Alginate beads were prepared by dripping sodium alginate gel into calcium chloride solution and then dried overnight at ambient temperature. The effects of alginate concentration, cross linker concentration, cross linking time, volume of cross linking solution and drug/polymer ratio on drug load, encapsulation efficiency, swelling ratio, mucoadhesion and drug release were investigated. Formulae containing sodium lauryl sulfate (SLS), gabapentin-ethylcellulose solid dispersion, mixture of free drug and solid dispersion were prepared for modifying the drug release rate.
Results: Mucoadhesion of alginate beads was shown to be decreased upon adding SLS (30% after 8 hrs). Drug release was so fast (92.46% after 2 hrs). The incorporation of solid dispersion has led to well accepted mucoadhesion (74.44% after 8 hrs) as well as release properties (93.35% after 10 hrs) Beads containing mixtures of drug and ethylcellulose-drug solid dispersion showed acceptable mucoadhesion (74.44% after 8 hrs) and control of gabapentin release (93.35% after 10 hrs). Statistical analysis of variance between groups was performed using the one-way layout ANOVA with duplication. Significant differences in mean values were evaluated by Student's unpaired t test (P < 0.05).
Conclusion: A finally optimized formula was suggested by incorporating a combination of solid dispersion and free gabapentin in alginate system to achieve burst release of gabapentin and hence fast effect (33.417% was released during the first 30 minutes in fasting-simulated conditions) and controlled release (91.217% after 6 hrs).

Open Access Original Research Article

Formulation, Evaluation and Pharmacokinetics of Flurbiprofen Fast Dissolving Tablets

Srikanth Reddy Mettu, Prabhakar Reddy Veerareddy

Journal of Pharmaceutical Research International, Page 617-631
DOI: 10.9734/BJPR/2013/3979

Aim: The intent of present study is to formulate fast dissolving tablets of flurbiprofen using different superdisintegrants to improve the dissolution and bioavailability.
Place and Duration of Study: Jyothishmathi Institute of Pharmaceutical Sciences, Karimnagar, Andhra Pradesh, India, between January 2011 and December 2012.
Methodology: Flurbiprofen fast dissolving tablets were prepared using different superdisintegrants and characterized for different physical parameters, DSC, FTIR studies, in vitro dissolution studies and in vivo pharmacokinetics to prove the enhancement of bioavailability.
Results: From the in vitro dissolution studies, the percent drug release in 15 min (Q15) was found to be 91.46±1.42% in case of optimized formulation where as the conventional tablets prepared by similar manner showed 22.92±0.47% in 15 min. The initial dissolution rate and dissolution efficiency for optimized formulation was 6.10%/min and 53.44 but it was 1.53%/min and 10.96 in conventional tablets. They increased by 4.0 folds when compared to conventional tablets. From the pharmacokinetic evaluation, the optimized fast dissolving tablets produced peak plasma concentration (Cmax) as 11433.32 ng/ml at 2 h Tmax, but they were found to be 8792.64 ng/ml at 3 h Tmax, in case of conventional tablets. The area under the curve for the optimized fast dissolving and conventional tablets were found to be 42691.23 and 30727.14 ng-h/ml.
Conclusion: In summary, formulation of fast dissolving tablets using superdisintegrants was a good approach to enhance the dissolution and absorption rates of flurbiprofen.

Open Access Original Research Article

Formulation and Evaluation of Carbamazepine 200 mg Controlled Release Tablets Using Different HPMC Grades

Wael Ali, Alia A. Badawi, Mahmoud A. Mahdy, Hanan M. El-Nahas

Journal of Pharmaceutical Research International, Page 632-647
DOI: 10.9734/BJPR/2013/3923

Possible interaction between carbamazepine and different HPMC grades was done using DSC thermal analysis. The results indicated that the drug was compatible with these grades. Seven preparations of carbamazepine 200 mg controlled release tablets were prepared by wet granulation method and one preparation was prepared by direct compression method where different HPMC grades with different ratios were used. Concerning uniformity of weight, hardness and assay; all tablets conformed to pharmacopeal limits. Dissolution of the prepared tablets was done using basket method for 24 hours and paddle method for 4 hours. Tablets prepared by 30.0, 35.0 and 40.0% w/w HPMC K 100, 25.0% HPMC K 100 in combination with 5.0% HPMC K 4M and 15.0% w/w HPMC K 4M were conforming to USP limits, while tablets prepared by 15% K4M are not conforming to these limits. Tablets prepared by 12.5% HPMC K 15M by direct compression technique showed similar dissolution values to the innovator in five different media: distilled water, distilled water containing 1.0% SLS, buffer pH 1.2, acetate buffer pH 4.5 and phosphate buffer pH 6.8. The difference and similarity factors were found very acceptable. Scaling up of carbamazepine 200 mg controlled release tablets formulation from lab scale (500 tablets) to full production scale (500,000 tablets) was done. All the results of the scaling up were conforming to specifications and indicated that scaling up process has been done successfully and drug release kinetics indicated that the drug dissolution was zero order.

Open Access Original Research Article

Ameliorative Effect of Leaves of Carica papaya in Ethanol and Antitubercular Drug Induced Hepatotoxicity

Aashish Pandit, Tarun Sachdeva, Pallavi Bafna

Journal of Pharmaceutical Research International, Page 648-661
DOI: 10.9734/BJPR/2013/4517

Aims: The leaves of Carica papaya Linn. (Caricaceae) have been traditionally used as a medicine against some forms of liver diseases. Its hepatoprotective activity against hepatotoxicants like CCl4 and paracetamol has been scientifically proved in animals. The aim of the present study is to examine the hepatoprotective effect of C. papaya leaves against ethanol and anti-tubercular drug-induced liver damage, the two clinically relevant animal models.
Study Design: The aqueous extract of leaves of the plant was administered orally to rats and effects on hepatic marker enzymes, tissue antioxidants and liver histology were determined.
Place and Duration of Study: The study was performed in Rayat Institute of Pharmacy, Railmajra, Dist. S.B.S. Nagar, Punjab, between Dec’ 2011 to July 2012.
Materials and Methods: The study was performed by administering the aqueous extract of C. papaya leaves at the dose of 400 mg/kg in rats prior to administration of ethanol or combination of Isoniazid and Rifampicin. The effects on the levels of serum indicators of liver damage (ALT, AST, alkaline phosphatase and total bilirubin) and tissue antioxidant parameters like TBARS, GSH and SOD were determined. Histopathology of liver was also performed to study the influence of drug on tissue integrity.
Results: Hepatoprotective activity of leaves of C. papaya was evident by the significant reduction in the levels of all serum markers in both the models. The extract also significantly increased the levels of SOD, GSH and total protein; and decreased the levels of TBARS, indicating its antioxidant effect. The results obtained were also confirmed by improvements in the histopathology of liver.
Conclusion: The results obtained in the current study justify the use of Carica papaya leaves in the prevention of liver damage induced by commonly consumed hepatotoxicants, namely ethanol and anti-tubercular drugs.

Open Access Original Research Article

Immunomodulatory Effects of Aqueous Extracts of Auricularia sp and Pleurotus sp Mushrooms in Cyclophosphamide-Immunosuppressed Wistar Rats

A. H. Kyakulaga, P. E. Ogwang, C. Obua, G. Nakabonge, E. N. Mwavu

Journal of Pharmaceutical Research International, Page 662-670
DOI: 10.9734/BJPR/2013/1994

Aims: To determine the immunomodulatory effect of aqueous extracts of Auricularia sp and Pleurotus sp mushrooms using an immunosuppression animal model.
Study Design: Pre-clinical experimental study.
Place and Duration of Study: Department of Pharmacology and Therapeutics, College of Health Sciences and Division of Pharmacology, Department of Physiological Sciences, School of Veterinary Medicine, Makerere University, between August 2010 and December 2011.
Methodology: A total of 80 Wistar rats divided into 8 groups (n=10) were used in the experimental study. Cyclophosphamide (10mg/kg) was administered orally (p.o) to fifty (50) Wistar rats in the first 5 groups for 28 days. In addition, rats in Group I received distilled water, groups II & III received 300mg/kg & 600mgkg of Auricularia sp extract respectively and Groups IV &V received 400mg/kg & 800mg/kg Pleurotus sp extract respectively. Wistar rats in Group VI received only 300mg/kg Auricularia sp extract, group VII received 400mg/kg Pleurotus sp extract and Group VIII received only distilled water. Blood samples were collected on days 0, 14 and 28 to determine the total and differential WBC counts. Data is presented as mean±SEM and analyzed using one-way ANOVA followed by a student’s t-test for statistical significance. Mean values are compared with initial values and the control group (Group VIII).
Results: No mortality of Wistar rats was observed over the 28-day experimental period. Cyclophosphamide though caused statistically significant (p<0.05) reduction in total WBC on day 14 and 28 compared with day 0 in control group from 11.26±0.59 on day 0 to 6.11±0.41 day 14, & 4.12±0.22 on day 28. Lymphocytes and Neutrophil counts were also significantly reduced in control group by day 28 compared to mushroom extract treated rats. Results show that aqueous extracts of Auricularia sp & Pleurotus sp mushrooms significantly (p<0.05) moderated the reductions in total & differential WBC on day 14 and 28 as compared to the control group. The mushroom extracts also increased total and differential WBC in normal rats as compared to the normal group (Group VIII).
Conclusion: Aqueous extracts of Auricularia sp and Pleurotus sp mushrooms moderated cyclophosphamide-induced reduction in WBC in Wistar rats indicating potential benefit in chemotherapy induced immunosuppression. Application of these mushrooms in immune suppression research appears to be new as reflected in the literature. These are however preliminary data to be more completely documented by further experiments, possibly investigating also some aspect of immune cell functions (e.g. cytotoxicity or cytokine production).

Open Access Original Research Article

Antioxidant and Antitumor Activity of Plumeria acuminata in Ehrlich Ascites Carcinoma Bearing Swiss Albino Mice

Gomathi Periyasamy, Malaya Gupta, Upal Kanti Mazumder, Mebrahtom Gebrelibanos, Biruk Sintayehu

Journal of Pharmaceutical Research International, Page 671-685
DOI: 10.9734/BJPR/2013/4472

Aim: This study was designed to determine the antitumor and antioxidant properties of crude methanol extract from the leaves of Plumeria acuminata (Apocynaceae) (MEPA) against Ehrlich Ascites Carcinoma (EAC) bearing Swiss albino mice.
Study Design: Study design is methodology, mentioned below.
Place and Duration of Study: Division of Pharmacology, Department of Pharmaceutical Technology, Jadavpur University, Jadavpur, Kolkata, India between 2006 and 2007.
Methodology: The extract was administered at the doses of 100, 250 and 500 mg/kg per day for 14 days, after 24 hr of tumor inoculation. After the administration of the last dose followed by 18 hr fasting, mice were then sacrificed for observation of antitumor activity. The effect of MEPA on the growth of transplantable murine tumor, life span of EAC bearing host, viable and non-viable cell count, packed cell volume, hematological profile and biochemical parameters such as lipid peroxidation (LPO), reduced glutathione content (GSH), superoxide dismutase (SOD) and catalase (CAT) activities were estimated.
Results: MEPA caused significant (P<0.01) decrease in tumor volume, packed cell volume and viable count; and it prolonged the life span of EAC-tumor bearing mice. Hematological studies reveal that the Hb content and RBC count were decreased in EAC treated mice, whereas the restoration to near normal levels was observed in extract treated animals. MEPA significantly (P<0.05) decreased the levels of LPO and significantly increased the levels of GSH, SOD and CAT. Moreover the MEPA was found to be devoid of conspicuous short-term toxicity in the mice when administered daily for 14 days at the doses of 100, 250 and 500 mg/kg
Conclusion: The results suggested that the methanol extract of Plumeria acuminata leaves exhibited antitumor effect by modulating lipid peroxidation and augmenting antioxidant defense system in EAC bearing Swiss albino mice.

Open Access Original Research Article

Study of Fluconazole Release from O/W Cream and Water Soluble Ointment Bases

Aml I.A.A. Mekkawy, M. Fathy, Sohair El-Shanawany

Journal of Pharmaceutical Research International, Page 686-696
DOI: 10.9734/BJPR/2013/3702

Aims: Study the release of fluconazole from different O/W creams and PEG ointments.
Study Design: In this study, different formulations were prepared with changing one of the added excipients and study the effect of this change on the drug release and then the selected formulations were subjected to antifungal activity study.
Place and Duration of Study: Faculty of Pharmacy, Department of Pharmaceutics, Assiut University, Assiut, Egypt, between December 2011 and March 2012.
Methodology: O/W creams were prepared with changing either fatty alcohol type or the concentration of the added emulsifying agent. Also, the PEG ointments were prepared with changing the type of the liquid PEG (low molecular weight). Then, the viscosity and the fluconazole release from the prepared formulations were studied.
Results: Changing the fatty alcohol type from stearyl to cetostearyl and cetyl alcohol in the O/W creams caused an increase in the viscosity and a decrease in the drug release. Also, changing the liquid PEG from PEG 400 to PEG 600 resulted in an increase in the formulation viscosity and subsequent decrease in the drug release. Both F1 and F6 showed a good inhibition to the fungal growth against Candida albicans and Trichophyton mentagrophyte using cup plate method, also PEG base showed a slight fungal growth inhibition.
Conclusion: Results obtained showed that the PEG ointment formulations exhibited higher fluconazole release after three hours over the O/W cream formulations. Also, the nature of the PEG base may be adjunctive to the efficacy of the antifungal agent.

Open Access Original Research Article

QSAR Rationale of Matrix Metalloproteinase Inhibition Activity in a Class of Carboxylic Acid Based Compounds

B. K. Sharma, P. Singh, Y. S. Prabhakar

Journal of Pharmaceutical Research International, Page 697-721
DOI: 10.9734/BJPR/2013/3903

The matrix metalloproteinase-13 (MMP-13) inhibitory activities of carboxylic acid based compounds, in presence and absence of bovine serum albumin (BSA), have been analyzed quantitatively in terms of chemometric descriptors. The statistically validated quantitative structure-activity relationship (QSAR) models obtained through combinatorial protocol in multiple linear regression (CP-MLR) analysis and the participated descriptors in these models provided rationales to explain the inhibitory activities of these congeners. For MMP-13 inhibition activity, the identified descriptors (BEHm1, BELm1 and BEHm8) have highlighted the role of the atomic mass in terms of the highest and lowest eigenvalues derived from Burden matrix. The positive correlation with activity suggested that their higher values are desirable in improving the activity of a compound. Additionally, the descriptor C-027 representing R-CH-X type fragment in a molecular structure advocates the absence of such type of fragment for the improved activity. On the other hand presence of RCO-N< or >N-X=X type fragment (descriptor N-072) would be beneficiary to the MMP-13 inhibitory activity.
The structural features, rationalized by the descriptors MSD (Balaban’s mean square distance index), nCrHR (number of ring tertiary C (sp3), H-047 (H attached to C1(sp3)/C0(sp2)) and H-050 (H attached to heteroatom) have imparted positive impact on the MMP-13 w/BSA inhibition activity. The atomic properties such as atomic polarizability and atomic Sanderson’s electronegativity have shown their positive impact on the activity via descriptors BELp4 and GATS3e in respective eigenvalues or lag. The other descriptors, MATS1m and MATS3e, have revealed the negative influence of atomic mass and electronegativity on the of MMP-13 w/BSA inhibition activity. The results obtained from CP-MLR analysis have been supported further through partial least-squares (PLS) study.

Open Access Original Research Article

Preparation and Evaluation of Solid Dispersions of Ibuprofen Using Glucosamine HCl as a Carrier

Abdul Wahab, Amjad Khan, Gul Majid Khan

Journal of Pharmaceutical Research International, Page 722-733
DOI: 10.9734/BJPR/2013/3479

Aims: The aim of this study was to enhance the solubility and dissolution rate of sparingly soluble drug ibuprofen using glucosamine HCL as a carrier by solid dispersion technique.
Methodology: As Ibuprofen is sparingly water-soluble drug and has low bioavailability, so to enhance its solubility and improve bioavailability solid dispersions with different drug to carrier ratios (1:1, 1:2 and 1:3) were prepared, as solid dispersion is the most effective method for enhancing the solubility and improving the bioavailability of poorly or sparingly water- soluble drugs. In this study Glucosamine HCl was used as a potential hydrophilic carrier to improve the solubility, dissolution rate and bioavailability of poorly water-soluble drug, Ibuprofen from physical mixtures and solid dispersions. Solid dispersions with different drug to carrier ratios were prepared, using solvent evaporation method. Physical mixtures of Ibuprofen and Glucosamine HCl were also prepared for comparison.
Results: All solid dispersions of Ibuprofen and Glucosamine showed considerably higher dissolution rate than corresponding physical mixtures and pure Ibuprofen. Different techniques such DSC, FT-IR, XRD and SEM were used to study the properties of pure Ibuprofen, solid dispersions and physical mixtures. These results confirmed that Glucosamine HCl can increase the solubility and dissolution rate of poorly water-soluble drug, Ibuprofen.
Conclusion: The study shows that the dissolution rate and solubility of sparingly soluble drug Ibuprofen can be improved and enhanced to great extent by solid dispersion technique, using Glucosamine HCl as a carreir. The current study also showed that amino sugar could be used as new carrier for solid dispersion formulations of non-steroidal anti-inflammatory drugs.

Open Access Original Research Article

In vitro Antioxidant, Cytotoxic and Antibacterial Screening of the leaves of Acridocarpous orientalis, Native to Sultanate of Oman

Ahlam Al-Abri, Hazaa Al-Maqbali, Afaf Weli, Sadri Said, Amzad Hossain, Md. Sohail Akhtar

Journal of Pharmaceutical Research International, Page 734-742
DOI: 10.9734/BJPR/2013/4113

Aims: To determine antioxidant, cytotoxic and antimicrobial activities of organic extracts from leaves of Acridocarpous orientalis (qafas) from Sultanate of Oman.
Study Design: Brine shrimp test, DPPH assay and Disc diffusion method.
Place and Duration of Study: School of Pharmacy, University of Nizwa, Oman, December 2012.
Methodology: Hexane, chloroform, ethylacetate and hydroalcoholic extract were obtained by Kupchan’s partitioning of ethanol extract isolated from leaves of A. orientalis by maceration. Antioxidant activity was determined by free radical scavenging of (2,2-diphenyl-1-picrylhydrazyl, DPPH). The antimicrobial activity was checked using agar disc diffusion method against Gram-positive bacteria (Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli and Pseudomonus aeruginosa). Brine shrimp test was used to measure cytotoxic activity.
Results: All extracts demonstrated potential antioxidant activities, hydroalcoholic extract showed the strongest activity (RC50 = 6.11 μg/ml). The order of antioxidant activity was hydro alcohol > ethyl acetate > chloroform > hexane extract. Ethylacetate extract showed low activity against Pseudomonus aeruginosa. None of the extracts was found to be active against brine shrimp larvae.
Conclusion: A. orientalis could be considered as a good source of antioxidant compounds.

Open Access Original Research Article

Preparation and Characterization of Mucoadhesive Buccal Film for Delivery of Meloxicam

A. R. Gardouh, M. M. Ghorab, S. S. Badawy, R. B. Gales

Journal of Pharmaceutical Research International, Page 743-766
DOI: 10.9734/BJPR/2013/4288

Aims: Preparation of mucoadhesive buccal films able to deliver the meloxicam drug to the site of application through oral mucosal tissues. This dosage form is advantageous due to absence the problems of the ordinary dosage forms.
Study Design: In this research, it was prepared a lot of formulations from different polymers and plasticizers to select the best one which has the optimum and required characteristics.
Place and Duration of Study: Department of Pharmaceutics, Faculty of Pharmacy, Suez Canal University and Misr International University, Egypt, between July 2009 and July 2012.
Methodology: There are different polymers used in preparation of the films which are hydroxypropylmethyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, pectin and polyvinyl alcohol. Also, the plasticizers used are glycerin, propylene glycol and polyethylene glycol. The film was prepared by solvent casting technique. Firstly, the calibration curve of meloxicam was carried out. Then, the properties of the formulations were examined through some experiments which are determination of drug content, study of efficacy of mucoadhesion, in-vitro drug release studies and differential scanning calorimetry.
Results: It was found that the formula containing polyvinyl alcohol 2% (w/w) and propylene glycol 20% from the weight of the polymer has ideal characteristics. Results showed that this formula has optimum drug content, acceptable mucoadhesion and fast drug release with compatibility between drug and excipents.

Open Access Original Research Article

In vitro Antibacterial Activity of Cichorium intybus against some Pathogenic Bacteria

Renu Verma, Ashish Rawat, Showkat Ahmad Ganie, Rajneesh K Agnihotri, Rajendra Sharma, Surabhi Mahajan, Ankur Gupta

Journal of Pharmaceutical Research International, Page 767-775
DOI: 10.9734/BJPR/2013/3887

The root and leaf extracts of Cichorium intybus were investigated for antibacterial activity against gram negative pathogenic bacteria viz. Escherichia coli and Pseudomonas aeruginosa. The sensitivity was analyzed using Disk diffusion method at various concentrations where zone of inhibition was compared with the standard drug Cephotaxime. The extracts showed a wide spectrum of inhibition against the test pathogens. Methanolic extract of root and leaf proves to have the strongest antibacterial activity. Antibacterial activity of the test extracts at different inhibitory concentration varied significantly at 0.05 level of significance. The maximum activity was recorded at 200mg/ml concentration, the activity decreased with the decrease in the concentration of the extract. The present study reveals that the root and leaf extracts of Cichorium intybus would exert several beneficial effects by virtue of their antibacterial activity and could potentially be exploited as a source of natural antibacterial.

Open Access Original Research Article

Angiotensin-Converting Enzyme Inhibitory Activity of Passiflora edulis f. flavicarpa and Petroselinum crispum (Mill) Fuss

Rodrigo A. Restrepo, Nelsy Loango, Mónica V. Moncada, Patricia Landazuri

Journal of Pharmaceutical Research International, Page 776-785
DOI: 10.9734/BJPR/2013/3517

Aims: To determinate the angiotensin-converting enzyme inhibitory activity of several extracts from the species Passiflora edulis f. flavicarpa and Petroselinum crispum (Mill) Fuss.
Study Design: Collection of plant material, extraction, preliminary phytochemical screening and evaluation of angiotensin-converting enzyme inhibitory activity of the plant extracts.
Place and Duration of Study: Faculty of Health Sciences, Universidad del Quindío, Armenia, Quindío, Colombia, between November 2009 and August 2010.
Methodology: The fruit juice and the leaves ethanolic extract of Passiflora edulis (passion fruit) and the leaves ethanolic extract of Petroselinum crispum (Mill) Fuss (parsley) were assessed in vitro regarding their capacity to inhibit ACE. This enzyme’s activity was determined in serum by the method based on the enzymatic hydrolysis of the Furilacriloil - L - phenylalanyl - glycyl - glycine (FAPGG), by the serum ACE, to Furilacriloil - L - phenyl (FAP) and glycyl – glycine (Gly – Gly). Secondary metabolites families were identified using chemical qualitative assays.
Results: Significant lowering of ACE activity was obtained with Passiflora edulis extracts but not with Petroselinum crispum (P = .05). The fruit juice and the leaves ethanolic extract from passion fruit, as well as the parsley leaves ethanolic extract showed inhibition percentages of 40.0 ± 11.5, 27.4 ± 8.6, and 1.1 ± 11.2%, respectively, by working with 0.1 mg/ml extract concentration in the reaction mixture. Preliminary phytochemical screening revealed the presence of flavonoids in the juice and in the Passiflora edulis leaves.
Conclusion: Considerable angiotensin-converting enzyme inhibitory activity was found for Passiflora edulis extracts but not for Petroselinum crispum. The results suggest that there are potential ACE inhibiting secondary metabolites in the Passiflora edulis fruit juice and in the ethanolic extract of its leaves, possibly flavonoids, but not in Petroselinum crispum leaves.

Open Access Original Research Article

Antimicrobial Activity of Stem Bark of Faidherbia albida

Wurochekke Abdullahi Usman, Mahmoud, Suleiman Jada, Zailani Hauwa Ahmed

Journal of Pharmaceutical Research International, Page 786-794
DOI: 10.9734/BJPR/2013/3209

This study was aimed at evaluating the antimicrobial activity of stem bark extract of Faidherbia albida on E. Coli, Salmonella typhi and Shigella sp. The study was conducted in laboratory of Biochemistry department of Modibbo Adama University of Technology, Yola, Adamawa, Nigeria, between July and October, 2012. The antimicrobial activity was carried out using agar disc diffusion method and the crude extract was separated using column chromatography. The phytochemical analysis of the crude methanolic stem bark extract of Faidherbia albida revealed the presence of tannins, saponins and alkaloids. The in vitro antimicrobial activity of the crude methanolic extract of the stem bark showed highest activity on Salmonella typhi with zone of inhibition of 12.0 ± 0.17mm compared to E. coli and Shigella sp. Column chromatography of the crude extract eluted with benzene/methanol, acetic acid/methanol and ethylacetate/methanol gave three fractions designated: I, II and III; of which fraction III showed highest activity against the test organisms. Minimum inhibitory concentration of the most active fraction is 60mg/ml on E. coli and Salmonella typhi and 80mg/ml on Shigella sp.The in vitro antimicrobial activity of the crude methanolic stem bark extract of Faidherbia albida was also compared to some standard antibiotics. The results showed that azithromycin had highest activity ranging from 17.0 ± 0.11mm to 23.0 ± 0.12mm against the test organisms with no significance difference (P<0.05) compared to the activity of fraction III. There was also no significant (p<0.05) difference between the effect of the crude methanolic stem bark extract and that of cirprofloxacin with zone of inhibition ranging between 12.0±0.08mm to 20.0± 0.15.mm These results reveal the antibacterial nature of the stem bark of Faidherbia albida and suggest that it could be exploited in the management of diseases caused by the tested organisms in human.

Open Access Original Research Article

Bacterial Endophytes of the Medicinal Herb Hygrophila spinosa T. Anders and Their Antimicrobial Activity

Arundhati Pal, A. K. Paul

Journal of Pharmaceutical Research International, Page 795-806
DOI: 10.9734/BJPR/2013/3698

Aims: The ethnobotanical herb Hygrophila spinosa T. Anders (Acanthaceae) is native to India and used in traditional ayurvedic medicines for its pharmacologically important phytochemicals. This study aims to isolate and characterize the culturable bacterial endophytes of H. spinosa and evaluate their antimicrobial properties.
Place and Duration of Study: The experiments were performed in the Department of Botany, Serampore College, Serampore as well as in the Microbiology Laboratory, Department of Botany, University of Calcutta, Kolkata during 2011 to 2012.
Methodology: Bacterial endophytes were isolated from healthy plant tissues following surface sterilization and plating on nutrient agar, glycerol asparagine agar and tryptic soy agar. They were characterized physio-biochemically following standard microbiological and biochemical methods. The endophytes were screened for production of antimicrobial compounds following cross-streak assay against test strains Bacillus subtilis, B. cereus, Escherichia coli, Pseudomonas cepacia, Klebsiella pneumoniae and Staphylococcus aureus on nutrient agar plates.
Results: Eleven phenotypically distinguishable bacterial endophytes were isolated from surface sterilized leaf, stem and root tissues and Shannon Weaver diversity index clearly revealed more diverse (0.83) types of endophytes in leaves than in stem (0.48) and root (0.41) tissues. Physio-biochemical features of the isolates clearly indicated distinct variation in their sugar fermentation profiles along with NaCl tolerance. The endophytes produced important enzymes like catalase, amylase, gelatinase, nitrate reductase and lipase. The bacterial isolates belonged to the genera Bacillus, Paenibacillus, Pseudomonas, Ralstonia, Staphylococcus, Micrococcus and Acidomonas. Antibiotic sensitivity profile, however, have indicated that the isolates were mostly resistant to amoxycillin and bacitracin, while they were highly susceptible to tetracycline followed by neomycin and streptomycin. Interestingly, the bacterial endophytes of H. spinosa give a definite stamp on their antimicrobial activity against E. coli and K. pneumoniae followed by S. aureus. Two isolates, Paenibacillus HGS 202 and Acidomonas HGR 302 obtained from stem and root segments respectively showed antimicrobial activity against B. subtilis, B. cereus, E. coli, K. pneumoniae and S. aureus.
Conclusion: This study identified 11 bacterial endophytes harbored by the leaves, stem and root of H. spinosa which demonstrated antibacterial activity against Gram-positive as well as Gram-negative bacterial strains. Moreover these endophytic bacterial isolates could be exploited as sources of antibacterial substances.

Open Access Original Research Article

Anticholinesterase, Antioxidant and Nitric Oxide Scavenging Activity of the Aqueous Extract of Some Medicinal Plants

Renu Agarwal, S. K. Gupta, Puneet Agarwal, S. Srivastava, Renad Alyayutdin

Journal of Pharmaceutical Research International, Page 807-816
DOI: 10.9734/BJPR/2013/4833

Aims: Enhancement of cholinergic activity and reduction of oxidative stress by scavenging free radicals such as nitric oxide are well recognized therapeutic approaches in several pathological conditions. We evaluated the anticholinesterase, antioxidant and nitric oxide scavenging activity of the aqueous extracts of Ocimum basilicum, Curcuma longa and Solanum nigrum.
Study Design: Experimental.
Place and Duration of Study: Delhi Institute of Pharmaceutical Sciences & Research, Delhi University, New Delhi, India between January 2008 and December 2008.
Methodology: The aqueous extracts of the rhizome of Curcuma longa, berries of Solanum nigrum and seeds of Ocimum basilicum were authenticated by HPTLC fingerprinting. The anticholinesterase activity of these extracts was estimated spectrophotometrically as described by Ellman in 1961 and IC50 was calculated. Total antioxidant capacity of extracts was also estimated spectrophotometrically based on the reduction of molybdenum (Mo) (VI) to Mo(V) by the sample and the subsequent formation of a green phosphate/Mo(V) complex at acidic pH. Ascorbic acid was used as standard. Estimation of nitric oxide scavenging activity of extracts was based on the diazotization reaction.
Results: The anticholinesterase activity (IC50) was observed at the concentrations of 2.73 ± 0.09, 3.38 ± 0.05 and 3.88 ± 0.11 gram/l for Solanum nigrum, Curcuma longa, and Ocimum basilicum respectively. At these concentrations, maximum antioxidant capacity equivalent to 4.36 ± 0.14 mM of ascorbic acid was shown by Curcuma longa, followed by Solanum nigrum, and Ocimum basilicum. Curcuma longa showed the maximum nitric oxide scavenging activity equivalent to 29.78 ± 1.28 mM of sodium nitrite followed by Solanum nigrum and Ocimum basilicum.
Conclusion: Plant derived pharmacological agents may provide an attractive therapeutic option in future for several pathological conditions especially the neurodegenerative diseases due to their anticholinesterase, antioxidant and nitric oxide scavenging properties.

Open Access Original Research Article

Gastroprotective Activity of Methanol Leaves Extract of Barleria prionitis Linn. on Ethanol and Indomethacin Induced Ulcer in Rats

Manjusha ., Vipin Kumar, Surender Singh

Journal of Pharmaceutical Research International, Page 817-829
DOI: 10.9734/BJPR/2013/3806

Aims: Barleria prionitis L. (Family Acanthaceae) is a medicinal plant found road side in India and whole plant or its various parts like leaves, root, bark, stem and flowers are used traditionally for various treatments like toothache, inflammation, boils, glandular swellings and ulcer. Leaf juice is useful in gastric ulcer. Here, we attempt to prove the use of this plant as gastroprotective agent.
Study Design: This study was conducted to evaluate the antiulcer activity of methanol extract obtained from the leaves of Barleria prionitis Linn.
Place and Duration of Study: The experiments were conducted at Pharmacology lab of Institute of Pharmaceutical Sciences, Kurukshetra University during the period of July 2012 to December 2012.
Material and Methods: Antiulcer activity was performed using the protocols of ulcer induced by ethanol and indomethacin at two different doses (250 and 500mg/kg). Parameters like volume of gastric juice, pH, free acidity, total acidity, aspartate amino transferase (AST) and alanine amino transferase (ALT) were also determined in ethanol induced ulcer model.
Results: The reduction in ulcer index in Barleria prionitis treated animals was found to be statistically significant (P=.05), when compared with control groups in both the models. Significant changes were observed in total acidity only at dose 500mg/kg only and changes were significant in AST, ALT levels at both the doses. Other parameters showed non-significant results.
Conclusion: The results of the present study show that the methanolic extract of Barleria prionitis L. possess antiulcer activity. This work supports the traditional use of this plant in treating gastric ulcer.

Open Access Original Research Article

A Study Investigating the Absorption and Pharmacokinetics of a Newly Developed Paracetamol/Caffeine Formulation Containing Sodium Bicarbonate in Healthy Volunteers

Dongzhou J. Liu, Ashok Gupta, Mark J. Allison

Journal of Pharmaceutical Research International, Page 839-853
DOI: 10.9734/BJPR/2013/4104

Aims: To assess pharmacokinetic (PK) bioequivalence between a newly developed formulation, rapid-relese paracetamol plus sodium bicarbonate and caffeine (RAPC), containing 500 mg paracetamol + 65 mg caffeine + 325 mg sodium bicarbonate), and the currently marketed Panadol® Extra product in both the fasted and semi-fed states.
Study Design: A single center, randomized, open label, four-way crossover, PK study.
Place and Duration of Study: MDS Pharma Services (Now Celerion), 2420, W. Baseline Road, Tempe, AZ 85283, between July 17, 2009 to August 10, 2009.
Methodology: We included 30 healthy volunteers (20 males, 10 females; age range 18-55 years). The characterized PK parameters included total and partial area under the concentration time curve (AUC0-30min, AUC0-60min, AUC0-t/AUC0-∞), time to reach peak drug plasma concentration/therapeutic level (Tmax/Tc≥4ug/ml), and maximum measured plasma concentration (Cmax). The safety of the study treatments was also assessed.
Results: In both fasted and semi-fed states, the exposure to paracetamol and caffeine for new RAPC formulation was bioequivalent to Panadol® Extra for AUC0-10 hrs, AUC0-∞ and Cmax with 90% confidence intervals (CIs), all being within the range 0.80 to 1.25, except for a higher paracetamol Cmax for RAPC in fasted state. RAPC exhibited significantly greater early absorption for both paracetamol (≥1.8-fold greater) and caffeine (≥1.3-fold greater) as determined by AUC0-30min and AUC0-60min, as well as significantly faster Tmax for both paracetamol (about 30 minutes faster) and caffeine (≥15 minutes faster) compared to currently marketed Panadol® Extra in both fasted and semi-fed states. The time to reach the therapeutic paracetamol plasma concentration (Tc≥4µg/ml) was about 12 and 33 minutes faster in fasted and semi-fed states respectively. The new formulation was safe and well tolerated.
Conclusion: The newly developed RAPC formulation was found to be bioequivalent to Panadol® Extra caplets, and showed significantly faster absorption in both fasted and semi-fed states.

Open Access Original Research Article

Analgesic, Anti-Inflammatory and Antipyretic Effect of Mentha spicata (Spearmint)

Patwary Md Hajjaj Yousuf, Nusrat Yousuf Noba, Mohammad Shohel, Rajib Bhattacherjee, Biplab Kumar Das

Journal of Pharmaceutical Research International, Page 854-864
DOI: 10.9734/BJPR/2013/4640

Aim: Mentha spicata (L.) is popularly used as herbal remedy for various ailments. But the scientific basis for its medicinal use especially in pain and inflammation remains unknown. Therefore, the present study was aimed to investigate the analgesic, anti-inflammatory and antipyretic effects of whole plant of Mentha spicata in laboratory animals.
Materials and Method: The methanol extract of Mentha spicata (MEMS) was used to investigate the acute effect on analgesia by Hot-plate test and acetic acid induced writhing method (By acetic acid) in mice and on inflammation in rats by carrageen induced paw edema method. Subcutaneous injection of 20% aqueous suspension of Brewer’s yeast in wistar rats leads to pyrexia.
Results: The extract showed a significant (p<0.001) dose dependent increase in reaction time in mice in the hot-plate test at the doses of 250 mg/kg and 500 mg/kg body weight. The extract showed a significant (p<0.05) dose dependent increase in reaction time in mice in writhing method at the doses of 250 and 500 mg/kg body weight. The extract also exhibited promising anti-inflammatory effect as demonstrated by statistically significant (p<0.05) inhibition of paw volume by 42.58% at the dose of 250 mg/kg body weight and 45.10% at the dose of 500 mg/kg body weight at the sixth hour of study. Intraperitoneal administration of MEMS showed dose dependent decrease in body temperature in brewer’s yeast induced hyperthermia in rats at both doses. However, MEMS significantly decreased body temperature (p<0.05) at 500mg/kg compared to control.
Conclusion: This study suggests that the methanol extract of Mentha spicata have analgesic, anti-inflammatory and antipyretic activity in a dose dependent manner which supports its use as an analgesic, anti-inflammatory and antipyretic drug in folk medicine.

Open Access Original Research Article

Formulation & Evaluation of Fast Dissolving Tablets of Amlodipine Besylate by Using Co-Processed Superdisintegrants

Jeevan T. Naikwade, Vikas V. Patil, Mayur H. Katkade, Vaibhav D. Thorat, Tahir Ansari, Chetan R. Vaidya

Journal of Pharmaceutical Research International, Page 865-879
DOI: 10.9734/BJPR/2013/4092

Aims: To formulate fast dissolving tablets of amlodipine besylate using co-processed superdisintigrant and evaluate the properties of fast dissolving tablets.
Study Design: Formulation, evaluation of fast dissolving tablets of amlodipine besylate.
Place and Duration of Study: Department of Quality Assurance S. N. D. College of Pharmacy Babhulgoan Yeola Dist Nashik 423401, between July 2012 to February 2013.
Methodology: In the present study, novel co-processed superdisintegrants were developed by solvent evaporation method using crospovidone and sodium starch glycolate in different ratios (1:1, 1:2 1:3 2:1, 3:1) in the fast dissolving tablet formulations. Drug and the developed excipients were characterized for compatibility studies with FTIR and DSC. The co-processed superdisintigrant mixture was evaluated for angle of repose, Carr’s index and Hausner’s ratio in comparison with physical mixture of superdisintegrants. Fast dissolving tablets of Amlodipine Besylate were prepared using co-processed superdisintegrants and evaluated for pre-compression and post-compression parameters. Effect of co-processed superdisintegrants (crospovidone and sodium starch glycolate) on wetting time, disintegrating time, drug content, in-vitro release, and stability parameters have been studied.
Results: The angle of repose of the developed excipients was found to be < 300 Compressibility (%) index in the range of 13.14 to 14.63 % and Hausner’s ratio in the range of 1.15-1.19. The prepared tablets were characterized by FTIR and DSC Studies there was no change in the result. Based on in-vitro dispersion time (approximately 40 sec), promising formulation CP5 was tested for in-vitro drug release pattern in phosphate buffer pH 6.8.
Conclusion: Among the designed formulations, the formulation (CP5) containing co-processed superdisintegrant (3:1 mixture of crospovidone and sodium starch glycolate) emerged as the overall best formulation based on drug release characteristics in phosphate buffer pH 6.8. From this study, it can be concluded that dissolution rate of amlodipine besylate could be enhanced by tablets containing co-processed superdisintegrant.

Open Access Original Research Article

Effect of Ethanolic Stem Bark Extract of Blighia unijugata (Sapindaceae) on Monosodium Glutamate-Induced Uterine Leiomyoma in Sprague-Dawley Rats

George Asumeng Koffuor, Kofi Annan, James Oppong Kyekyeku, Hope Korshie Fiadjoe, Ernest Enyan

Journal of Pharmaceutical Research International, Page 880-896
DOI: 10.9734/BJPR/2013/5402

Aims: To establish the presence of monosodium glutamate (MSG) as an ingredient of artificial food seasonings on the Ghanaian market, and to evaluate the anti-fibroid property of an ethanolic stem bark extract of Blighia unijugata on MSG-induced uterine leiomyoma in Sprague-Dawley rats and its safety for use.
Study Design: Survey and Experimental.
Place and Duration of Study: Department of Pharmacology, CHS; September 2012 and May 2013.
Methodology: A survey was conducted to ascertain MSG as an ingredient of Food and Drugs Board approved artificial food seasonings on the Ghanaian Market. Phytochemical screening was performed on an ethanolic, aqueous, and petroleum ether extract of B. unijugata. Thin layer and high performance liquid chromatographic analysis were performed on the ethanolic extract of B. unijugata (EBU), selected after phytochemical screening, to obtain fingerprint chromatograms for identification. Preventive and curative studies (measuring total plasma cholesterol and plasma estradiol and uterus weight) using 50 and 100 mg kg-1 EBU, per os, on 600 and 800 mg kg-1 MSG-induced uterine leiomyoma in Sprague-Dawley rats was conducted. Acute and Delayed toxicity on EBU was tested.
Results: Of 21 FDB approved artificial food seasonings, 85.7% had MSG as an ingredient. MSG administration to rats elevated significantly (P ≤ .001) cholesterol, estradiol and uterus weight and size (indicating hyperplasia). Curative treatment reduced significantly (P ≤ .01-.001) the elevated plasma cholesterol and estradiol than preventive treatment. Both treatments however significantly decreased (P ≤ .01-.001) elevated uterus weight. The lethal dose was less than 1000 mg kg-1 p.o.
Conclusion: MSG is found in almost all artificial food seasoning on the Ghanaian market which could be a risk factor to the development of uterine leiomyoma. The ethanolic extract of Blighia unijugata reversed hyperplasia induced in the uterus by MSG, making it useful as an anti-fibroid drug.

Open Access Original Research Article

Flavonol Glycosides from the Aerial Parts of Indigofera hirsuta and Anti-inflammatory Activity of n-butanol Fraction

L. S. Abbas, A. M. Musa, M. I. Abdullahi, M. G. Magaji, M. I. Sule, B. Bawa

Journal of Pharmaceutical Research International, Page 897-905
DOI: 10.9734/BJPR/2013/3609

Aims: The study aimed to phytochemically investigate the n-butanol soluble fraction of Indigofera hirsuta aerial parts and to evaluate the anti-inflammatory activity of the fraction using laboratory animal models.
Study Design: Isolation and elucidation of the bioactive compounds and anti-inflammatory activity investigation on n-butanol soluble fraction.
Place and Duration of Study: Department of Pharmaceutical and Medicinal Chemistry, Ahmadu Bello University, Zaria - Nigeria. The study was completed between January-October, 2011.
Methodology: The compounds isolated were identified using different spectroscopic techniques. The n-butanol fraction was investigated for its effect on carrageenan-induced oedema in rat’s experimental model.
Results: Two Flavonol glycosides were isolated; Kaempferol-3-O-β-D-glucopyranoside (T2) and Kaempferol-7-O-β-D-glucopyranoside (Q3).The fraction significantly (P = .05) inhibited the carrageenan-induced paw oedema at doses of 150 and 300 mg/kg tested. The percentage anti-inflammatory effect of the highest dose tested (300 mg/kg) at the peak hour was higher than that of ketoprofen (10 mg/kg), the standard anti-inflammatory agent.
Conclusion: The result of this research suggests that the n-butanol soluble fraction of Indigofera hirsuta aerial parts contains bioactive compounds with anti-inflammatory activity.

Open Access Original Research Article

Comparative Hepatoprotective Potential of Tinospora cordifolia, Tinospora sinensis and Neem-guduchi

Bhagyashri Nagarkar, Rohan Kulkarni, Prashant Bhondave, Deepak Kasote, Omkar Kulkarni, Abhay Harsulkar, Suresh Jagtap

Journal of Pharmaceutical Research International, Page 906-916
DOI: 10.9734/BJPR/2013/4003

Aims: Aim of this study was to evaluate the comparative efficacy of Tinospora cordifolia (Willd.) Miers ex Hook. F., Tinospora sinensis (Lour.) Merrill and T. cordifolia growing on Neem (Azadirachta indica A. Juss.) called Neem-guduchi.
Study Design: Selected species have been widely used in the traditional medicine systems in various dosage forms to treat liver disorders. They are of common occurrence and are being used as substitutes to each other. There is no comparative hepatoprotection study yet published, therefore, present study has carried out.
Place and Duration of Study: Interactive Research School for Health Affairs, Pune and Amrutvahini College of Pharmacy, Sangamner, between November 2011 and August 2012.
Methodology: Guduchi-Satwa, a well-known dosage form was prepared according to the traditional procedure. Hepatoprotective potential was assessed using paracetamol-induced hepatotoxicity model in rats and evaluated by using biochemical parameters viz. alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (BIL).
Results: Both T. cordifolia and T. sinensis Satwa significantly reduced the paracetamol induced elevated levels of serum ALT, AST, ALP and BIL at dose of 200 mg/kg, i.p. as compared to Neem-guduchi.
Conclusions: Satwa preparation form of T. sinensis offers exploitable level of hepatoprotection potential.

Open Access Original Research Article

Aqueous Extract of Balanites aegyptiaca Del Fruit Mesocarp Protects against CCl4 – Induced Liver Damage in Rats

Salihu Mariam, Nwozo Sarah Onyenibe, Oloyede B Oyelola

Journal of Pharmaceutical Research International, Page 917-928
DOI: 10.9734/BJPR/2013/4576

Aim: Carry out preliminary phytochemical screening of Balanites aegyptiaca fruit mesocarp and to evaluate the ability of the aqueous extract to ameliorate carbon tetrachloride-induced hepatotoxicity in rats by determining liver enzymes, blood parameters and histopathology.
Study Design: Sixty albino rats (Wistar rats) were randomly placed into four groups of fifteen animals: Group 1 (normal control), group 2 ( Untreated CCl4 –intoxicated group) while groups 3 and 4 are test groups both administered CCl4 and 0.08 mgkg-1 and 0.19 mgkg-1 body weight of concentrated fruit extract respectively orally daily. Administration of CCl4 was 3 times in a week for 4 weeks at a dose of 1.2 g/kg body weight and plant extract for 3 weeks.
Results: Phytochemical screening indicated the presence of saponin, flavonoids, steroids, alkaloids and cardiac glycosides in the fruit mesocarp. Serum total proteins, albumin and conjugated bilirubin were elevated while the liver enzymes activities (alanine transaminase and alkaline phosphatase) were significantly reduced in the test groups 3 and 4 compared to the untreated rats (Group 2). Histological examinations of the rats’ tissues showed reduced inflammation in the liver of the CCl4-damage rats treated with the extracts when compared to the control and the cell architecture on the 21st day of the animal treated with extract resembled that of the normal control.
Conclusion: The mesocarp of desert dates ameliorates hepatotoxicity induced by CCl4 in rats and this study has further added credibility to the ethnobotanical use of the fruit.

Open Access Original Research Article

Prescription Pattern of Antibiotics among Physicians in a Secondary Health Facility in Abuja, Nigeria

Abu-Saeed Kamaldeen, Joseph Gbenga S., Joseph Folake L.

Journal of Pharmaceutical Research International, Page 940-947
DOI: 10.9734/BJPR/2013/4787

Aim: This study was aimed at assessing the prescription pattern of antibiotics by physicians in Federal Staff Clinic, Abuja: A secondary health care facility in Nigeria.
Study Design: It was a descriptive cross sectional study
Place and Duration of Study: Federal Staff Clinic, Abuja, Nigeria between August 2012 and February 2013.
Methodology: A total number of 1022 prescription sheets containing 1648 prescribed antibiotics were obtained retrospectively and examined. Results were analysed using SPSS version 15 and presented in form of descriptive statistics.
Results: Results showed that Amoxicillin was the most prescribed antibiotic followed by Metronidazole (31.79% and 27.37% respectively). The mean number of antibiotics prescribed per prescription was 1.61± 0.55. The drug per prescription ranged from 1 to 9 with a mean of 3.04± 1.51. About Ninety five percent of the antibiotics were prescribed correctly in terms of frequency and duration of use. Only 21.2% of the antibiotic was prescribed in generic name. Almost all of the antibiotics were prescribed in oral form (98.3%) and were available for dispensing at the pharmacy as at the time of prescription (97.59%). All antibiotics prescribed were found in the Essential Drug List.
Conclusion: Antibiotic usage in this health facility was largely in accordance with National Drug policy which promotes rationale use of drugs. However, majority of antibiotics were not prescribed in generic form, an area where the physicians need to be educated on and monitored further.

Open Access Original Research Article

Evaluation of Microbial Purity and Acute and Sub-acute Toxicities of a Nigerian Commercial Polyherbal Formulation Used in the Treatment of Diabetes Mellitus

S. O. Ogbonnia, G. O. Mbaka, A. M. Nwozor, H. N. Igbokwe, A. Usman, P. A. Odusanya

Journal of Pharmaceutical Research International, Page 948-962
DOI: 10.9734/BJPR/2013/4117

Objective: This study evaluated acute and sub-acute toxicities in rodents and microbial purity of a polyherbal formulation, Bobwell® popular among the natives for the management of diabetes mellitus (DM). It was prepared with unspecified quantities of the following plant materials viz. Gongronema latifolium. Garcinia kola, Vernonia amgydalina, Sphenocentrum jollyanum and Kigelia africana leaves.
Materials and Methods: Microbial purity was evaluated on some bacterial and fungal organisms using appropriate diagnostic media. Toxicity of the polyherbal preparation was evaluated in Swiss albino mice by administering to the animals graded oral doses of the lyophilized preparation in the ranges of 1.0 to 20.0 g/kg body weight (bwt) and observed for changes. Wistar rats were also fed with different doses of the lyophilized formulation for 30 days and the effects on the biochemical profiles and haematological parameters were evaluated.
Results: The purity evaluation test revealed presence of some bacterial organisms with the load within officially acceptable limits except Escherichia coli having a load of 1.50x102 cfu/ml while no fungal organisms were observed. The median acute toxicity value (LD50) of the polyherbal medicine was determined to be 15.2 g/kg bwt. There was significant increase (P ≤0.05) in the body weight of the animals treated with the highest dose of the formulation compared to the control. The biochemical parameters showed marked decrease in the plasma glucose level compared to the control. Increase in creatinine level was observed only in the animals that received the highest dose of the formulation while aspartate aminotransferase (AST) decreased significantly. On the other hand, alanine aminotransferase (ALT) exhibited significant increased (P ≤0.05) at the highest dose. The photomicrograph of hepatic tissue showed focal necro-inflammation around the portal hepatics. There was marked increase in the haemoglobin level and in the red blood cell (RBC) count at the highest doses. There was also significant increase in white blood cells (WBC).
Conclusion: The high LD50 value indicated that the polyherbal preparations could be safe for use but its safety was negated by high presence of E coli load. Although the formulation showed good hypoglycaemic activity and beneficial effects on cardiovascular risk factors, at the highest dose, the formulation exhibited deleterious effect on the hepatic tissue.

Open Access Original Research Article

In vitro Antioxidant Potential of Momordica charantia Fruit Extracts

Md. Ehsan Uddin Talukder, Jannatul Aklima, Talha Bin Emran, Sayedul Islam, Atiar Rahman, Robiul Hasan Bhuiyan

Journal of Pharmaceutical Research International, Page 963-971
DOI: 10.9734/BJPR/2013/4722

This research investigated the antioxidant potential of Momordica charantia fruit extracts in ethanol and ethyl acetate. The extracts have been assessed for DPPH free radical scavenging effect, FeCl3 reducing power and superoxide scavenging effect. In DPPH method IC50 value of ascorbic acid, ethanol and ethyl acetate extract were found 2.19 μg/ml, 111.87 μg/ml and 157.03 μg/ml respectively. In power reducing method, IC50 value of ascorbic acid ethanol and ethyl acetate extract were found 50 μg/ml, 931.63 μg/ml and 754.86 μg/ml respectively. In super oxide scavenging method, IC50 value of curcumin, ethyl acetate and ethanol extract were found 29.51 μg/ml, 331.26 μg/ml and 489.77 μg/ml respectively. The results of all three in vitro antioxidant assays exhibited that M. charantia possess relatively moderate antioxidant property than standards. The data obtained in the in vitro models clearly establish the antioxidant potency of the fruits extracts.

Open Access Original Research Article

Pharmacovigilance Analysis of Adverse Psychiatric Events and Suicidality Reported for Roflumilast, an Add-On COPD Therapy

Ayad K. Ali

Journal of Pharmaceutical Research International, Page 972-982
DOI: 10.9734/BJPR/2013/5633

Aims: Roflumilast is a phosphodiesterase-4-inhibitor used as add-on therapy to long-acting bronchodilators in chronic obstructive pulmonary disease. Although roflumilast is well tolerated, there have been concerns regarding psychiatric problems, including suicide tendencies. This study aims to identify and characterize signals of adverse psychiatric events reported for roflumilast in the US FDA Adverse Event Reporting System (FAERS).
Study Design: Retrospective pharmacovigilance analysis.
Place and Duration of Study: Adverse event reports submitted to FAERS from October 1997 through September 2012.
Methodology: Multi-item Gamma Poisson Shrinker data-mining algorithm was applied to adverse psychiatric events (APE) that were submitted to the FAERS (3Q1997-3Q2012). Empirical Bayes Geometric Mean (EBGM) and 95% confidence interval (EB05-EB95) were calculated for roflumilast-associated APE compared to all drugs in FAERS. The following Preferred Terms of the MedDRA terminology were used to define the outcome of interest: “anxiety”, “depressed mood”, “depression”, “insomnia”, “suicide attempt”, and “suicidal ideation”. Signals with EB05>2 are considered significant disproportional reporting (>twice that expected) of APE.
Results:126 reports of APE were identified for roflumilast, corresponding to mutually non-exclusive events of insomnia (n=53), anxiety (n=38), depression (n=36), suicidal ideation (n=30), depressed mood (n=8), and suicide attempt (n=6). EBGM (EB05-EB95) were: APE, 3.55 (3.06-4.11); insomnia, 4.55 (3.62-5.66); anxiety, 2.96 (2.26-3.82); depression, 2.88 (2.19-3.75); suicidal ideation, 5.65 (4.16-7.52); depressed mood, 3.90 (2.20-6.53); and suicide attempt, 1.66 (0.86-2.95).
Conclusion: Roflumilast is associated with higher than expected reporting of APE, including suicidal thoughts, but not suicide attempts. Given the inherent confounding and bias limitations of spontaneous reporting systems, pharmacoepidemiologic studies are required to test these hypotheses; meanwhile, prescribers should consider alternative add-on therapies to patients with past or present depression or suicidality.

Open Access Original Research Article

Vaginal Mucosa – A Promising Site for Drug Therapy

Vinita Vijay Kale, Alok Ubgade

Journal of Pharmaceutical Research International, Page 983-1000
DOI: 10.9734/BJPR/2013/3895

The vagina provides a promising site for local effect as well as systemic drug delivery because of its large surface area, rich blood supply, avoidance of the first-pass effect, relatively high permeability to many drugs and self-insertion. The pharmaceuticals currently used for vaginal delivery includes those that provide protection against viral infections, including Acquired Immune Deficiency Syndrome (AIDS) and other sexually transmitted infection (STDs). The anti infectives used in treatment of vulvovaginal infection, and vaginitis includes chemicals, for example, clotrimazole, miconazole, clindamycin, sulfonamide and probiotics. Currently, there is a variety of pharmaceutical products available on the market designed for intravaginal therapy (tablets, creams, suppositories, pessaries, foams, solutions, ointments, intravaginal rings, films and gels). However, their efficacy is often limited by a poor retention at the site of action due to the self-cleansing action of the vaginal tract. The vaginal cell lining is covered with a viscous and elastic gel. The physicochemical properties of this gel can influence the rate of diffusion from the bulk to the site of absorption. The choice of absorption model depends totally on the questions to be answered with respect to the test compound being studied. Having studied this review, thus one should able to: understand the anatomy and physiology of the vagina as site of drug administration; understand the pharmaceuticals preferred for administration via vagina; understand the different vaginal delivery system; understand the in vitro models to study vaginal permeability.

Open Access Original Research Article

Clinical Efficacy of Topical Terbinafine Versus Topical Luliconazole in Treatment of Tinea Corporis/Tinea Cruris Patients

C. P. Vidhya Lakshmi, Girish M. Bengalorkar, V. Shiva Kumar

Journal of Pharmaceutical Research International, Page 1001-1014
DOI: 10.9734/BJPR/2013/4348

Aims: Tinea corporis & cruris of skin respond well to topical antifungal therapy, but there is a need to apply cream 2- 3 times daily for up to four weeks will impair compliance & lead to treatment failure. Luliconazole is one of those drugs offering good efficacy & tolerability with a short duration of treatment. Terbinafine, an allylamine antifungal agent, acts by selective inhibition of fungal squalene epoxidase.
Luliconazole, an imidazole antifungal agent is considered to be more effective in inhibition of ergosterol biosynthesis and its reservoir property in stratum corneum is greater than that of terbinafine. As there are lack of studies between terbinafine & luliconazole, the present study was undertaken to compare the clinical efficacy in tinea corporis/tinea cruris patients.
Study Design: Prospective parallel study.
Place and Duration of Study: Study was conducted on 60 patients presenting to the Dermatology out-patient department of RL Jalapa Hospital, Kolar, from 1st December 30th April 2012.
Methodology: Patients alternatively assigned to either terbinafine or luliconazole & advised to apply test drugs topically for 14 days. Clinical symptoms & signs were assessed using 4-point (pruritus, erythema, scaling) scale & 10% KOH mount at base line, end of treatment visit (15th day) & later 30th day. The data was analysed based on age, gender distribution, duration of lesion, clinical score & KOH mount.
Results: Of the 60 patients recruited, all came for 1st follow up (14th day) & 51 patients for 2nd follow-up (30th day). Mean age of the patients was 33.80± 9.58 years in terbinafine & 33.90 ± 9.58 years luliconazole group. Majority of patients were in 12- 40 years aged in both group. Sixty patients and 51 patients were negative for KOH mount preparation on 15th & 30th day respectively. At the end of first follow-up, the clinical score was reduced from 3 to zero (P=0.0001) in both the treatment groups. Mycological cure was 100% in both the drug groups. There was no relapse in 51 patients who came for 2nd follow-up. Four in terbinafine and 5 in luliconazole group were lost to follow up.
Conclusion: Only mild forms of tinea infections were included as compared to other studies where moderate to severe (pustules, incrustations, vesiculation). Hence the onset of illness, treatment duration and severity of illness were favorable in this study for two weeks. In both the treatment arms, clinical & mycological cure was comparable, hence once a day application for two weeks of terbinafine & luliconazole were equally effective for treatment of tinea corporis/cruris infection.

Open Access Original Research Article

Enhanced Bioavailability of Nimodipine from Bioadhesive Buccal Bilayered Patches in Human Volunteers

Y. Vamshi Vishnu, V. Kishan, Y. Madhusudan Rao

Journal of Pharmaceutical Research International, Page 1015-1030
DOI: 10.9734/BJPR/2013/5670

Aims: The objective of the present study was to develop a bioadhesive bilayered buccal patch of Nimodipine (15 mg) using Eudragit Rs 100 as secondary layer and a primary layer with Hydroxy propyl methyl cellulose and Hydroxy propyl cellulose JF.
Methodology: Bilayered buccal patches were prepared by solvent casting technique. The absence of physiochemical interactions between NMDP and the polymer were investigated by differential scanning calorimetry (DSC). Bilayered buccal patches of NMDP were evaluated for in vitro drug permeation through porcine buccal membrane, in vitro drug release, moisture absorption, surface pH, mechanical properties and in vitro bioadhesion.
Results: The results indicated that suitable bioadhesive bilayered buccal patches with desired permeability could be prepared. The bioavailability study was performed in healthy humans in a crossover experimental design. Bioavailability studies revealed that nimodipine possessed good buccal absorption. The relative bioavailability of the optimized buccal patch was found to be 205% in comparison to 30 mg marketed oral tablet. The formulation CC3 showed 68.84 ± 1.4% release and 46.85 ± 5.1% of drug permeated through porcine buccal membrane in 4 hr. A good correlation was seen between percentage in vitro release the extent of bioavailability for nimodine buccal patch.
Conclusion: An improvement of bioavailability was obtained by buccal route to the extent of 2.05 times higher than that of oral route for NMDP. Hence, the development of a bioadhesive bilayered buccal patch for NMDP might be a promising one, as the necessary dose of drug could be decreased, resulting less side effects. Good ex vivo - in vivo correlation was obtained for NMDP.

Open Access Original Research Article

Solid State Characterization and Effect of PEG 20000 and Lecithin on Particle Size Reduction and Stability of Complexed Glibenclamide Nanocrystals

B. Sajeev Kumar, R. Saraswathi, K. Venkates Kumar, T. A. Sam, S. K Jha, S. A. Dhanaraj

Journal of Pharmaceutical Research International, Page 1031-1044
DOI: 10.9734/BJPR/2013/5515

Aims: To formulate and characterize GLB-PEG-LEC NCs (lecithin complexed Glibenclamide nanocrystals) and to analyze the effect of PEG 20000 and lecithin on drug properties, particle size reduction and stability of GLB NCs.
Study Design: Precipitated (GLB-PEG) and complexed nanocrystals (GLB-PEG-LEC) of glibenclamide were characterized for particle size, size distribution, zeta potential and stability assessment using photon correlation spectroscopy. The crystallinity was analyzed by X-ray powder diffraction spectroscopy and differential scanning calorimetry. The chemical stability was assessed by means of infrared spectroscopy and surface morphology by scanning electron microscopy.
Place and Duration of Study: Asian Institute of Medicine Science and Technology, Malaysia, between May 2102 and June 2013.
Methodology: GLB-PEG NCs were prepared by precipitation technique using PEG 20000 and complexed by soybean lecithin. The effect of lecithin in particle size reduction, change in crystallinity, stability and surface properties of NCs were analyzed and compared with pure glibenclamide (GLB) and precipitated NCs. The formulations were optimized and its stability was assessed during a 3 month period.
Results: Pure GLB exhibited an average particle size of 1551 nm. The average particle size of precipitated NCs was between 236 - 7000 nm, while that of complexed NCs was between 155 - 842 nm. The particle size of NC was found to decrease, whereas its zeta potential was found to increase after complexation. DSC studies showed no change in crystalline structure. PXRD studies proved that crystallinity was maintained in NCs. SEM analysis showed presence of spherical shape particles with a lipid coat on the surface after complexation. Stability studies revealed no change in particle size during 3 month period. FTIR studies showed the compatability of excipients with the drug.
Conclusion: These results show that lecithin complexed GLB NCs could be utilized as promising carriers in development of various formulations due to its high stability and decreased particle size.

Open Access Original Research Article

Phytochemical Screening and Investigation of the Central and Peripheral Analgesic and Anti-Inflammatory Activity of Ethanol Extract of Hiptage benghalensis (L) Kurz

Shehla Unaiza Hridi, Nafisa Ferdous, Fakhar Uddin Majumder, J. M. A Hannan

Journal of Pharmaceutical Research International, Page 1045-1057
DOI: 10.9734/BJPR/2013/4454

Aims: Hiptage benghalensis is used in the traditional system of medicine. The leaf is considered one of the important plant organs for the treatment of various diseases such as rheumatism, leprosy, wounds, ulcer, burning sensation, scabies, inflammation and cough. Hence, the present studies were carried out to evaluate chemical constituents and possible pharmacological activities of the leaf.
Study Design: Our present studies were focused on the assessment of probable analgesic and anti-inflammatory activities of ethanol extract of Hiptage benghalensis in laboratory animals and the statistical significance of such effects.
Place and Duration of Study: The experiments were carried out in Pharmacology lab of Department of Pharmacy North South University Dhaka, Bangladesh during the period of June 2012-February 2013.
Methodology: Carrageenan induced Hind Paw Edema test in Long Evans rat was the experiment for anti-inflammatory activity of the ethanol extract of Hiptage benghalensis while Hot Plate test and Acetic Acid induced Writhing method were was carried out to assess its analgesic activity in Swiss albino mice. At two different doses of the leaf extract, 250 and 500 mg/kg body weight, the analgesic test was evaluated on mice and the anti-inflammatory test was evaluated on rats.
Result: Phytochemical analysis of ethanol extract of Hiptage benghalensis has indicated the presence of steroid, carbohydrate, flavonoid, alkaloid, tannin, phenol and, mangiferin and terpenoids-compounds. The ethanol extract of Hiptage benghalensis exhibited statistically significant (p<0.05) anti-inflammatory effect in Carrageenan induced Hind Paw Edema in Long Evans rats and incited significant analgesic response to Hot plate and acetic acid induced writhing in Swiss albino mice.
Conclusion: In conclusion, these observations provide evidence and possible mechanisms of action for the anti-inflammatory and analgesic properties of leaf of Hiptage benghalensis claimed in Ayurveda medicine.

Open Access Original Research Article

In Silico Optimized Mechlorethamine Based Drug Structures Targeting Brain and Spinal Cord Tumors

Ronald Bartzatt

Journal of Pharmaceutical Research International, Page 1058-1069
DOI: 10.9734/BJPR/2013/5761

Aims: Brain and spinal cord tumors are the third most common type of childhood cancer following leukemia and lymphoma. Mechlorethamine (or mustine) is a nitrogen mustard antineoplastic drug. Eleven variants of mechlorethamine are presented that possess molecular properties enabling substantial access to tumors of the central nervous system.
Study Design: An extensive in silico search within a data library of molecular structures identifieddrug scaffolds suitable for targeting brain tumors.
Place and Duration of Study:University of Nebraska, Durham Science Center, Department of Chemistry, Omaha, Nebraska 68182 USA, between July 2012 to December 2012.
Methodology: Following extensive in silico search and identification of potential drug structures, a conclusive set of brain penetrating structures were compiled. Extensive characterization of structure properties was accomplished followed by multivariate numerical analysis utilizing pattern recognition and statistical analysis.
Results: All twelve compounds (including mechlorethamine) exhibited zero violations of Rule of 5, indicating favorable bioavailability. The range in Log P, formula weight, and polar surface area for these compounds are: 1.554 to 3.52, 156.06 to 324.12, and 3.238 A2to 22.24A2,respectively. High resolution hierarchical cluster analysis determined that agent 2 and 6 are most similar to the parent compound mechlorethamine. The average Log P, formula weight, polar surface area, and molecular volume are 2.446, 235.433, 8.58 A2, and 213.8 A3, respectively.
Conclusion: These eleven drug designs possess attributes that effectuate high permeation into the central nervous system.

Open Access Original Research Article

Effect of Ethanol Extract of Coccinia grandis Lin leaf on Glucose and Cholesterol Lowering Activity

Md. Mamun Al-Amin, Mir Muhammad Nasir Uddin, Ashfique Rizwan, Md. Siddiqul Islam

Journal of Pharmaceutical Research International, Page 1070-1078
DOI: 10.9734/BJPR/2013/4583

Aims: To investigate the effect of ethanol extract of Coccinia grandis Lin (Cucurbitaceae) leaf in glucose and cholesterol lowering activity in animal model.
Study Design: Extraction, glucose and cholesterol lowering activity evaluation.
Place and Duration of Study: Department of Pharmacy, North South University, Dhaka between June 2012 and December 2012.
Methodology: Glucose and cholesterol lowering effect of the ethanol extract of C. grandis leaf was evaluated using the alloxan-induced diabetic rat and compared the activity with diabetic control and antidiabetic drug (Glibenclamide). Ethanol extract (25mg/kg) of C. grandis and Glibenclamide were administered to normal and experimental diabetic rats for the duration of 10 days.
Results: Phytochemical screening showed the presence of alkaloids, flavonoids, saponins, cardenolides and polyprenols in significant amounts. In the alloxan-induced diabetic rat model, C. grandis (25 mg/kg) significantly (p<0.05) lowered fasting blood glucose levels. C. grandis extract (25 mg/kg) also produced significant (p<0.05) total cholesterol lowering and HDL increasing (p<0.05) effects. Surprisingly, body weight was increased significantly (p<0.05) in the C. grandis treated diabetic group.
Conclusion: These results suggest that the ethanol extract of C. grandis leaf possesses significant glucose and cholesterol lowering activity in animal model, thus supporting the usage of the plant in traditional medicine as an anti-diabetic medication.

Open Access Original Research Article

Preparation and Evaluation of Novel Expandable Drug Delivery System

D. Sathish, S. Himabindu, P. Pavan Kumar, Y. Madhusudan Rao

Journal of Pharmaceutical Research International, Page 1079-1093
DOI: 10.9734/BJPR/2013/4891

Aims: The purpose of this research is to develop a novel expandable gastroretentive dosage form (GRDF), based on unfolding mechanism. It consists of a drug loaded bilayer polymeric film, folded into a hard gelatin capsule. Gastric retention is achieved due to unfolding of the dosage form within 15-20 min. Furosemide is selected as the drug candidate for this work. Due to its narrow absorption window, Furosemide has to be administered to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a GRDF.
Methodology: Films were prepared by solvent-casting technique using Ethyl cellulose, HPMC E15 and Eudragit RLPO as polymers and dibutyl phthalate as the plasticizer in both layers. The film with zigzag folding in the capsule was shown to unfold in the gastric juice and provide drug release up to 12 h in the acidic medium. The films were evaluated for weight & thickness variation, mechanical properties, in vitro drug release and unfolding behavior based on the mechanical shape memory of polymers. Absence of drug polymer interaction and uniform drug dispersion in the polymeric layers was revealed by DSC, XRD studies and SEM. The GRDF location in the gastrointestinal tract was determined by X-ray studies.
Results: X-ray studies revealed that the GRDF is retained in the stomach up to 6± 0.5 h in fasting condition and 8 h in fed state.
Conclusion: The polymers used in the development of GRDFs were safe and proper combination of these polymers will yield a novel expandable GRDF with good in vitro drug release in acidic media, mechanical properties, and unfolding behaviour. These outcomes demonstrate that the GRDF may be used to improve furosemide therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input.

Open Access Original Research Article

Study of the Hypoglycemic Effect of Tamarindus indica Linn. Seeds on Non-Diabetic and Diabetic Model Rats

Anzana Parvin, Md. Morshedul Alam, Md. Anwarul Haque, Amrita Bhowmik, Liaquat Ali, Begum Rokeya

Journal of Pharmaceutical Research International, Page 1094-1105
DOI: 10.9734/BJPR/2013/4865

Aim: The present study was undertaken to evaluate the antidiabetic effects of the Tamarindus indica Linn seed in normal (non-diabetic), type-I and type-II model rats and to investigate their effect on gastrointestinal motility and intestinal glucose absorption.
Methodology: T. indica seed powder was used at a dose of 1.25g/kg bw/10 ml water. Male Long-Evans rats (160-210g body weight) were used for the experiment. Experiments were done in non-diabetic and streptozotocin-induced diabetic model rats with a single feeding in different prandial states and blood was collected. An intestinal perfusion technique was used to study the effects of T. indica seed powder on intestinal glucose absorption in normal and type-II model rats. Gut motility was evaluated using barium sulfate milk. Glucose was measured by Glucose oxidase-peroxidase (GOD-POD) method.
Result: The screening results showed that T. indica seed powder had no effect on fasting or postprandial serum glucose level of normal and type-I diabetic rat. The seed powder also showed no hypoglycemic effect in the fasting state and no antihyperglycemic effect in type-II model rats when fed simultaneously with oral glucose load, but it exhibited significant antihyperglycemic effect when the seed powder was fed 30 minutes prior to the glucose load at 105 minutes (p<0.03). Glibenclamide significantly lowered postprandial serum glucose levels of non-diabetic and type-II diabetic model rats (p<0.02-0.001). T. indica exerted inhibition on glucose absorption in type-II rats during the whole perfusion period when compared with control. On the other hand, T. indica seed powder significantly inhibited the gastrointestinal motility in type-II rats.
Conclusion: The present data suggest that T. indica possesses antihyperglycemic properties in type-II rats which are at least partly due to its inhibitory effect on intestinal glucose absorption. This effect cannot be attributed to the acceleration of intestinal transit.

Open Access Original Research Article

Effect of Paraquat on Organ Indices and Heamatology in Clarias gariepinus after Chronic Exposure

Edori Onisogen Simeon, Ekpete Ozioma Adaunwo, Edori Enize Simeon

Journal of Pharmaceutical Research International, Page 1106-1114
DOI: 10.9734/BJPR/2013/3647

The effect of paraquat on Clarias gariepinus (220.50 ± 15.33g mean weight and 30.43 ± 1.22cm mean total length) was examined by the assessment of the organ indices and haematological parameters after twenty one days of exposure. It was observed that paraquat caused decline in the fish condition, renatosomatic index, splenosomatic index and cardiosomatic index. However, there was an increase in the hepatosomatic index. There was decline in most of the blood parameters measured such as packed cell volume (PCV), haemoglobin (Hb), red blood cells (RBC) and RBC indices, though the decline were not significant (P≥0.05). Leucocrit fluctuated significantly (P≥0.05) in all the exposure concentrations. Platelets increased in level above the control value. White blood cells (WBC) declined slightly in all the exposure concentrations. The WBC counts, mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) and mean corpuscular volume (MCV) did not show any appreciable decline in levels, while lymphocytes showed slight decline in the lower concentrations and appreciated slightly in the highest concentration. Neutrophils increased in levels above that of the control value in all the concentrations except at the highest concentration where decline in level was observed.

Open Access Original Research Article

Ocular Hypotensive Effect of Topical Verapamil and Diltiazem in Steroid Induced Glaucoma Model of Rabbits

Prabhakar Adake, H. S. Somashekar, C. G. Gokul, Abhishek Acharya, M. Naveen Kumar, R. Santosh

Journal of Pharmaceutical Research International, Page 1115-1126
DOI: 10.9734/BJPR/2013/4389

Objectives: To evaluate possible ocular hypotensive effect of 0.5% diltiazem and 0.1% verapamil eye drops on intraocular pressure in steroid induced glaucoma model of rabbits. And compare with 0.5% timolol eye drops.
Methodology: Glaucoma was induced in rabbits (N=18) by bilateral topical instillation of 1% prednisolone eye drop (10 µl) twice a day for a period of 40 days. Before the induction of glaucoma, baseline intraocular pressure (IOP) in both the eyes of all rabbits was measured under sedation (i.v midazolam) by Schiotz tonometer. At the end of 40 days induced IOP was measured for all rabbits and rabbits were divided into three groups of six rabbits in each. Right eyes of group A, B and C rabbits received 0.5% diltiazem, 0.1% verapamil, and 0.5% timolol eye drops twice daily for 12 days respectively. Whereas, left eyes of all rabbits received distilled water hence represented as control. IOP was measured in all rabbits on every 4th day till 12 days of treatment period.
Results: Intra-group comparisons of IOP changes were made by paired‘t’ test. And unpaired‘t’ test for inter group comparisons. One way ANOVA was used for multiple group comparisons followed by post-hoc Tukey’s test for group wise comparisons. In 0.5% diltiazem treated eyes, the mean IOP significantly reduced from 22.9±1.9 mmHg (10%) on 4th day to 16.9±1.1 mmHg(S, P<.001) on 12th day (34%). Similarly, mean IOP in 0.1% verapamil treated eyes significantly reduced from 22.7±1.3 mmHg (7%) on 4th day to 15.5±1.4 mmHg(S, P<.001) on 12th day (37%). Whereas, mean IOP significantly reduced from 22.4±1.9 mmHg (14%) on 4th day to 16.4±1.4 mmHg (S, P=.001) on 12th day (36%) in 0.5% timolol treated eyes.
Conclusion: Topical 0.5% diltiazem and 0.1% verapamil significantly reduced the IOP in steroid induced glaucoma model of rabbits. However, Further research has to be carried out both in experimental and clinical subjects to reveal its efficacy and safety profile.