Open Access Short Communication

Anticancer Properties of Novel Rhenium Pentylcarbanato Compounds against MDA-MB-468(HTB-132) Triple Node Negative Human Breast Cancer Cell Lines

Carl Parson, Valerie Smith, Christopher Krauss, Hirendra N. Banerjee, Christopher Reilly, Jeanette A. Krause, James M. Wachira, Dipak Giri, Angela Winstead, Santosh K. Mandal

Journal of Pharmaceutical Research International, Page 362-367
DOI: 10.9734/BJPR/2014/4697

Aim: To study the efficacy of novel rhenium compounds to treat triple node negative breast cancer.
Study Design: Six (6) novel rhenium pentycarbanato compounds (PC1-6) were synthesized and triple node negative breast cancer cell lines HTB-132 and Balb/c mouse kidney cell lines were treated with each of them for 48 hours. The results were analyzed by a common trypan blue cell death assay system and statistically analyzed.
Place and Duration: The compounds were synthesized, analyzed and evaluated at the Department of Chemistryof Morgan State University, Baltimore, Maryland and the Pharmaceutical Sciences Department of Elizabeth City State University campus of the University of North Carolina system.
Methodology: The novel rhenium compounds were synthesized from one-pot reactions of Re2(CO)10 with the corresponding α-diimine ligands in 1-pentanol.The compounds were characterized spectroscopically.
The cell lines were cultured by standard cell culture procedure and treated with each of the six compounds in DMSO for 48 hours with a negative control and a DMSO vehicular control along with a cisplatin positive control.The cytotoxicity was evaluated by standard trypan blue assay and the results were statistically analyzed.
Results: The trypan blueassay reveals that these compounds have significant cytotoxicity against MDA-MB-468 (HTB-132) triple node negative breast cancer cell lines and are less nephrotoxic than cisplatin.
Conclusion: The novel rhenium compounds PC 1-6 can potentially find applications in the treatment of highly malignant triple node negative breast cancer.

Open Access Original Research Article

The Effect of Green Tea on Sildenafil Pharmacokinetics in Egyptian Healthy Volunteers

Sahar K. Hegazy

Journal of Pharmaceutical Research International, Page 289-300
DOI: 10.9734/BJPR/2014/6905

Aim: To investigate the interaction of slidenafil and green tea in normal healthy male volunteers using probe drugs (midazolam, CYP3A4 activity).

Study Design:  Ten healthy males were included in random crossover single dose study.  Each volunteer received one tablet of sildenafil 50 mg and one tablet of midazolam 7.5 mg concurrently either after drinking 250 ml of water or 250 ml of fresh extract of 2 gram of green tea. After one week washout period, each volunteer received the other intervention. Plasma samples were analyzed for sildenafil and midazolam using HPLC.

Place and Duration of Study: The Laboratory of Pharmaceutical Research Center of Faculty of Pharmacy, Tanta University, Egypt, between June to July 2013.

Methodology: Blood samples were obtained after the insertion of peripheral cannula into the forearm. Samples were obtained before sildenafil and midazolam intake (blank) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 5, 8, 10, and 12 hours after sildenafil and midazolam administration. The samples were collected in clean heparinized tubes. Plasma was obtained by centrifugation and was stored at –20° until assay. Plasma samples were analyzed for sildenafil and midazolam using HPLC.

Results: Coadministration of green tea with sildenafil tea increased the extent but not the rate of sildenafil absorption. It resulted in higher plasma concentrations (AUC∞ increased from 484.2 ± 67.27 μg hr/L to 731.5 ± 111.01 μg hr/L (90% CI 1.50 (1.36-1.66) and the Cmax from 318.9 ± 46.8 μg /L to 414.9 μg/L ± 67.0 μg/L (90% CI 1.29 (1.15-1.43). The elimination rate constant of sildenafil was significantly decreased and the elimination half life was prolonged by about 36%. However, AUC∞ of midazolam increased by 16% and Cmax by 14%; suggesting a small reduction CYP 3A4 activity.

Conclusion: Increased bioavailability of sildenafil after green tea intake may be caused by the effect of catechins which can alter spontaneous activity of small intestine or an effect on transporters. Patients who are taking green tea may need smaller doses of sildenafil, and those at higher risk of developing sildenafil adverse effects and are taking green tea should seek medical advice before taking their sildenafil therapy.

Open Access Original Research Article

In vitro Antioxidant, Antihyperglycaemic and Antihyperlipidaemic Activities of Ethanol Extract of Lawsonia inermis Leaves

Oyesola O. Ojewunmi, Tope Oshodi, Omobolanle I. Ogundele, Chijioke Micah, Sunday Adenekan

Journal of Pharmaceutical Research International, Page 301-314
DOI: 10.9734/BJPR/2014/6359

Aim: This present study investigated the free radical scavenging activities, antihperglycaemic and antihyperlipidaemic activities of ethanol extract of Lawsonia inermis leaves.
Study Design: Twenty male rats were randomly and evenly distributed into four groups, and were subsequently exposed to the following treatments for twenty-one days: Group I (Control): Normal saline; Group II: Untreated Diabetic control; Group III: Diabetic rats treated with glibenclamide (600mg/Kg. b.wt); Group IV: Diabetic rats treated with ethanol extract of Lawsonia inermis (400mg/Kg b.wt).
Place and Duration of Study: This work was carried out in the Department of Biochemistry, University of Lagos, Lagos, Nigeria between November 2012 and February 2013.
Methodology: Phytochemical screening and the antioxidant activities of the plant extract were carried out. Brine shrimp lethality assay was also carried out on the plant extract for In vitro toxicity assay. Blood samples collected from the experimental rats were used for the determination of fasting blood sugar and biochemical profiles following the last oral treatment and an overnight fast.
Results: Lawsonia inermis showed maximum inhibition of 77.39%, 50.78% and 83.18 % at 100µg/ml DPPH free radical scavenging activity, in vitro lipid peroxidation and nitric oxide respectively. Following twenty-one days of treatment with oral administration of ethanol extract of Lawsonia inermis leaves, fasting blood glucose was significantly reduced (P<0.001) compared to the untreated diabetic control. Activities of AST, ALT, and ALP were significantly decreased (P<0.001) in the diabetic rats treated with the extract compared to the untreated diabetic control rats. Diabetic rats treated with ethanolic leaf extract of Lawsonia inermis showed statistically significant decrease (P<0.001) in the levels of total cholesterol, total triglyceride and low density lipoprotein cholesterol when compared with untreated diabetic rats.
Conclusion: The ethanol extract of Lawsonia inermis leaves showed antioxidant, antihyperglycaemic and antihyperlipidaemic activities.

Open Access Original Research Article

Evaluation of Anti-diabetic Potentials of Methanol Extract of Ficus hispida Linn. Leaves Against Alloxan Induced Diabetic Rats

V. D. Ravichandra, Padmaa M. Paarakh

Journal of Pharmaceutical Research International, Page 315-324
DOI: 10.9734/BJPR/2014/5187

Objective: The present study was designed to evaluate the acute and chronic effects of the methanol extract of Ficus hispida against alloxan (150 mg/kg) induced diabetic rats.
Methods: In acute study, hypoglycemic potency of methanol extract of Ficus hispida was assessed by oral glucose tolerance test (OGTT) and in chronic study of 21 days, extract at different doses ( ie 100, 200 and 400 mg/kg) was screened for itsanti-diabetic activity. Blood glucose level had been estimated at 0, 7th, 14th and 21st and addition to this serum concentrations of insulin, triglycerides, cholesterol, serum glutamate oxaloacetae transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and urea determined at 21st day of the study.
Results: In OGTT, standard glibenclamide and extract (200 and 400 mg/kg) have shown significant reduction in blood glucose level compared to control group. In chronic model, the methanol extract was effective in reducing the blood glucose levels (P <0.001) at higher dose (200 mg/kg and 400 mg/kg) and effect was comparable to that of standard. The extract could also significantly (P<0.001) reduced level of SGOT, triglycerides and cholesterol in serum and significantly (P<0.001) increased the insulin level in blood which proves beneficial antidiabetic potentials of the extract in diabetic model. The change in concentrations of SGPT and urea were not significant (P>0.05).
Conclusion: The methanol extract of Ficus hispida posses significant anti-diabetic activity in alloxan induced diabetis in rats model.

Open Access Original Research Article

The Utilization Pattern and Costs Analysis of Psychotropic Drugs at a Neuropsychiatric Hospital in Nigeria

Charles C. Ezenduka, Vincent N. Ubochi, Brian O. Ogbonna

Journal of Pharmaceutical Research International, Page 325-337
DOI: 10.9734/BJPR/2014/5988

Background/Aim: Drug utilisation study is essential for evaluating patient care to improve service delivery through awareness creation for appropriate choice of drugs. The study analysed the prescription pattern and associated costs of psychotropic drugs at the outpatient unit of a mental health facility in Nigeria, to assess and document information for enhancing rational and cost-effective use of psychotropic medicines.
Methods: A retrospective analysis of prescription records covering 8 September and 28 October 2008, was carried out using the WHO recommended use indicators, adapted for mental health care. Data was analysed for number of drugs, number of prescriptions, cost of prescription and cost per defined daily dose (DDD).
Results: 1,756 prescriptions were analysed. Each prescription contained an average of 2.1 (±0.75) drugs, at a mean cost of N1, 089 (±N2, 127). Antipsychotics accounted for the highest number of prescribed drugs in 82% (1441/1756) of prescriptions, followed by antidepressants, 13%. Atypical antipsychotics were the most expensive psychotropics at an average cost per DDD of N241.67 (±N97.77), about 35 times the average cost per DDD of traditional psychotropics at N7.00 (±N2.65), which were the cheapest, accounting for over 90% of total prescriptions.
Conclusion: The high use frequency of antipsychotics suggests psychosis as the prevalent mental health disorders in the environment. Significant antipsychotic-antipsychotic combinations indicate scope for improving the use of antipsychotics. Average cost of prescription reflects the economic status of patients’ population where cost appears to be the major consideration of the choice of prescribers, limiting the use of newer and better tolerated psychotropics. Policy measures are required to improve access to the utilisation of newer psychotropics for enhanced quality of life of patients. The study provides a baseline data for carrying out further utilisation studies, to provide regular information for improving psychotropic drugs utilisation in mental health facilities in Nigeria.

Open Access Original Research Article

Superporous Hydrogel Composites of Acrylamide Using Starch-silicone Dioxide Coprecipitate as Composite Agent

Ashwani Goyal, Manju Nagpal, Shikha Bhalla, Gitika Arora Dhingra

Journal of Pharmaceutical Research International, Page 338-351
DOI: 10.9734/BJPR/2014/6277

Aim: Present study includes the development and evaluation of superporous hydrogel composites of acrylamide using starch silicone dioxide coprecipitate (SSC) as composite agent.
Methodology: Gas blowing method was used for synthesis of superporous hydrogels. Different ingredients were mixed in specified amount in test tube and foaming agent was added at last. Simultaneous foaming and gelation lead to formation of porous hydrogel networks. Effect of different treatments (acetone dehydration and simulated gastric fluid (SGF) treatment) and drying conditions on the porous structure was evaluated. The prepared superporous hydrogels were evaluated for density, porosity, equilibrium swelling ratio, equilibrium swelling time, mechanical strength, scanning electron microscopy studies. The pure drug (Verapamil Hydrochloride) mixed with Carbopol 934 (1:0.5 and 1:1 ratio) was loaded into the selected batches of SPHC using in situ method of drug loading (drug added directly into the reaction mixture). The in vitro drug release was carried out using USP II dissolution apparatus.
Results: Acetone dehydrated superporous hydrogel composites were observed as better floating devices due to least density and maximum porosity values. Maximum swelling ratio was found in case of oven dried conventional superporous hydrogel and superporous hydrogel composites with equilibrium swelling time of more than 25 min. On the other hand, acetone dehydrated SPH showed less equilibrium swelling ratio with equilibrium swelling time of 5-10 min. Minimum swelling ratio was observed in case of SGF treated hydrogels with equilibrium swelling time of 15-19 min. Mechanical strength was improved by addition of starch silicone dioxide coprecipitate as composite agent. SGF treatment also leads to enhanced mechanical strengthbut compromised swelling characteristics. SEM images showed uniformity in pore structure in case of acetone dehydrated hydrogels. Acetone dehydrated SPHC showed sustained drug release behavior with 71.14% and 57.84% of verapamil released in 12 h in the batches with Drug: Carbopol 934ratio of (1:0.5 and 1:1) respectively.
Conclusion: Acetone dehydrated SPHC were found to be promising formulations with sufficient swelling and mechanical properties for achieving sustained drug delivery.

Open Access Original Research Article

Reduction in Serum Bilirubin Concentration Following Administration of Crude Leaf Extract of Viscum album (Mistletoe) in High Salt Fed Rats

Ofem Ofem Effiong, Nna Victor Udo, Essien Nsima Monday

Journal of Pharmaceutical Research International, Page 352-361
DOI: 10.9734/BJPR/2014/7359

Aims: This study was designed to determine the effect of a high salt diet on serum bilirubin concentration and to ascertain the impact of treatment with Viscum album on same.
Methodology: Twenty male albino wistar rats weighing 150 - 200g were used for this study. After seven days of habituation, the animals were randomly divided into four (4) groups of five rats each. Group 1 (NC) served as control and were fed with normal rat pellet and water; group 2(NT) served as the control treated group (administered 150 mg/kg Viscum album orally, in addition to rat pallet and water); group 3 (SF) served as the high salt diet fed group (without treatment), while group 4 (ST) served as the high salt diet fed group, treated orally with 150 mg/kg Viscum album. The feeding regimen lasted for six weeks, after which the animals were sacrificed and blood samples collected for analysis.
Results: Mean serum total bilirubin concentration was significantly (p<0.001) higher in the SF group compared to control, NT and ST group. It was also significantly (p<0.001) lower in the ST group compared to SF group. Serum conjugated bilirubin concentration was significantly (p<0.001) increased in the SF group compared to NC, NT and ST group. It was also significantly (p<0.001) reduced in the ST group compared to the SF group. Serum unconjugated bilirubin concentration was significantly (p<0.001) increased in the SF group compared to NC, NT and ST group. Serum unconjugated bilirubin concentration was significantly (p<0.01) lower in the ST group compared to SF group.
Conclusion: Our results are indicative of the fact that oral administration of Viscum album reduces serum bilirubin concentration in high salt fed animals.

Open Access Original Research Article

Hepatoprotective Effect of Momordica charantia Extract against CCl4 Induced Liver Damage in Rats

S. B. Mada, H. M. Inuwa, M. M. Abarshi, H. A. Mohammed, A. Aliyu

Journal of Pharmaceutical Research International, Page 368-380
DOI: 10.9734/BJPR/2014/4885

Aim: The study was aimed to evaluate Momordica charantia leaves extract for hepatoprotective effect against carbon tetrachloride (CCl4) induced hepatotoxicity in rats.
Methodology: A total of twenty five male rats were randomly divided into five groups of five rats each. The extract was administered orally for fifteen days at 200 and 400 mg/g body weight.
Results: The results obtained showed that, treatment with the extract significantly (P<0.05) restored liver weight to near normal. The result showed a significant (P<0.05) increase in Heamoglobin (Hb) and Packed Cell Volume (PCV) compared to toxin control group. Also treatment with the extract caused a significant (P<0.05) decrease in the activities of Alanine Transaminase (ALT), Aspartate Transaminase (AST), Alkaline Phosphatise (ALP) and the level of total bilirubin: and a significant (P<0.05) increase in total protein level compared to control group. Similarly, the extract caused a significant (P<0.05) decrease in the level of reduced Glutathione (GSH) and Malondialdehyde (MDA) and a significant (P<0.05) elevation in the activities of Superoxide Dismutase (SOD) and Catalase (CAT) compared to toxin control group.
Conclusion: This study found that, administration of aqueous leaves extract of M. charantia ameliorated hepatotoxicity induced experimentally by CCl4.

Open Access Original Research Article

Design and Evaluation of Imatinib Mesylate Loaded Microspheres for Stomach Specific Drug Delivery

Rangasamy Manivannan, Bandaru Lakshmi Narayana Rao, Venkata Krishna Reddy

Journal of Pharmaceutical Research International, Page 381-396
DOI: 10.9734/BJPR/2014/6444

Aims: The aim of the present work was to design and evaluate the Imatinib mesylate microspheres using natural and semi synthetic polymers for stomach specific drug delivery.
Study Design: Design and Evaluation of Imatinib Mesylate loaded microspheres
Place and Duration of the Study: The study was carried out in Department of Pharmaceutics, JKKMMRF’s Annai JKK Sampoorani Ammal College of Pharmacy, between November 2012 and July 2013.
Methodology: The microspheres were prepared using Sodium alginate as a polymer by Emulsification Ionic Gelation Technique. Copolymers of natural origin namely Guar gum, Karaya gum, Chitosan and semi synthetic origin namely Hydroxy propoylmethyl cellulose K4M, K15M, K100M are used as mucoadhesive polymers. The prepared microspheres were evaluated for their percentage yield, entrapment efficiency, degree of swelling, particle size, surface morphology and in-vitro mucoadhesion, drug release studies. Drug release kinetics was determined from drug release data. Selected formulations are subjected to stability studies under varying conditions of temperature and humidity.
Results: The production yields of microspheres were found to be between 76.74 to 88.18%. Percentage drug entrapment efficiency of Imatinib mesylate microspheres was ranged from 65.51 to 88.78%. Particle size of the prepared microspheres was in the size range of 440-810µm. SEM analysis revealed that all the prepared microspheres were discrete, spherical in shape. The in-vitro mucoadhesive study demonstrated that Hydroxy propoylmethyl cellulose adhered to the mucus to a greater extent than other polymers. The in-vitro release study shows that, retarded release with increase in percentage of polymers. The release of drug from the microspheres followed Krosmeyer Peppas kinetics. After the stability studies, the formulations remained stable at the end of storage period.
Conclusion: Based on the results, it was concluded that, the formulations with natural polymers were found to be best than semi synthetic polymers for the oral delivery of Imatinib mesylate.

Open Access Original Research Article

Evaluation of the Antioxidant Activities of Psidium guajava and Aloe vera

Chibuike Ibe, Conrad Chimezie Jacobs, Chinedu Imo, Kelechi Uzoma Osuocha, Monday Uchenna Okoronkwo

Journal of Pharmaceutical Research International, Page 397-406
DOI: 10.9734/BJPR/2014/6989

This paper aimed to study the antioxidant properties of two Nigerian plants Psidium guajava (guava) Myrtaceae and Aloe vera Liliaceae plants which have a broad application in phytomedicine. The plants were assessed by quantifying their individual chemical contents and their 1:1 (mass/mass) homogenous combination (guava+A. vera) simultaneously. The non-antioxidant phytochemical quantified included total alkaloids. There was a significant difference in the total alkaloids content (measure on dry weight basis, mg/g) in the analysed plant materials in the order of guava (111.13±0.45)>guava+A. guava (65.99±0.37)>A. vera (22.86±0.15). The antioxidant properties measured were the levels of total phenol, tannin, total flavonoid, total saponin, vitamin C, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging ability and trolox equivalent antioxidant capacity (TEAC). P. guajava recorded significantly higher (p<0.05) antioxidant phytochemicals contents than A. vera except for vitamin C where it recorded significantly lower (p<0.05) value. There was no significant difference (p>0.05) in the vitamin C contents of A. vera and the combined plant materials, guava+A. vera. Guava had also significantly higher (p<0.05) DPPH scavenging ability (0.056 mg/ml), and TEAC (12.51±0.40 mM/gdw) than A. vera. The combined plant materials guava+ A. vera showed synergistic properties in the DPPH free radical scavenging ability (0.15 mg/ml) and antagonistic activity in the TEAC (4.58±0.17 mM/gdw). This study suggests that while guava may be a better antioxidant than A. vera when used separately, the combined plant materials produces synergistic antioxidant interaction, which could be used to enhance their medicinal applications.