Open Access Original Research Article

Anti-bacterial and in vitro Anti-diabetic Potential of Novel Isoxazole Derivatives

Lincy Joseph, Mathew George

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/BJPR/2016/21926

Aim: To synthesize novel Isoxazole derivatives, characterize them and subject for screening anti-bacterial action and in vitro anti-diabetic activity.

Methodology: Chalcones were prepared by the reaction of aromatic aldehydes with aromatic ketones in aqueous alcoholic alkaline medium. Then these were made to react with hydroxylamine hydrochloride and sodium acetate to prepare title compounds. The prepared isoxazole compounds were subjected to in vitro anti-diabetic screening by yeast and enzymatic method. All compounds were screened for antibacterial action by disc diffusion method.

Results: The structure of the synthesized compounds were confirmed by IR, NMR spectral datas and screened for anti-bacterial, and anti-diabetic activities. Most effective antibacterial one possessed chlorine in the Phenyl ring attached at 5-C of isoxazole and have NH2 substitution in phenyl ring attached at 3-C of isoxazole. Compounds with significant in vitro anti-diabetic action by studying the glucose uptake by yeast cell method are with Br/NO2 substituted forR2/R3 in phenyl ring when R’2 is OH/NH2.

Conclusion: Presence of halogenated aromatic ring at 5-C and amine substituted phenyl ring at 3-Cof Isoxazole exhibited moderate anti-bacterial activity. In the anti-diabetic study halogenated or nitrated phenyl ring at 5-C and hydroxyl/amine substituted phenyl ring at 3-C of isoxazole exhibited anti-diabetic action.

Open Access Original Research Article

Development, Characterization and Ex vivo Evaluation of Various Liposome-encapsulated Aceclofenac Formulations

Fathy Ibrahim Abd-Allah

Journal of Pharmaceutical Research International, Page 1-12
DOI: 10.9734/BJPR/2016/22501

Aim: Formulation of aceclofenac (ACE) into liposomal gel, improving its skin permeation and potentiate its local anti-inflammatory effect.

Methodology: ACE liposomes were fabricated by lipid film hydration technique. The prepared formulations were traditional liposomes containing cholesterol (F1), ultra-deformable liposomes containing Tween 60 (F2) and modified liposomes containing both cholesterol and Tween 60 (F3). All formulations were incorporated in 1% carbopol 974 as gelling agent. The developed liposomal formulations were evaluated for its particle size, zeta potential, drug entrapment efficiency percent and stability for 90 days at 4°C. While the developed liposomal gel formulations were characterized for its in vitro ACE release and ex vivo permeation through rat skin. Anti-inflammatory effect of ACE gel formulations were evaluated in rats using carrageenan induced paw edema.

Results: The prepared liposomes had a mean vesicle size of 577 nm, 218 nm and 332 nm for F1, F2 and F3 respectively and entrapment efficiency percent of 76.8%, 58.3% and 66.2% for F1, F2 and F3 respectively. The stability study revealed that F1 vesicles have the highest physical stability followed by F3, while F2 showed the lowest stability in terms of vesicles size and entrapment efficiency percent. The in vitro and ex vivo results showed higher drug release and permeability from F2 and F3 than that of F1. In addition, ACE liposomal formulations have significant higher anti-inflammatory effect than that of marketed product Bristaflam cream®.

Conclusion: All liposomal gel formulations have the ability to enhance ACE anti-inflammatory effect in rats paw edema in comparison with marketed product Bristaflam cream®.

Open Access Original Research Article

Phytochemical and Pharmacological Basis for the Ethnomedicinal Use of Root Extracts from Anogeissus leiocarpus as an Antidiabetic in Eastern Nigeria

Edwin O. Omeje, Patience O. Osadebe, Wilfred O. Obonga, Christopher E. Ugwuoke

Journal of Pharmaceutical Research International, Page 1-8
DOI: 10.9734/BJPR/2016/22289

Purpose: To obtain and validate evidence for or against the continued traditional use of A. leiocarpus root extract as an antidiabetic.

Methods: Aqueous methanol, ethanol, trona-treated ethanol extracts of the plant whole root, were screened for antidiabetic activity using alloxan-induced diabetic rats at three different oral dose levels (100-500 mg kg-1day-1) against standards. Phytochemical and acute toxicity tests were also carried out on the extracts.

Results: Tannins, saponins, carbohydrates occurred in very high amounts while steroids, terpenoids alkaloids, flavonoids and resins were moderate. The extracts exhibited a dose-dependent potent and statistically significant (p<0.05, ANOVA) antidiabetic activities up to the dose of 200 mg kg-1 compared to the untreated group with a glucose reduction values of 52.69±5.99% and 66.61±5.79%, respectively, at 12 and 24 h compared to 24.39±1.54% and 38.79±4.06% recorded for the positive control. Above 200 mg/kg dose, the extract did not produce additional activity. The calculated LD50 values of all the extracts were above 10,000 mg kg-1 in mice.

Conclusion: This study validates the traditional use of root extracts of A. leiocarpus as a potent, cheap and alternative antidiabetic remedy.

Open Access Original Research Article

Comparision of Different Techniques Involved in the Development of Ivabradine HCL Floating Pulsatile Multiparticulate Systems for Chronotherapeutic Delivery

Vani Prasanna Tubati, T. E. Gopala Krishna Murthy, A. Samba Siva Rao

Journal of Pharmaceutical Research International, Page 1-12
DOI: 10.9734/BJPR/2016/22566

Aims: To develop Ivabradine HCl floating pulsatile multiparticulate (beads/ pellets) dosage forms containing calcium alginate beads/ pellets coated with pH-dependent polymer Eudragit S 100, by ionic gelation, pan coating, fluidized bed coating techniques and optimization of technique by comparing evaluation parameters with statistical data.

Study Design: Ionic Gelation, Pan Coating, Fluidized Bed Coating Techniques and comparison and optimization of suitable technique.

Place and Duration of Study: Bapatla College of Pharmacy. Bapatla, Guntur (district), Andhra Pradesh, India - 522101. June 2015 to September 2015.

Methodology: Multiparticulates were prepared by Ionic gelation, pan coating , fluidized bed coating methods employing 1:5 drug : polymer (sodium alginate5%w/v) ratio ,5%w/v cacl2 as cross-linking agent and further coated with 6% w/w Eudragit S100 dispersed in 10% w/v of oil. These multi particulates were evaluated for % drug entrapment efficiency, Micromeritics, in vitro floating behaviour, in vitro drug release at PH 1.2 and 7.4, Kinetics and statistical analysis of these parameters.

Results: Multiparticulates prepared by Ionic gelation technique exhibited very less % drug entrapment efficiency when compared to other two techniques. 

In pan coating technique lumps were formed and these particles exhibited poor flow properties besides low % of buoyancy when compared to other two techniques.

Multiparticulates prepared by fluidized bed coating technique exhibited excellent flow properties, good entrapment efficiency and floating behaviour furthermore these particles also showed lag phase and pulsatile release.

Statistical analysis revealed that there was no significant difference between pan and fluidized bed coating techniques in % drug entrapment efficiency.

In case of  floating lag time  significant difference was not exhibited by multiparticulates prepared by ionic gelation technique and fluidized bed coating technique as (P >.05).

Conclusion: The results confirmed that Fluidized bed coating technique was optimized for preparation of floating pulsatile multiparticulates of Ivabradine HCl.

Open Access Original Research Article

Effects of Ethanolic Extract of Dioscorea villosa Tubers on Male Reproductive Parameters in Wistar Rats

Seriki A. Samuel, Adebayo O. Francis, Nnanna J. Uche, Ike C. Emmanuel

Journal of Pharmaceutical Research International, Page 1-14
DOI: 10.9734/BJPR/2016/21719

Aim: The current study investigates the effect of the ethanoic extract of Dioscorea villosa on male reproductive parameters using wistar rats.

Study Design: Twenty four male rats were randomly sorted into 6 groups (4 rats/group). Group 1 served as the short term control group and Group 2 served as the long term control group. Both groups were given water and rat chow ad libitum with no dose of the extract. Group 3 served as the short term low dose group and Group 4 as the long term low dose group. Both groups were administered 100 mg/kg body weight of Dioscorea villosa extract for 14 days and 28 days respectively using distilled water as the medium. Group 6 served as the short term high dose group and group 5 as the long term high dose group. Both groups were administered 400 mg/kg body weight of the Dioscorea villosa extract for 14 days and 28 days respectively, using distilled water as the medium.

Methodology: After the last day of administration (the 15th for the short term groups and the 29th day for the long term groups), the animals were sacrificed by cervical dislocation, fasting serum samples were obtained for the sex hormone analysis, cauda epididymis were dissected for sperm count, motility and viability, and organ weights of the testis and seminal vesicle were taken. Histopathological changes of the testis were also studied.

Results: Dioscorea villosa extract caused significant changes in the sperm count, serum FSH, LH and Testosterone levels of the short term groups and a significant change in the serum Testosterone level of the long term group. There was an increase in the sperm count in the short term groups when compared to the short term control group with that of the high dose being statistically greater than the low dose group. The serum levels of follicle stimulating hormones (FSH), luteinising hormones (LH) and Testosterone decreased in the low dose group but were all increased in the high dose group when compared to the short term control. The long term group recorded an increase in the serum testosterone level in the high dose group when compared with the long term control group. There however was no significant improvement in the sperm motility and viability of the groups given low and high dose of extract when compared to that of the control group. There was no any statistically significant changes in the weight differences of the rats between the experimental and control groups. The control group showed a decrease in weight of -8.30±6.86% while the low dose (100 mg/kg bwt) and high dose (400 mg/kg bwt) groups showed differences of -6.80±3.25% and 1.44±1.73% respectively. There was also no significant weight loss or weight gain of the reproductive organs (testis and seminal vesicles) was noticed, in both the short term low dose (100 mg/kg bwt) and high dose (400 mg/kg bwt) groups when compared to that of the control group.

Conclusion: The result suggests that Dioscorea villosa has significant effects on male reproductive parameters both in short term and long term administration. It also showed significant effect both in low and high doses.

Open Access Original Research Article

Assessment of Knowledge and Awareness about Atherosclerosis and Incidence of Cardiovascular Events among Undergraduate Pharmacy Students in Bangladesh

Md. Sahab Uddin, Md. Asaduzzaman, Abdullah Al Mamun, Mamunur Rashid

Journal of Pharmaceutical Research International, Page 1-13
DOI: 10.9734/BJPR/2016/22068

Aims: To examine how much knowledge and awareness undergraduate pharmacy students of Bangladesh have about atherosclerosis and incidence of cardiovascular events.

Study Design: The study was conducted on 500 undergraduate pharmacy students randomly selected, in which 48% were males and remaining 52% were females. Nearly 50% of the participants were 3rd year students and remaining 50% were 4th year students. Each willing participant shared their knowledge.

Place and Duration of Study: Department of Pharmacy, Southeast University, Dhaka-1213, Bangladesh, from May to July 2015.

Methodology: A questionnaire was distributed among the students, information on the knowledge and awareness about atherosclerosis and incidence of cardiovascular events were collected.

Results: The present study revealed that 75% students have knowledge and awareness about the general information 69% about the risk factors, 60% about the symptoms, 80% about the treatments and 44% about the diagnosis of atherosclerosis and incidence of cardiovascular events.

Conclusion: Undergraduate pharmacy students have good knowledge about treatments of atherosclerosis and incidence of cardiovascular events, since pharmacists are more prone to drugs. But considerable knowledge and awareness are necessary about the risk factors, symptoms, especially diagnosis of respective diseases in order to be competent pharmacists.

Open Access Original Research Article

Effect of Resveratrol on Some Haematological Parameters of Lead-intoxicated Male Wistar Rats

Salisu Muhammad Highab, Danjuma Nuhu Muhammad, Musa Aliyu, Bala Yauri Muhammad

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/BJPR/2016/22341

The aim of this experiment was to investigate the effect of resveratrol on haematological parameters of lead-induced toxicity in male wistar rats. The study employed 36 male wistar rats (150 - 250 g) divided equally into six (6) groups. The first group (negative control) was administered carboxymethylcellulose (CMC) 10 g/L body weight (BW) daily for 19 days. The second group (positive control) was administered lead acetate solution (120 mg/kg BW) daily for 2 weeks. The third group was administered lead acetate solution (120 mg/kg BW) daily for 2 weeks then treated with succimer (10 mg/kg BW) daily for 5 days. The fourth group was administered lead acetate solution (120 mg/kg BW) daily for 2 weeks then treated with resveratrol (200 mg/kg BW) daily for 5 days. The fifth group was administered lead acetate solution (120 mg/kg BW) daily for 2 weeks then treated with resveratrol (400 mg/kg BW) daily for 5 days. The sixth group was pretreated with resveratrol (400 mg/kg BW) daily for 5 days then administered lead acetate solution (120 mg/kg BW) daily for 2 weeks and considered as prophylactic group. All treatments were administered orally by gavage. The animals were euthanized and blood sample were taken for heamatological analysis. In the result, there was significant (P < 0.05) increase in platelet counts in group 5 compared to both negative and positive control groups. No significant (P > 0.05) change was recorded for the other heamatological parameters, when the resveratrol-treated groups were compared to negative and positive control groups. No significant (P > 0.05) change was recorded for the other heamatological parameters, when the resveratrol-treated groups were compared to negative and positive control groups. Thus, the effect of resveratrol in platelet level is dose dependent. This study also observed that all the groups had normal levels of packed cell volume (absence of anemia).

Open Access Original Research Article

Ion-pair HPLC Method for the Quantification of Metformin in Human Plasma and Its Application to a Pharmacokinetic Study

Eva Troja, Leonard Deda, Gëzim Boçari

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/BJPR/2016/21436

Aims: To develop and validate a rapid, selective and sensitive ion-pairing HPLC-UV method for the determination of metformin in human plasma, using a conventional reverse phase column.

Study Design: Experimental study.

Place and Duration of Study: Department of Department of Biomedical Sciences, Faculty of Medicine, University of Medicine, “Mother Tereza” hospital center, between November 2014 and February 2015.

Methodology: Ion-pair separation followed by UV detection performed on deproteinised and dichloromethane washed plasma samples was chosen for the determination of metformin. The separation was performed on an analytical LiChrocart® 100 RP 18 (125 × 4.0 mm i.d., 5 µm particle size) C18 column. A mobile phase consisting of acetonitrile and 10 mM sodium phosphate buffer (pH=6.0; 32.5:67.5, v/v) and sodium dodecyl sulfate (0.3%) was pumped at an isocratic flow rate of 1.25 mL/minute, and quantification was achieved at 236 nm using a UV/Vis DAD.

Results: The calibration curves were linear (r > 0.9998) in the concentration ranges of 50-1600 ng/mL for metformin in plasma. The assay enables the measurement of metformin for therapeutic drug monitoring with a minimum detectable limit of 18 ng/ml. The coefficients of variation for inter-day and intra-day assay were within the range of clinical usefulness. Absolute recovery was found to be > 90% for all three concentrations of plasma quality controls studied.

Conclusion: The proposed method was found to be rapid, precise and accurate for quantification of metformin in human plasma. This method was successfully applied to a pharmacokinetic study at humans through oral administration.