International Journal of Pharmaceutical Sciences and Drug Research

362-371

Authors: I. Srinivas, D.V.R.N Bhikshapathi*

In the present study, immediate release solid dispersion of Repaglinide was formulated by solvent evaporation technique. Repaglinide solid dispersions were prepared using PEG 8000, Pluronic F 127 and Gelucire 44/14 by solvent evaporation method. A 3-factor, 3-level central composite design employed to study the effect of each independent variable on dependent variables. FTIR studies revealed that no drug excipient interaction takes place. From powder X-ray diffraction (p-XRD) and by scanning electron microscopy (SEM) studies it was evident that polymorphic form of Repaglinide has been converted into an amorphous form from crystalline within the solid dispersion formulation. The correlation coefficient showed that the release profile followed Higuchi model anomalous behavior and hence release mechanism was indicative of diffusion. From in vivo studies, the AUC0→24 h and peak plasma concentration (Cmax) was doubled when compared with pure drug. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The obtained results suggested that developed solid dispersion might be an efficacious approach for enhancing the solubility and bioavailability of Repaglinide.

379-385

Authors: Dhiraj Kumar1*, Susanta Kumar Panda2, Sudhir Kumar Sahoo2

A precise, accurate, economical and simple stability indicating RP-HPLC method was developed for the estimation of Amlodipine (AML) and Olmesartan (OLM) in bulk and pharmaceutical dosage form. Method was performed on a octadecyl silane column with dimensions 4.6 x 250 mm having particle size 5 micron. The mobile phase used in the method is TEA Buffer (pH 3.0) and acetonitrile in proportion of 25:75 respectively. The flow rate was maintained at 1.0 ml/ min and effluent was monitored at 258 nm. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis and heat as stress conditions. The method was validated for specificity, linearity, precision, accuracy, robustness and system suitability. The retention times were observed at 2.39 min and 3.33 min for AML and OLM respectively. The standard curve was found linear over a range of 05–35 µg/ml for AML and OLM. Similarly an average correlation coefficient was also obtained at 0.999 for AML and OLM. The limit of quantitation (LOQ) of this method was 2µg/ml for Amlodipine and Olmesartan. The absolute recovery was 100% for Amlodipine and 100.3 for Olmesartan. Degradation products produced as a result of stress studies did not interfere with the detection of AML and OLM and the assay can thus be considered stability-indicating.

394-405

Authors: Jeetu Gangil1*, Bhaswat S. Chakraborty2

Despite progress in antimalarial management and intensive care, the prevalence of malaria is growing and the mortality rate is very high. Yet even with timely treatment of quinine in maximum doses, the death in patients of severe malaria is very high. The successive synthesis of artemether and artesunate has supplied highly successful substitutes to quinine. This systematic review and meta-analysis approach provides a comparative outcome analysis of Artemisinin derivatives (intervention) and other antimalarials (comparison) in the paediatric and adult population. From the year 1985 to the year 2015, studies were recognized using database searches, citation searches of selected articles. The electronic databases searched engines: Pubmed, Web of Science, Global Health, Medline & Cochrane review of Journals up to April 2015. We selected published randomized controlled clinical trials information comparing artemisinin derivatives and quinine for the management of severe malaria in adult and paediatric population as per WHO malaria treatment guideline, any gender, age group less than or greater than 15 years who were diagnosed with severe malaria. The primary outcome was efficacy in terms of parasite clearance time (PCT), Parasite clearance at D7 and D28 and fever clearance time (FCT). The secondary outcome was the mortality and adverse events. We measured 95% confidence interval by the using of REVMAN software version 5.3 for meta-analysis and summarized the collected data on the basis of characteristics of inclusion criteria of articles. We included total 33 RCTs, enrolling 8396 paediatric and adult patients who were suffering from severe malaria. Artemisinin and its derivatives showed mean parasite clearance time (PCT) (MD -8.50 hours, 95% CI -9.41 to -7.60) and mean fever clearance time (FCT) (MD -9.51 hours, 95% CI -11.22 to -7.81) P<0.00001 statistically significant as compared to quinine therapy. Artemisinin and its derivatives showed a statistically significant clearance of parasites when compared to quinine at Day 7 (OR 0.41, 95% CI 0.21, 0.81, random effect model, P=0.01). Overall artemisinin derivatives has shown more parasite clearance at D28 than quinine group (Odds ratio 0.54, 95% CI 0.23, 1.29, random effect model, P=0.17). We evaluated secondary outcomes mortality which showed artemisinin or its derivatives a statistically significant mortality reduction as compared to quinine. (Odds Ratio 0.77, 95% CI 0.67 to 0.89; 27 trials, 8396 participants) P=0.0002 and also showed a statistically significant reduction in the adverse events as compared with quinine (RR0.73, 95% CI 0.62 to 0.87) P=0.003. An overall positive result was found with artemisinin derivatives across all evaluated outcomes.

410-417

Authors: B. Ram Prasad, D.V.R.N. Bhikshapathi*

The purpose of the present study was to develop and optimize multi-layered matrix tablets of Gliclazide trilayer tablets to achieve zero-order drug release for sustained plasma concentration. Gliclazide tablets were prepared by direct compression and consist of middle active layer with different grades of hydroxypropyl methylcellulose (HPMC K 4M, K 15M and K100M), Guar gum and Eudragit L 100. The tablets were also evaluated for physicochemical characteristics and release kinetics. The physicochemical characteristics of the prepared tablets were satisfactory. The developed drug delivery systems showed prolonged drug release rates over a period of 24 h. In vivo bioavailability studies were carried out on the optimized formulation (EF14), mean time to attain peak drug concentration (Tmax) was 6.00 ± 0.14 and 4.02 ± 0.12 h for the optimized and marketed product respectively, while mean maximum drug concentration (Cmax) was 124.80 ± 1.02 ng/ml and 95.12 ± 1.05 ng/ml respectively. AUC0-α and AUC0-t for optimized formulation was significantly higher (p<0.05) as compared to marketed product. A fair correlation between the dissolution profile and bioavailability for the optimized formulation was observed. The results indicate that the approach used could lead to a successful development of a controlled release formulation of the drug. The EF14 was shown significant plasma concentration with controlled release and maintained for 24 hours with patient compliance by reducing the dosage frequency, when compared with marketed product in the efficient management of Diabetes mellitus.