Journal Article

Modulation of Drug Release from Natural Polymer Matrices by Response Surface Methodology: in vitro and in vivo Evaluation

Moin, Afrasim, Ashraf, Syed A, Allam, Ahmed N, Patel, Mitesh, Gangadharappa, Hosahalli V, Abu Lila, Amr S, Adnan, Mohd, Rizvi, Syed M

2020

Overview

The present work aimed at challenging the efficacy of natural gums, karaya and locust bean gum, as matrix-forming polymers for the formulation of sustained-release tablets of diltiazem, a model drug. Central design composite was adopted for the formulation and optimization of tablet formulations. The two gums have been selected as independent variables. The dependent factors chosen were the amount of drug released in 1st hour (Y1), amount of drug released after 12 h (Y2), diffusion exponent (Y3), and time for half of the total drug released (T ) (Y4). Wet granulation approach was used for the formulation of tablets. FT-IR, DSC, in vitro dissolution, swelling-erosion investigations, SEM, and stability studies were carried out. It was evident that the release pattern from the prepared formulations was significantly influenced by the quantity of gum(s) in the tablet. FT-IR and DSC results confirm drug-polymer compatibility. Polynomial equations were used for the prediction of quantitative impact of independent factors at different levels on response variables. After ANOVA analysis, the significant factors were considered for constrained optimization to get the optimized formula. The optimized formula generated by the response surface methodology was evaluated both for in vitro and in vivo properties. The optimized formula and a sustained-release marketed product were subjected to in vivo studies in rabbits and the results of the -test demonstrated insignificant variation in pharmacokinetic parameters among the two formulations, confirming that the prepared tablet showed sustained-release profile. The results indicated that karaya and locust bean gum can be effectively used to formulate sustained-release tablets.

• Publisher: Dove Medical Press Limited,Taylor & Francis Ltd,Dove Press,Dove,Dove Medical Press
• Subject: Analysis / Animals / Antihypertensive Agents - chemistry / Antihypertensive Agents - pharmacokinetics / Beans / Biocompatibility / Biological Products - chemistry / Controlled release / Dependent variables / Diltiazem / Diltiazem - chemistry / Diltiazem - pharmacokinetics / diltiazem hydrochloride / Drug development / Drug dosages / Drug Liberation / Formulations / Fourier transforms / Galactans - chemistry / Granulation / Gums / In vitro methods and tests / In vivo methods and tests / Independent variables / Investigations / karaya gum / Locust bean gum / Mannans - chemistry / Methods / Natural polymers / Optimization / Original Research / Patient compliance / Pharmaceuticals / Pharmacokinetics / Plant Gums - chemistry / Polymer blends / Polymers / Polymers - chemistry / Polynomials / Product introduction / Rabbits / Response surface methodology / Sterculia - chemistry / Surface Properties / sustained release / Tablets / Variance analysis