A Cost Effective (QbD) Approach in the Development and Optimization of Rosiglitazone Maleate Mucoadhesive Extended Release Tablets -In Vitro and Ex Vivo.

Suryaprakash Reddy Chappidi,Mounika Jutur,Eranti Bhargav,Mujahid Shaik Mahammad,Mallela Vijaya Jyothi,Sailaja Yadav,Moinuddin Syed,Mrunalini Poura,Muralidhar Pisay,Venkataranganna Marikunte,Haranath Chinthaginjala

doi:10.15171/apb.2019.032

Abstract

Purpose: The purpose of the study was to develop and optimize rosiglitazone maleate mucoadhesive extended-release tablets by quality by design (QbD) approach. Based on QTPP (quality target product profile) CQAs (critical quality attributes) were identified. Methods: Failure mode and effects analysis (FMEA) method were adopted for risk assessment. Risk analysis by the evaluation of formulation and process parameters showed that the optimizing the levels of polymers could reduce high risk to achieve target profile. Drug-excipient compatibility studies by Fourier transforms infra-red and DSC studies showed that the drug was compatible with the polymers used. Design of experiment (DoE) performed by Sigma tech software, Carbopol 934P and sodium carboxymethyl cellulose (SCMC) were identified as independent variables and hardness, drug release at 12 hours and ex vivo mucoadhesion time were adopted as responses. Contour plots generated from the software were used for identification of design space. Results: Carbopol 934P and SCMC had positive and negative effects respectively on the selected responses. Higher the concentration of Carbopol 934P and lower the concentration of SCMC mucoadhesive extended release criteria could be achieved. Drug release kinetics followed first order release with Higuchi diffusion and Fickian diffusion. Ex vivo mucoadhesion test on goat stomach mucosa indicated that adhesion time increased at higher concentrations of Carbopol 934P. Optimized formula satisfying all the required parameters was selected and evaluated. The predicted response values were in close agreement with experimental response values, confirmed by calculating standard error. Conclusion: It has been concluded that the application of QbD in the optimization reduced the number of trials to produce a cost-effective formula.

Highlights

Diabetes mellitus occurs due to inadequate production of insulin by the pancreas or may be due to insulin resistance which results in increased blood glucose levels
Design of experiment (DoE) performed by Sigma tech software, Carbopol 934P and sodium carboxymethyl cellulose (SCMC) were identified as independent variables and hardness, drug release at 12 hours and ex vivo mucoadhesion time were adopted as responses
It has been concluded that the application of quality by design (QbD) in the optimization reduced the number of trials to produce a cost-effective formula

Summary

Introduction

Diabetes mellitus (type 2) occurs due to inadequate production of insulin by the pancreas or may be due to insulin resistance which results in increased blood glucose levels. Oedema and weight gain are frequently reported adverse effects with repeated immediate release dosage forms. It is soluble and absorbed in the stomach especially in the upper parts of the gastrointestinal tract, its bioavailability is greatly reduced as the gastric emptying is faster and reduction of its stay in the stomach.[2] there is a need to develop an extended release dosage form to reduce frequent administrations which maintain steady-state plasma concentrations and by extending its release in the stomach. Mucoadhesive polymers were selected to reduce emptying time and to extend the release of the drug rosiglitazone maleate in the stomach. Apart from an antidiabetic drug, the clinical trials[4] have shown that rosiglitazone maleate

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