Implementation of Quality by Design Principles for the Evolution of Optimized Sustained Release Drug Delivery System

Abstract

Aim: The aim of the present work is the implementation of Quality by Design principles for the evolution of optimized sustained release drug delivery system. Background: Quality by Design (QbD) approach refers to an advance approach to develop an optimized dosage form. QbD has become a vital modern scientific approach to develop a quality dosage form. In the modern era of science, researchers can develop an optimized dosage form with least effort, money and manpower. Objectives: Objective of the research work was the successful development of optimized floating bioadhesive tablets of glipizide using floating-bioadhesive potential of cellulosic polymer and carbomersusing quality by design (QbD) approach. Methods: Quality Target Product Profile (QTPP) of drug delivery system was defined as well as critical quality attributes (CQAs) were identified. A face centered central composite design (CCD) was utilized in assessing the impact of the individual critical material attribute (CMA) like Hydro Propyl Methyl Cellulose K4M(HPMC K4M)and Carbopol 934P (CP 934P) and their interactions, using least experimentation. Formulations were developed and quantitative impact on CQAs was determined using mathematical model. The optimized formulation was obtained and characterized for in-vitro as well as in-vivo parameters. Results: A Fishikawa diagram and Failure Mode and Effect Analysis (FMEA) was performed to identify potential failure modes associated with the dosage form. The optimum formulation was embarked upon using mathematical model developed yielding desired CQAs followed for confirmation of data. Sustained release drug delivery system was successfully developed by using QbD approach. In-vivo X-ray imaging in rabbit and γ-scintigraphic study in manconfirmed the buoyant nature of the mucoadhesive floating tablet for 8 h in the upper gastrointestinal tract. Conclusion: Optimized formulation shows phenomenal floating, bioadhesive properties and drug release retardation characteristics, utilizing a mixture of cost-effective polymers Hence, QbD approach may be regarded as an important tool in development of floating bioadhesive CR dosage forms.