Development, Optimization and Evaluation of Immidiate Release Tablet of Anti-Hypertensive Drug Using Concept of Quality by Design

Abstract

The present experimental work deals with the systematic quality by design (QbD) based development of DM01 immediate release tablet for treatment for hypertension. The quality target product profile (QTPP) was defined based on the properties of the drug substance, characterization of the RLD (Reference listed drug) product, pre -formulation study and literature. Identification of critical quality attributes (CQAs) was based on the safety & efficacy, Moreover; risk assessment was carried out throughout development to identify potentially high risk formulation and process variables and to determine which studies were necessary to achieve product and process understanding. Each risk assessment was then updated after development and its level was reduced. Two methods were tried namely direct compression and wet granulation by RMG (rapid mixture granulator) However, wet granulation method was selected based on the drug substance characteristics and release profile to achieve desired QTPP. Optimization of formulation was done using design of experiment (DoE), in which Box-behnken design was used..Impact of change of critical formulation factors on dissolution and disintegration was investigated. Critical process optimization studies were conducted to established consistency of process within targeted ranges. A control strategy was derived that includes the material attributes and process parameters identified as potentially high risk variables during the initial risk assessment. In conclusion, development of immediate release tablet of anti-hypertensive drug DM01 using QbD provides robust, cost effective and industrially applicable formulation in short period of time.