Formulation Development of Extended Release Tablet of an Anti-Muscarinic Agent

Abstract

Nowadays the oral route represents the predominant and most preferable route for drug delivery. Over-active bladder (OAB) is associated with a strong desire to urinate and correlates with an over-active detrusor muscle. ASTONT2013 is widely used as an anti muscarinic agent. Conventional dosage form of ASTONT2013 exhibits side effects like dry mouth (most common), constipation, urinary retention, etc. Hence, to overcome side effects, once a day formulation was developed to maintain drug therapeutic level and for better patient compliance. The aim of the present investigation was to systematically formulate and optimize tablet which follows zero order kinetics using quality by design (QbD) approach. Initially tablets were formulated after identifying critical quality attributes. Tablets were formulated by direct compression method by using different grades of HPMC. However, release profile did not comparable with the innovator. Hence, release of drug was delayed by applying coat of pH dependent polymer. Results revealed that optimized batch was found within the acceptable range. The second approach was explored to develop delayed release using hydrophobic agent. However, using alone hydrophobic agent, drug release could not be delayed. Hence, incorporation of hydrophobic agent (Gelucire 43/01) with hydrophilic matrix (HPMC) was investigated. These both factors were scientifically studied using Design of Experiment (DoE). 32 factorial design was employed to optimize the ratio of Gelucire 43/01 and HPMC K 100 M. The optimize batch was developed by validated model from the desired response region. Hence, the aim of present study was to formulate once a day dosage form of ASTONT2013 by employing two different approaches. From the above result it can be concluded that, by employing pH dependent coat over matrix tablet gave better delayed release profile than by incorporating hydrophobic agent with matrix tablet.