Formulation Development and Optimization of Matrix Type Extended-Release Oral Solid Dosage Form of Highly Soluble Antipsychotic Drug

Abstract

Antipsychotic medication was newly introduced in the USA and Europe in 2010. Among several orally controlled-release drug delivery systems, the Hydrophilic matrix system is a well-established technology already in use for CNS drugs (e.g., methylphenidate and hydromorphone). The development of controlled-release dosage forms provides efficacy against psychotic symptoms based on D2-receptor and 5HT2A-receptor antagonism and very low affinity for muscarinic receptors resulting in absence of anticholinergic side effects which are usually observed in the immediate-release dosage form. The matrix technology leads to considerably lower plasma peak levels compared with nonextendedrelease formulations, thus possibly reducing side effects. A hydrophilic polymer-based controlled drug delivery system is more advantageous as compared to the conventional delivery system as it reduces the dosing frequency, improves therapeutic efficacy, reduces side effects, and probably enhances patient compliance. A non-ionic hydrophilic polymer is one of the most widely used polymers for extending drug release. This research mainly focuses on developing therapeutically equivalent dosage forms and matches the dissolution profile with that of the marketed formulation. Various matrix-forming polymers are evaluated against the combination of innovator composition. The dissolution profiles were carried out for 24 hrs to monitor drug release from the matrix tablet. The effect of two variables polyox WSR 303 and Avicel 102 contents, on the release of drug from a tablet using a 32 factorial design. T1Hr, T6Hr, T12Hr, and T24Hr (dissolution time point respectively) were used as response parameters to study the effect of drug dissolution from the core of the tablet.