Abstract

DEVELOPMENT OF TOPIRAMATE SUSTAINED-RELEASE MINITABLET CAPSULES BY CHEMOMETRIC MODELING AND COMPUTER SIMULATION

Yong Li*, Bill Wei, Weiyong Li, Yu An, Xinguo Wang and Herling Uang

ABSTRACT

This article studies a sustained-release capsule formulation of topiramate filled with minitablets that utilizes a modified matrix tablet technology. In the R&D process, There are many formulation and process related variables that affect drug release profile of the new formulation. Four partial least squares regression models were created to study dissolution profiles of the new formulation at 4 different pH. Each of the model can predict dissolution rate of the development samples at 5 time points simultaneously. More importantly, the experiment will demonstrate that the models can be used to assess the impact of key excipients on the dissolution rate to understand the drug release mechanism. The models were also used in the formulation optimization based on 864 simulated formulations. An optimized formulation was obtained by matching dissolution profiles with a reference drug. Validity of the novel development approach was verified by the matching drug release characteristics of an independently prepared development batch.

Keywords: Chemometric Model, Computer simulation, Sustained-release, Mini-tablets, Partial least squares regression.