INFLUENCE OF DISSOLUTION CONDITIONS ON THE DISSOLUTION RATE AND RELEASE MECHANISM OF KETOPROFEN FROM EXTENDED RELEASE HYDROPHILIC MATRIX SYSTEMS

Abstract

Development of a hydrophilic matrix based extended release system involves the appropriate selection of polymer type, excipients and active ingredient with suitable physicochemical properties in order to obtain the desired release profile. Considering the multivariate nature of factors affecting the dissolution rate from hydrophilic matrix tablets, this study evaluates the effect of dissolution media, device type and stirring rate on the dissolution rate and release mechanism of ketoprofen from hydroxyethylcellulose and hydroxypropylmethylcellulose K4M matrices. The results show that dissolution media type influenced the release rate mostly by limiting solubility, but also by influencing polymer hydration time and solubility. The effect of stirring rate was dependent on device type, dissolution media and product type. Results also show that the selection of device type is an important step in the development of an appropriate dissolution test considering the sticking properties of hydrophilic matrices. Using multivariate data analysis, by developing O2PLS models, the systematic variation between dissolution profiles, kinetic parameters and dissolution conditions was integrated, highlighting joint and unique sources of variations. O2PLS results show that drug release mechanism is mostly influenced by media type, followed by stirring rate and at last by product type.