Development and Evaluation of a pH-Dependent Sustained Release Tablet for Irritable Bowel Syndrome

Abstract

The overall objective of this study was to develop a pH-dependent sustained release tablet formulation of a model drug, tegaserod maleate (TM), which is a poorly water soluble and acid labile drug in gastric milieu. The formulation's goal was to allow the dosage form to pass through the stomach intact, start disintegrating in the upper small intestine and slowly release the active in a controlled manner. Partition coefficient, contact angle and drug-excipient compatibility were investigated as part of the preformulation studies. A pH-dependent sustained release tablet was prepared using a combination of Eudragit^® L100 and Eudragit^® S100. The effects of solubilizer, disintegrant, binder, coating polymer concentration, pore former, and plasticizer on the drug release rate were determined. The results demonstrated that approximately 90% of the drug was released in a sustained release manner in the pH 6.8 phosphate buffer within 12 h while no drug was detected when subjected to drug release studies in 0.1 mol/L hydrochloric acid for 2 h. The drug release mechanism involved stress points and/or pore formation in the coated film. The coated tablets were stable at 40°C/75% RH for 3 months. These results highlighted the feasibility of this coated tablet system containing TM, which may contribute to the successful treatment of irritable bowel syndrome.

Keywords:

• tegaserod maleate
• pH-dependent
• sustained release
• Eudragit
• preformulation

ACKNOWLEDGMENTS

This project was supported by Grant Number P20RR021929 from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.