A mixed polymer tablet matrix for oral controlled release of dextromethorphan hydrobromide

Alton Dale Johnson, Purdue University

Abstract

Controlled drug delivery is an important method for improving the therapeutics of some pharmacologically active compounds. The physical composition of the dosage form, especially an oral solid, influences drug delivery. To insure optimal design the critical compositional factors should be identified and studied. An oral controlled drug delivery system was developed which was composed of a complex mixture of water soluble and water insoluble materials. These materials were processed into an oral tablet matrix using conventional tablet technology and equipment. The system provided twelve hours of controlled drug delivery. It was established, however, that the drug dissolution time profile was sensitive to the physical composition of the system. The extreme vertices statistical design method was used to systematically quantitate the functional relationship between the physical composition of the system and the release of the active ingredient. A surface response model was determined by multiple regression analysis and shown to accurately describe this functional relationship. The model then was validated for predicting the drug dissolution time profile for any formulation selected from the mixture space. Although the predicted drug release profile for a proposed formulation must be verified experimentally, the model allowed the selection of formulations with the highest probability of achieving the target drug dissolution characteristics for further study. A prototype controlled release formulation was selected and evaluated. Surface erosion and matrix diffusion were proposed as the primary mechanisms of drug release. The system was evaluated in human subjects and demonstrated to have suitable bioavailability in a study conducted by an outside laboratory.

Degree

Ph.D.

Advisors

Peck, Purdue University.

Subject Area

Pharmaceuticals

COinS