Development of sustained release fast -melting tablets using ion -exchange resin complexes

Seong Hoon Jeong, Purdue University

Abstract

Fast-melting tablets have received ever-increasing demands and have become a rapidly growing area in the pharmaceutical industry. However, fast-melting technology limits the number of drugs which can be incorporated into the tablets. The main objective of this work is to develop new sustained release fast-melting tablets based on the complex formation between drugs and ion-exchange resins. Complexes of resins and dextromethorphan were prepared with different resin functional groups, ion-exchange capacities, degrees of crosslinking, and particle sizes. Our results demonstrated that DM could be loaded up to a ratio of 3:1 (drug:resin), depending on the physicochemical properties of the resins. As the crosslinking ratio and particle size increased, the drug loading and release rate decreased due to a reduced effective diffusion coefficient and surface area. Sustained drug release was not fully achieved only with the ion-exchange resins; thus, to further the sustained release effects, coatings using various polymers were applied. Several aqueous polymeric dispersions, ethylcellulose (Aquacoat® ECD and Surelease®) and polyvinyl acetate (Kollicoat® SR 30D), were investigated as coatings. Because the drug release rate was quite dependent on the coating level, the release rate can be easily modified by changing different levels. Ethylcellulose was not resistant to the tablet manufacturing process because some cracks were observed after dissolution testing. However, films of Kollico ® SR 30D were resistant to the process, so the coated particles can be compressed into tablets without any rupture, resulting in no significant changes of the release rates. To investigate the exact release kinetics of polymer-coated resin complexes, results of new mathematical modeling were compared with experimental results. The Boyd and Higuchi models were used to describe the release kinetics. A comprehensive numerical model was developed for further theoretical evaluations. The rate-limiting factor of the uncoated resin particles was the drug diffusion through the core matrix as opposed to an ion-exchange reaction. Similarly, in the coated resin particles, the rate-limiting factor was the diffusion of the drug through the coating membrane. The numerical model fully captured the phenomena observed during experimental evaluation, and the release dynamics from the uncoated and coated particles was accurately predicted.

Degree

Ph.D.

Advisors

Park, Purdue University.

Subject Area

Pharmaceuticals

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