Fatty Acid and Water-Soluble Polymer-Based Controlled Release Drug Delivery System

Sustained release capsule formulations based on three components, drug, water-soluble polymer, and water-insoluble fatty acid, were developed. Theophylline, acetaminophen, and glipizide, representing a wide spectrum of aqueous solubility, were used as model drugs. Povidone and hydroxypropyl cellulose were selected as water-soluble polymers. Stearic acid and lauric acid were selected as water-insoluble fatty acids. Fatty acid, polymer, and drug mixture was filled into size #0 gelatin capsules and heated for 2 h at 50°C. The drug particles were trapped into molten fatty acid and released at a controlled rate through pores created by the water-soluble polymer when capsules were exposed to an aqueous dissolution medium. Manipulation of the formulation components enabled release rates of glipizide and theophylline capsules to be similar to commercial Glucotrol® XL tablets and Theo-24® capsules, respectively. The capsules also exhibited satisfactory dissolution stability after exposure to 30°C/60% relative humidity (RH) in open Petri dishes and to 40°C/75% RH in closed high-density polyethylene bottles. A computational fluid dynamic-based model was developed to quantitatively describe the drug transport in the capsule matrix and the drug release process. The simulation results showed a diffusion-controlled release mechanism from these capsules.