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

• Published in: Journal of pharmaceutical sciences Vol. 100; no. 5; pp. 1900 - 1912
• Main Authors: Desai, Divyakant, Kothari, Sanjeev, Chen, Wei, Wang, Jennifer, Huang, Ming, Sharma, Laxmikant
• Format: Journal Article
• Language: English
• Published: Hoboken Elsevier Inc 01.05.2011; Wiley Subscription Services, Inc., A Wiley Company; Wiley; American Pharmaceutical Association; Elsevier Limited
• Subjects: Biological and medical sciences; Cellulose - analogs & derivatives; Cellulose - chemistry; Delayed-Action Preparations - chemistry; diffusion; dissolution; dissolution rate; excipients; Fatty Acids - chemistry; formulation; General pharmacology; Hydrodynamics; Lauric Acids - chemistry; Medical sciences; Models, Chemical; oral drug delivery; Pharmaceutical Preparations - administration & dosage; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; polymeric drug delivery systems; Polymers - chemistry; Povidone - chemistry; solid dosage form; Solubility; Stearic Acids - chemistry; Water - chemistry; dissolution rate; diffusion; oral drug delivery; dissolution; formulation; excipients; polymeric drug delivery systems; solid dosage form; Pharmaceutical technology; Controlled release form; Vehicle(excipient); Oral administration; Polymer; Drug carrier; Fatty acids; Dissolution; Water soluble compound; Formulation; Dosage form; Water solubility; Solid form; Diffusion
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1002/jps.22397

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 2h 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.