Use of spray-dried chitosan acetate and ethylcellulose as compression coats for colonic drug delivery: Effect of swelling on triggering in vitro drug release

• Published in: European journal of pharmaceutics and biopharmaceutics 2009-02, Vol.71 (2), p.356-361
• Main Authors: Nunthanid, J., Luangtana-anan, M., Sriamornsak, P., Limmatvapirat, S., Huanbutta, K., Puttipipatkhachorn, S.
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; beta-Glucosidase - metabolism; Biological and medical sciences; Cellulose - analogs & derivatives; Cellulose - chemistry; Chitosan - chemistry; Chitosan acetate; Colon - metabolism; Colonic drug delivery; Compression-coated tablets; Delayed-Action Preparations; Diffusion; Drug Delivery Systems; Ethylcellulose; Excipients - chemistry; Gels; General pharmacology; Hydrogen-Ion Concentration; Medical sciences; Mesalamine - administration & dosage; Mesalamine - pharmacokinetics; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Solubility; Swelling; Tablets
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2008.08.002

Spray-dried chitosan acetate (CSA) and ethylcellulose (EC) were used as new compression coats for 5-aminosalicylic acid tablets. Constrained axial or radial swelling of pure CSA and EC/CSA tablets in 0.1 N HCl (stage I), Tris–HCl, pH 6.8 (stage II), and acetate buffer, pH 5.0 (stage III), was investigated. Factors affecting in vitro drug release, i.e., % weight ratios of coating polymers, dip speeds of dissolution apparatus or pH of medium or colonic enzyme (β-glucosidase) in stage III, and use of a super disintegrant in core tablets, were evaluated. Swollen CSA gel dissolved at lower pH and became less soluble at higher pH. The mechanism of swelling was Fickian diffusion fitting well into both Higuchi’s and Korsmeyer–Peppas models. EC:CSA, at 87.5:12.5% weight ratio, provided lag time rendering the tablets to reach stage III (simulated colonic fluid of patients), and the drug was released over 90% within 12 h. The system was a dual time- and pH-control due to the insolubility of EC suppressing water diffusion and the swelling of CSA in the stages I and II. The erosion of CSA gel in the stage III induced the disintegration of the coat resulting in rapid drug release. The lower dip speed and higher pH medium delayed the drug release, while a super disintegrant in the cores enhanced the drug release and no enzyme effect was observed.