A novel pH- and time-based multi-unit potential colonic drug delivery system. I. Development

• Published in: International journal of pharmaceutics Vol. 213; no. 1; pp. 83 - 91
• Main Authors: Gupta, Vishal K., Beckert, Thomas E., Price, James C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.02.2001; Elsevier
• Subjects: Acrylic Resins; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Colon - physiology; Colonic delivery; Controlled-release; Drug Delivery Systems; Eudragit; Excipients; General pharmacology; Hydrogen-Ion Concentration; Medical sciences; Mesalamine - administration & dosage; Mesalamine - chemistry; Microscopy, Electron, Scanning; Particle Size; Pellets; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymethacrylates; Polymethacrylic Acids - chemistry; Site-specific delivery; Solubility; Time Factors; Site-specific delivery; Controlled-release; Eudragit; Colonic delivery; Pellets; Polymethacrylates; Pharmaceutical technology; Targeting; Digestive system; Controlled release form; Control release polymer; Drug carrier; Dissolution; In vitro; Formulation; Dosage form; pH; Aminosalicylic acid; Active ingredient; Colon; Coating; Methacrylate copolymer; Release; Pellet(dosage form); Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(00)00649-9

A novel delivery system was developed for delivering drugs to the colon by selecting polymethacrylates with appropriate pH dissolution characteristics for the distal end of the small intestine and relying upon the relatively constant transit time of the small intestine. Pellets were prepared by powder layering of 5-aminosalicylic acid (5-ASA) on nonpareils (0.5–0.6 mm) in a conventional coating pan. Drug-layered pellets were coated with an inner layer of a combination of two pH-independent polymers Eudragit ® RL and RS (2:8), and an outer layer of a pH-dependent polymer, Eudragit FS. Scanning electron micrograph (SEM) pictures of the coated pellets showed the uniformity of both the coatings. The release profile of 5-ASA was studied in three phosphate buffers after a simulated gastric pre-soak for 2 h in pH 1.2 media. There was no drug release for 12 h at pH 6.5. There was a sustained release of 5-ASA for over 12 h both at pH 7.0 and 7.5 after a lag time at pH 7.0 and no lag time at pH 7.5. The release rate was faster at pH 7.5 than at pH 7.0. The delivery system demonstrated its potential for colonic delivery by resisting drug release until pH 6.5 and the combination of Eudragit RL and RS proved successful for the sustained delivery of 5-ASA at the expected pH of the colon.