Biphasic release of indomethacin from HPMC/pectin/calcium matrix tablet: I. Characterization and mechanistic study

• Published in: European journal of pharmaceutics and biopharmaceutics 2007-11, Vol.67 (3), p.707-714
• Main Authors: Wu, Baojian, Chen, Zhukang, Wei, Xiuli, Sun, Ningyun, Lu, Yi, Wu, Wei
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Biological and medical sciences; Biphasic release; Calcium - analysis; Calcium Chloride; Calcium ions; Calibration; Chemistry, Pharmaceutical; Delayed-Action Preparations; General pharmacology; HPMC; Hypromellose Derivatives; In situ crosslinking; Indomethacin - administration & dosage; Indomethacin - chemistry; Matrix; Medical sciences; Methylcellulose - analogs & derivatives; Pectin; Pectins; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Tablets; Water - analysis
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2007.04.016

Calcium-induced crosslinking of pectin acts as the dominating factor controlling drug release from pectin-based matrices. The same interaction was employed to modify indomethacin release from HPMC/pectin/calcium matrix in this study. The aim was to characterize the release profiles, and to study the formulation variables and the underlying mechanisms. The matrix tablet was made up of pectin HM 70, calcium chloride and HPMC K4M, and prepared by the wet granulation method. In vitro release was performed in water and characterized by the power law. Matrix erosion was evaluated by studying the weight loss and pectin release. Biphasic release of indomethacin from the HPMC/pectin/calcium matrix tablet was observed, and extraordinary power law exponent n values of over 1.0 were observed. Increase in calcium amount led to more significant retardation on drug release. The two power law parameters, n and K, correlated to the amount of calcium in the matrix. A lag time of over 4 h can be achieved at HPMC/pectin/calcium chloride amount of 100 mg/100 mg/100 mg. Both matrix weight loss and pectin release were linearly correlated to indomethacin release, indicating erosion-controlled drug release mechanisms. The hybrid matrix showed retarded erosion and hydration rate, which served as the basis for retarded indomethacin release. It is concluded that the pectin/calcium interaction can be employed to modify drug release from HPMC/pectin/calcium matrix tablet with biphasic release patterns for potential timed or site-specific drug delivery.