Design and evaluation of pH modulated controlled release matrix systems for colon specific delivery of indomethacin.
Indomethacin, a potent non steroidal anti-inflammatory drug (NSAID), is indicated for the local treatment of colorectal carcinoma. The aim of the present study was to design and investigate various matrix systems for controlled and site specific delivery of indomethacin to the colon. Various pH sensitive and hydrophobic polymers were investigated for their effect on drug release and site specificity. Effect of proportion of Eudragit L100 and Eudragit S100 in matrix either alone or in combination was evaluated. Effect of hydrophobic non-swellable polymer ethyl cellulose on the release pattern of drug from the Eudragit bases was also investigated. Matrix tablets prepared with Eudragit showed pH dependent release profile with the formulations of Eudragit L100 showing faster rate of drug release than Eudragit S100 in alkaline pH. The release profile from matrix tablets containing Eudragit L100 and Eudragit S100 in combination or with ethyl cellulose correlated well with the relative proportion of the two polymer types in the matrix base. Selected formulations when evaluated in simulated gastric fluid pH without enzymes showed negligible to low drug release (less than 10%) in the first 4-6 h followed with controlled release for 14-16 h. It was concluded that pH sensitive matrix bases in combination with a hydrophobic polymer like ethyl cellulose canbe ideal for site specific delivery of drugs to colon with controlled release profile.
Asghar
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LF
Formulation Development & Pharmacokinetic Laboratory, Pharmacy Group, Birla Institute of Technology & Science, Pilani, India.
Chandran
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S
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002482:Cellulose / Q000031:analogs & derivatives; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D003106:Colon / Q000378:metabolism*; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000008:administration & dosage*; D007700:Kinetics; D011109:Polymethacrylic Acids; D015203:Reproducibility of Results; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C013517:ethyl cellulose; D002482:Cellulose; D007213:Indomethacin