Modifying matrix micro-environmental pH to achieve sustained drug release from highly laminating alginate matrices.
Lamination of alginate matrix tablet at acidic pH can compromise its function as a sustained release carrier. This phenomenon is associated with the conversion of sodium alginate to alginic acid. An innovative approach for controlling the release of a highly water-soluble drug from such matrices is presented in this paper. Inclusion of pH-modifiers was employed to raise the micro-environmental pH within matrices undergoing dissolution at gastric pH. The changes in micro-environmental pH of hydrating alginate matrices were visualized with the aid of a pH-indicator and subsequently quantified using image analysis. Transient elevation in micro-environmental pH impeded alginate protonation and minimized or prevented matrix lamination, contributing to preservation of drug diffusion barrier. Significant reduction in the rate of drug release at pH 1.2 was achieved in the presence of such additives. The action of pH-modifiers was synergistically enhanced in the presence of a carbon dioxide barrier formed by effervescing sodium bicarbonate, reducing drug release in the acidic medium from 60 to 20%. Further insight into the influence of lamination on drug release from alginate compacts was given.
Ching
Ai Ling
AL
Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.
Liew
Celine Valeria
CV
Chan
Lai Wah
LW
Heng
Paul Wan Sia
PW
D000464:Alginates / Q000737:chemistry*; D002744:Chlorpheniramine / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D012995:Solubility; D013608:Tablets, Enteric-Coated / Q000737:chemistry*
D000464:Alginates; D006603:Hexuronic Acids; D013608:Tablets, Enteric-Coated; D002744:Chlorpheniramine; D020723:Glucuronic Acid