title: Oral controlled release formulation for highly water-soluble drugs: drug--sodium alginate--xanthan gum--zinc acetate matrix.
abstract: An oral controlled release formulation matrix for highly water-soluble drugs was designed and developed to achieve a 24-hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH 7.5) and simulated gastric fluid (SGF, pH 1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24-hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl--sodium alginate--xanthan gum--zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross-linking structure. The cross-linking structure might control a highly water-soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.
authors.affiliation: Research and Development, Toronto Institute of Pharmaceutical Technology, Toronto, Ontario, Canada. wenming@tipt.com
authors.forename: W M
authors.initials: WM
authors.lastname: Zeng
mesh_terms: D000284:Administration, Oral; D000464:Alginates; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000737:chemistry*; D001672:Biocompatible Materials; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D011135:Polysaccharides, Bacterial; D011899:Ranitidine / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D019345:Zinc Acetate
chemical_list: D000464:Alginates; D000897:Anti-Ulcer Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D011135:Polysaccharides, Bacterial; D011899:Ranitidine; D020723:Glucuronic Acid; D019345:Zinc Acetate; C002563:xanthan gum