Design of controlled release system with multi-layers of powder.
Pellets containing active ingredients were coated with water-insoluble powders, i.e. hydrogenated caster oil (Lubliwax (WAX)) and magnesium stearate (Mg-St). The influences of the structural difference of the sustained release layer and curing conditions on the drug release rate were investigated. Sodium valproate (VP-Na) was used as a highly water-soluble model drug. Drug release profiles were influenced by the combination of the WAX layer and the Mg-St layer. Even if the formula of sustained release layers were the same, drug release rate could be affected by the structural difference of the controlled release layer. The Mg-St layer was more effective in prolonging drug release than the WAX layer. Compared with single and double layer types, the triple layer (sandwich) type was most effective in obtaining a long sustained drug release. Heat-treatment retarded drug release mainly by increasing the density of the sustained release layer of the WAX. The Mg-St was effective in protecting the agglomeration between particles during heat-treatment. Optimal heat-treatment conditions were found to exist. Scanning electron microscopy (SEM) analysis indicated that heat-treatment caused the WAX to melt, formed a film-like structure and made the release layer dense. Furthermore, heat-treatment changed the release pattern of VP-Na from sustained release pellets with a multi-layer of powder, leading to zero-order release.
Shimono
Norihito
N
Formulation Group, Pharmaceutical Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan. norihito-shimono@dainippon-pharm.co.jp
Ueda
Masumi
M
Nakamura
Yasuhiko
Y
D003692:Delayed-Action Preparations / Q000138:chemical synthesis*; D005079:Excipients; D007700:Kinetics; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013229:Stearic Acids; D014635:Valproic Acid / Q000008:administration & dosage / Q000737:chemistry; D014885:Waxes
D003692:Delayed-Action Preparations; D005079:Excipients; D011208:Powders; D013229:Stearic Acids; D014885:Waxes; C031183:stearic acid; D014635:Valproic Acid