Preparation Of Solid Dispersions And Sustained-Release Tablets Of Idebenone

Drug dissolution of Idebenone(IDB) tablets on market after oral administration was slowly due to low water-solubility of IDB. In order to improve the dissolution of IDB, solid dispersions of IDB were prepared using Pluronic F127(F127) as the matrix material. Meanwhile, long-term administration of IDB is necessary for its users. Frequent administration of IDB tablets on market(3 times a day) always makes the patients poor compliance, Therefore, based on the solid dispersions of IDB, its hydrogel sustained release of IDB using hydroxypropyl methyl cellulose as the matrix material were further prepared for improving drug bioavailability and patient compliance.The influences of preparation methods and the ratio of the drug to poloxamer 407 on drug dissolution from the formed solid dispersions of IDB were investigated. The results showed that drug dissolution from solid dispersions of idebenone and F127 prepared by both hot melt and solvent methods were both increased significantly as compared with the pure drug and physical mixtures of idebenone and F127. Higher F127 content led to faster drug dissolution. When idebenone/F127 ratio was 1:3, drug dissolution was up to 80%. And there almost had no effect on the drug dissolution as the ratio was further increased. The mixture of PEG6000 and F 127 was selected as the matrix material of IDB solid dispersions. The results indicated that the addition of PEG6000 had no effect on drug dissolution. The state of idebenone in matrix of solid dispersion was further determined by using FTIR, DSC and XRD, which suggested that the vast majority of idebenone existed in the solid dispersion at amorphous forms or molecular state.The factors influenced drug release of the sustained-release tablets of IDB were investigated by single factor design, including the content of HPMC, the ratio of lactose to microcrystalline cellulose, the content of magnesium stearate, impeller speed, and release medium. The obtained optimal sustained-release tablet formulation was listed as following: tablet weight 200mg; 20 mg of IDB per tablet; solid dispersion(IDB/F127 ratio 1:3) 40%; HPMC 15%; lactose 30%; microcrystalline cellulose 15%; magnesium stearate 1%. The friability and tablet weight difference tests of the optimal sustained-release tablets complyed with Chinese Pharmacopoeial requirements. The tablets released IDB smoothly, slowly and completely during a period time of 12 h, and no burst effect was observed in vitro.