Yang Yue, Zhao Zhinan, Wang Yongfei, Yang Lu, Liu Dandan, Yang Xinggang, Pan Weisan
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology, Benxi 117004, PR China.
Int J Pharm. 2016 Jun 15;506(1-2):340-50. doi: 10.1016/j.ijpharm.2016.04.061. Epub 2016 Apr 27.
In this study, a novel asymmetric membrane osmotic pump capsule of gliclazide (GLC) solid dispersion was developed to achieve a controlled drug release. The capsule shells were obtained by wet phase inversion process using cellulose acetate as semi-permeable membrane, glycerol and kolliphor P188 as pore formers, then filled with the mixture of GLC solid dispersion and pH modifiers. Differentiate from the conventional formulations, sodium carbonate was chosen as the osmotic agent and effervescent agent simultaneously to control the drug release, instead of the polymer materials. The ternary solid dispersion of GLC, with polyethylene glycol 6000 and kolliphor P188 as carriers, was prepared by solvent-evaporation method, realizing a 2.09-fold increment in solubility and dissolution rate in comparison with unprocessed GLC. Influence of the composition of the coating solution and pH modifiers on the drug release from the asymmetric membrane capsule (AMC) was investigated. The ultimate cumulative release of the optimal formulation reached 91.32% in an approximately zero-order manner. The osmotic pressure test and dye test were conducted to validate the drug release mechanism from the AMC. The in vivo pharmacokinetic study of the AMC indicated a 102.66±10.95% relative bioavailability compared with the commercial tablet, suggesting the bioequivalence between the two formulations. Consequently, the novel controlled delivery system with combination of solid dispersion and AMC system is capable of providing a satisfactory alternative to release the water-insoluble drugs in a controlled manner.
在本研究中，开发了一种新型的格列齐特（GLC）固体分散体非对称膜渗透泵胶囊，以实现药物的控释。通过湿相转化法，以醋酸纤维素为半透膜，甘油和聚氧乙烯蓖麻油EL（Kolliphor P188）为致孔剂制备胶囊壳，然后填充GLC固体分散体和pH调节剂的混合物。与传统制剂不同，选择碳酸钠同时作为渗透剂和泡腾剂来控制药物释放，而不是使用高分子材料。以聚乙二醇6000和聚氧乙烯蓖麻油EL（Kolliphor P188）为载体，采用溶剂蒸发法制备了GLC的三元固体分散体，与未处理的GLC相比，其溶解度和溶出速率提高了2.09倍。研究了包衣液组成和pH调节剂对非对称膜胶囊（AMC）药物释放的影响。最优制剂的最终累积释放率以近似零级方式达到91.32%。进行了渗透压试验和染料试验，以验证AMC的药物释放机制。AMC的体内药代动力学研究表明，与市售片剂相比，相对生物利用度为102.66±10.95%，表明两种制剂具有生物等效性。因此，固体分散体与AMC系统相结合的新型控释系统能够为以可控方式释放水不溶性药物提供令人满意的替代方案。
