利用球晶造粒技术盐析方法制备齐酞酸钠肠溶微球

目的为了防止齐墩果酸邻苯二甲酸单酯钠(齐酞酸钠)在胃液中被转变成水不溶性化合物齐墩果酸邻苯二甲酸单酯(齐酞酸)，提高齐酞酸钠的生物利用度,制备肠溶微球。方法根据球晶造粒技术，利用盐析方法，以羟丙甲纤维素邻苯二甲酸酯(HP-55)为肠溶基质将水溶性药物和水不溶性辅料共沉淀制备肠溶微球。在制备过程中，以0.1 mol·L^-1氯化钠水溶液为贫溶剂、水和乙醇混合溶液为良溶剂，二氯甲烷为架桥剂，同时考察了微球的特性及影响因素。结果制备的20-60目肠溶微球具有理想的粉体学性质，相对于齐酞酸钠粉剂,肠溶微球的生物利用度是181.6%。结论水溶性药物微球可以使用水相代替有机溶剂为贫溶剂来制备，从而减少了有机溶剂的用量，有利于环境保护。

Preparation of enteric microsphere of oleanolic acid dihemiphthalate sodium by salting-out action using spherical crystallization technique

AIM: Enteric microspheres were prepared to prevent the interaction of drug with gastric acid and to improve its bioavailability. METHODS: The enteric microspheres with a matrix structure were successfully produced using a spherical crystallization technique. Hydroxypropyl methylcellulose phthalate (HP-55), an enteric material, was coprecipitated with the drug by salting-out effect during the preparation process. A mixture of water and ethanol was chosen as a good solvent and dichloromethane was used as a bridging agent while 0.1 mol x L(-1) sodium chloride solution was selected as a poor solvent. RESULTS: It is the first time to prepare microspheres by making the water-soluble drug and water-insoluble excipient coprecipitated. In vivo test demonstrated that the drug absorption from the enteric oleanolic acid dihemiphthalate sodium (OADHPS) microspheres was significantly prolonged compared to that with OADHPS powder after a lag-time. Furthermore, the drug bioavailability was 181.6% greater than that with the OADHPS powder. CONCLUSION: The microspheres of water soluble drug could be prepared by using water phase replacing organic phase as poor solvent which decrease the quantity of organic solvent and benefit the environment prevention.