不同盐型对加兰他敏缓释微球性能影响的初步考察

A Preliminary Investigation on Influences of Different Salt Forms on Properties of Galantamine Sustained-release Microspheres

为开发加兰他敏的缓释微球制剂,首先合成了加兰他敏不同盐型,即棕榈酸加兰他敏、双羟萘酸加兰他敏、硬脂酸加兰他敏;然后以丙交酯乙交酯共聚物(PLGA)为载体,采用o/w型乳化-溶剂挥发法制备了加兰他敏、3种酸加成盐及氢溴酸加兰他敏的缓释微球。分别表征了所得微球的形貌、粒径、载药量、包封率、溶剂残留量及体外释药特性。结果显示,相比于加兰他敏和氢溴酸加兰他敏,另3种盐型的脂溶性显著提高,用其制备的微球形态圆整、表面光滑,载药量最高增至23.65%,包封率最高增至78.83%。不同微球的粒度分布差异不明显,但微球中二烷的残留量稍高。体外释放试验表明,3种自制盐型药物的微球具有明显的缓释性能,释放时间达到30 d以上。本试验结果对其他低溶解性药物制备缓释微球制剂具有一定的指导意义。

Three salt forms of galantamine,namely galantamine palmitate,galantamine pamoate and galantamine stearate,were synthesized to develop sustained-release microspheres with poly(lactide-co-glycolide)(PLGA)as drug carriers by oil-in-water emulsion-solvent evaporation method.Additionally,PLGA microspheres loaded with galantamine or galantamine hydrobromide were also prepared by the same method.Then,the prepared microspheres were characterized in terms of morphology,particle size,drug loading,encapsulation efficiency,solvent residue and in vitro drug release,respectively.The results indicated that the solubilities of above prepared salts were significantly increased in fat-soluble solvent,by comparison with free galantamine and galantamine hydrobromide.The microspheres loaded with above three galantamine salts were spherical and smooth,the highest drug loading and encapsulation efficiency were up to 23.65%and 78.83%,respectively.There were no obvious differences in particle size among five kinds of microspheres.But the residual dioxane was slightly higher than dichloromethane in microspheres,which did not comply with the requirement of Chinese pharmacopeia.In vitro release study showed the microspheres loaded with above three salts of galantamine exhibited an obvious sustained-release behaviors,and maintained release for more than 30 days.This study might provide a reference for the preparation of the sustained-release microspheres for poorly soluble drugs.