长春西丁包合物的制备和体外溶出度考察

Preparation of Vinpocetine Inclusion Complexes and Investigation of in vitro Drug Dissolution Rate

目的制备长春西丁(VIN)包合物,对其体外溶出度进行考察。方法测定长春西丁在不同浓度枸橼酸(CA)和环糊精(CD)水溶液中的溶解度;选用β-环糊精(-βCD)和羟丙基-β-环糊精(HP--βCD),分别采用研磨法(KE)、旋转蒸发法(CE)和冷冻干燥法(FD)制备了VIN/CD和VIN/CD/CA包合物;按照中国药典2000年版二部附录桨法对包合物中药物溶出度进行考察。结果VIN溶解度随CA浓度的升高而线性增加;药物在CD水溶液中的相溶解度曲线呈现典型的AL型;制备方法对药物的体外溶出行为有影响;采用CE或FD法制备的VIN/CD/CA包合物比相应的VIN/CD包合物表现出更令人满意的体外药物溶出行为,它能明显提高药物在水中的溶解度和溶出速度;VIN/CD/CA包合物中,CD种类和用量对药物溶出行为无显著影响。结论对于生物碱类难溶性药物,在包合物中加入酸性辅料(如枸橼酸)可以显著降低增溶同等用量药物所需的环糊精的用量,近而减低生产成本,减小制剂服用体积。

OBJECTIVE To prepare the vinpocetine inclusion complexes and investigate the in vitro drug dissolution rate from inclusion complexes. METHODS The solubility of vinpocetine in citric acid and CD solution with different concentration were determined respectively. The complexation of vinpocetine with β-CD or HP-β-CD was prepared using kneading（KE）, co-evaporating（CE） and froeze-drying （FD） methods. Binary complex inclusion（vinpoeetine/CD） and ternary complex inclusion （vinpocetine/citfic acid/CD） were obtained respectively. In vitro dissolution tests were carried out using CP2000 paddle （ apparatus Ⅱ ） method. RESULTS With the increasing concentration of citric acid in water, the solubility of vinpocetine increased significantly with a geod linear relationship. The phase-solnhility diagram of vinpocetine in aqueous CD solutions at room temperature, was classified as AL-type. A significant enhancement in drug release rate was observed for the complex prepared by CE and FD methods, and more satisfying drug dissolution behavior （rapid, complete and lasting） was obtained from ternary complexes comparing with binary complexes. The drug dissolution behavior showed no significant difference between ternary complexes with different CD types and different molar ratios.CONCLUSION A small amount of citric acid presented in inclusion complexes significantly deceases the amount of CD needed to solubilize the same amount of vinpocetine,and thereby reduces the formulation bulk,especially to the alkaloid thug.