Ni Nina, Sanghvi Tapan, Yalkowsky Samuel
College of Pharmacy, The University of Arizona, Tucson, AZ 85721, USA.
Int J Pharm. 2002 Sep 5;244(1-2):99-104. doi: 10.1016/s0378-5173(02)00318-6.
The solubilization of carbendazim by pH in combination with cosolvents, surfactants or complexants was investigated. At pH 7 the total drug solubility is 6.11 +/- 0.45 microg/ml which increases by 1-7 fold with cosolvent, surfactant or complexant. However, at pH 2 the solubility increases by 250 times. Cosolvents have a negligible effect (50% increase) on the total drug solubility at pH 2 because of the high polarity of the cationic drug. Also pH combined with nonionic surfactants does not improve solubility, as relatively less polar micelles are not able to accommodate the cationic drug. Interestingly, the total drug solubility increases by combining pH 2 with complexants, as they can form a complex with the isolated aromatic ring of both the unionized and the ionized drug. The proposed oral formulation of 1 mg/ml carbendazim at pH 2 does not precipitate in the presence of Seven Up or water. But it does precipitate with pH 7 buffer when diluted 1:10 but not 1:100 or 1:250.
研究了pH值与助溶剂、表面活性剂或络合剂联合作用对多菌灵增溶的影响。在pH 7时，药物总溶解度为6.11±0.45微克/毫升，使用助溶剂、表面活性剂或络合剂后溶解度可增加1至7倍。然而，在pH 2时，溶解度增加了250倍。由于阳离子药物的高极性，助溶剂对pH 2时的药物总溶解度影响可忽略不计（增加50%）。此外，pH值与非离子表面活性剂联合使用并不能提高溶解度，因为极性相对较小的胶束无法容纳阳离子药物。有趣的是，将pH 2与络合剂联合使用时，药物总溶解度会增加，因为它们可以与未离子化和离子化药物的孤立芳香环形成络合物。拟议的pH 2条件下1毫克/毫升多菌灵口服制剂在七喜或水存在下不会沉淀。但当用pH 7缓冲液以1:10稀释时会沉淀，而以1:100或1:250稀释时则不会。
