Blanchard J, Ugwu S O, Bhardwaj R, Dorr R T
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Pharm Dev Technol. 2000;5(3):333-8. doi: 10.1081/pdt-100100548.
The objective of this study was to increase the solubility of phenytoin by complexing it with varying concentrations of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) and create an entirely aqueous formulation with a pH significantly closer to physiologic pH (7.4). The phenytoin-HPBCD complexation was characterized using phase-solubility analysis at HPBCD concentrations ranging from 10 to 50% w/v over the pH range of 7.4-11.0. The two most promising formulations, i.e., a formulation consisting of 40% HPBCD at pH 10.4, and a second formulation consisting of 20% HPBCD at pH 11.0, were selected for further study. Both formulations were entirely aqueous and had a significantly decreased pH compared to the original commercial formulation (Parke-Davis, pH 12.0). These formulations also exhibited a significantly decreased tendency to precipitate in vitro. The tissue irritation potential of the 20% w/v HPBCD formulation at pH 11.0 was found to be reduced considerably compared to the commercial injection in a BALB/c mouse model.
本研究的目的是通过将苯妥英与不同浓度的2-羟丙基-β-环糊精（HPBCD）络合来提高其溶解度，并制备一种完全水性的制剂，其pH值更接近生理pH值（7.4）。在7.4 - 11.0的pH范围内，使用相溶解度分析对HPBCD浓度范围为10%至50% w/v的苯妥英-HPBCD络合进行了表征。选择了两种最有前景的制剂，即pH值为10.4时含40% HPBCD的制剂和pH值为11.0时含20% HPBCD的制剂进行进一步研究。与原始商业制剂（Parke-Davis，pH 12.0）相比，这两种制剂均完全为水性，且pH值显著降低。这些制剂在体外沉淀的趋势也显著降低。在BALB/c小鼠模型中发现，pH值为11.0时20% w/v HPBCD制剂的组织刺激潜力比商业注射剂大大降低。
