Johnson Jennifer L H, He Yan, Jain Akash, Yalkowsky Samuel H
University of Arizona Pharmaceutical Sciences, 85721, Tucson, AZ.
AAPS PharmSciTech. 2006 Mar;7(1):E125-E130. doi: 10.1208/pt070118. Epub 2017 Mar 8.
The purpose of this study was to develop and evaluate a solid nonaqueous oral dosage form for a new hepatitis C drug, PG301029, which is insoluble and unstable in water. Hydroxypropyl-β-cyclodextrin (HPβCD) and PG301029 were dissolved in glacial acetic acid. The acetic acid was removed by rotoevaporation such that the drug exists primarily in the complexed form. The stability of formulated PG301029 was determined upon dry storage and after reconstitution in simulated intestinal fluid (SIF), simulated gastric fluid (SGF), and water. Formulated PG301029 was found to be stable upon storage and can be reconstituted with water to a concentration 200 times that of the intrinsic solubility. Once reconstituted, the powder dissolves rapidly and PG301029 remains stable for 21 hours in SGF, SIF, and water. The unique use of acetic acid and HPβCD results in a solid dosage form of PG301029 that is both soluble and stable in water.
本研究的目的是开发并评估一种用于新型丙型肝炎药物PG301029的固体非水口服剂型，该药物在水中不溶且不稳定。将羟丙基-β-环糊精（HPβCD）和PG301029溶解于冰醋酸中。通过旋转蒸发除去醋酸，使药物主要以络合形式存在。在干燥储存以及在模拟肠液（SIF）、模拟胃液（SGF）和水中复溶后，测定所制备的PG301029的稳定性。发现所制备的PG301029在储存时稳定，并且可以用水复溶至固有溶解度200倍的浓度。一旦复溶，该粉末迅速溶解，并且PG301029在SGF、SIF和水中可保持稳定21小时。醋酸和HPβCD的独特应用产生了一种在水中既可溶又稳定的PG301029固体剂型。
