Alvarez-Lorenzo C, Gómez-Amoza J L, Martínez-Pacheco R, Souto C, Concheiro A
Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain.
Drug Dev Ind Pharm. 2000 Jan;26(1):13-20. doi: 10.1081/ddc-100100322.
The behavior of 40:60 anhydrous theophylline/hydroxypropylcellulose (HPC) direct compression tablets obtained using a variety of hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively) was determined immediately following their preparation and after storage for 6 months at 20 degrees C and a relative humidity (RH) of either 70.4% or 93.9%. The lower relative humidity did not bring about hydration of the active principle in any formulation, but the higher relative humidity totally hydrated the drug in all except one L-HPC formulation, in which hydration remained incomplete. Both relative humidities caused significant tablet swelling, with L-HPC formulations being more affected than HPC formulations. Drug release was slowed by hydration of the active principle, but accelerated with tablet swelling. The lower relative humidity caused significant alteration of drug release characteristics in only two L-HPC formulations, release from which was accelerated, while the higher relative humidities only failed to cause such alterations in two HPC formulations, with release from all except one of the others slowed (in the exceptional formulation, which exhibited incompletely hydrated theophylline and the greatest swelling of all, release was accelerated).
使用多种具有低取代度或中高取代度的羟丙基纤维素（分别为低取代羟丙基纤维素和高取代羟丙基纤维素）制得的40:60无水茶碱/羟丙基纤维素直接压片，在制备后立即以及在20℃、相对湿度（RH）为70.4%或93.9%的条件下储存6个月后，对其行为进行了测定。较低的相对湿度在任何制剂中均未导致活性成分水合，但较高的相对湿度使除一种低取代羟丙基纤维素制剂外的所有制剂中的药物完全水合，在该制剂中水合仍不完全。两种相对湿度均导致片剂显著膨胀，低取代羟丙基纤维素制剂比高取代羟丙基纤维素制剂受影响更大。活性成分的水合使药物释放减慢，但片剂膨胀使其加速。较低的相对湿度仅在两种低取代羟丙基纤维素制剂中导致药物释放特性发生显著改变，其释放加速，而较高的相对湿度仅在两种高取代羟丙基纤维素制剂中未导致此类改变，除一种制剂外，其他制剂的释放均减慢（在该特殊制剂中，茶碱水合不完全且膨胀最大，释放加速）。
