Spireas S, Sadu S, Grover R
Division of Pharmaceutics & Industrial Pharmacy, Arnold & Marie Schwartz College of Pharmacy & Health Sciences, Long Island University, Brooklyn, New York 11201, USA.
J Pharm Sci. 1998 Jul;87(7):867-72. doi: 10.1021/js970346g.
The potential of liquisolid systems to improve the dissolution properties of water-insoluble agents was investigated using hydrocortisone as the model medication. The in vitro release patterns of this very slightly water-soluble corticosteroid, formulated in directly compressed tablets and liquisolid compacts, were studied at different dissolution conditions. The new formulation technique of liquisolid compacts was used to convert liquid medications such as solutions or suspensions of hydrocortisone in propylene glycol, a nonvolatile liquid vehicle, into acceptably flowing and compressible powders by blending with selective powder excipients. Several liquisolid tablet formulations were prepared using a new mathematical model to calculate the appropriate quantities of powder and liquid ingredients required to produce acceptably flowing and compressible admixtures. Due to their increased wetting properties and surface of drug available for dissolution, liquisolid compacts demonstrated significantly higher drug release rates than those of conventionally made, directly compressed tablets containing micronized hydrocortisone. The in vitro drug dissolution rates of liquisolid tablets were found to be consistent and independent of the volume of dissolution medium used, in contrast to the plain tablets which exhibited declining drug release patterns with decreasing dissolution volumes. It has been also shown that the fraction of molecularly dispersed drug in the liquid medication of liquisolid systems is directly proportional to their hydrocortisone dissolution rates.
以氢化可的松作为模型药物，研究了液固系统改善水不溶性药物溶出特性的潜力。在不同溶出条件下，研究了这种微溶于水的皮质类固醇以直接压片和液固型压制片形式存在时的体外释放模式。液固型压制片这种新的制剂技术，通过与选择性粉末辅料混合，将氢化可的松在丙二醇（一种不挥发液体载体）中的溶液或悬浮液等液体药物转化为具有可接受流动性和可压性的粉末。使用一种新的数学模型制备了几种液固型片剂配方，以计算生产具有可接受流动性和可压性混合物所需的粉末和液体成分的合适用量。由于其润湿性增加以及药物可用于溶出的表面积增大，液固型压制片的药物释放速率显著高于含有微粉化氢化可的松的传统直接压片。与普通片剂在溶出体积减小时呈现药物释放模式下降相反，液固型片剂的体外药物溶出速率被发现是一致的，且与所用溶出介质的体积无关。还表明，液固系统液体药物中分子分散药物的比例与它们的氢化可的松溶出速率成正比。
