液固压缩技术改善丹参酮ⅡA释药的评价研究

材料，二氧化硅为涂层材料制备液固压缩片，并对其流动性（休止角，卡尔指数及豪森指数）、药物与辅料相互作用（DSC，XRPD）等进行研究。通过对比不同液固压缩片与普通片剂溶出曲线，探讨该技术在改善丹参酮Ⅱ_A溶出度方面的特性及其影响因素。结果表明，溶出度随液相溶剂的溶解度增高而增大，R及载药量对以丹参酮Ⅱ_A单体为模型药物的制剂影响较为明显，但对以丹参脂溶性有效部位为模型药物者影响较小。表明“液固压缩”技术能够显著改善丹参酮Ⅱ_A的溶出度，同时能够与丹参中的其他脂溶性成分发生协同作用，更好地促进丹参酮Ⅱ_A的释放，提示“液固压缩”技术在中药中具有较好的发展前景。

[关键词] 丹参酮Ⅱ_A；液固压缩；溶出度；难溶性药物

[Abstract] The technique of liquisolid compress is a new technique developed in 1990s， which was considered to be the most promising technique to improve the dissolution of water-insoluble drugs. In this article， tanshinone Ⅱ_A and the extracts of the ester-solubility fractions were chosen as the model drugs to evaluate the effects of the liquisolid technique for enhancement of dissolution properties of tanshinone Ⅱ_A. Several liquisolid tablets （LS） formulations containing different dosage of drugs and various liquid vehicle were prepared and for all the formulations， microcrystalline cellulose and silica were chosen as the carrier and coating materials to evaluate their flow properties， such as angle of repose， Carr′s compressibility index and Hausner′s ratio. The interaction between drug and excipients in prepared LS compacts were studied by differential scanning calorimetry（DSC） and X-ray powder diffraction（XRPD）. The dissolution curves of tanshinone Ⅱ_A from liquisolid compacts were investigated to determine the technique′s effect in improving the dissolution of tanshinone ⅡA and its impacting factors. According to the results， the dissolution increased with the rise in the dissolution of the liquid-phase solvent. The R-value and drug dosage can significantly affect the drug release， but with less impact on active fractions. This indicated that liquisolid technique is a promising alternative for improvement of dissolution property of water-soluble drugs， and can make a synergistic effect with other ester-soluble constituents and bettern improve the release of tanshinone Ⅱ_A. Therefore， the technique of liquisolid compress will have a better development prospect in traditional Chinese medicines.

[Key words] tanshinone Ⅱ_A； liquisolid compress； dissolution； water-insoluble drug

doi：10.4268/cjcmm20152421

“液固压缩”技术（liquisolid technology，LST）^[1]是一种使液态药物通过加入特定的辅料（载体材料和涂层材料），经搅拌形成看似干燥、无黏性、有较好的流动性和可压型的混合物的新型制剂技术。与利用纳米技术、微乳技术、固体分散技术等^[2-6]提高难溶性药物溶出性能的技术相比，具有工艺简单、易于工业化的特点^[7]，LST是一种改善难溶性药物溶出的、实用性强的新技术，具有很好的发展前景。在液固体系中，药物溶解于非挥发性液体^[8]中，以分子状态或混悬状态存在，当片剂崩解后，药物迅速的从片剂中溶出，药物的溶出速度加快，溶出度增加，最终实现提高生物利用度的目的。