University of Liège, Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, Avenue Hippocrate, B36 (+2) 4000 Liège, Belgium.
University of Liège, Laboratory of Pharmaceutical Technology and Biopharmacy, CIRM, Avenue Hippocrate, B36 (+2) 4000 Liège, Belgium.
Int J Pharm. 2022 Feb 5;613:121372. doi: 10.1016/j.ijpharm.2021.121372. Epub 2021 Dec 11.
The objective of this work was to evaluate the impact of physico-chemical properties of pharmaceutical drugs on the optimal mesoporous silica loading methods. Indeed, a good combination between drug and loading process has to be studied to promote the deepest penetration of the drug inside the mesopores, allowing high drug amorphization. Six molecules, namely lidocaine and its hydrochloride, ibuprofen, ketoprofen, artemether and miconazole, with different physico-chemical properties (the ionized character, the acid-base character, the HBDA number, the solubility in sc-CO and the behavior under subcritical CO) were used to produce drug-silica formulations. Different impregnation processes (physical mixing, melting, wetting, sc-CO and subcritical CO impregnations) have been compared for each drug, in terms of drug recovery and crystallinity. Formulations showed drug percentage close to 100% except for supercritical soluble drug formulations impregnated by using sc-CO. However, the basic drug character provided less or no drug loss during impregnation. Processing insoluble sc-CO molecule under supercritical conditions led to less crystallinity than the correspondent physical mixture suggesting an interesting repulsive effect that forces the drug penetration within the mesopores. Besides, it has been also highlighted that the HBDA number is not sufficient to predict the final drug loading. Melting methods have high interest considering the drugs tested and subcritical CO could increase the loading, especially for drugs with high molten viscosity. This study showed that a plethora of loading methods can be used to provide high drug loaded MS formulations with a wide choice of equipment.
这项工作的目的是评估药物的物理化学性质对最佳介孔硅负载方法的影响。实际上，必须研究药物与负载过程之间的良好结合，以促进药物在介孔内的最深渗透，从而允许药物高度非晶化。使用了六种具有不同物理化学性质（电离特性、酸碱特性、HBDA 数、在 sc-CO 中的溶解度和亚临界 CO 下的行为）的分子，即利多卡因及其盐酸盐、布洛芬、酮洛芬、青蒿素和咪康唑，来制备药物-硅石制剂。对于每种药物，从药物回收率和结晶度方面比较了不同的浸渍工艺（物理混合、熔融、润湿、sc-CO 和亚临界 CO 浸渍）。除了用 sc-CO 浸渍的超临界可溶性药物制剂外，制剂中药物的百分比接近 100%。然而，碱性药物特性在浸渍过程中提供了较少或没有药物损失。在超临界条件下处理不溶性 sc-CO 分子导致的结晶度低于相应的物理混合物，这表明存在一种有趣的排斥效应，迫使药物渗透到介孔中。此外，还强调了 HBDA 数不足以预测最终的药物负载。考虑到测试的药物，熔融方法具有很高的应用价值，而亚临界 CO 可以增加负载，特别是对于熔融粘度高的药物。这项研究表明，可以使用多种负载方法来提供高载药 MS 制剂，从而有广泛的设备选择。
