Yang Jiaojiao, Alvebratt Caroline, Zhang Peng, Zardán Gómez de la Torre Teresa, Strømme Maria, Bergström Christel A S, Welch Ken
Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-75121, Sweden.
Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, P.O. Box 580, Uppsala SE-751 23, Sweden.
Int J Pharm. 2017 Jun 15;525(1):183-190. doi: 10.1016/j.ijpharm.2017.04.018. Epub 2017 Apr 8.
The need to combat poor water solubility has increased interest in supersaturating drug delivery systems. In this study, amorphous mesoporous magnesium carbonate (MMC) was used as a drug carrier to achieve supersaturation of tolfenamic acid and rimonabant, two drug compounds with low aqueous solubility. The potential synergy between MMC and hydroxypropyl methylcellulose (HPMC), a polymer commonly included as a precipitation inhibitor in drug delivery systems, was explored with the aim of extending the time that high supersaturation levels were maintained. Release was studied under physiological conditions using USP-2 dissolution baths. A new small-scale method was developed to enable measurement of the initial drug release occurring when the MMC is immersed in the water phase. It was shown that MMC and HPMC together resulted in significant supersaturation and that the polymer enabled both the achievement of a higher API concentration and extension of the supersaturation period. The new small-scale release method showed that the release was linearly increasing with the dose and that similar release rates were observed for the two model compounds. It was hence concluded that the MMC release was diffusion limited for the compounds explored.
应对药物水溶性差的需求增加了人们对过饱和给药系统的兴趣。在本研究中，无定形介孔碳酸镁（MMC）被用作药物载体，以实现托芬那酸和利莫那班这两种水溶性低的药物化合物的过饱和。探索了MMC与羟丙基甲基纤维素（HPMC，一种在给药系统中常用作沉淀抑制剂的聚合物）之间的潜在协同作用，目的是延长维持高过饱和水平的时间。在生理条件下使用USP-2溶出浴研究释放情况。开发了一种新的小规模方法，以测量MMC浸入水相时发生的初始药物释放。结果表明，MMC和HPMC共同导致显著的过饱和，并且该聚合物能够实现更高的活性药物成分（API）浓度并延长过饱和期。新的小规模释放方法表明，释放随剂量呈线性增加，并且两种模型化合物的释放速率相似。因此得出结论，对于所研究的化合物，MMC的释放受扩散限制。
