Institute of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Int J Pharm. 2012 Nov 1;437(1-2):288-93. doi: 10.1016/j.ijpharm.2012.08.014. Epub 2012 Aug 20.
Amorphous solid dispersions (ASDs) represent a promising formulation approach for poorly soluble drugs. We explored the formulation-related impact of ASDs on permeation rate, apparent solubility and molecular solubility of the poorly soluble drug ABT-102. The influence of fasted state simulated intestinal fluid (FaSSIF) as dispersion medium was also studied. ASDs were prepared by hot-melt extrusion. Permeation rate was assessed by the Caco-2 transwell assay. Cell viability and barrier integrity were assured by AlamarBlue©, TEER and permeability of the hydrophilic marker carboxyfluorescein. Apparent solubility and molecular solubility were evaluated by using centrifugation and inverse dialysis, respectively. The in vitro permeation rate of ABT-102 from aqueous dispersions of the ASD was found 4 times faster than that from the dispersions of the crystals, while apparent solubility and molecular solubility of ABT-102 were increased. Yet, a further increase in apparent solubility due to micellar solubilization as observed when dispersing the ASD in FaSSIF, did not affect molecular solubility or permeation rate. Overall, a good correlation between permeation rate and molecular solubility but not apparent solubility was seen.
无定形固体分散体（ASD）是一种有前途的难溶性药物制剂方法。我们研究了 ASD 对难溶性药物 ABT-102 的渗透速率、表观溶解度和分子溶解度的制剂相关影响。还研究了作为分散介质的空腹状态模拟肠液（FaSSIF）的影响。通过热熔挤出法制备 ASD。通过 Caco-2 跨膜测定法评估渗透速率。通过 AlamarBlue©、TEER 和亲水性标记物羧基荧光素的通透性来确保细胞活力和屏障完整性。通过离心和反向透析分别评估表观溶解度和分子溶解度。从 ASD 水性分散体中的 ABT-102 的体外渗透速率比从晶体分散体中的渗透速率快 4 倍，而 ABT-102 的表观溶解度和分子溶解度都增加了。然而，当将 ASD 分散在 FaSSIF 中时，由于胶束增溶而观察到的表观溶解度的进一步增加，并不影响分子溶解度或渗透速率。总体而言，渗透速率与分子溶解度之间存在良好的相关性，但与表观溶解度无关。
