Sugita Kazuya, Takata Noriyuki, Yonemochi Etsuo
Department of Physical Chemistry, Hoshi University, 2-4-41, Ebara, Shinagawa, Tokyo 142-8501, Japan.
Quality Development Department, Chugai Pharma Manufacturing Co., Ltd., 5-5-1, Ukima, Kita, Tokyo 115-8543, Japan.
Pharmaceutics. 2021 Mar 2;13(3):323. doi: 10.3390/pharmaceutics13030323.
We investigated the solubility-permeability interplay using a solubilizer additive under non-sink conditions. Sodium lauryl sulfate (SLS) was used as a solubilizer additive. The solubility and permeability of two poorly soluble drugs at various doses, with or without SLS, were evaluated by flux measurements. The total permeated amount of griseofulvin, which has high permeability, increased by the addition of SLS. On the other hand, triamcinolone, which has low permeability, showed an almost constant rate of permeation regardless of the SLS addition. The total permeated amount of griseofulvin increased by about 20-30% when the dose amount exceeded its solubility, whereas its concentration in the donor chamber remained almost constant. However, the total permeated amount of triamcinolone was almost constant regardless of dose amount. These results suggest that the permeability of the unstirred water layer (UWL) may be affected by SLS and solid drugs for high-permeable drugs. The effect of solid drugs could be explained by a reduction in the apparent UWL thickness. For the appropriate evaluation of absorption, it would be essential to consider these effects.
我们在非漏槽条件下使用增溶剂添加剂研究了溶解度-渗透性相互作用。月桂醇硫酸酯钠（SLS）用作增溶剂添加剂。通过通量测量评估了两种难溶性药物在不同剂量下（有或无SLS）的溶解度和渗透性。加入SLS后，高渗透性的灰黄霉素的总渗透量增加。另一方面，低渗透性的曲安奈德无论是否添加SLS，其渗透速率几乎恒定。当剂量超过其溶解度时，灰黄霉素的总渗透量增加了约20%-30%，而其在供体室中的浓度几乎保持不变。然而，曲安奈德的总渗透量无论剂量如何几乎恒定。这些结果表明，对于高渗透性药物，未搅拌水层（UWL）的渗透性可能受SLS和固体药物的影响。固体药物的作用可以通过表观UWL厚度的减小来解释。为了对吸收进行适当评估，考虑这些影响至关重要。
