Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom.
Mol Pharm. 2012 Sep 4;9(9):2505-12. doi: 10.1021/mp300127f. Epub 2012 Aug 2.
There is a need to understand how solvent structuring influences drug presentation in pharmaceutical preparations, and the aim of this study was to characterize the properties of propylene glycol (PG)/water supramolecular structures such that their functional consequences on drug delivery could be assessed. Shifts to higher wavenumbers in the C-H and C-O infrared stretching vibrations of PG (up to 8.6 and 11 cm(-1), respectively) implied that water supramolecular structures were being formed as a consequence of hydrophobic hydration. However, unlike analogous binary solvent systems, water structuring was not enhanced by the presence of the cosolvent. Two discrete populations of supramolecular structures were evident from the infrared spectroscopy: water-rich structures, predominant below a PG volume fraction (f(PG)) of 0.4 (unmoving water bending vibration at 1211 cm(-1)) and PG-rich structures, predominant above 0.4 f(PG) (both C-H and water peaks moved to lower wavenumbers). The un-ionized diclofenac log-linear solubility and transmembrane transport altered dramatically when f(PG) > 0.55 (a 10-fold increase in transport from 0.28 ± 0.06 μg·cm(-2)·h(-1) at 0.2 f(PG) to 2.81 ± 0.16 μg·cm(-2)·h(-1) at 0.9 f(PG)), and this demonstrated the ability of the PG rich supramolecular structures, formed in the PG/water solvent, to specifically modify the behavior of un-ionized diclofenac.
需要了解溶剂结构如何影响药物在药物制剂中的呈现，本研究的目的是表征丙二醇（PG）/水超分子结构的性质，以便评估其对药物传递的功能后果。PG 的 C-H 和 C-O 红外伸缩振动向更高波数的移动（分别高达 8.6 和 11 cm(-1)）表明，水超分子结构是由于疏水水合作用而形成的。然而，与类似的二元溶剂系统不同，溶剂的存在并没有增强水的结构。红外光谱显示存在两种离散的超分子结构群体：富水结构，在 PG 体积分数（f(PG)）低于 0.4 时占主导地位（1211 cm(-1)处的不动水弯曲振动），PG 富结构，在 0.4 f(PG)以上占主导地位（C-H 和水的峰值都移向较低的波数）。未离解的双氯芬酸的对数线性溶解度和跨膜转运在 f(PG) > 0.55 时发生了巨大变化（从 0.28 ± 0.06 μg·cm(-2)·h(-1)在 0.2 f(PG)增加到 2.81 ± 0.16 μg·cm(-2)·h(-1)在 0.9 f(PG)），这表明 PG 富超分子结构在 PG/水溶剂中形成，能够特异性地改变未离解的双氯芬酸的行为。
