Department of Formulation Design and Pharmaceutical Technology, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Neutron Science and Technology Center, Comprehensive Research Organization for Science and Society, Tokai, Ibaraki 319-1106, Japan.
J Colloid Interface Sci. 2024 Sep;669:975-983. doi: 10.1016/j.jcis.2024.05.038. Epub 2024 May 11.
Hydroxypropyl methylcellulose phthalate (HPMCP) is an enteric polymer that has been employed in drug delivery systems to delay the release of the encapsulated active pharmaceutical ingredients through its pH-responsive solubility change. This has been recently demonstrated as an effective means for delaying the drug release from gelatin/HPMCP hydrogels at gastric pH values. However, structural characteristics of HPMCP agglomeration in gelatin/HPMCP hydrogels is not well understood thus limiting further tailoring of their material properties.
We investigated the multiscale structure of a gelatin/HPMCP hydrogel (1:1 by weight) between pH 2 and 6 at 37 °C, i.e. above the upper critical solution transition temperature of gelatin, using small-angle X-ray scattering and contrast-variation small-angle neutron scattering to understand the pH-responsive structure of HPMCP and the cross-correlation between gelatin and HPMCP.
Agglomeration of HPMCP between pH 2 and 4 was evidenced by the formation of mass fractal structures, with a fractal dimension ranging from 1.5 to 2.7, comprising primary particles with a radius of gyration ranging from 70 to 140 Å. Blending with gelatin influenced the fractal structure of HPMCP and the primary particle size. Gelatin and HPMCP exhibited negative cross-correlation in all probed length scales and pH values, which was attributed to volume-exclusion interaction in a double-network-like solution architecture.
羟丙基甲基纤维素邻苯二甲酸酯（HPMCP）是一种肠溶性聚合物，已被用于药物传递系统中，通过其对 pH 值响应的溶解度变化来延迟包裹的活性药物成分的释放。这在最近已被证明是一种有效的方法，可以延缓明胶/HPMCP 水凝胶在胃 pH 值下的药物释放。然而，HPMCP 在明胶/HPMCP 水凝胶中的团聚结构特征尚不清楚，因此限制了对其材料性能的进一步调整。
我们在 37°C 下，在 pH 2 到 6 之间研究了明胶/HPMCP 水凝胶（重量比为 1:1）的多尺度结构，即高于明胶的上临界溶液转变温度，使用小角 X 射线散射和对比变化小角中子散射来了解 HPMCP 的 pH 响应结构以及明胶和 HPMCP 之间的交叉相关性。
在 pH 2 到 4 之间，HPMCP 的团聚体被证明形成了质量分形结构，分形维数范围从 1.5 到 2.7，由旋转半径范围从 70 到 140 Å 的初级粒子组成。与明胶混合影响了 HPMCP 的分形结构和初级粒子的大小。在所有探测的长度尺度和 pH 值下，明胶和 HPMCP 表现出负的交叉相关性，这归因于双网络样溶液结构中的体积排斥相互作用。
