am Ende M T, Peppas N A
School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47907-1283, USA.
Pharm Res. 1995 Dec;12(12):2030-5. doi: 10.1023/a:1016224813626.
The purpose of this work was to study solute (drug and protein)/polymer interactions that affect solute diffusion in and subsequent release from swellable dosage forms based on environmentally responsive, pH-sensitive polymer networks.
Ionizable pH-sensitive hydrogels were synthesized by free-radical polymerization of acrylic acid (AA) and 2-hydroxyethyl methacrylate (HEMA) with ethylene glycol dimethacrylate as crosslinking agent. The degree of crosslinking and degree of hydrophilicity were controlled by varying the relative concentration of crosslinking agent and comonomer, respectively. The role of solute distribution within the hydrogels as related to the transport behavior was investigated by Fourier transform infrared (FTIR) microscopy.
The solute-loaded hydrogels were cryotomed into 4 microns thin sections. The concentration profile of the solute was constructed from the two dimensional intensities measured by monitoring the infrared vibrational band indicative of that compound in the x and y direction. These studies indicated that the model solute, oxprenolol HCl, was evenly distributed throughout the bulk and surface of the hydrogel samples. Solute/polymer interactions were investigated as a function of the polymer composition and swelling media pH. The concentration profiles of oxprenolol HCl solution loaded into PAA and P(AA-co-HEMA) hydrogels were analyzed by scanning electron microscopy by FTIR microscopy. For hydrophilic polymers (hydrogels) containing ionizable pendant groups, the molecular weight between crosslinks, the degree of swelling, and the degree of ionization were altered by local changes in pH and ionic strength.
The data demonstrated that it is possible to evaluate the polymer/solute interactions by using FTIR microscopy.
本研究旨在探讨溶质（药物和蛋白质）/聚合物相互作用，该相互作用会影响基于环境响应型、pH敏感聚合物网络的可溶胀剂型中溶质的扩散及其后续释放。
以乙二醇二甲基丙烯酸酯为交联剂，通过丙烯酸（AA）和甲基丙烯酸2-羟乙酯（HEMA）的自由基聚合反应合成了可电离的pH敏感水凝胶。分别通过改变交联剂和共聚单体的相对浓度来控制交联度和亲水性程度。通过傅里叶变换红外（FTIR）显微镜研究了水凝胶中溶质分布与传输行为之间的关系。
将负载溶质的水凝胶冷冻切片成4微米厚的薄片。通过监测指示该化合物的红外振动带在x和y方向上测量的二维强度构建溶质的浓度分布图。这些研究表明，模型溶质盐酸氧烯洛尔在水凝胶样品的整体和表面均匀分布。研究了溶质/聚合物相互作用与聚合物组成和溶胀介质pH的函数关系。通过扫描电子显微镜和FTIR显微镜分析了负载到PAA和P（AA-co-HEMA）水凝胶中的盐酸氧烯洛尔溶液的浓度分布图。对于含有可电离侧基的亲水性聚合物（水凝胶），交联点之间的分子量、溶胀度和电离度会因pH值和离子强度的局部变化而改变。
数据表明，使用FTIR显微镜可以评估聚合物/溶质相互作用。
