Simancas-Herbada Rebeca, Fernández-Carballido Ana, Aparicio-Blanco Juan, Slowing Karla, Rubio-Retama Jorge, López-Cabarcos Enrique, Torres-Suárez Ana-Isabel
Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.
Institute of Industrial Pharmacy, Complutense University of Madrid, 28040 Madrid, Spain.
Pharmaceutics. 2020 Feb 19;12(2):174. doi: 10.3390/pharmaceutics12020174.
The potential of a new poly(magnesium acrylate) hydrogel (PAMgA) as a pharmaceutical excipient for the elaboration of matrix tablets for the extended release of highly hydrophilic drugs was evaluated. The polymer was synthetized with two different crosslinking degrees that were characterized by FTIR and DSC. Their acute oral toxicity was determined in a mouse model, showing no toxicity at doses up to 10 g/kg. Matrix tablets were prepared using metformin hydrochloride as a model drug and the mechanisms involved in drug release (swelling and/or erosion) were investigated using biorrelevant media. This new hydrogel effectively controlled the release of small and highly hydrophilic molecules as metformin, when formulated in matrix tablets for oral administration. The rate of metformin release from PAMgA matrices was mainly controlled by its diffusion through the gel layer (Fickian diffusion). The swelling capacity and the erosion of the matrix tablets influenced the metformin release rate, that was slower at pH 6.8, where polymer swelling is more intensive, than in gastric medium, where matrix erosion is slightly more rapid. The crosslinking degree of the polymer significantly influenced its swelling capacity in acid pH, where swelling is moderate, but not in intestinal fluid, where swelling is more intense.
评估了一种新型聚丙烯酸镁水凝胶（PAMgA）作为药物辅料用于制备用于长效释放高亲水性药物的骨架片的潜力。该聚合物通过两种不同的交联度合成，并通过傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）进行表征。在小鼠模型中测定了它们的急性口服毒性，结果表明在高达10 g/kg的剂量下无毒性。以盐酸二甲双胍为模型药物制备了骨架片，并使用生物相关介质研究了药物释放所涉及的机制（溶胀和/或侵蚀）。当制成口服给药的骨架片时，这种新型水凝胶有效地控制了小的高亲水性分子如二甲双胍的释放。二甲双胍从PAMgA骨架中的释放速率主要受其通过凝胶层的扩散控制（菲克扩散）。骨架片的溶胀能力和侵蚀影响了二甲双胍的释放速率，在pH 6.8时释放较慢，此时聚合物溶胀更强烈，而在胃介质中，骨架侵蚀稍快。聚合物的交联度显著影响其在酸性pH下的溶胀能力，此时溶胀适中，但在肠液中则不然，肠液中溶胀更强烈。
