Kulkarni Raghavendra V, Sa Biswanath
Department of Pharmaceutical Technology, Center for Advanced Research in Pharmaceutical Sciences, Jadavpur University, Kolkata, India.
J Drug Target. 2008 Feb;16(2):167-77. doi: 10.1080/10611860701792399.
Novel pH-sensitive hydrogel beads were prepared using a hydrolyzed poly(acrylamide-g-xanthan) (PAAm-g-XG) copolymer from a complete aqueous environment and evaluated for targeting ketoprofen to the intestine. The PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The copolymer was characterized by FTIR spectroscopy, (1)H NMR spectroscopy, elemental analysis and thermogravimetric analysis. Pulsatile swelling study indicated that the copolymer exhibits considerable pH-sensitive behavior unlike pristine xanthan gum. Ketoprofen-loaded pH-sensitive beads were prepared by ionotropic gelation with Al(3 + ) ions. Release of drug from all the copolymeric beads was much lesser than that from pristine xanthan beads. Moreover, a maximum of 20% ketoprofen was released from the copolymeric beads in pH 1.2-5.5 during a period of 3 h, while a major portion of the drug was released in pH 6.8-7.4 gradually over a longer period. Pharmacodynamic activity and stomach histopathology of albino rats indicated that the beads were able to retard the drug release in stomach, and gastric side effects such as ulceration, hemorrhage and erosion of gastric mucosa were diminished when the drug was entrapped into PAAm-g-XG-based pH-sensitive beads.
新型pH敏感水凝胶珠粒是在完全水性环境中使用水解聚（丙烯酰胺-g-黄原胶）（PAAm-g-XG）共聚物制备的，并评估了其将酮洛芬靶向肠道的能力。PAAm-g-XG共聚物在氮气气氛下通过自由基聚合合成，随后进行碱性水解。通过傅里叶变换红外光谱（FTIR）、核磁共振氢谱（¹H NMR）、元素分析和热重分析对该共聚物进行了表征。脉冲溶胀研究表明，与原始黄原胶不同，该共聚物表现出显著的pH敏感行为。通过与Al(³⁺)离子进行离子凝胶化制备了负载酮洛芬的pH敏感珠粒。所有共聚物珠粒的药物释放量远低于原始黄原胶珠粒。此外，在3小时内，共聚物珠粒在pH 1.2 - 5.5条件下最多释放20%的酮洛芬，而大部分药物在pH 6.8 - 7.4条件下在更长时间内逐渐释放。白化大鼠的药效学活性和胃组织病理学表明，这些珠粒能够延缓药物在胃中的释放，并且当药物被包封在基于PAAm-g-XG的pH敏感珠粒中时，胃溃疡、出血和胃黏膜糜烂等胃部副作用会减轻。
