Kassem Abeer Ahmed, Ismail Fatma Ahmed, Naggar Vivian Fahim, Aboulmagd Elsayed
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt,
AAPS PharmSciTech. 2014 Aug;15(4):1021-8. doi: 10.1208/s12249-014-0118-7. Epub 2014 May 16.
In situ gelling formulations allow easy application to the target area. Gelation is induced by physiological stimuli at the site of application where the formula attains semisolid properties and exerts sustained drug release. In situ gelling formulations containing either 3% meloxicam (Mx) or 2% minocycline HCl (MH) were prepared for local application into the periodontal pockets. Gel formulations were based on the thermosensitive Pluronic(®) (Pl) and the pH-sensitive Carbopol(®) (C) polymers. C gels were prepared in combination with HPMC (H) to decrease its acidity. The total percent drug released from Pl formulae was 21.72% after 1 week for Mx and 85% after 3 days for MH. Their release kinetics data indicated anomalous non-Fickian behavior that could be controlled by both diffusion and chain relaxation. Addition of MH to C/H gels (1:2.5) resulted in liquefaction, followed by drug precipitation. Regarding C/H gel containing Mx, it showed a prolonged release rate up to 7 days with an initial burst effect; the kinetics data revealed Fickian-diffusion mechanism. The in vitro antibacterial activity studies for MH gel in Pl revealed that the drug released exceeded the minimum inhibitory concentration (MIC) of MH against Staphylococcus aureus ATCC 6538; placebo gel showed no effect on the microorganism. Clinical evaluation of Pl gels containing either Mx or MH showed significant improvement in chronic periodontitis patients, manifested by decrease in pocket depth and gingival index and increase in bone density.
原位凝胶制剂便于应用于目标区域。在应用部位,生理刺激会引发凝胶化,此时制剂获得半固体性质并实现药物的持续释放。制备了含3%美洛昔康(Mx)或2%盐酸米诺环素(MH)的原位凝胶制剂,用于局部注入牙周袋。凝胶制剂基于热敏性普朗尼克(®)(Pl)和pH敏感性卡波姆(®)(C)聚合物。制备C凝胶时与羟丙基甲基纤维素(H)联合使用以降低其酸度。对于Mx,Pl制剂在1周后药物释放总量为21.72%;对于MH,3天后药物释放总量为85%。其释放动力学数据表明呈现非菲克异常行为,这可由扩散和链松弛共同控制。向C/H凝胶(1:2.5)中添加MH会导致液化,随后药物沉淀。对于含Mx的C/H凝胶,其显示出长达7天的延长释放速率且有初始突释效应;动力学数据揭示为菲克扩散机制。对Pl中MH凝胶的体外抗菌活性研究表明,释放的药物超过了MH对金黄色葡萄球菌ATCC 6538的最低抑菌浓度(MIC);安慰剂凝胶对该微生物无作用。对含Mx或MH的Pl凝胶的临床评估显示,慢性牙周炎患者有显著改善,表现为牙周袋深度减小、牙龈指数降低以及骨密度增加。