Vemula Sateesh Kumar
Department of Pharmacy, College of Medical and Health Sciences, Wollega University, Post Box No: 395, Nekemte, Ethiopia.
Department of Pharmaceutics, Chaitanya College of Pharmaceutical Sciences, Hanamkonda, Warangal, Telangana, 506001, India.
AAPS PharmSciTech. 2015 Dec;16(6):1465-73. doi: 10.1208/s12249-015-0340-y. Epub 2015 May 28.
A significant plan is executed in the present study to study the effect of double-compression coating on flurbiprofen core mini-tablets to achieve the pulsatile colonic delivery to deliver the drug at a specific time as per the patho-physiological need of the disease that results in improved therapeutic efficacy. In this study, pulsatile double-compression-coated tablets were prepared based on time-controlled hydroxypropyl methylcellulose K100M inner compression coat and pH-sensitive Eudragit S100 outer compression coat. Then, the tablets were evaluated for both physical evaluation and drug-release studies, and to prove these results, in vivo pharmacokinetic studies in human volunteers were conducted. From the in vitro drug-release studies, F6 tablets were considered as the best formulation, which retarded the drug release in the stomach and small intestine (3.42 ± 0.12% in 5 h) and progressively released to the colon (99.78 ± 0.74% in 24 h). The release process followed zero-order release kinetics, and from the stability studies, similarity factor between dissolution data before and after storage was found to be 88.86. From the pharmacokinetic evaluation, core mini-tablets producing peak plasma concentration (C max) was 14,677.51 ± 12.16 ng/ml at 3 h T max and pulsatile colonic tablets showed C max = 12,374.67 ± 16.72 ng/ml at 12 h T max. The area under the curve for the mini and pulsatile tablets was 41,238.52 and 72,369.24 ng-h/ml, and the mean resident time was 3.43 and 10.61 h, respectively. In conclusion, development of double-compression-coated tablets is a promising way to achieve the pulsatile colonic release of flurbiprofen.
本研究执行了一项重要计划，以研究双层压片包衣对氟比洛芬片芯微片的作用，从而实现脉冲式结肠给药，根据疾病的病理生理需求在特定时间释放药物，进而提高治疗效果。在本研究中，基于时间控制的羟丙基甲基纤维素K100M内压包衣和pH敏感型丙烯酸树脂S100外压包衣制备了脉冲式双层压片包衣片。然后，对片剂进行了物理评价和药物释放研究，并为验证这些结果，在人类志愿者中进行了体内药代动力学研究。从体外药物释放研究来看，F6片剂被认为是最佳制剂，其在胃和小肠中延缓了药物释放（5小时内为3.42±0.12%），并逐渐在结肠中释放（24小时内为99.78±0.74%）。释放过程遵循零级释放动力学，从稳定性研究来看，储存前后溶出数据的相似因子为88.86。从药代动力学评价来看，产生血浆峰浓度（Cmax）的片芯微片在3小时达峰时间（Tmax）时为14,677.51±12.16 ng/ml，而脉冲式结肠片在12小时Tmax时显示Cmax = 12,374.67±16.72 ng/ml。微片和脉冲式片剂的曲线下面积分别为41,238.52和72,369.24 ng-h/ml，平均驻留时间分别为3.43和10.61小时。总之，开发双层压片包衣片是实现氟比洛芬脉冲式结肠释放的一种有前景的方法。
