Asghar Laila Fatima Ali, Chandran Sajeev
Pharmacy Group, Formulation Development and Pharmacokinetics Laboratory, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
J Drug Target. 2008 Dec;16(10):741-57. doi: 10.1080/10611860802473345.
The purpose of the present study was to investigate the effect of incorporating pH-responsive polymers Eudragit (L100 or S100) in matrix bases composed of hydrophilic polymers polycarbophil and carbopol to design oral controlled release formulations with sigmoidal release profile for colon-specific delivery. Matrix tablets were prepared by wet granulation technique using indomethacin as model drug and were characterized for physical parameters, in vitro drug release, release kinetics, and stability on storage. The gastrointestinal (GI) transit of selected formulations was also investigated in human subjects using gamma scintigraphy. In vitro release studies indicated that the presence of pH-sensitive polymers in hydrophilic polymer base retarded the initial release significantly (10-15% release in 6 h) followed with controlled release for the next 8-10 h in simulated GI fluid pH (without enzymes). The presence of Eudragit in hydrophilic matrix base retarded the swelling of the matrix base in acidic to weakly acidic pH, but in alkaline pH, enhancement in drug release rate was observed due to the dissolution of Eudragit from the base resulting in a porous matrix structure, resulting in around 80-90% release in 14 h of study. In vivo gamma scintigraphy studies in healthy human subjects proved that the formulations had acceptable matrix strength to withstand gastric and colonic transit. The mean colonic residence time of selected designed formulations varied between 15 and 19 h. Such a matrix design could have potential application as colon-specific drug delivery systems with pH- and time-dependent drug release profile.
本研究的目的是研究将pH响应性聚合物Eudragit（L100或S100）掺入由亲水性聚合物聚卡波非和卡波姆组成的基质中，以设计具有用于结肠特异性递送的S形释放曲线的口服控释制剂。以吲哚美辛为模型药物，采用湿法制粒技术制备基质片剂，并对其物理参数、体外药物释放、释放动力学和储存稳定性进行表征。还使用γ闪烁显像技术在人体受试者中研究了所选制剂的胃肠道转运。体外释放研究表明，亲水性聚合物基质中pH敏感聚合物的存在显著延迟了初始释放（在6小时内释放10-15%），随后在模拟胃肠道流体pH（无酶）下的接下来8-10小时内进行控释。亲水性基质中Eudragit的存在延迟了基质在酸性至弱酸性pH下的溶胀，但在碱性pH下，由于Eudragit从基质中溶解导致形成多孔基质结构，观察到药物释放速率增加，在14小时的研究中释放约80-90%。在健康人体受试者中进行的体内γ闪烁显像研究证明，这些制剂具有可接受的基质强度以承受胃和结肠转运。所选设计制剂的平均结肠滞留时间在15至19小时之间变化。这种基质设计作为具有pH和时间依赖性药物释放曲线的结肠特异性药物递送系统可能具有潜在应用。
