El-Gibaly Ibrahim
Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Int J Pharm. 2002 Jan 31;232(1-2):199-211. doi: 10.1016/s0378-5173(01)00903-6.
A new oral timed-release system was developed for colon-targeted delivery of drugs. The system which consists of ketoprofen-loaded Zn-pectinate gel (ZPG) microparticles together with pectin/dextran mixtures in a tablet form, has been investigated, in vitro, using conditions chosen to simulate the pH and times likely to be encountered during transit to the colon. In order to find the suitable ZPG microparticles, the formulations were prepared by utilizing 2(3) factorial design and the effect of various formulation factors on the release and surface characteristics of the microparticles was studied. The results obtained implied that the release of ketoprofen from ZPG microparticles was greatly extended with the pectinate microparticles, which were prepared with 2.5 or 3% w/v pectin, 2.75% w/v Zn(CH3COO)2 and 2.5% w/v drug. Additionally, the analysis of variance results showed that the release of ketoprofen in simulated intestinal fluid (S.I.F., pH 7.4) was strongly affected by crosslinking agent concentration and initial drug amount, but not particularly affected by the amount of pectin added. The investigated drug concentration factor has significantly increased the drug entrapment efficiency (EE). The optimum colonic drug delivery ZPG/tablet system provided the expected delayed-release sigmoidal patterns with a lag-time of 4.125-4.85 h and t(50%) (the time for 50% of the drug to be released) at 7.45-8.70 h, depending on pectin/dextran ratio employed. The results also demonstrated that the untableted ZPG microparticles exhibited drug release profiles which were able to retard the release of ketoprofen in S.I.F. (pH 7.4) to be 5.28-37.82 times (depending on formulation parameters), lower than the conventional calcium pectinate beads. Therefore, this approach suggests that ZPG microparticles and their modified-release formulations are promising as useful controlled-release carriers for colon-targeted delivery of drugs.
一种用于药物结肠靶向递送的新型口服定时释放系统被开发出来。该系统由负载酮洛芬的果胶锌凝胶（ZPG）微粒与果胶/葡聚糖混合物制成片剂形式，已在体外进行研究，采用了模拟药物转运至结肠过程中可能遇到的pH值和时间条件。为了找到合适的ZPG微粒，利用2(3)析因设计制备制剂，并研究了各种制剂因素对微粒释放和表面特性的影响。所得结果表明，用2.5%或3%（w/v）果胶、2.75%（w/v）醋酸锌和2.5%（w/v）药物制备的果胶微粒能极大地延长酮洛芬从ZPG微粒中的释放时间。此外，方差分析结果表明，在模拟肠液（S.I.F.，pH 7.4）中酮洛芬的释放受交联剂浓度和初始药物量的强烈影响，但受添加果胶量的影响不明显。所研究的药物浓度因素显著提高了药物包封率（EE）。最佳的结肠给药ZPG/片剂系统呈现出预期的延迟释放S形模式，滞后时间为4.125 - 4.85小时，t(50%)（药物释放50%的时间）为7.45 - 8.70小时，这取决于所采用的果胶/葡聚糖比例。结果还表明，未制成片剂的ZPG微粒的药物释放曲线能够将S.I.F.（pH 7.4）中酮洛芬的释放速度延缓5.28 - 37.82倍（取决于制剂参数），低于传统的果胶钙珠。因此，这种方法表明ZPG微粒及其缓释制剂有望成为用于药物结肠靶向递送的有用控释载体。
