Department of Pharmaceutics, Institute of Pharmacy, Nirma University, Sarkhej-Gandhinagar Highway, Ahmedabad 382481, Gujarat, India.
J Pharm Sci. 2011 May;100(5):1760-72. doi: 10.1002/jps.22406. Epub 2010 Dec 13.
The objective of the present work was to develop a delayed-onset controlled-release colon-targeted system of theophylline, and to achieve the chronotherapy of nocturnal asthma. The formulation consisted of a core tablet containing hydroxypropyl methylcellulose used for achieving controlled release of drug, and a Eudragit S100:ethyl cellulose (EC) coating capable of delaying the drug release. The system was optimized using a 3(2) full factorial design, wherein two factors [ratio of Eudragit S100:EC and the coating level (% w/w)] were evaluated for lag time, t(50) and t(80) . The optimum formulation consisted of Eudragit S100:EC in a 60:40 ratio and a coating level of 7.5% (w/w). Results showed that the tablets prepared according to the optimized values released no drug in the upper part of gastrointestinal tract; drug release was initiated at pH 6.4 (colon) after a lag time of 5 h. In vivo evaluation (pharmacokinetic studies and roentgenography) in rabbits revealed that the tablet remained intact until it reaches the colon and the drug release was initiated after a lag time of 5 h. Thus, it can be concluded that the developed system exhibited a promising colonic targeting and hence may be used for chronotherapy of nocturnal asthma.
本工作旨在开发茶碱的迟释型结肠定位释放系统,实现夜间哮喘的时间治疗。该制剂由含有羟丙甲纤维素的核心片组成,用于实现药物的控制释放,以及能够延迟药物释放的 Eudragit S100:乙基纤维素(EC)包衣。该系统采用 3(2)完全因子设计进行优化,其中两个因素[Eudragit S100:EC 的比例和包衣水平(%w/w)]用于评估滞后时间 t(50)和 t(80)。最优制剂由 Eudragit S100:EC 的 60:40 比例和 7.5%(w/w)的包衣水平组成。结果表明,根据优化值制备的片剂在上胃肠道中不释放药物;在滞后时间为 5 小时后,在 pH 6.4(结肠)开始释放药物。在兔子体内评估(药代动力学研究和 X 射线照相)表明,片剂在到达结肠之前保持完整,滞后时间为 5 小时后开始释放药物。因此,可以得出结论,开发的系统表现出有前途的结肠定位,因此可用于夜间哮喘的时间治疗。