Sinha V R, Mittal B R, Bhutani K K, Kumria Rachna
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Int J Pharm. 2004 Jan 9;269(1):101-8. doi: 10.1016/j.ijpharm.2003.09.036.
Compression coating has been found to be useful for colonic drug delivery. The aim of the present investigation was to design a formulation with a considerably reduced coat weight and gum concentration for colonic delivery of 5-fluorouracil for the treatment of colorectal cancer. Rapidly disintegrating core tablets containing 50 mg of 5-fluorouracil were prepared and compression coating with 175 mg of granules containing a mixture of xanthan gum (XG) and guar gum (GG) in varying proportions was done. With this coat weight, a highly retarded drug release was observed. After 24h of dissolution the mean percent drug release from the compression coated XG:GG 20:20, 20:10 and 10:20 tablets were found to be around 18+/-1.23%, 20+/-1.54% and 30+/-1.77%, respectively. So, the coat weight was further reduced to 150 mg. It was observed that reduction of coat weight did not affect the initial drug release rate in simulated upper gastrointestinal tract (GIT) conditions. At the end of 24h of dissolution the amount of drug released increased to 25+/-1.22%, 36.6+/-1.89% and 42.6+/-2.22%, respectively in XG:GG 20:20, 20:10 and 10:20 tablets. Studies of XG:GG (10:20) tablets in presence of colonic contents showed an increased cumulative percent drug release of 67.2+/-5.23% in presence of 2% cecal content and 80.34+/-3.89% in presence of 4% cecal content after 19 h of incubation.
已发现压制包衣对结肠给药有用。本研究的目的是设计一种包衣重量和胶浓度显著降低的制剂，用于结肠递送5-氟尿嘧啶以治疗结直肠癌。制备了含50mg 5-氟尿嘧啶的快速崩解片芯，并对其进行压制包衣，包衣材料为175mg含有不同比例黄原胶（XG）和瓜尔胶（GG）混合物的颗粒。在这种包衣重量下，观察到药物释放高度延迟。在溶出24小时后，发现压制包衣的XG:GG 20:20、20:10和10:20片剂的平均药物释放百分比分别约为18±1.23%、20±1.54%和30±1.77%。因此，将包衣重量进一步降低至150mg。观察到包衣重量的降低并不影响模拟上消化道（GIT）条件下的初始药物释放速率。在溶出24小时结束时，XG:GG 20:20、20:10和10:20片剂中的药物释放量分别增加到25±1.22%、36.6±1.89%和42.6±2.22%。在结肠内容物存在的情况下对XG:GG（10:20）片剂进行的研究表明，在孵育19小时后，在2%盲肠内容物存在的情况下，药物累积释放百分比增加到67.2±5.23%，在4%盲肠内容物存在的情况下增加到80.34±3.89%。
