Gurunanak College of Pharmacy, Khasra No. 81/1, Mauza Nari, Near Kamgaar Nagar, Behind C. P. Foundry, Kamptee Road, Nagpur, 440026 Maharashtra, India.
AAPS PharmSciTech. 2010 Mar;11(1):336-43. doi: 10.1208/s12249-010-9389-9. Epub 2010 Mar 3.
In the present study, an attempt was made to prepare immediate-release enteric-coated pellets of aceclofenac, a poorly soluble nonsteroidal anti-inflammatory drug that has a gastrointestinal intolerance as its serious side effect. Formulation of enteric-coated pellets with improved solubility of aceclofenac could address both of these problems. To achieve these goals, pellets were prepared by extrusion-spheronization method using pelletizing agents that can contribute to the faster disintegration and thereby improve the solubility of the drug. Different disintegrants like beta-cyclodextrin, kollidon CL, Ac-Di-Sol, and sodium starch glycolate were tried in order to further improve disintegration time. The pellets were characterized for drug content, particle size distribution, flow properties, infrared spectroscopy, surface morphology, disintegration rate, and dissolution profile. The formulations, which showed best disintegration and dissolution profiles, were coated with Eudragit L100-55, an enteric-coated polymer which does not dissolve at gastric pH but dissolves at intestinal pH, releasing the drug immediately in the dissolution medium. The optimized enteric-coated formulation containing 20% kappa-carrageenan, lactose, and sodium starch glycolate as a disintegrant did inhibit the release of the drug for 2 h in 0.1 N HCl, whereas 87% of the drug was released within 45 min. The improvement was substantial when it was compared with solubility of pure drug under the same conditions. Thus, dissolution profiles suggested that combination of kappa-carrageenan and sodium starch glycolate resulted into fast-disintegrating, immediate-release pellets, overcoming the bioavailability problem of the poorly soluble drug, aceclofenac, and enteric coating of these pellets avoids the exposure of aceclofenac to ulcer-prone areas of the gastrointestinal tract.
在本研究中，尝试制备一种快速释放肠溶包衣的 aceclofenac 微丸，aceclofenac 是一种难溶性非甾体抗炎药，其严重的副作用是胃肠道不耐受。通过改善 aceclofenac 的溶解性来制备肠溶包衣微丸，可以解决这两个问题。为了实现这些目标，使用可以促进更快崩解从而提高药物溶解性的制粒剂通过挤出造球法制备微丸。尝试了不同的崩解剂，如β-环糊精、共聚维酮 CL、Ac-Di-Sol 和交联聚维酮，以进一步缩短崩解时间。对微丸进行了药物含量、粒径分布、流动特性、红外光谱、表面形态、崩解速率和溶解特性的表征。显示出最佳崩解和溶解特性的配方用 Eudragit L100-55 进行包衣，Eudragit L100-55 是一种肠溶包衣聚合物，在胃 pH 下不溶解，但在肠 pH 下溶解，立即在溶解介质中释放药物。含有 20%卡拉胶、乳糖和交联聚维酮作为崩解剂的优化肠溶配方在 0.1 N HCl 中可抑制药物释放 2 小时，而 87%的药物在 45 分钟内释放。与相同条件下的纯药物的溶解度相比，这是一个实质性的提高。因此，溶解特性表明卡拉胶和交联聚维酮的组合形成了快速崩解的即刻释放微丸，克服了难溶性药物 aceclofenac 的生物利用度问题，这些微丸的肠溶包衣避免了 aceclofenac 暴露于胃肠道易患溃疡的区域。
