Cao Qing-Ri, Choi Han-Gon, Kim Dong-Chool, Lee Beom-Jin
National Research Laboratory for Bioavailability Control, College of Pharmacy, Kangwon National University, Chuncheon, South Korea.
Int J Pharm. 2004 Apr 15;274(1-2):107-17. doi: 10.1016/j.ijpharm.2004.01.020.
An orally applicable nifedipine-loaded core tablets was coated using high viscosity grade HPMC (100,000 cps) in ethanol/water cosolvent. The release of coated tablet was evaluated using USP paddle method in 900 ml of simulated gastric fluid (pH 1.2) for 2 h followed by intestinal fluid (pH 6.8) for 10 h. The surface morphologies using scanning electron microscope and photo-images using digital camera of coated tablet during the release test were also visualized, respectively. The viscosity of hydro-alcoholic HPMC solution largely decreased as the amount of ethanol increased. There was no significant difference in viscosity among plasticizers used. The distinct and continuous coated layer was observed using scanning electron microscope. However, the surface morphologies were highly dependent on HPMC concentration and ratio of coating solvents. The higher ratio of ethanol/water gave a longer lag time prior to drug release. Lag time also increased as a function of the coating levels based on weight gains due to increased thickness of coated layer. Lag time is inversely correlated with HPMC concentration in ethanol/water (5:1) cosolvent. As the HPMC concentration slightly decreased from 3.8 to 3.2% in hydroalcoholic coating solution, a large increase of lag time was observed. As the swelling (mixing) time of high viscosity grade HPMC in ethanol/water cosolvent increased from 1 to 5 h, the release rate was decreased due to enough plasticization of polymer. Based on photo-imaging analysis, the coated tablet was initially swelled and gelled without erosion and disintegration over 5 h. The disintegration of the coated tablet was occurred approximately 7 h after dissolution, resulting in pulsed release of drug. The high viscosity grade HPMC can be applicable for polymeric coating after careful selection of solvent systems. The release behavior and lag time could be controlled by coating conditions such as HPMC concentration, ethanol/water ratio as a coating solvent, coating level and swelling (mixing) time of coating solution. The current time-controlled release tablet coated with high viscosity grade HPMC with a designated lag time followed by a rapid release may provide an alternative to site specific or colonic delivery of drugs. In addition, the release behavior can be matched with body's circadian rhythm pattern in chronotherapy.
一种口服的硝苯地平片芯用高粘度等级的羟丙基甲基纤维素（100,000厘泊）在乙醇/水混合溶剂中进行包衣。采用美国药典桨法，在900毫升模拟胃液（pH 1.2）中对包衣片进行2小时的释放度评估，随后在肠液（pH 6.8）中进行10小时的评估。在释放试验期间，还分别通过扫描电子显微镜观察了包衣片的表面形态，并使用数码相机拍摄了照片图像。随着乙醇用量的增加，水醇性羟丙基甲基纤维素溶液的粘度大幅下降。所用增塑剂之间的粘度没有显著差异。通过扫描电子显微镜观察到了清晰且连续的包衣层。然而，表面形态高度依赖于羟丙基甲基纤维素的浓度和包衣溶剂的比例。乙醇/水比例越高，药物释放前的滞后时间越长。滞后时间也随着基于增重的包衣水平的增加而增加，这是由于包衣层厚度增加所致。滞后时间与乙醇/水（5:1）混合溶剂中羟丙基甲基纤维素的浓度呈负相关。当水醇性包衣溶液中羟丙基甲基纤维素的浓度从3.8%略微降至3.2%时，观察到滞后时间大幅增加。随着高粘度等级的羟丙基甲基纤维素在乙醇/水混合溶剂中的溶胀（混合）时间从1小时增加到5小时，由于聚合物充分增塑，释放速率降低。基于照片成像分析，包衣片最初在5小时内溶胀并形成凝胶，没有发生侵蚀和崩解。包衣片在溶解约7小时后发生崩解，导致药物脉冲释放。经过仔细选择溶剂体系后，高粘度等级的羟丙基甲基纤维素可用于聚合物包衣。释放行为和滞后时间可以通过包衣条件来控制，如果羟丙基甲基纤维素浓度、作为包衣溶剂的乙醇/水比例、包衣水平以及包衣溶液的溶胀（混合）时间等。当前用高粘度等级的羟丙基甲基纤维素包衣的具有指定滞后时间随后快速释放的定时释放片，可能为药物的定位或结肠给药提供一种替代方法。此外，在时间治疗中，释放行为可以与人体的昼夜节律模式相匹配。
