Kim C J
School of Pharmacy, Temple University, 3307 N. Broad St., Philadelphia, PA 19140, USA.
Eur J Pharm Sci. 1999 Feb;7(3):237-42. doi: 10.1016/s0928-0987(98)00029-3.
Coated, donut-shaped tablets (CDST) were designed to achieve parabolic and linear drug release profiles. When rapidly erodible polymers (HPMC E3, HPC, PEG8000, PEOs (Mw=100000 and 200000)) were used, the release profiles of diltiazem HCl from the tablets becomes parabolic whereas zero-order release was achieved by using slowly erodible polymers (HPMC E5, HPMC E15, PEO (Mw=300000)). Drug release from the rapidly erodible polymers was governed by the pure erosion of the polymer while both polymer erosion and drug diffusion controlled drug release from the slowly erodible polymers. As drug loading was increased from 10% to 39% w/w, the drug release rate from CDST based on HPMC E3 became faster and parabolic whereas that from CDST based on HPMC E5 was linear. The slowly erodible polymer (HPMC E5) provided parabolic release profiles when drug loading was greater than 49% w/w. In this case, drug release mechanisms likely shifted from a combination of polymer erosion and drug diffusion to pure polymer erosion due to the enhancement of polymer erosion by faster influx of water. As drug solubility decreased from 61.6% w/v (diltiazem HCl), 1.0% w/v (theophylline), to 0.5% w/v (nicardipine HCl), the drug release rate from CDST based on HPMC E3 decreased due to polymer erosion mechanism but there was little difference in release rate from CDST based on HPMC E5 due to the greater contribution of drug diffusion to drug release kinetics along with polymer erosion. As expected, the drug release rate of diltiazem HCl from HPMC E3 and E5 was significantly influenced by stirring rate and hole size.
包衣的环形片（CDST）旨在实现抛物线型和线性药物释放曲线。当使用快速可蚀性聚合物（羟丙甲纤维素E3、羟丙基纤维素、聚乙二醇8000、聚氧化乙烯（分子量 = 100000和200000））时，盐酸地尔硫䓬从片剂中的释放曲线变为抛物线型，而使用缓慢可蚀性聚合物（羟丙甲纤维素E5、羟丙甲纤维素E15、聚氧化乙烯（分子量 = 300000））时则实现零级释放。快速可蚀性聚合物的药物释放受聚合物的纯侵蚀控制，而聚合物侵蚀和药物扩散共同控制缓慢可蚀性聚合物的药物释放。随着药物载量从10%（w/w）增加到39%（w/w），基于羟丙甲纤维素E3的CDST的药物释放速率加快且呈抛物线型，而基于羟丙甲纤维素E5的CDST的药物释放速率则呈线性。当药物载量大于49%（w/w）时，缓慢可蚀性聚合物（羟丙甲纤维素E5）呈现抛物线型释放曲线。在这种情况下，由于水的更快流入增强了聚合物侵蚀，药物释放机制可能从聚合物侵蚀和药物扩散的组合转变为纯聚合物侵蚀。随着药物溶解度从61.6%（w/v）（盐酸地尔硫䓬）、1.0%（w/v）（茶碱）降至0.5%（w/v）（盐酸尼卡地平），基于羟丙甲纤维素E3的CDST的药物释放速率因聚合物侵蚀机制而降低，但基于羟丙甲纤维素E5的CDST的释放速率差异不大，这是因为药物扩散对药物释放动力学的贡献更大，同时伴有聚合物侵蚀。正如预期的那样，盐酸地尔硫䓬从羟丙甲纤维素E3和E5的药物释放速率受到搅拌速率和孔径的显著影响。
