Kim H, Fassihi R
Temple University, School of Pharmacy, Philadelphia, PA 19140, USA.
J Pharm Sci. 1997 Mar;86(3):323-8. doi: 10.1021/js960307p.
The significance of factors such as drug solubility, polymer molecular weight, drug loading dose, compression force, and hydrodynamic conditions on drug release from a swellable hydrophilic delivery system was investigated. Hydroxypropyl methylcellulose (HPMC) and pectin were major polymeric constituents of the delivery system. Nifedipine, prednisolone, theophylline anhydrous, and diltiazem hydrochloride with solubilities of < 0.001%, <0.1%, <1%, and >50%, respectively, were used as drug models. Results show that changes in pectin:HPMC ratios, HPMC molecular weight, and hydrodynamic conditions exert notable influences on release rate and release duration from the designed system. In the case of prednisolone, drug loading up to 30% (w/w) of the matrix composition (pectin:HPMC K4M; 3:6) had no effect on zero-order release kinetics, and the delivery system was insensitive to changes in compression force (2000 to 5000 lb). For nifedipine, theophylline, and diltiazem, determination of mean dissolution time (MDT) for 50 and 80% drug release provided accurate information on release behavior. The dominating effect of matrix composition over variations in drug solubilities in controlling drug release from the delivery system was evident from similarities in dissolution profiles. It is further shown that hydrodynamic stress and intensity of fluid flow causes greater attrition at the swollen periphery and is responsible for dramatic increases in release rates. This latter observation confirms that the mechanism of drug release from this swellable system is erosion dependent. Influence of polymer molecular weight and drug solubility on release kinetics and the potential of the delivery system is discussed.
研究了药物溶解度、聚合物分子量、载药量、压力以及流体动力学条件等因素对可溶胀亲水性给药系统中药物释放的影响。羟丙基甲基纤维素（HPMC）和果胶是该给药系统的主要聚合物成分。分别选用溶解度小于0.001%、小于0.1%、小于1%和大于50%的硝苯地平、泼尼松龙、无水茶碱和盐酸地尔硫䓬作为药物模型。结果表明，果胶与HPMC的比例、HPMC分子量以及流体动力学条件的变化对所设计系统的释放速率和释放持续时间有显著影响。对于泼尼松龙，载药量高达基质组成（果胶：HPMC K4M；3:6）的30%（w/w）对零级释放动力学没有影响，并且该给药系统对压力变化（2000至5000磅）不敏感。对于硝苯地平、茶碱和地尔硫䓬，测定50%和80%药物释放的平均溶解时间（MDT）可提供有关释放行为的准确信息。从溶出曲线的相似性可以明显看出，在控制给药系统中药物释放方面，基质组成比药物溶解度变化的主导作用更为显著。进一步表明，流体动力学应力和流体流动强度会导致溶胀周边的磨损加剧，并导致释放速率急剧增加。后一观察结果证实，该可溶胀系统的药物释放机制是依赖于侵蚀的。讨论了聚合物分子量和药物溶解度对释放动力学的影响以及该给药系统的潜力。
