Development of an oral sustained release drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer.
Development of an oral sustained release drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer.
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利用羧乙烯基聚合物的 pH 依赖性膨胀开发口服缓释药物递送系统。
DOI：
10.1016/j.jconrel.2005.12.018
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Y. Akiyama
中科院分区：
文献类型：
--
作者：
Kenji Nakamura;E. Nara;Y. Akiyama
利用羧乙烯基聚合物（CP）的pH依赖性溶胀，提出了一种新的口服缓释（SR）给药系统。这种溶胀聚合物掺入层系统，称为SPILA系统，由用CP、水不溶性聚合物和水溶性聚合物（WP）的混合物包衣的核心颗粒组成。酒石酸美托洛尔（ME）在SPILA系统中的释放具有pH依赖性：在pH 1.2的介质中释放比在pH 6.8的介质中释放慢，这是由于包衣层含有pH依赖性溶胀聚合物CP。与具有无CP包衣层的pH非依赖性SR颗粒相比，将基于SPILA系统的SR颗粒给予比格犬后获得较低的Cmax、较长的Tmax、较长的MRT和较高的AUC值，而两种SR颗粒提供相似的体外释放曲线。此外，以盐酸吗啡（MO）为靶点，考察了SPILA系统的体内外性能。随着CP掺入量的增加，MO在SPILA体系中的释放曲线呈现出更明显的pH依赖性。对比格犬给予包衣层含8% CP的MO SR颗粒后的AUC和MRT值分别为191 ng h/mL和10.6 h，而对比格犬给予包衣层含1% CP的MO SR颗粒后的AUC和MRT值分别为86.4 ng h/mL和5.86 h。从SPILA系统的体内性能证实了CP在SPILA系统的释放调节层中的重要作用，以保持更高和更长的血浆吗啡游离碱水平。
A new oral sustained-release (SR) drug delivery system utilizing pH-dependent swelling of carboxyvinyl polymer (CP) has been proposed. This swelling polymer incorporation layer system, referred to as SPILA system, consists of core granules coated with a mixture of CP, water insoluble polymer, and water-soluble polymer (WP). Release profiles of metoprolol tartrate (ME) from SPILA system were pH dependent: drug release was slower in the medium of pH 1.2 than in the medium of pH 6.8 due to a coating layer with pH-dependent swelling polymer, CP. Lower Cmax, longer Tmax, longer MRT and higher AUC values were obtained following administration of SR granules based on SPILA system to beagle dogs compared with pH-independent SR granules having a coating layer without CP, while both SR granules provided similar in vitro release profiles. Moreover, using morphine hydrochloride (MO), in vitro and in vivo performances of the SPILA system were investigated. pH-dependency on the release profiles of MO from SPILA system was more evident when the amount of CP incorporated in SPILA system was increased. AUC and MRT values following administration of SR granules of MO with a coating layer containing 8% of CP to beagle dogs were 191 ng h/mL and 10.6 h respectively, while those following SR granules of MO with a coating layer containing 1% of CP to beagle dogs were 86.4 ng h/mL and 5.86 h, respectively. An important role of CP in the release-regulating layer of SPILA system for keeping the higher and more extended plasma levels of morphine free base was confirmed from the in vivo performance of SPILA system.