用於腸道藥物控釋之尼古丁／藻酸鈣微粒膠囊的製備與特性研究

Preparation and Characterization of Nicotine/Ca-alginate Composite Microcapsules for the Enteric Controlled Drug Release

本研究之目的擬發展一具有結腸標靶特性之口服微粒膠囊藥物輸移系統以增進生體可用率，文中選用尼古丁為親脂性模式藥物，明膠、甘油與聚乙烯二醇6000為添加物分別加入藻酸鈣中，採用改良乳化技術製成微粒膠囊，進而探討添加物對微粒膠囊之產率、包埋率、理化性質以及藥物釋離的影響。結果顯示，所製成之圓形含尼古丁的微粒膠囊其平均粒徑介於40 μm至500 μm，粒徑大小可藉由製備條件加以控制，包埋率則與粒徑大小有關。微粒膠囊FTIR光譜圖指出，負載尼古丁的微粒膠囊各成分間未有化學性交互作用發生。添加物對延遲藥物在pH 1.2的條件下自微粒膠囊釋出之影響依序為：聚乙烯二醇6000>甘油>明膠，在pH 7.4的條件下，微粒膠囊的膨脹度急劇增加甚至造成粒子崩解，導致藥物釋離加速，此種微粒膠囊性質適合用於腸道疾病之標靶作用。為了更有效的控制藥物自微粒膠囊之釋離，可藉由增加藻酸鹽含量以及添加甘油與聚乙烯二醇6000加以改善。

The aim of the present study was to develop drug-loaded microcapsules to increase drug bioavailability at target site especially for colon-targeted oral delivery. Nicotine was selected as a model lipophilic drug. Additives such as gelatin, glycerin and PEG 6000 were added into Ca-alginate composite to prepare microcapsules by using a modification of the emulsion technique. The effect of additives on process yield, encapsulation efficiency, physical-chemical properties of microcapsules as well as drug release was investigated. The results show that a mean particle size ranging from 40 μm to 500 μm was obtained and nicotine-loaded microcapsules were spherical in shape. The preparing condition would affect particle size but not additives added. Encapsulation efficiency of microcapsules is well relative to the particle size. The FTIR spectra of microcapsules indicated that the chemical interaction does not occur among the components of nicotine-loaded microcapsules. The effect of additives on retarding release of drug from microcapsules in pH 1.2 medium conformed to the following order: PEG 6000 > glycerin > gelatin. At pH 7.4, the degree of swelling increased dramatically even degradation that cause accelerated drug release. The properties of the microcapsules are suitable for bowel disease targeting. To get more control over the drug delivery the current composite of microcapsules could be improved by increasing alginate content and adding additives such as PEG 6000 or glycerin.