制造Zein/甲基丙烯酸共聚物混合物的延迟释放硬胶囊壳
Hard capsule shells with an inherent delayed release action are useful for oral administration of active ingredients, which are acid-labile and/or enzymatically degradable in the gastric environment, without the need of film涂层. The objective of this study was to fabricate delayed release hard capsule shells by the dip coating method. The film coating formulations comprised blends of zein and methacrylic acid copolymer (Eudragit® L100–55), with and without the addition of the plasticizer, polyethylene glycol 1000.
流变学参数(损耗模量(G), storage modulus (G”) and loss tangent (tan δ, G”/G’)) of the film coating solution were measured to investigate the processability. Central composite design was used to investigate the main, interaction and quadratic effects of the proportion of methacrylic acid copolymer, solid content of the film formers and level of polyethylene glycol 1000 on the capsule wall thickness and mechanical strength. Multiple response optimization was further conducted, and the design space was established. Thein vitro比较了设计空间中三种不同制剂的模拟胃和肠道中的药物释放。结果表明，凝胶化点后的棕褐色值应<0.9，以形成薄而坚固的胶囊壳。
The gelation time and viscosity of the coating solution were related to the thickness of the capsule shell. The study showed that drug release from the capsule with a specified thickness and mechanical strength can be modulated by varying the ratio of zein to methacrylic acid copolymer. The delayed drug release profile was achieved through the capsule shell fabricated from zein to methacrylic acid copolymer at the ratios of 75:25 and 83.2:16.8, with 10% polyethylene glycol 1000.
Materials:Zein (α-zein, 14.0% of total nitrogen, Tokyo Chemical Industry Co., Ltd., Tokyo, Japan), methacrylic acid copolymer type C, or methacrylic acid/ethyl acrylate 1:1 copolymer (Eudragit® L100–55,埃文克Röhm GmbH, Darmstadt, Germany, supplied by Jebsen & Jessen Ingredients, Ltd., Bangkok, Thailand),平均分子量为1000的聚乙烯乙二醇(Merck, Darmstadt, Germany), magnesium nitrate hexahydrate (默克，德国达姆施塔特），胃蛋白酶（632单位/毫克实心，西格玛 - 阿尔德里奇，密苏里州，美国）和胰腺素（1倍USP规范，25个蛋白酶活性，蛋白酶活性，默克，德国，德国）。乙醇（95％V/V，药品级，白酒酿酒厂组织，泰国Chachoengsao）和去离子水被用作溶剂。Diltiazem盐酸盐（印度Telangana，Telangana，Piramal Enterprises Ltd.in vitrodrug release test. Other reagents used for assay and drug release studies were of analytical grade.
Article information: Yada Vattanagijyingyong, Poj Kulvanich, Jittima Chatchawalsaisin, Fabrication of delayed release hard capsule shells from zein/methacrylic acid copolymer blends, European Journal of Pharmaceutical Sciences, Volume 171, 2022. doi.org/10.1016/j.ejps.2022.106124.