Dashevsky A, Kolter K, Bodmeier R
College of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Eur J Pharm Biopharm. 2004 Jul;58(1):45-9. doi: 10.1016/j.ejpb.2004.03.013.
The objective of this study was to obtain pH-independent release profiles from coated pellets containing drugs with pH-dependent solubility. pH-independent release of the basic model drug verapamil HCl was achieved by coating with a combination of the neutral polymer dispersions Kollicoat SR 30 D (aqueous dispersion of polyvinyl acetate) and the enteric polymer dispersion Kollicoat MAE 30 DP (aqueous dispersion of methacrylic acid and ethyl acrylate copolymer; methacrylic acid copolymer type C). The two polymers where applied either as separate layers (enteric polymer + extended release polymer or vice versa) or as a polymer blend. A careful balance of the ratios of the polymers allowed the achievement of a pH-independent release. Higher amounts of the enteric polymer in the polymer blend resulted in a reversal of the pH-dependency, e.g. a faster release at pH 6.8 than in 0.1 N HCl.
本研究的目的是从含有pH依赖性溶解度药物的包衣微丸中获得pH非依赖性释放曲线。通过用中性聚合物分散体Kollicoat SR 30 D(聚醋酸乙烯酯水分散体)和肠溶聚合物分散体Kollicoat MAE 30 DP(甲基丙烯酸和丙烯酸乙酯共聚物水分散体;C型甲基丙烯酸共聚物)的组合进行包衣,实现了碱性模型药物盐酸维拉帕米的pH非依赖性释放。这两种聚合物既可以作为单独的层(肠溶聚合物+缓释聚合物,或反之亦然)应用,也可以作为聚合物共混物应用。聚合物比例的仔细平衡使得能够实现pH非依赖性释放。聚合物共混物中肠溶聚合物含量较高会导致pH依赖性逆转,例如在pH 6.8时的释放速度比在0.1 N HCl中更快。