Institute of Pharmacy, Chemistry and Biomedical Sciences, University of Sunderland, Sunderland, UK.
Eur J Pharm Biopharm. 2009 Aug;72(3):587-94. doi: 10.1016/j.ejpb.2009.02.010. Epub 2009 Mar 3.
This work reports an investigation into free-film properties of a high amylose maize starch-based film coating that has been used in the preparation of formulations for drug delivery to the colon (WO 2008/012573 A1) and relates these properties to in vitro drug release from pellets. Maize starch/ethylcellulose free films were prepared and characterised by scanning electron microscopy (SEM), light microscopy, modulated differential scanning calorimetry (mDSC), Fourier-transform infrared (FT-IR), X-ray and % swelling in aqueous fluids with pH conditions similar to the stomach and small intestine. 5-ASA release from film-coated pellets was tested in enzyme free simulated gastric fluid and phosphate buffer pH 7.2. Selected formulations were further assessed in simulated gastric and intestinal fluids containing pepsin and pancreatin, respectively. The free films prepared were smooth and homogeneous in their appearance. The two polymers are immiscible, and neither mDSC nor FT-IR could detect interactions between them. Films made from high amylose starches were found to have a considerably lower swelling ability than high amylopectin-based films, and they suppressed drug release in the enzyme free media successfully. 5-ASA release from pellets coated with mixtures of high amylose starches (Hylon VII, Hylon V or LAPS) and Surelease in a ratio of 1 to 2 w/w was found to be minimal in simulated gastric and intestinal fluids. This suggests that these mixed films provide starch domains that are resistant to the enzymes present in the upper GI tract and thus can potentially be used in the preparation of colon-specific delivery devices. Starches with a minimum amylose content of 56% such as the starches used in this study (Hylon VII and Hylon V) are preferred, and although pure amylose can also be used this is not essential.
本工作报道了对高直链玉米淀粉基薄膜包衣的自由膜性能的研究，该包衣已用于制备用于结肠递药的制剂（WO 2008/012573 A1），并将这些性能与微丸体外药物释放相关联。通过扫描电子显微镜（SEM）、光显微镜、调制差示扫描量热法（mDSC）、傅里叶变换红外（FT-IR）、X 射线和在与胃和小肠相似的 pH 条件下的水性流体中的溶胀度%对玉米淀粉/乙基纤维素自由薄膜进行了表征。在无酶模拟胃液和 pH7.2 的磷酸盐缓冲液中测试了从包衣微丸中释放的 5-ASA。选择的制剂分别在含有胃蛋白酶和胰酶的模拟胃液和肠液中进一步评估。所制备的自由薄膜外观光滑且均匀。两种聚合物不混溶，mDSC 和 FT-IR 均无法检测到它们之间的相互作用。发现高直链淀粉淀粉制成的薄膜具有明显较低的溶胀能力，并且它们在无酶介质中成功地抑制了药物释放。在无酶模拟胃液和肠液中，用高直链淀粉（Hylon VII、Hylon V 或 LAPS）和 Surelease 以 1 比 2 w/w 的比例混合的包衣微丸的 5-ASA 释放量最小。这表明这些混合膜提供了对存在于上胃肠道中的酶具有抗性的淀粉域，因此可潜在地用于制备结肠特异性递药装置。优选使用直链淀粉含量最低为 56%的淀粉，如本研究中使用的淀粉（Hylon VII 和 Hylon V），尽管也可以使用纯直链淀粉，但这不是必需的。
