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[使用丙烯酸聚合物的抗炎镇痛贴剂的药学性质]

[Pharmaceutical Properties of Anti-inflammatory Analgesic Patches Using Acrylic Polymer].

作者信息

Gato Katsuhiko, Shikaku Ryogo, Kato Suguru, Yoshimura-Fujii Mika, Koide Tatsuo, Fukami Toshiro

机构信息

Department of Molecular Pharmaceutics, Meiji Pharmaceutical University.

Division of Drugs, National Institute of Health Sciences.

出版信息

Yakugaku Zasshi. 2020;140(9):1175-1183. doi: 10.1248/yakushi.20-00108.

Abstract

The mock patches were prepared with novel acrylic polymers as adhesive layer where biphenyl-4-ylacetic acid (BAA) or 2-(2-fluorobiphenyl-4-yl) propanoic acid (FPA) was used as model active pharmaceutical ingredients (APIs). In addition, the mock patches were formulated with typical ester ingredients for transdermal dosage forms. The molecular state of the model APIs in the adhesive layer was observed by polarized microscope and microscopic Raman spectroscopy, which contains both conventional and low frequency (LF) region. Crystallization behavior would be depended on the interaction between API and polymers in the adhesive layer. In particular, LF Raman measurement was useful to discriminate API polymorphs. The pharmaceutical properties including dissolution and skin permeation of APIs were also evaluated for mock patches. The drug release and transdermal permeation were enhanced with the ester ingredients such as isopropyl myristate and diethyl sebacate due to their diffusion to the test solution or the skin stratum corneum as well as reducing the interaction between API and polymers. Further, the tack strength was not changed, but the peel strength was weakened by the additives. Thus, the adhesive properties were controllable by formulation with the additives. These findings could enable to evaluate the interaction between API and the polymers for adhesive layer and select the appropriate polymer and additives for used APIs when designing the drug products.

摘要

模拟贴剂采用新型丙烯酸聚合物作为黏附层制备,其中联苯-4-基乙酸(BAA)或2-(2-氟联苯-4-基)丙酸(FPA)用作模型活性药物成分(API)。此外,模拟贴剂还采用了用于透皮剂型的典型酯类成分。通过偏光显微镜和包含常规和低频(LF)区域的显微拉曼光谱观察黏附层中模型API的分子状态。结晶行为将取决于API与黏附层中聚合物之间的相互作用。特别是,低频拉曼测量有助于区分API的多晶型物。还对模拟贴剂的API的药物性质包括溶解和皮肤渗透进行了评估。由于肉豆蔻酸异丙酯和癸二酸二乙酯等酯类成分扩散到测试溶液或皮肤角质层以及减少API与聚合物之间的相互作用,药物释放和透皮渗透得到增强。此外,添加剂使黏性强度不变,但剥离强度减弱。因此,通过添加添加剂可控制黏附性能。这些发现能够在设计药品时评估API与黏附层聚合物之间的相互作用,并为所用API选择合适的聚合物和添加剂。

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