Kääriäinen Tommi O, Kemell Marianna, Vehkamäki Marko, Kääriäinen Marja-Leena, Correia Alexandra, Santos Hélder A, Bimbo Luis M, Hirvonen Jouni, Hoppu Pekka, George Steven M, Cameron David C, Ritala Mikko, Leskelä Markku
Laboratory of Inorganic Chemistry, University of Helsinki, P.O. Box 55 (A.I.Virtasen aukio 1), FI-00014 Helsinki, Finland; Department of Chemistry and Biochemistry and Department of Mechanical Engineering, University of Colorado, Boulder, CO 80309, United States; NovaldMedical Ltd Oy, Telkäntie 5, 82500 Kitee, Finland.
Laboratory of Inorganic Chemistry, University of Helsinki, P.O. Box 55 (A.I.Virtasen aukio 1), FI-00014 Helsinki, Finland.
Int J Pharm. 2017 Jun 15;525(1):160-174. doi: 10.1016/j.ijpharm.2017.04.031. Epub 2017 Apr 18.
Active pharmaceutical ingredients (APIs) are predominantly organic solid powders. Due to their bulk properties many APIs require processing to improve pharmaceutical formulation and manufacturing in the preparation for various drug dosage forms. Improved powder flow and protection of the APIs are often anticipated characteristics in pharmaceutical manufacturing. In this work, we have modified acetaminophen particles with atomic layer deposition (ALD) by conformal nanometer scale coatings in a one-step coating process. According to the results, ALD, utilizing common chemistries for AlO, TiO and ZnO, is shown to be a promising coating method for solid pharmaceutical powders. Acetaminophen does not undergo degradation during the ALD coating process and maintains its stable polymorphic structure. Acetaminophen with nanometer scale ALD coatings shows slowed drug release. ALD TiO coated acetaminophen particles show cytocompatibility whereas those coated with thicker ZnO coatings exhibit the most cytotoxicity among the ALD materials under study when assessed in vitro by their effect on intestinal Caco-2 cells.
活性药物成分（API）主要是有机固体粉末。由于其整体性质，许多API需要进行加工，以改善药物制剂和制造工艺，为各种药物剂型做准备。改善粉末流动性和保护API通常是药物制造中预期的特性。在这项工作中，我们通过一步涂覆工艺，利用共形纳米级涂层，通过原子层沉积（ALD）对乙酰氨基酚颗粒进行了改性。根据结果，利用用于AlO、TiO和ZnO的常见化学方法的ALD，被证明是一种用于固体药物粉末的有前途的涂覆方法。乙酰氨基酚在ALD涂覆过程中不会发生降解，并保持其稳定的多晶型结构。具有纳米级ALD涂层的乙酰氨基酚显示出药物释放减缓。当通过其对肠道Caco-2细胞的影响在体外进行评估时，ALD TiO涂覆的乙酰氨基酚颗粒显示出细胞相容性，而那些涂覆有较厚ZnO涂层的颗粒在研究的ALD材料中表现出最大的细胞毒性。
