Surface modification of acetaminophen particles by atomic layer deposition

Tommi O Kääriäinen; Marianna Kemell; Marko Vehkamäki; Marja-Leena Kääriäinen; Alexandra Correia; Hélder A Santos; Luis M Bimbo; Jouni Hirvonen; Pekka Hoppu; Steven M George; David C Cameron; Mikko Ritala; Markku Leskelä

doi:10.1016/j.ijpharm.2017.04.031

Surface modification of acetaminophen particles by atomic layer deposition

Int J Pharm. 2017 Jun 15;525(1):160-174. doi: 10.1016/j.ijpharm.2017.04.031. Epub 2017 Apr 18.

Affiliations

¹ 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. Electronic address: tommi.kaariainen@helsinki.fi.
² Laboratory of Inorganic Chemistry, University of Helsinki, P.O. Box 55 (A.I.Virtasen aukio 1), FI-00014 Helsinki, Finland.
³ 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.
⁴ Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
⁵ NovaldMedical Ltd Oy, Telkäntie 5, 82500 Kitee, Finland.
⁶ Department of Chemistry and Biochemistry and Department of Mechanical Engineering, University of Colorado, Boulder, CO 80309, United States.
⁷ R&D Centre for Low-Cost Plasma and Nanotechnology Surface Modification, Masaryk University, Kotlářská 267/2, 611 37 Brno, Czech Republic.

PMID: 28432020
DOI: 10.1016/j.ijpharm.2017.04.031

Abstract

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 Al₂O₃, TiO₂ 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 TiO₂ 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.

Keywords: Acetaminophen; Atomic layer deposition; Cytocombatibility; Drug delivery system; Drug release.

MeSH terms

Acetaminophen / chemistry*
Caco-2 Cells
Excipients / chemistry*
Humans
Nanotechnology*
Powders
Surface Properties

Substances

Excipients
Powders
Acetaminophen