title: Polymer Encapsulation of an Amorphous Pharmaceutical by initiated Chemical Vapor Deposition for Enhanced Stability.
abstract: The usage of amorphous solids in practical applications, such as in medication, is commonly limited by the poor long-term stability of this state, because unwanted crystalline transitions occur. In this study, three different polymeric coatings are investigated for their ability to stabilize amorphous films of the model drug clotrimazole and to protect against thermally induced transitions. For this, drop cast films of clotrimazole are encapsulated by initiated chemical vapor deposition (iCVD), using perfluorodecyl acrylate (PFDA), hydroxyethyl methacrylate (HEMA), and methacrylic acid (MAA). The iCVD technique operates under solvent-free conditions at low temperatures, thus leaving the solid state of the encapsulated layer unaffected. Optical microscopy and X-ray diffraction data reveal that at ambient conditions of about 22 °C, any of these iCVD layers extends the lifetime of the amorphous state significantly. At higher temperatures (50 or 70 °C), the p-PFDA coating is unable to provide protection, while the p-HEMA and p-MAA strongly reduce the crystallization rate. Furthermore, p-HEMA and p-MAA selectively facilitate a preferential alignment of clotrimazole and, interestingly, even suppress crystallization upon a temporary, rapid temperature increase (3 °C/min, up to 150 °C). The results of this study demonstrate how a polymeric coating, synthesized directly on top of an amorphous phase, can act as a stabilizing agent against crystalline transitions, which makes this approach interesting for a variety of applications.
authors.affiliation: Institute of Solid State Physics, NAWI Graz, Graz University of Technology , 8010 Graz, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Christian
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz , 8010 Graz, Austria.
authors.forename: Heike M A
authors.initials: HM
authors.lastname: Ehmann
authors.affiliation: Institute of Solid State Physics, NAWI Graz, Graz University of Technology , 8010 Graz, Austria.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Coclite
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz , 8010 Graz, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werzer
mesh_terms: D003460:Crystallization; D005740:Gases; D006358:Hot Temperature; D011108:Polymers / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D005740:Gases; D011108:Polymers
keywords: X-ray diffraction; amorphous; clotrimazole; encapsulation; iCVD; molecular arrangement; stabilization; thin film