title: Wrinkle formation in a polymeric drug coating deposited via initiated chemical vapor deposition.
abstract: Polymer encapsulation of drugs is conventionally used as a strategy for controlled delivery and enhanced stability. In this work, a novel encapsulation approach is demonstrated, in which the organic molecule clotrimazole is enclosed into wrinkles of defined sizes. Having defined wrinkles at the drug/encapsulant interface, the contact between the encapsulating polymer and the drug can be improved. In addition, this can also allow for some control on the drug delivery as the available surface area changes with the wrinkle size. For this purpose, thin films of clotrimazole were deposited onto silica substrates and were then encapsulated by crosslinked poly(2-hydroxyethyl methacrylate) (pHEMA) via initiated chemical vapor deposition (iCVD). The thickness and the solid state (crystalline or amorphous) of the clotrimazole layer were varied so that the conditions under which surface wrinkles emerge can be determined. A (critical) clotrimazole thickness of 76.6 nm was found necessary to induce wrinkles, whereby the wrinkle size is directly proportional to the thickness of the amorphous clotrimazole. When the pHEMA was deposited on top of crystalline clotrimazole instead, wrinkling was absent. The wrinkling effect can be understood in terms of elastic mismatch between the relatively rigid pHEMA film and the drug layer. In the case of amorphous clotrimazole, the relatively soft drug layer causes a large mismatch resulting in a sufficient driving force for wrinkle formation. Instead, the increased elastic modulus of crystalline clotrimazole reduces the elastic mismatch between drug and polymer, so that wrinkles do not form.
authors.affiliation: Institute of Solid State Physics, NAWI Graz, Graz University of Technology, 8010 Graz, Austria. anna.coclite@tugraz.at.
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 and BioTechMed, Graz, Austria.
authors.forename: Heike M A
authors.initials: HM
authors.lastname: Ehmann
authors.affiliation: Institute of Pharmaceutical Science, Department of Pharmaceutical Technology, University of Graz, 8010 Graz, Austria and BioTechMed, Graz, Austria.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werzer
authors.affiliation: Institute of Solid State Physics, NAWI Graz, Graz University of Technology, 8010 Graz, Austria. anna.coclite@tugraz.at and BioTechMed, Graz, Austria.
authors.forename: Anna Maria
authors.identifier: http://orcid.org/0000-0001-5562-9744
authors.initials: AM
authors.lastname: Coclite
mesh_terms: D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005740:Gases / Q000737:chemistry*; D011102:Polyhydroxyethyl Methacrylate / Q000737:chemistry*
chemical_list: D005740:Gases; D011102:Polyhydroxyethyl Methacrylate