title: Dissolution testing of hardly soluble materials by surface sensitive techniques: clotrimazole from an insoluble matrix.
abstract: OBJECTIVE
  The low aqueous solubility of many drugs impedes detailed investigation as the detection limit of standard testing routines is limited. This is further complicated within application relevant thin films typical used in patches or stripes for buccal or topical routes.
  
  
  METHODS
  In this work a model system is developed based on spin - casting technique allowing defined clotrimazole and clotrimazole - polystyrene composite films preparation at a solid surface. Various highly sensitive techniques including quarz crystal microbalance (QCM), X-ray reflevtivity (XRR) and X-ray photon spectroscopy (XPS) are used to investigate the drug release over time into an aqueous media.
  
  
  RESULTS
  The results reveal a steady drug release for both samples over the course of the experiments but with the release from the composite being significantly slower. In addition the dissolution rate of the clotrimazole sample initially increases up to 30 min after which a decrease is noted. XRR shows that this is a result of surface roughening together with film thickness reduction. The results for the composite show that the release in the composite film is a result of drug diffusion within the matrix and collapsing PS film thickness whereby XPS shows that the amount of clotrimazole at the surface after 800 min immersion is still high.
  
  
  CONCLUSIONS
  It can be stated that the applied techniques allow following low mass drug release in detail which may also be applied to other systems like pellets or surface loaded nano-carriers providing information for processing and application relevant parameters.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Universititätsplatz 1, 8010, Graz, Austria.
authors.forename: Heike M A
authors.initials: HM
authors.lastname: Ehmann
authors.forename: Sascha
authors.initials: S
authors.lastname: Winter
authors.forename: Thomas
authors.initials: T
authors.lastname: Griesser
authors.forename: Roman
authors.initials: R
authors.lastname: Keimel
authors.forename: Simone
authors.initials: S
authors.lastname: Schrank
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Oliver
authors.initials: O
authors.lastname: Werzer
mesh_terms: D002152:Calorimetry, Differential Scanning; D003022:Clotrimazole / Q000008:administration & dosage* / Q000737:chemistry*; D004304:Dosage Forms; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D008027:Light; D056951:Photoelectron Spectroscopy; D011137:Polystyrenes / Q000737:chemistry*; D012542:Scattering, Radiation; D012995:Solubility; D013499:Surface Properties
chemical_list: D004304:Dosage Forms; D004337:Drug Carriers; D011137:Polystyrenes; D003022:Clotrimazole
references.citation: Nanotoxicology. 2012 Jun;6(4):399-413
references.pmid: 21591874
references.citation: Science. 2010 Jun 25;328(5986):1676-9
references.pmid: 20576887
references.citation: Langmuir. 2013 Jul 2;29(26):8328-34
references.pmid: 23745520
references.citation: Drug Discov Today. 2003 Oct 1;8(19):898-905
references.pmid: 14554018
references.citation: Adv Drug Deliv Rev. 2007 Jul 30;59(7):617-30
references.pmid: 17597252
references.citation: Mater Sci Eng C Mater Biol Appl. 2012 Oct 1;32(7):2103-2108
references.pmid: 34062702
references.citation: Arch Pharm Res. 2007 Feb;30(2):249-54
references.pmid: 17366748
references.citation: J Biomater Sci Polym Ed. 2012;23(5):697-714
references.pmid: 21375809
references.citation: J Pharm Sci. 2010 Sep;99(9):3826-38
references.pmid: 20533435
references.citation: Faraday Discuss. 1997;(107):229-46
references.pmid: 9569776
references.citation: Macromol Biosci. 2008 Nov 10;8(11):981-90
references.pmid: 18615874
references.citation: Cryst Growth Des. 2014 Mar 5;14(3):1386-1391
references.pmid: 24624042
references.citation: Mol Pharm. 2012 Nov 5;9(11):3396-402
references.pmid: 23025556
references.citation: Nat Mater. 2010 Feb;9(2):101-13
references.pmid: 20094081
references.citation: Eur J Pharm Biopharm. 2011 Nov;79(3):635-45
references.pmid: 21801834