title: Drug release from cast films of ethylene vinyl acetate (EVA) copolymer: Stability of drugs by 1H NMR and solid state 13C CP/MAS NMR.
abstract: The study utilizes an oral biocompatible material based on ethylene vinyl acetate copolymer (EVA) designed to release drugs in vitro at therapeutic levels over several days. We examined the drug stability during film casting process using proton and solid state NMR techniques. The drug-loaded EVA films were prepared from the dry sheet obtained by solvent (dichloromethane) evaporation of polymer casting solutions. Drugs tested include chlorhexidine diacetate (CDA), doxycycline hydrochloride (DOH), tetracycline hydrochloride (TTH) and nystatin (NST). Drug release from the films was examined for at least 14 days in 10 ml ddH2O (NST in water/ethanol (4:1)) which was replaced daily. Changes in optical density were followed spectraphotometrically. Effect of temperature on rate measurements was studied and the energies of activation (E*) were calculated using Arrhenius plots. Effect of EVA copolymer composition on CDA release rate was also investigated. The enhanced rates with temperature increase may be attributed to the formation of channels with increased geometry in the polymer. The highest E* observed for CDA compared to DOH and TTH may be related to their average molecular weights. Spectral analyses for CDA and NST revealed that the chemical and physical structures of the drugs remained unaffected during the film casting process.
authors.affiliation: Center for Oral and Systemic Diseases, Department of Periodontology, School of Dentistry, Dental Research Center, University of North Carolina, Chapel Hill, NC 27599-7450, USA. sid_kalachandra@dentistry.unc.edu
authors.forename: S
authors.initials: S
authors.lastname: Kalachandra
authors.forename: D M
authors.initials: DM
authors.lastname: Lin
authors.forename: E O
authors.initials: EO
authors.lastname: Stejskal
authors.forename: A
authors.initials: A
authors.lastname: Prakki
authors.forename: S
authors.initials: S
authors.lastname: Offenbacher
mesh_terms: D001672:Biocompatible Materials / Q000032:analysis / Q000737:chemistry; D002247:Carbon Isotopes; D003692:Delayed-Action Preparations / Q000032:analysis / Q000737:chemistry*; D004058:Diffusion; D004337:Drug Carriers / Q000032:analysis / Q000737:chemistry*; D004355:Drug Stability; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008422:Materials Testing; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry*; D011145:Polyvinyls / Q000032:analysis* / Q000737:chemistry*
chemical_list: D001672:Biocompatible Materials; D002247:Carbon Isotopes; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D006859:Hydrogen