title: A polymeric device for delivery of anti-microbial and anti-fungal drugs in the oral environment: effect of temperature and medium on the rate of drug release.
abstract: OBJECTIVE
  The use of drug delivery systems in dentistry is a relatively new area of research with the exception of fluoride ion release from polyalkenoate cements and their predecessor silicate cements. The present study is based on the use of a bio-compatible material ethylene vinyl acetate copolymer (EVA) that enables constant release of drugs of therapeutic levels over extended periods of time at doses suitable for the treatment of oral conditions.
  
  
  METHODS
  Polymer casting solutions were made by dissolving EVA and the drug in the ratio of 40:1 in 70 ml of dichloromethane at 38 degrees C for 6 h. Thin square films of 3 x 3 cm2 with a thickness of 1 mm were cut from the dry sheet obtained by solvent evaporation technique. Drug loaded samples were extracted for a minimum of 14 days in 10 ml medium (double distilled water or water/ethanol (4:1)) which was replaced daily. Spectral measurements were made to follow changes in optical densities (OD) during release kinetics. Effect of temperature (24 and 37 degrees C) on the rate of drug release was studied and the energies of activation (DeltaE not equal ) were calculated using Arrehenius equation for the diffusion (translocation) of molecules of tetracycline hydrochloride (TTH), doxycycline hydrochloride (DOH), and chlorhexidine diacetate (CDA) in water as extracting medium. Effect of extracting medium (water and water/ethanol (4:1)) was also investigated on the rate of drug release measurements at 24 degrees C.
  
  
  RESULTS
  Analysis of variance of the data revealed that significantly enhanced rates were observed at the higher temperature (37 degrees C) and when extracting medium was changed to water/ethanol (4:1) for TTH, DOH and CDA (p<0.0015). The enhanced rate values seem to be due to the formation of channels in the polymer. The largest activation energy (21.83 kcal mol(-1)) observed for CDA was interpreted as due to the highest average molecular weight (626) compared to TTH (481) and DOH (481).Significance. These in vitro rate of drug release measurements will provide a basis for establishing a novel approach (treatment modality) for sustained intra-oral drug delivery over extended time periods using laboratory methods and materials that are readily available to dentists.
authors.affiliation: Department of Periodontology, Center for Oral and Systemic Diseases, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7455, USA. kalachan@email.unc.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Lin
authors.forename: S
authors.initials: S
authors.lastname: Kalachandra
authors.forename: J
authors.initials: J
authors.lastname: Valiyaparambil
authors.forename: S
authors.initials: S
authors.lastname: Offenbacher
mesh_terms: D000704:Analysis of Variance; D000891:Anti-Infective Agents, Local / Q000008:administration & dosage; D002710:Chlorhexidine / Q000008:administration & dosage; D004318:Doxycycline / Q000008:administration & dosage; D016503:Drug Delivery Systems; D000431:Ethanol; D007700:Kinetics; D009761:Nystatin / Q000008:administration & dosage; D011145:Polyvinyls; D012995:Solubility; D013696:Temperature; D013752:Tetracycline / Q000008:administration & dosage; D014867:Water
chemical_list: D000891:Anti-Infective Agents, Local; D011145:Polyvinyls; D014867:Water; D009761:Nystatin; C016438:ethylenevinylacetate copolymer; D000431:Ethanol; D013752:Tetracycline; D004318:Doxycycline; D002710:Chlorhexidine