Effects of solubilizing surfactants and loading of antiviral, antimicrobial, and antifungal drugs on their release rates from ethylene vinyl acetate copolymer.
OBJECTIVE
This study investigates the effects of surfactants and drug loading on the drug release rate from ethylene vinyl acetate (EVA) copolymer. The release rate of nystatin from EVA was studied with addition of non-ionic surfactants Tween 60 and Cremophor RH 40. In addition, the effect of increasing drug load on the release rates of nystatin, chlorhexidine diacetate and acyclovir is also presented.


METHODS
Polymer casting solutions were prepared by stirring EVA copolymer and nystatin (2.5wt.%) in dichloromethane. Nystatin and surfactants were added in ratios of (1:1), (1:2) and (1:3). Drug loading was studied with 2.5, 5.0, 7.5, and 10.0wt.% proportions of nystatin, chlorhexidine diacetate and acyclovir incorporated into a separate polymer. Three drug loaded polymer square films (3cmx3cmx0.08cm) were cut from dry films to follow the kinetics of drug release at 37 degrees C. Ten milliliters of either distilled water or PBS was used as the extracting medium that was replaced daily. PBS was used for nystatin release with addition of surfactants and water was used for the study on drug loading and surfactant release. The rate of drug release was measured by UV-spectrophotometer. The amount of surfactant released was determined by HPLC.


RESULTS
The release of nystatin was low in PBS and its release rate increased with the addition of surfactants. Also, increasing surfactant concentrations resulted in increased drug release rates. The release rates of chlorhexidine diacetate (p<0.0001), acyclovir (p<0.0003) and nystatin (p<0.0017) linearly increased with increasing drug loads. The amount of surfactants released was above the CMC.


CONCLUSIONS
This study demonstrates that the three therapeutic agents show a sustained rate of drug release from EVA copolymer over extended periods of time. Nystatin release in PBS is low owing to its poor solubility. Its release rate is enhanced by addition of surfactants and increasing the drug load as well.
Tallury
Padmavathy
P
Center for Oral and Systemic Diseases, Department of Periodontology, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599-7455, USA.
Randall
Marcus K
MK
Thaw
Khin L
KL
Preisser
John S
JS
Kalachandra
Sid
S
D000212:Acyclovir / Q000008:administration & dosage / Q000737:chemistry; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry; D002710:Chlorhexidine / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations; D016014:Linear Models; D008422:Materials Testing; D008823:Micelles; D009761:Nystatin / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols; D011136:Polysorbates; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D008823:Micelles; D011136:Polysorbates; D011145:Polyvinyls; D013501:Surface-Active Agents; D009761:Nystatin; C016438:ethylenevinylacetate copolymer; C022131:cremophor; D011092:Polyethylene Glycols; D002710:Chlorhexidine; D000212:Acyclovir