Effects of solubilizing surfactants and loading of antiviral, antimicrobial, and antifungal drugs on their release rates from ethylene vinyl acetate copolymer

Abstract

Objectives-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.Method-Polymer casting solutions were prepared by stirring EVA copolymer and nystatin (2.5 wt %) 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 10.0% wt. proportions of nystatin, chlorhexidine diacetate and acyclovir incorporated into a separate polymer. Three drug loaded polymer square films (3cm × 3cm × 0.08 cm) were cut from dry films to follow the kinetics of drug release at 37°C. 10 ml 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 UVspectrophotometer. 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.Significance-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.

Fenugreek gum derivatives with improved bioadhesion and controlled drug release: In vitro and in vivo characterization

“…The present study employed nystatin sample containing >90% of constituent A 1 with a potency of 6830units/mg as specified and supplied by the manufacturer. Nystatin has a poor aqueous solubility so Tween 60 (1:1 drug to Tween 60) was incorporated into the films in accordance with previous literature reports to aid solubilization of drug [52]. The addition of tween into fenugreek gum and aminated fenugreek gum films did not lead to a statistically significant difference in physical, mechanical, bioadhesive, swelling or interfacial properties of the films (data not shown).…”

Bioadhesive vaginal drug delivery of nystatin using a derivatized polymer: Development and characterization

“…47 Vulvovaginal candidiasis is considered to be the second most 48 common cause of vaginitis after bacterial vaginosis in United 49 States [1]. The main causative organism for vulvovaginal candidia- 50 sis is the yeast Candida albicans. It has the highest prevalence in 51 women aged 20-30 years [2] and affects 70-75% of women at least 52 once in their lifetime, while 40-50% experience a recurrence [3].…”

Antimicrobial activity and local release characteristics of chlorhexidine diacetate loaded within the dental copolymer matrix, ethylene vinyl acetate

“…Our observations of the equivalence of Clinical grade and Sigma reagent CDA assures that our previous in vitro studies 18,19,24 should be predictive of the behavior of the oral drug-delivery devices in clinical trials now being conducted under guidance from the U.S. Food and Drug Administration via IND 73,126.…”