VII Simposio Internacional de Ciencias Farmacéuticas 2019 "VII SICF" -VII Simposio "Diseño, Obtención y Desarrollo de Fármacos"

VII Simposio Internacional de Ciencias Farmacéuticas 2019

VII SICF

``IN VITRO`` BIOLOGICAL AND BIOPHARMACEUTICAL EVALUATION OF THE INCLUSION COMPLEXES OF THE ANTIFUNGAL COMPOUND 2-(2-NITROVINYL)FURAN WITH BETA- CYCLODEXTRIN DERIVATIVES

Resumen [ES]

Introduction 2-(2-nitrovinyl)furan has antifungal activity, but limited stability. Inclusion complexes with β-CD derivatives are alternatives to solve this problem. This work aimed to evaluate their influence on the drug release, permeability and cytotoxicity, intended for vaginal administration. Methods Freeze-dried complexes (FD ICs) were prepared using a reported method (Ruz et al., 2012). Dissolution studies of pure drug and complexes were carried out in USP dissolution apparatus I. Dissolution efficiency (DE) was calculated from the release curves. Permeability through cellulose acetate membrane and bovine vaginal mucosa were performed using Franz Cell Diffusion Chamber. Samples were dispersed in SVF and the receptor was a PBS solution. Cumulative drug release as function of time were plotted. Retention was also tested. Cytotoxicity of cyclodextrins, drug and complexes was evaluated on L929 and HaCaT cell lines using the MTT assay and CC50 was calculated by non-linear regression model. Results Both FD complexes improved the drug dissolution rate. %DE15 min followed the ranking order: FD Drug/HP-β-CD > FD Drug/SBE-β-CD > Free drug. More than 50% of the drug permeated through cellulose acetate membrane but not through vaginal mucosa, however approximately 2-3 % of drug was recovery from mucosal homogenates, without statistical differences between drug and ICs (p>0.05). CC50 determined for pure drug were 32.68μM on L929 and 17.08μM on HaCaT. Both inclusion complexes increased CC50 values, being higher for FD Drug/SBE-β-CD for both cell lines (122.36 and 53.88μM). Conclusions FD inclusion complexes have fast dissolution, low retention in vaginal mucosa and less cytotoxicity than pure drug.

Resumen [EN]

Introduction 2-(2-nitrovinyl)furan has antifungal activity, but limited stability. Inclusion complexes with β-CD derivatives are alternatives to solve this problem. This work aimed to evaluate their influence on the drug release, permeability and cytotoxicity, intended for vaginal administration. Methods Freeze-dried complexes (FD ICs) were prepared using a reported method (Ruz et al., 2012). Dissolution studies of pure drug and complexes were carried out in USP dissolution apparatus I. Dissolution efficiency (DE) was calculated from the release curves. Permeability through cellulose acetate membrane and bovine vaginal mucosa were performed using Franz Cell Diffusion Chamber. Samples were dispersed in SVF and the receptor was a PBS solution. Cumulative drug release as function of time were plotted. Retention was also tested. Cytotoxicity of cyclodextrins, drug and complexes was evaluated on L929 and HaCaT cell lines using the MTT assay and CC50 was calculated by non-linear regression model. Results Both FD complexes improved the drug dissolution rate. %DE15 min followed the ranking order: FD Drug/HP-β-CD > FD Drug/SBE-β-CD > Free drug. More than 50% of the drug permeated through cellulose acetate membrane but not through vaginal mucosa, however approximately 2-3 % of drug was recovery from mucosal homogenates, without statistical differences between drug and ICs (p>0.05). CC50 determined for pure drug were 32.68μM on L929 and 17.08μM on HaCaT. Both inclusion complexes increased CC50 values, being higher for FD Drug/SBE-β-CD for both cell lines (122.36 and 53.88μM). Conclusions FD inclusion complexes have fast dissolution, low retention in vaginal mucosa and less cytotoxicity than pure drug.

Sobre el ponente

Vivian Ruz

Dr. Vivian Ruz

UCLV Flag of Cuba
Información Práctica
English (US)
No definido
30 minutos
No definido
Autores
Leda robusti
Dr. Vivian Ruz
guy vanden mooter
camila rodero
iracilda zeppone
mirtha mayra gonzález
anselmo gomes de oliveira
Palabras clave
2-(2-nitrovinyl)furan
cytotoxicity
dissolution
inclusion complexes
molecular inclusion complexes
permeability