PURPOSE:
To develop fenretinide oral mucoadhesive patch formulations and evaluate their in vitro and in vivo release performance for future site-specific chemoprevention of oral cancer.
METHODS:
Solubilization of fenretinide in simulated saliva (SS) was studied by incorporating nonionic surfactants (Tween® 20 and 80, and Brij® 35 and 98), bile salts (sodium salt of cholic, taurocholic, glycocholic, and deoxycholic acids), phospholipid (lecithin), and novel polymeric solubilizer (Souplus®). Adhesive (polycarbophil: hydroxypropyl methylcellulose 4KM) and drug release (Fenretinide/Eudragit® RL PO with or without solubilizers) layers were prepared by solvent casting. Oral mucoadhesive patches were formed by attaching drug and adhesive layers onto backing layer (Tegaderm™ film). Physical state of drug in Eudragit® films was examined by X-ray diffraction (XRD). Evaluation of in vitro and in vivo fenretinide release from the patch was conducted in SS containing 5%w/v sodium deoxycholate and rabbits, respectively. Fenretinide was quantified by HPLC.
RESULTS:
Tween® 20 and 80, Brij® 98, and sodium deoxycholate exhibited the highest fenretinide solubilization potential among the solubilizers. Drug loading efficiency in Eudragit® films was 90%-97%. XRD suggested fenretinide was amorphous in solubilizer-free and solubilizer-loaded films. Solubilizer-free patch exhibited poor in vitro and in vivo controlled drug release behavior. Increases in drug loading (5-10 wt%) or changes in polymeric matrix permeability did not provide continuous drug release. Co-incorporation of either single or mixed solubilizers in fenretinide/Eudragit® patches, (20 wt% Tween® 20, Tween® 80 and sodium deoxycholate or 20 wt% Tween® 80 + 40 wt% sodium deoxycholate solubilizers) led to significantly improved continuous in vitro/in vivo fenretinide release.
CONCLUSION:
Fenretinide/Eudragit® RL PO patches with 20 wt% Tween® 80 + 40 wt% sodium deoxycholate solubilizers exhibit excellent release behavior for further preclinical and/or clinical evaluation in oral cancer chemoprevention.
Free full text
Development and in vitro-in vivo evaluation of fenretinide-loaded oral mucoadhesive patches for site-specific chemoprevention of oral cancer.
Riferimento:
Pharm Res. 2011 Oct;28(10):2599-609.
Autori:
Desai KG, Mallery SR, Holpuch AS, Schwendeman SP.
Fonte:
Pharm Res. 2011 Oct;28(10):2599-609.
Anno:
2011
Azione:
Sviluppare formulazioni di patch mucoadesive orali con fenretinide e valutare le loro prestazioni di rilascio, in vitro e in vivo, per il futuro della chemio-prevenzione del cancro orale.
Target:
Fenretinide/cancro orale.
Sostanze: