Innovative Drug Discovery and Nanotechnology (Track)





OPTIMIZATION AND EX-VIVO PERMEATION OF PHYTOSOMES AS PLATFORMS FOR IMPROVED DIOSMIN DELIVERY


Yosra S.R. Elnaggar, May S. Freag and Ossama Y. Abdallah

Department of Pharmaceutics, Faculty of Pharmacy, University of Alexandria, 1 Khartoum Square, Azarita, Messalla Post Office, P.O.Box 21521, Alexandria, Egypt

Abstract:

OBJECTIVE：

Diosmin (Ds) is an outstanding phytopharmaceuical for venous insufficiency with a recent potential in hepatocellular carcinoma. Being highly insoluble, Ds bioavailability suffers inter-subject variation due to variable amounts permeated. This work endeavored to develop novel Ds phytosomes aim to improve drug dissolution and intestinal permeability. Three preparations methods (solvent evaporation, salting out and lyophilization) were compared. Formula optimization encompassed different solvents, different phospholipids PL and different Ds:PL ratios. In-vitro appraisal included Particle size (PS), Zeta potential (ZP), Differential scanning calorimetry (DSC), IR spectroscopy, transmission electron microscopy (TEM), and in-vitro dissolution. Ex-vivo intestinal permeation study was performed utilizing non-everted sac technique and HPLC. Among others, lyophilization technique was amenable for phytosomal preparation using LIPOID S 100 and solvent mixture DMSO: TBA (1:2). All Ds:PL ratios exhibited significant enhancement in Ds dissolution efficiency (88.16 % DE60) compared to plain suspension (45.82%). Formulation ratio of 1:2 exhibited the lowest PS (295 nm) and adequate ZP (-27mV). Complex formation was contended by DSC and IR data. Well formed vesicles were revealed by TEM. Ex-vivo studies inferred 70% Ds permeated through oxygenated rat intestine from phytosomes compared to non-detected amounts from suspension. Diosmin phyto-vesicles could be successfully optimized with improved dissolution and permeation characteristics promising for better drug delivery.