Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline

Abstract

Pentoxifylline (PTX) is a xanthine derivative indicated in treatment of intermittent claudication and chronic occlusive arterial diseases. It has low oral bioavailability and short half-life; thus, it was considered as a good candidate drug for the transdermal transfersomes formulation. In the present study, an attempt has been made for development, in-vitro and in-vivo evaluation of transdermal transfersomes using sodium cholate (SC) and non-ionic surfactants as edge activators. The optimal formulation, F4(Gcholate), exhibited drug entrapment efficiency of 74.9±1.6%, vesicles elasticity of 145±0.6 (mgs(-1)cm(-2)), zeta potential of -34.9±2.2mV, average vesicle diameter of 0.69±0.049μm with PDI of 0.11±0.037 and permeation flux of 56.28±0.19μgcm(-2)h(-1). It attained a prolonged drug release where 79.1±2.1% of PTX released after 10h of the run. The drug release kinetic obeys Higuchi model (R(2)=0.997) with Fickian diffusion mechanism. Moreover, the formula enhanced drug permeation through the excised rat's skin predominantly via the carrier-mediated mechanism by 9.1 folds in comparison with the control. Results of the in vivo pharmacokinetics study in male volunteers showed that F4(Gcholate) transfersomes formulation increased PTX absorption and prolonged its half-life comparing to the commercial oral SR tablets. Hence, the elastic transfersomes formulation of PTX possesses admirable potential to avoid drug metabolism, improve PTX bioavailability and sustain its release.

Keywords: Elasticity; Pentoxifylline; Pentoxifylline (PubChem CID: 4740); Pharmacokinetics; Phosphatidylcholine (PubChem CID: 45266626); Phospholipon 90G; Sodium cholate; Sodium cholate (PubChem CID: 23668194); Span 20 (PubChem CID: 16218599); Transdermal; Transfersomes; Tween 20 (PubChem CID: 486150); Tween 80 (PubChem CID: 9920342).