Enhanced Both in vitro and in vivo Kinetics by SLNs Induced Transdermal System of Furosemide: A Novel Approach.

BACKGROUND

Furosemide is a potent diuretic agent used to treat pulmonary arterial hypertension. Variable dosage regimen and poor pharmacokinetic parameters have led to the development of transdermal drug delivery system.

OBJECTIVE

Patent on suitability of multi-lamellar structures for excellent transdermal delivery (US0367475A1) has encouraged us to formulate the solid lipid nanoparticles (SLNs) induced transdermal systems of furosemide to enhance the kinetic properties without incorporating any penetration enhancer and rate limiting polymers.

METHODS

SLNs were prepared by hot homogenization and ultra-sonication method; optimization was done based on entrapment efficiency and particle size. Optimized SLNs were incorporated in to transdermal patches by solvent casting method. In vitro and in vivo studies were carried out for characterization of transdermal patches.

RESULTS

SLNs of F9 (GMS: Span 60: Pluronic F 68 in 6:2.5:0.2) were optimized for incorporating in to transdermal system (entrapment efficiency 96.5±0.045%, particle size 69.6±1.48nm and in vitro release 94.38±1.02%). Transdermal patches were formulated using combinations of hydrophilic and hydrophobic polymers to study the diffusion kinetics. Formulation FS1 (HPMC 4 parts) was optimized for further studies (in vitro release 98.11±1.21% with flux of 58.726±0.023µg/cm2/h) and no significant difference from ex vivo permeation studies was observed. Drug release followed mixed order diffusion kinetics and super case -II transport mechanism. In vivo pharmacokinetic data of SLNs induced transdermal system suggested a 3.6 times increase in AUC and 5.4 times increase in MRT when compared with oral route.

CONCLUSION

The SLNs induced transdermal patch was found to beneficial in enhancing kinetic properties both in vitro and in vivo.