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.