Abstract
Purpose: The main objective of the current research work was to
formulate and evaluate furosemide loaded silica lipid hybrid microparticles for
improved oral delivery. A novel silica-lipid hybrid microparticulate system is
used for enhancing the oral absorption of low solubility and low permeability
of (BCS Class IV) drugs. Silica-lipid hybrid microparticles include the drug
solubilising effect of dispersed lipids and stabilizing effect of hydrophilic
silica particles to increase drug solubilisation, which leads to enhanced oral
bioavailability.
Methods: The slica lipid hybrid (SLH) microparticles were composed
of poorly soluble drug (furosemide), dispersion of oil phase (Soya bean oil and
miglyol) in lecithin (Phospholipoid 90H), non-ionic surfactant (Polysorbate 80)
and adsorbent (Aerosol 380). Saturation solubility studies were performed in
different oils and surfactants with increased concentration of drug revealed
increased solubility of furosemide.
Results: In vitro dissolution studies
conducted under simulated gastric medium revealed 2-4 fold increase in
dissolution efficiencies for SLH microparticles compared to that of pure drug
(furosemide) and marketed formulation Lasix®. Ex vivo studies showed
enhanced lipid digestibility, which improved drug permeability. Solid-state
characterization of SLH microparticles by X-ray powder diffraction and Fourier
transform infrared spectroscopic analysis confirmed non-crystalline nature and
more compatibility of furosemide in silica-lipid hybrid microparticles.
Conclusion: It can be concluded that the
role of lipids and hydrophilic silica based carrier highlighted in enhancing
solubility and permeability, and hence the oral bioavailability of poorly
soluble drugs.