Formulation and Evaluation of Silica Lipid Hybrid Microparticles Containing Furosemide

Abstract

The study of the silica-lipid hybrid (SLH) microparticles is to enhance bioavailability and efficacy of poorly water-soluble drugs after oral administration. Lipid-based delivery systems recognized as a potential strategy for improving the oral absorption. Clinical applications of any lipid-based formulations are limited by the lack of clear guidelines of incomplete understanding of absorption mechanism and invitro, invivo formulation performance. Withstanding these problems, the availability of 2-4% oral lipid based products in the pharmaceutical market worldwide has supported in addressing low bioavailability of poorly soluble drugs. 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, that has been developed for the drug, furosemide. It describes the systematic invitro characterization of dissolution and lipolysis properties. Silica-lipid hybrid microparticles include the drug solubilizing effect of dispersed lipids and stabilizing effect of hydrophilic silica particles to increase drug solubilization, which leads to enhanced oral bioavailability. Furosemide is mainly used in the treatment of hypertension and congestive heart failure. The role of lipids and hydrophilic silica based carrier highlighted in enhancing solubility and permeability, and hence the oral bioavailability of poorly soluble drugs. The formulation composed of poorly soluble drug (furosemide) and dispersion of oil phase (Soya bean oil) in lecithin (Phospholipoid 90H), surfactant and vortexed until no crystals of drug is observed and are subsequently adsorbed by Aerosol 380 (hydrophilic fumed silica) and stabilized after being transformed to powder state. Saturation solubility studies were performed in different oils and surfactants with increased concentration of drug revealed increased solubility of furosemide. In vitro dissolution studies conducted under stimulated gastric medium revealed 2-4 fold increase in dissolution efficiencies for furosemide formulated as SLH microparticles, when compared to that of pure drug (furosemide) and a marketed formulation. Ex vivo studies showed enhanced lipid digestibility, which improved drug permeability. Solid-state characterization of SLH microparticles by XRPD (X-ray powder diffraction) and FTIR (Fourier transform infrared spectroscopy) analysis confirmed non-crystalline nature and less compatibility of furosemide in silica-lipid hybrid microparticles.