Raloxifene hydrochloride is a relatively new selective estrogen receptor modulator. Clinical studies revealed
that absolute bioavailability of raloxifene in humans is 2%. The major problems that have limited the therapeutic efficacy
of raloxifene as an oral dosage form are its low solubility in physiological pH conditions, extensive first pass metabolism,
high inter-individual and intra-individual variability (30%) following oral administration. The objective of the present investigational
study was to improve the bioavailability and minimize variability of raloxifene hydrochloride by preparing
solid lipid nanoparticles (SLN) using Tristearin (TS), Trimyristin (TM) and Tripalmitin (TP), by hot homogenization
technique. Formulation and process variables were studied and evaluated. Particle size and zeta potential were measured
by photon correlation spectroscopy using Malvern Zetasizer (ZS-90). The solid state properties of the drug in SLN’s were
characterized by DSC and X-ray powder diffraction (XRPD) analysis. In-vitro release studies were performed in physiologically
relevant media using modified franz diffusion cell. Systemic exposure of nanoparticle formulation was evaluated
in male Wistar rats for increase in the rate and extent of drug absorption. The results demonstrated that stable raloxifene
SLN formulations having a mean size range of 154 to 175 nm with a zeta potential range of –17 to –22 mV were developed.
The entrapment efficiency of drug was more than 98% indicating homogeneous dispersion of drug in the lipid matrix.
The in-vitro release studies showed that SLN (TM) formulation has significantly higher rate of drug dissolution as
compared to other SLN formulations. Systemic exposure studies in rats indicated a significant increase in the rate and extent
of drug absorption.
Keywords: Solid lipid nanoparticles, Lymphatic transport, Bioavailability, First-pass metabolism.
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Published on: 10 December, 2012
Page: [68 - 77]