Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced bioavailability

We disclose a self nanoprecipitating preconcentrate (SNP) of tamoxifen citrate (TMX), which forms TMX loaded polymeric nanoparticles, on dilution with aqueous media. SNP comprised TMX, polymer (Kollidon SR) and surfactant/s dissolved in a pharmaceutically acceptable vehicle. Binary surfactant mixtures of Aerosol OT (AOT) with Tween 80 revealed synergistic reduction in surface tension to enable both high entrapment efficiency (EE) and low particle size (PS). Synergism of the surfactants was confirmed by molecular interaction parameter(βσ). Combination of AOT and Tween 80 resulted in EE (∼85%) and PS (<250 nm). Formation of TMX-KSR nanoparticles in situ was reproducible under most experimental conditions and exhibited pH independent behavior. Dilution volume (>80 mL) influenced both PS and EE while dilution temperature influenced only PS. Marginal increase in size was evident at the end of 1 h nevertheless was not of concern as TMX SNP exhibited near complete release in 1 h. DSC and XRD studies revealed amorphous nature of TMX in nanoparticles. FTIR imaging confirmed uniform distribution of TMX in nanoparticles. ESEM and TEM revealed spherical nanoparticles. Biodistribution studies of 99mTc labeled TMX SNP in rats revealed no significant absorption however oral pharmacokinetics revealed enhanced oral bioavailability of TMX (165%) compared to TMX suspension. SNP presents a new in situ approach, for design of drug loaded polymeric nanoparticles.

Self nanoprecipitating preconcentrate of tamoxifen citrate presents an innovative approach for spontaneous preparation of drug loaded polymeric nanoparticles in situ by nanoprecipitation.Figure optionsDownload high-quality image (123 K)Download as PowerPoint slide