title: Self nanoprecipitating preconcentrate of tamoxifen citrate for enhanced bioavailability.
abstract: 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(β(σ)). Combination of AOT and Tween 80 resulted in EE (∼85%) and PS (<250nm). Formation of TMX-KSR nanoparticles in situ was reproducible under most experimental conditions and exhibited pH independent behavior. Dilution volume (>80mL) influenced both PS and EE while dilution temperature influenced only PS. Marginal increase in size was evident at the end of 1h nevertheless was not of concern as TMX SNP exhibited near complete release in 1h. 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 (99m)Tc 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.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400 019, India.
authors.forename: Sonali V
authors.initials: SV
authors.lastname: Kapse
authors.forename: Rajiv V
authors.initials: RV
authors.lastname: Gaikwad
authors.forename: Abdul
authors.initials: A
authors.lastname: Samad
authors.forename: Padma V
authors.initials: PV
authors.lastname: Devarajan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D011232:Chemical Precipitation; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D015195:Drug Design; D005260:Female; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D011205:Povidone / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013500:Surface Tension; D013501:Surface-Active Agents / Q000737:chemistry; D013629:Tamoxifen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013696:Temperature
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011136:Polysorbates; D013501:Surface-Active Agents; D013629:Tamoxifen; D004143:Dioctyl Sulfosuccinic Acid; D011205:Povidone