title: Development of tamoxifen-phospholipid complex: novel approach for improving solubility and bioavailability.
abstract: In the present study, tamoxifen-phospholipid complex (TMX-PLC) was developed and evaluated for its impact on solubility and bioavailability of tamoxifen. TMX-PLC was prepared by solvent evaporation method and characterized. FTIR revealed the disappearance of the characteristic peaks of TMX in the complex, which can be due to weakening, removal or shielding by the phospholipid molecule. This phenomenon could be due to packing of TMX in the hydrophobic cavity of phospholipid and being held by van der Waals forces and hydrophobic interactions. This observation was confirmed by DSC and PXRD. TMX-PLC exhibited increased solubility, dissolution rate with decreased distribution coefficient indicating its increased hydrophilicity. Oral bioavailability of TMX and TMX-PLC were evaluated in Sprague-Dawley (SD) rats. TMX-PLC exhibited considerable enhancement in the bioavailability with an increase in Cmax (0.85 vs. 0.40 μg/mL), t1/2 (22.47 vs. 13.93 h), and AUC0-∞ (15.29 vs. 8.62 μg h/mL) with 212.25% relative bioavailability. This enhancement can be attributed to the improvement of the aqueous solubility of the complex and a probable decrease in its extent of intestinal and hepatic metabolism. Thus, phospholipid complexation holds a promising potential for increasing oral bioavailability of TMX.
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S Nagar-160062, Punjab, India.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Jena
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S Nagar-160062, Punjab, India.
authors.forename: Charan
authors.initials: C
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S Nagar-160062, Punjab, India.
authors.forename: Chander Parkash
authors.initials: CP
authors.lastname: Dora
authors.affiliation: Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S Nagar-160062, Punjab, India. Electronic address: ssuresh@niper.ac.in.
authors.forename: Sarasija
authors.initials: S
authors.lastname: Suresh
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D005260:Female; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000493:pharmacokinetics*; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013629:Tamoxifen / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D010713:Phosphatidylcholines; D013629:Tamoxifen
keywords: Oral bioavailability; Phospholipid; Solubility; Tamoxifen; Tamoxifen-phospholipid complex