title: Development and pharmacokinetic evaluation of a curcumin co-solvent formulation.
abstract: Poor solubility and bioavailability are limiting factors for the clinical application of curcumin. The objective of the current study was to develop a liquid formulation with increased solubility and systemic bioavailability. A co-solvent formulation with increased solubility of 20 mg/ml was developed and optimized. Pharmacokinetics of the new formulation were evaluated using rats receiving 30 mg/kg intravenous or 50 mg/kg intramuscular administration of co-solvent formulation, compared against a control group receiving 50 mg/kg of curcumin in DMSO through intramuscular injection. Plasma concentrations were measured using liquid chromatography-mass spectrometry (LC-MS/MS). The intramuscular injection of formulation resulted in 30% absolute bioavailability and provided sustained release by maintaining plasma concentrations of curcumin above 240 ng/ml for up to 4 h. A 29-fold increase in the maximum plasma concentration (Cmax) and 28-fold increase in the area under the plasma concentration versus time curve (AUC) led to a 28-fold increase in relative bioavailability for the co-solvent formulation. The findings reported here suggest that the clinical application of curcumin can be better-exploited through an intramuscular administration of the co-solvent formulation developed in the present study.
authors.affiliation: College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne Street, Houston, TX 77004, U.S.A. liang_dx@tsu.edu.
authors.forename: Mathew K
authors.initials: MK
authors.lastname: John
authors.forename: Huan
authors.initials: H
authors.lastname: Xie
authors.forename: Edward C
authors.initials: EC
authors.lastname: Bell
authors.forename: Dong
authors.initials: D
authors.lastname: Liang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000431:Ethanol / Q000737:chemistry; D007273:Injections, Intramuscular; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011136:Polysorbates; D011760:Pyrrolidinones; D012997:Solvents; D000431:Ethanol; D011092:Polyethylene Glycols; D003474:Curcumin; C038678:N-methylpyrrolidone
keywords: Curcumin formulation; intramuscular; pharmacokinetics