title: Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS).
abstract: Limited aqueous solubility of exemestane leads to high variability in absorption after oral administration. To improve the solubility and bioavailability of exemestane, the self-microemulsifying drug delivery system (SMEDDS) was developed. SMEDDS comprises of isotropic mixture of natural or synthetic oil, surfactant, and cosurfactant, which, upon dilution with aqueous media, spontaneously form fine o/w microemulsion with less than 100 nm in droplet size. Solubility of exemestane were determined in various vehicles. Ternary phase diagrams were plotted to identify the efficient self-emulsification region. Dilution studies, droplet size, and zeta potential of the formulations were investigated. The release of exemestane from SMEDDS capsules was studied using USP dissolution apparatus in different dissolution media and compared the release of exemestane from a conventional tablet. Oral pharmacokinetic study was performed in female Wistar rats (n = 8) at the dose of 30 mg kg(-1). The absorption of exemestane from SMEDDS form resulted in about 2.9-fold increase in bioavailability compared with the suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as exemestane by the oral route.
authors.affiliation: Dabur Research Foundation, Sahibabad 201010, Ghaziabad Uttar Pradesh, India. ajeetrj@rediffmail.com
authors.forename: Ajeet K
authors.initials: AK
authors.lastname: Singh
authors.forename: Akash
authors.initials: A
authors.lastname: Chaurasiya
authors.forename: Anshumali
authors.initials: A
authors.lastname: Awasthi
authors.forename: Gautam
authors.initials: G
authors.lastname: Mishra
authors.forename: Dinesh
authors.initials: D
authors.lastname: Asati
authors.forename: Roop K
authors.initials: RK
authors.lastname: Khar
authors.forename: Rama
authors.initials: R
authors.lastname: Mukherjee
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D047072:Aromatase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004563:Electrochemistry; D004655:Emulsions; D005079:Excipients; D005260:Female; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; C056516:exemestane