Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS).
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.
Singh
Ajeet K
AK
Dabur Research Foundation, Sahibabad 201010, Ghaziabad Uttar Pradesh, India. ajeetrj@rediffmail.com
Chaurasiya
Akash
A
Awasthi
Anshumali
A
Mishra
Gautam
G
Asati
Dinesh
D
Khar
Roop K
RK
Mukherjee
Rama
R
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
D000730:Androstadienes; D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; C056516:exemestane