Microemulsion as a tool for the transdermal delivery of ondansetron for the treatment of chemotherapy induced nausea and vomiting.
The main objective of this study was to develop a microemulsion (ME) formulation for transdermal delivery of ondansetron for chemotherapy induced nausea and vomiting (CINV). For the formulation development oil was selected on the basis of drug solubility in it while the surfactants and co-surfactants (S(mix)) were screened on the basis of their capacity to solubilize the oil as well as their efficiency to provide the microemulsion area. The microemulsion existence ranges were defined through the construction of the pseudo-ternary phase diagram and various formulations were developed. Effect of surfactant and cosurfactant mass ratio (S(mix)) on the microemulsion formation and its permeation through excised rat skin was studied. A significant increase in permeability parameters such as steady-state flux (J(ss)), permeability coefficient (K(p)), and enhancement ratio (ER) was observed in ME. Formulation B4 which consisted of 0.5% (w/w) of ondansetron, 5% (w/w) of oleic acid, 30% (w/w) S(mix) (2:1, Tween 20 and PEG 400) and 64.5% (w/w) of distilled water showed the best permeability profile. The formulation B4 was subjected to various in vitro attributes and converted to microemulsion gel (OMG). In order to predict the efficacy, pharmacokinetic studies were performed and pharmacokinetic profile was compared with ondansetron conventional gel (OCG) and oral marketed syrup (ONDANZ). The absorption of ondansetron from OMG resulted in 6.03 fold increase in bioavailability as compared to oral conventional syrup and 9.66 times with reference to the OCG gel. The future perspective includes preclinical, toxicological and clinical studies for developing clinically viable formulation.
Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Raid M
RM
Al Abood
Sushama
S
Talegaonkar
Mohammad
M
Tariq
Farhan J
FJ
Ahmad
D000279:Administration, Cutaneous; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002498:Centrifugation; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004655:Emulsions; D005260:Female; D005615:Freezing; D005782:Gels; D009325:Nausea / Q000188:drug therapy*; D017294:Ondansetron / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D010938:Plant Oils; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D013501:Surface-Active Agents; D013816:Thermodynamics; D014839:Vomiting / Q000188:drug therapy*
D000932:Antiemetics; D004655:Emulsions; D005782:Gels; D010938:Plant Oils; D013501:Surface-Active Agents; D017294:Ondansetron