title: Intranasal mucoadhesive microemulsions of zolmitriptan: preliminary studies on brain-targeting.
abstract: The aim of this investigation was to prepare microemulsions containing zolmitriptan (ZT) for rapid drug delivery to the brain to treat acute attacks of migraine and to characterize microemulsions and evaluate biodistribution in rats. Zolmitriptan microemulsions (ZME) were prepared using the titration method and were characterized for globule size distribution and zeta potential. ZT was radiolabeled using (99m)Tc (technetium) and radiolabeled-drug formulations of ZT were used to carry out biodistribution of drug in the brain of Swiss albino rats after intranasal and intravenous administration. The pharmacokinetic parameters, drug targeting efficiency (%DTE) and direct nose-to-brain drug transport (%DTP) were calculated. Brain scintigraphy imaging in rats were also performed to ascertain the uptake of drug into the brain. ZME were transparent and stable with mean globule size of 35 +/- 25 nm and zeta potential of - 38- - 52 mV. (99m)Tc-labeled-drug formulations of ZT were found to be stable and suitable to perform in vivo studies. Following intranasal administrations of zolmitriptan mucoadhesive microemulsion (ZMME), ZME, Zolmitriptan solution (ZS) and intravenous administration of ZS, brain/blood uptake ratios at 0.50 h were found to be 0.70, 0.56, 0.27 and 0.13, respectively, indicating effective brain-targeting following intranasal administration of ZMME. Comparing intranasal administration of ZMME with intravenous administration of ZME, the %DTE and %DTP were found higher indicating effective drug transport following intranasal administration and highest brain-targeting following ZMME administration. Rat brain scintigrams showed substantial uptake of drug into the brain after intranasal administration of ZMME. Studies of this investigation conclusively demonstrated rapid and larger extent of transport into the rat brain following intranasal administration of ZMME and can play a promising role in the treatment of acute attacks of migraine.
authors.affiliation: The Maharaja Sayajirao University of Baroda, Pharmacy Department, Faculty of Technology and Engineering, Kalabhavan, Post Box No.51, Vadodara, 390 001, Gujarat, India.
authors.forename: Tushar K
authors.initials: TK
authors.lastname: Vyas
authors.forename: A K
authors.initials: AK
authors.lastname: Babbar
authors.forename: R K
authors.initials: RK
authors.lastname: Sharma
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000187:drug effects*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004655:Emulsions; D009092:Mucous Membrane / Q000187:drug effects; D023303:Oxazolidinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013667:Technetium; D014014:Tissue Adhesives; D014018:Tissue Distribution; D014363:Tryptamines
chemical_list: D004655:Emulsions; D023303:Oxazolidinones; D017366:Serotonin Receptor Agonists; D014014:Tissue Adhesives; D014363:Tryptamines; C089750:zolmitriptan; D013667:Technetium