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 ^99mTc (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. ^99mTc-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.

Keywords: :

• Intranasal
• Microemulsion
• Zolmitriptan
• Radiolabel
• Brain-targeting

Acknowledgements

The authors are thankful to Lt. Gen. T. Ravindranath, AVSM, VSM, Director, INMAS, New Delhi for providing the radiolabelling facilities. The authors express their gratitude to Dr Nabil Farah (Gattefosse, France), Ms Jayshree Sreedhar (Colorcon, India) for providing excipients and Ms Aimil Limited, Bangalore, India (Malvern Instrument, UK) for providing facility for globule size/zeta potential determination, Dr A K Mishra, Scientist E, INMAS, for providing technical guidance on radiolabeling techniques, and Dr Aarti Majumdar, English Department, Faculty of Arts, for checking the manuscript.

Notes

^§Zomig product information. http://www.zomig.info/Nasal_Spray/viewhtmlcontent106.htm