Nasal Drug Delivery of a Short Acting Hypnotic and Antimigraine Agent for the Treatment of Insomnia Associated Migraine

Abstract

The present study examined the feasibility of simultaneous delivery of Zolpidem tartrate and Zolmitriptan in the treatment of insomnia associated migraine through in situ nasal delivery system. 3 approaches were followed for the development of nasal in situ gels. They were thermoresponsive, pH responsive and dual acting. Preformulation study was performed through DSC and FT-IR spectral analysis of the drug and the polymers and it was found there was no interaction of the drugs in the presence of polymers. Initially, in situ nasal gels were developed separately for Zolpidem tartrate and Zolmitriptan i.e. thermoreversible nasal in situ gel of Zolmitriptan and pH responsive nasal in situ gel of Zolpidem tartrate. The pH responsive nasal in situ gel of Zolpidem tartrate included carbopol 934, HPMC K4M and sodium chloride in various ratios and these formulations were screened for viscosity, t80% drug release, pH, mucoadhesive strength and gel strength. The thermoreversible nasal in situ gel of Zolmitriptan included 3 polymers poloxamer 407, poloxamer 188 and PEG in various ratios. Gelation temperature was examined for Zolmitriptan gel. The formulations were coded as TISG-01 to TISG-08 and PISG-01 to PISG-08 and the results were compared. Based on the performance of the above findings another formulation, thermoreversible and pH responsive nasal in situ gel containing both Zolpidem tartrate and Zolmitriptan was developed with different ratios of poloxamer 407, carbopol 934, sorbitol, screened for the physicochemical and drug release characteristics as described above and the formulations were coded as DISG-01 to DISG-20. The physicochemical characteristics and the drug release profile of all the developed formulations were compared and it was found that all the formulations provided the results within the pharmaceutically acceptable limits. The results of the study demonstrates that a thermodynamic in situ nasal gel is beneficial for simultaneous delivery of Zolpidem tartrate and Zolmitriptan in the treatment of insomnia associated migraine effectively.