Rizatriptan produces antimigraine activity by acting as selective agonist of 5-HT1B and 5-HT1D receptors present on intracranial and extracerebral blood vessels. Absorption from oral tablet is slow with Tmax of approximately 1-1.5â¯h. A few attempts have been made to promote rapid absorption such as oral or sublingual films with limited success. The aim of our study was to develop intranasal spray formulation of rizatriptan with quick onset of action. Solubility was enhanced by a co-solvent system where we studied solubility of rizatriptan benzoate in pure solvents, binary and ternary mixtures. Binary and ternary co-solvents using ethanol, water, propylene glycol and polyethylene glycol resulted rizatriptan equivalent base solubility more than 60â¯mg/mL. Same co-solvents were used at different level to make nasal spray formulations and evaluated pharmacokinetics using beagle dog animal model. Nasal spray formulation containing 20% w/w ethanol exhibited highest exposure, where Cmax (312â¯ng/mL) reached in 5â¯min and maintained higher concentration than oral dose for more than 30â¯min.
Drug Compounding/methods , Migraine Disorders/drug therapy , Solvents/chemistry , Triazoles/administration & dosage , Tryptamines/administration & dosage , Administration, Intranasal , Administration, Oral , Animals , Area Under Curve , Capsules , Dogs , Ethanol/chemistry , Humans , Models, Animal , Polyethylene Glycols/chemistry , Propylene Glycol/chemistry , Solubility , Time Factors , Triazoles/chemistry , Triazoles/pharmacokinetics , Tryptamines/chemistry , Tryptamines/pharmacokinetics , Water/chemistry
