Abstract: 
Almotriptan malate, indicated for the treatment of migraine with or without aura in adults is not a drug candidate feasible to be administered via oral route during the attack due to its associated symptoms such as nausea and vomiting. This obviates an alternative dosage form. Nasal delivery of this drug is a good substitute to oral and parenteral administration, due to its numerous advantages. In the present study, sodium alginate microspheres of Almotriptan malate, for intranasal delivery, were prepared by water-in-oil (w/o) emulsification cross-linking technique. A 2³ factorial design was employed with drug to polymer ratio, calcium chloride concentration and cross-linking time as independent variables while particle size and in vitro mucoadhesion of the microspheres were the dependent variables. Regression analysis was performed to identify the best formulation conditions. The microspheres were evaluated for characteristics like particle size, incorporation efficiency, swellability, zeta potential, in vitro mucoadhesion, thermal analysis, X-ray diffraction study and in vitro drug release. The shape and surface characteristics were determined by scanning electron microscopy which revealed spherical nature and nearly smooth surfaces of the microspheres. The drug encapsulation efficiency was found to be in the range of 69.62±1.15 – 89.11±0.95%. In vitro mucoadhesion was performed by adhesion number using sheep nasal mucosa and was observed in a range from 77.58±1.49 – 93.15±1.25%. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of drug in the microspheres. In vitro drug diffusion studies in phosphate buffer, pH 6.4 indicated non-Fickian or anomalous type of transport for the release of Almotriptan from the microspheres.

Keywords: Almotriptan Malate, Sodium Alginate, Mucoadhesive, Microspheres, Emulsification Cross-linking Technique, Factorial Design, Nasal Drug Delivery.