Development and Evaluation of in-situ Nasal Gel Formulations of Nanosized Transferosomal Sumatriptan: Design, Optimization, in vitro and in vivo Evaluation

Background Sumatriptan succinate (SUT) is a potent drug used for relieving or ending migraine and cluster headaches. SUT bioavailability is low (15%) when it is taken orally owing to its gastric breakdown and bloodstream before reaching the target arteries. Aim The aim of the study was to enhance SUT bioavailability through developing an intranasal transferosomal mucoadhesive gel. Methods SUT-loaded nanotransferosomes were prepared by thin film hydration method and characterized for various parameters such as vesicle diameter, percent entrapment efficiency (%EE), in vitro release and ex vivo permeation studies. The in-situ gels were prepared using various ratios of poloxamer 407, poloxamer 188, and carrageenan and characterized for gelation temperature, mucoadhesive strength, and rheological properties. Results The prepared transferosomes exhibited percent entrapment efficiencies (%EE) of 40.41±3.02 to 77.47±2.85%, mean diameters of 97.25 to 245.01 nm, sustained drug release over 6 hours, and acceptable ex vivo permeation findings. The optimum formulae were incorporated into poloxamer 407 and poloxamer 188-based thermosensitive in-situ gel using carrageenan as a mucoadhesive polymer. Pharmacokinetic evaluation showed that the prepared in-situ gel of SUT-loaded nano-transferosomes gave enhanced bioavailability, 4.09-fold, as compared to oral drug solution. Conclusion Based on enhancing the bioavailability and sustaining the drug release, it can be concluded that the in-situ gel of SUT-loaded nano-transferosomes were developed as a promising non-invasive drug delivery system for treating migraine.