QUALITY BY DESIGN ENABLES FORMULATION DEVELOPMENT OF ZOLMITRIPTAN LOADED ETHOSOMAL INTRA-NASAL GEL FOR BRAIN TARGETING: IN VITRO AND EX VIVO EVALUATION

Abstract

Objective: Although zolmitriptan's 50% oral bioavailability and recurrence of migraine-associated disorders make it one of the most essential drugs for managing the illness, adverse effects linked to dosage are still a concern. A unique intra-nasal brain targeting strategy may significantly extend the drug's residence duration at the absorption site and resolve the current problems. Methods: To effectively adjust the drug's residence via the intra-nasal route, the current study focuses on the development of zolmitriptan-loaded ethosomal gel with the help of soya lecithin, ethanol, poloxamer 407, and HPMC K100M utilizing the thin film hydration technique. The optimized formulation (F12) was completely characterized in terms of polydispersity index, vesicle size (nm), and entrapment efficiency (%). In vitro drug release at 24 h, stability study, and ex-vivo skin permeation pharmacodynamic studies were all evaluated. Results: The ethosomal formulations were optimized using 32 Central Composite Design (CCD) about the observed responses, which comprised vesicle size, entrapment efficiency, and percent drug release after 24 h, all included in this study. The optimal size range and zeta potential for the F12 formulation were determined to be 110.23 nm and -35.69, respectively. The generated drug-loaded ethosomal gel was spherical with a consistent size distribution and particle size. Morphological studies showed that Scanning Electron Microscope (SEM) was utilized to better study spherical multilamellar vesicles. The optimized ethosomal gel of zolmitriptan was determined to meet the stability criterion, as the Critical Quality Attributes (CQAs) did not vary significantly during the study period. Conclusion: For all formulations, the F12 batch showed vesicle size (110.23 nm), entrapment efficiency (82.02%), and drug release percentage of 89.26% at 24 h.