Zolmitriptan Intranasal Spanlastics for Enhanced Migraine Treatment; Formulation Parameters Optimized via Quality by Design Approach

Abstract

Zolmitriptan is a potent second-generation triptan prescribed for migraine attacks. It suffers low bioavailability (40%) after oral administration due to the hepatic first-pass metabolism. Spanlastics are surfactant-based elastic vesicular drug carrier systems. This study aimed to design and optimize intranasal spanlastic formulations as an alternative approach that directly targets brain delivery, enhancing its bioavailability and avoiding the first-pass effect. The quality by design approach was applied to correlate the formulation parameters (Span 60 and Tween 80 concentrations) and critical quality attributes (entrapment efficiency (EE%) and particle size). Spanlastic formulations were designed based on response surface central composite design and prepared via an ethanol injection method. Designed formulations were characterized by EE% and particle size measurements to select the optimized formula (with a combination of small particle size and high EE%). The optimized formula was further subjected to transmission electron microscopy, zeta potential measurement and ex vivo permeation study. The optimized formulation showed a particle size of 117.5 nm and EE% of 45.65%, with a low percentage of error between the observed and predicted values. Seventy percent of zolmitriptan was permeated through the nasal membrane within 30 min, and it completely permeated within 2 h with a significantly higher steady-state flux compared to plain gel. This study introduced a successful and promising intranasal formulation suitable for further brain delivery analysis.

Nanoparticles of a Pyrazolo-Pyridazine Derivative as Potential EGFR and CDK-2 Inhibitors: Design, Structure Determination, Anticancer Evaluation and In Silico Studies

“…Zeta potential values were evaluated by using the same equipment in a single-use capillary zeta cell at 25 • C and dissolved in deionized water. The particle size and ZP values given are the averages of 3 measurements [45,46].…”

Topical delivery of extracted curcumin as curcumin loaded spanlastics anti-aging gel: Optimization using experimental design and ex-vivo evaluation

“…A key consideration in formulating Spanlastics materials is selecting the appropriate EA that provides the necessary elasticity and deformability to navigate the tight connections of relatively impermeable membranes ( Saleh et al, 2021 ).…”

Spanlastics as a Potential Approach for Enhancing the Nose-To-Brain Delivery of Piperine: In Vitro Prospect and In Vivo Therapeutic Efficacy for the Management of Epilepsy

“…Several studies have demonstrated that spanlastics can deliver specific drugs to the brain through nose-to-brain delivery. For example, Saleh et al observed the “increased drug penetration across the nasal membrane in zolmitriptan-loaded spanlastic formulations, confirming the promising impact of intra-nasal dosing for brain delivery” [ 26 ]. Furthermore, Rehab et al observed that “the formation of granisetron hydrochloride spanlastic gel appears to promote the brain bioavailability of the carried drug, providing a higher level of treatment in the brain” [ 27 ].…”