QbD-driven development of dissolving microneedle patch loaded with ultradeformable liposomes encapsulated Noopept: Exploring a patient friendly, once-daily option to manage dementia

Noopept (NPT), a potent neuroprotective agent, suffers the problem of poor oral bioavailability (~10%) and thus demands exploration of ways of bioavailability improvement. Present work focuses on confronting this issue via development of NPT loaded ultradeformable liposomes (UDL) and its further incorporation in fast dissolving microneedle patch (MNP) for transdermal route. A combination of Phospholipon 90 G and Phospholipon 90H was used as bilayer forming lipids while sodium deoxycholate was used as edge activator to formulate NPT UDL by ethanol injection method. QbD approach was adapted to optimize NPT UDL considering vesicle size and entrapment efficiency as critical quality attributes (CQA). Fractional factorial design established amount of lipids, surfactant and NPT as critical material attributes and their optimum levels were statistically derived using combined D-optimal design. These optimized NPT UDL were fabricated as fast dissolving MNP and exhaustively evaluated to establish their safety, efficacy and stability. NPT UDL MNP possessed axial needle fracture force of 0.688 N which was sufficient enough to breach stratum corneum. Physical stability evaluation revealed that NPT UDL re-dispersion obtained from MNP matrix dissolution possessed identical vesicle shape and size while retaining > 99% NPT when compared to optimized NPT UDL. In vitro viability of HaCaT cells after exposure to NPT UDL MNP matrix was found to be 89.74% supporting the formulation as safe for transdermal application. NPT UDL MNP showed a 6.5-fold increase in steady state flux across full thickness pig ear skin as compared to NPT suspension. A 3-fold increase in relative bioavailability with similar pharmacological response as compared to oral NPT suspension was also observed during PK-PD studies in Sprague Dawley rats. Results were found fairly encouraging and created a scope of reducing both dose and dosing frequency to eventually improve the associated patient compliance. [Display omitted]