Novel nanosuspension-based dissolving microneedle arrays for transdermal delivery of a hydrophobic drug

A nanosuspension (NS) was formulated from the lipophilic molecule cholecalciferol (CL) for enhanced transdermal delivery by embedding this NS into hydrophilic polymer-based dissolving microneedles (DMNs). First, the NS was prepared by sonoprecpitation with different molecular weights of poly (vinyl alcohol) and poly (vinyl pyrrolidone) as stabilizers and using two different solvents for particle size and zeta potential optimization. DMN arrays were then prepared by centrifugation-assisted micromoulding and subsequently dried. Poly (vinyl alcohol) (10 kDa) produced a NS with the lowest particle size ( ̴ 300 nm). These particles yielded DMN with good mechanical properties when combined with aqueous blends of high molecular weight poly (vinyl pyrrolidone) (360 kDa). The particle size remained similar before and after MN preparation, as confirmed by scanning electron microscope. The CL was in the amorphous state in the free particles as well as in the DMN and, hence, no characteristic CL peak was observed in differential scanning calorimetry or X-ray diffraction. DMN arrays were found to be strong enough to bear a 32 N force, showed efficient skin insertion, and penetrated down to the third layer (depth ≈ 375 μm) of the validated skin model Parafilm M®. An ex vivo porcine skin permeation study using Franz diffusion cells compared the permeation of CL from CL-NS-loaded DMN arrays and MN-free CL-NS patches. It was observed that CL-NS-loaded DMN arrays showed significantly higher (498.19 μg ± 89.3 μg) ex vivo skin permeation compared with MN-free CL-NS patches (73.2 μg ± 26.5 μg) over 24 h. This is the first time a NS of a hydrophobic drug has been successfully incorporated into dissolving MN and suggest that NS-containing DMN systems could be a promising strategy for transdermal delivery of hydrophobic drugs.