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

Abstract

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.

Rapidly dissolving bilayer microneedle arrays – A minimally invasive transdermal drug delivery system for vitamin B12

“…This area could be reduced by increasing the drug load within the MN arrays. As vitamin B12 is only sparingly water soluble, formulating a nanosuspension prior to casting MN arrays is also a possible approach (Vora et al, 2018;McCrudden et al, 2018). Although there are considerable inherent differences between MN patches and currently marketed transdermal patches, relatively big patches are generally accepted by patients.…”

Localised and sustained intradermal delivery of methotrexate using nanocrystal-loaded microneedle arrays: Potential for enhanced treatment of psoriasis

“…Unfortunately, using biodegradable polymeric micro- or nanoparticles often necessitates high amounts of polymeric excipients to encapsulate the drug. Clearly, this results in a lower drug loading in the MN arrays ( Battisti et al., 2019 ; Vora et al., 2018 ). Alternatively, a commercially available MTX free acid (MTX), which is the poorly water-soluble form of the drug could be used.…”

“…However, this poorly water-soluble drug form exists as micron-sized crystals and incorporating such drug crystals into a hydrophilic polymeric hydrogel (which forms the MN matrix) has been reported to be a challenging task, due to the difficulty of micron-sized hydrophobic drug-polymeric hydrogel mixing. This could lead to production of inhomogeneous MN with variable drug loadings ( Vora et al., 2018 ; Mc Crudden et al., 2018 , Abdelghany et al., 2019 ). Water-miscible organic solvents can be used to facilitate drug mixing with the MN polymeric matrix hydrogel.…”

“…Water-miscible organic solvents can be used to facilitate drug mixing with the MN polymeric matrix hydrogel. However, using such organic solvents may affect the mechanical properties of the MN, thus reducing skin insertion capability ( Vora et al., 2018 ).…”

A Semi-Dissolving Microneedle Patch Incorporating TEMPO-Oxidized Bacterial Cellulose Nanofibers for Enhanced Transdermal Delivery

“…Microneedles that are a few hundred micrometers in length can physically pierce the skin with minimal invasion, which enables the simple, painless, and effective delivery of active ingredients into the skin. Their applicability has been widely studied in various fields, such as cosmetics, biomedicines, and vaccines [1][2][3][4][5]. Beginning with a study [6] in which microneedles consisting of silicon were observed to increase the skin permeability of calcein, various solid microneedles (SMNs) fabricated from metal, ceramic, or glass have been reported [7][8][9].…”