Successful application of large microneedle patches by human volunteers

Abstract

We describe, for the first time, the design, production and evaluation of large microneedle patches. Such systems, based on 16 individual microneedle arrays (needle height 600μm), were prepared from aqueous blends of 15% w/w Gantrez^® S97 and 7.5% w/w poly(ethyleneglycol) 10,000Da. Ester-based crosslinking was confirmed by FTIR and mechanical strength was good. Insertion depths in a validated skin model were approximately 500μm. Ten human volunteers successfully self-inserted the microneedles of these larger patches in their skin, following appropriate instruction, as confirmed by transepidermal water loss measurements. The mean insertion depth ranged between 300 and 450μm over the area of the large patches. That this was not significantly different to a single unit MN patch self-applied by the same volunteers is encouraging. Microneedle patch sizes much larger than the 1-2cm² will be required if this technology is to be successfully translated to clinic for delivery of drug substances. The work described here suggests that use of such larger patches by patients can be successful, potentially opening up the possibility for a significant expansion of the size of the market for transdermal drug delivery.

Keywords: Clinical translation; Large patches; Microneedles; Self-application.

Graphical abstract

Fig. 1

Tegaderm™ patch comprised of 16 individual MN arrays (A). MN patch numbered at the positions where the Optical Coherence Tomography (OCT) scans were taken (B). OCT image of a single MN penetrating a volunteer’s skin (C).

Fig. 2

3D reconstruction of needle tips from a MN array (A). FTIR spectra of MN arrays before and after crosslinking (B). Microscopy images of MN arrays before (C) and after (D) compression study. Needle height reduction after compression (E). Insertion profile in Parafilm^® for MN (F). (Means ± SD, n = 3).

Fig. 3

TEWL values before and after self-application of single MN arrays and patches comprised of multiple arrays (A). After the application of the multi-array patches TEWL was measured in the centre and at one edge of the region to which the larger patch was applied. Skin appearance following removal of larger patches in two representative volunteers (B).

Fig. 4

Insertion depth (A) and diameter of the created micropores (B) after the self-application of single and multi-array patches by 10 volunteers.

Fig. 5

Scanned images of the pressure-indicating sensor films used as a low-cost insertion feedback mechanism during self-application of large MN patches by human volunteers.

Fig. 6

Insertion distribution of self-applied MN multi-array over the patch surface for all the different volunteers.

Fig. 7

Maximum, minimum and mean forces applied by the volunteers when following the same instructions as for MN application/insertion (A). MN insertion as a function of the measured mean force applied by the volunteers (B). It is important to note than the insertion force and the insertion depth measurements were obtained in separate experiments.