Supplementary Information

Large Size Microneedle Patch to Deliver Lidocaine through Skin

Himanshu Kathuria 1, Hairui Li 1, Jing Pan 1, Seng Han Lim 1, Jaspreet Singh Kochhar 1, Chunyong Wu 2, Lifeng Kang 1*

1 Department of Pharmacy, National University of Singapore, Singapore 117543

2 Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China 210009

*Author for Correspondence. Department of Pharmacy, National University of Singapore, 18 Science Drive 2, Singapore 117546. Tel: + 65 6516 7519, Fax: +65 6779 1554. E-mail address:

1.  Effect of backing layer composition

The varying amount of PEG 200 (see Table 1) was found to affect the properties of backing layer. The peeling of primary backing layer was found to be easier with increasing amount of PEG 200 in the pre-polymer solution. However, at same instance, oozing of the liquid was also observed with higher amount of PEG 200 after keeping for 24 h at room temperature. Therefore, BL-2 was selected to be the optimum composition based on ease of manual peeling and oozing phenomena. When the amount of PEG 200 was low as in BL-1, it was found that primary backing layer was hard to peel from the glass side. The primary backing layer broke in between while peeling and never came as a whole layer. It was however, able to come off totally from the glass slide, just not in a complete full piece. This could be attributed to amount of PEG 200 in BL-1 was not sufficient to show the improvement for ease of removal while higher amount of PEG in BL-2 and BL-3 was sufficient to show the improvement. However, in the case of BL-3 with higher amount of PEG 200, it was found to peel off by itself from the glass slide without any external agitation and showed oozing after 24 h in room temperature. The self-peeling and oozing was observed in BL-3 alone as well as when the whole patch was fabricated (Figure S1).

The oozing phenomena can be attributed to an excess of PEG 200 left after complete accommodation in internal spaces of polymerized PEGDA structure. The addition of PEG 200 in the backing layer causes poor mechanical strength of microneedle and arise the need of another layer (secondary baking layer) without PEG 200. This reduction in strength could be attributed to a reduction in the number of covalent linkages of MN shaft PEGDA with the primary backing layer PEGDA. The reduction in number of covalent linkages could be due to PEG 200 which does not form any covalent links (during photo polymerization) with PEGDA. However, when the MNs were fabricated on the secondary backing layer, it had sufficient mechanical strength.

Figure S1: Images of backing layer on glass slide after 24 h at room temperature. A) Top view BL-2 B) Top view BL-3 C) Side view BL-3

2.  Effect of UV irradiation

Parameter for the fabrication of backing layers and the MN shafts i.e. ‘time of UV exposure’, was optimized based on ‘extent of polymerization’ while ‘distance of UV source’ was optimized based on ‘area of exposure’ required for polymerization. The lower time of UV exposure than the optimized can cause generation of fragile structures. In addition, continuous exposure of setup for longer time (> 6 s) was observed to cause excessive heating of the glass setup which further led to cracking of backing layer in some cases. The optimized distance of UV source was 14 cm because it was able to generate the area of exposure sufficient to form a 5cm×5cm MN patch. A higher distance may generate a bigger area but subsequently, intensity of the UV rays available for fabrication decreases. This may result in a longer time required for polymerization and processing to get the final patch. Furthermore, according to the inverse-square law of light, i.e., “the light loses energy as the distance away from the source increases” because of which the extent of polymerisation changes with the distance of UV source.(44) Therefore, it was difficult to directly produce the 100 cm2 patch using photolithography approach. Hence, to prepare a 100 cm2 patch, four 25 cm2 MN patch were pasted together on the scotch tape.

3.  Histological Examination


Figure S2: Various histological sections of pig skin after H & E staining. Figure A-E is in order of the increasing depth of penetration observed (written in blue).

4.  Proteinase K composition and preparation

Firstly, the stock solution of proteinase K was prepare as per composition mentioned in Table S1 and stored at -20 oC. Later, working stock of 75µg/ml was prepared by dilution of the stock solution with the 50 mM Tris-HCl pH 7.5 having 5 mM of Calcium ion.

Table S1: Composition of Proteinase K in stock solution

Stock Buffer
Glycerol / 50 ml
1M Tris-HCl pH 7.5 / 1ml
CaCl2 / 0.29 g
Deionized Water / Q.S to 100ml
Proteinase K (2 mg/ml) Stock Solution; Storage at -20 oC
Proteinase K / 50 mg
Stock Buffer / 25 ml