Microneedle-assisted transdermal delivery of Zolmitriptan: effect of microneedle geometry, in vitro permeation experiments, scaling analyses and numerical simulations

Abstract

Objective: The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation enhancement of Zolmitriptan (ZMT).

Methods: Two types of MN devices viz. AdminPatch^® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory fabricated polymeric MNs (PM) of 0.6 mm length were employed. In the case of PMs, arrays were applied thrice at different places within a 1.77 cm² skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Scaling analyses was done using dimensionless parameters like concentration of ZMT (C_t/C_s), thickness (h/L) and surface area of the skin (Sa/L²).

Results: Micro-injection molding technique was employed to fabricate PM. Histological studies revealed that the PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 3.17- and 3.65-fold increase in ZMT flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. Good correlations were observed between different dimensionless parameters with scaling analyses. Numerical simulations, using MATLAB and COMSOL software, based on experimental data and histological images provided information regarding the ZMT skin distribution after MN application.

Discussion: Both from experimental studies and simulations, it was inferred that PM were more effective in enhancing the transdermal delivery of ZMT when compared to ADM.

Conclusions: The study suggests that MN application enhances the ZMT transdermal permeation and the geometrical parameters of MNs play an important role in the degree of such enhancement.

Keywords:

• Histological sections
• microneedles
• microneedle geometry
• numerical simulations
• scaling analyses
• Zolmitriptan

Acknowledgements

The authors are thankful to Mylan Pharmaceuticals India Ltd, Hyderabad, India, for providing a gift sample of ZMT, to Dr. Naveen, Department of Pathology, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Vijayawada, India, for providing the required facilities for taking histological sections of skin samples and also to the Siddhartha Academy of General and Technical Education, Vijayawada, India, for providing necessary facilities to carry out the research work.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The authors extend their sincere thanks to Department of Science and Technology, Ministry of Science and Technology, Government of India and the British Council, London, UK, for funding this research work under the DST-UKIERI scheme (DST/INT/UK/P-60/2014).