Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications

Abstract

In this paper, we present a new design of hollow, out-of-plane polymeric microneedle with cylindrical side-open holes for transdermal drug delivery (TDD) applications. A detailed literature review of existing designs and analysis work on microneedles is first presented to provide a comprehensive reference for researchers working on design and development of micro-electromechanical system (MEMS)-based microneedles and a source for those outside the field who wish to select the best available microneedle design for a specific drug delivery or biomedical application. Then, the performance of the proposed new design of microneedles is numerically characterized in terms of microneedle strength and flow rate at applied inlet pressures. All the previous designs of hollow microneedles have side-open holes in the lumen section with no integrated reservoir on the same chip. We have proposed a new design with side-open holes in the conical section to ensure drug delivery on skin insertion. Furthermore, the present design has an integrated drug reservoir on the back side of the microneedles. Since MEMS-based, hollow, side-open polymeric microneedles with integrated reservoir is a new research area, there is a notable lack of applicable mathematical models to analytically predict structural and fluid flow under various boundary conditions. That is why, finite element (FE) and computational fluid dynamic (CFD) analysis using ANSYS rather than analytical systems has been used to facilitate design optimization before fabrication. The analysis has involved simulation of structural and CFD analysis on three-dimensional model of microneedle array. The effect of axial and transverse loading on the microneedle during skin insertion is investigated in the stress analysis. The analysis predicts that the resultant stresses due to applied bending and axial loads are in the safe range below the yield strength of the material for the proposed design of the microneedles. In CFD analysis, fluid flow rate and pressure drop in the microneedles at applied inlet pressures are numerically and theoretically investigated. The CFD analysis predicts uniform flow through the microneedle array for each microneedle. Theoretical and numerical results for the flow rate and pressure drop are in close agreement with each other, thereby validating the CFD analysis. For the proposed design of microneedles, feasible fabrication techniques such as micro-hot embossing and ultraviolet excimer laser methods are proposed. The results of the present theoretical study provide valuable benchmark and prediction data to fabricate optimized designs of the polymeric, hollow microneedles, which can be successfully integrated with other microfluidic devices for TDD applications.

Innovative design of hollow polymeric microneedles for transdermal drug delivery

“…The insertion force thus linearly increases with the tip surface of the microneedle (Davis et al 2004). This is confirmed by Bodhale et al (2010) who goes even further, stating that once the microneedles has penetrated the skin, the resistive force falls drastically (Frick 2003) and after the skin is pierced by the microneedle, the only force that acts on the microneedle is the frictional force due to the contact with the tissue. It is thus of the utmost importance to sharpen the tip of needles as much as possible.…”

“…Wall of the needles have a no slip condition insuring that the velocity is null and providing the velocity profile with a parabolic distribution. The outlet channel is assumed to be at 0 kPa as proposed by Bodhale et al (2010).…”

“…They have been described in literature, mainly made out of silicon (Roxhed et al 2008a, b;Moon and Lee 2005;Kim and Lee 2007;Stoeber and Liepmann 2005;Gardeniers et al 2003;Ji et al 2006;Mukerjee et al 2004;Griss and Stemme 2003). More recently the interest has been set on polymer microneedles (Sammoura et al 2007;Matteucci et al 2009;Bodhale et al 2010;Burton et al 2011) which present the advantages of robustness, biocompatibility and cheaper manufacturing processes. McAllister et al (2003) give an exhaustive review of microfabrication techniques possible for fabricating microneedles depending on the materials to be used.…”

Design, Fabrication and Analysis of Silicon Hollow Microneedles for Transdermal Drug Delivery System for Treatment of Hemodynamic Dysfunctions

“…Zahn et al (2004) fabricated microneedles for microdialysis applications. Although there are other application fields for microneedles, however a majority of microneedles reported so far in the literature are concerned with drug delivery in different applications (Bodhale et al 2009). Design and development of MEMS based microneedles is strongly dependent on the fabrication process.…”

Laser Engineering of Surface Structures

“…The nickel microneedle arrays were removed from the molds using a concentrated sodium hydroxide solution. Bodhale et al described use of micro-hot embossing and ultraviolet excimer laser processing to create arrays of 25 hollow polymer microneedles [115]. Pulsed laser deposition has also been used to modify microneedle surfaces.…”