Modeling of Microneedle Arrays in Transdermal Drug Delivery Applications

The use of computational tools for the development of technologies in fields such as medicine and engineering has facilitated the process of designing new components and devices for these areas. In this work, two proposals focused on a hollow microneedle array (MNA) for the administration of an analgesic drug are shown and evaluated by means of a computational fluid dynamics (CFD) simulation distributed in three stages. In the first stage, the behavior of lidocaine through the MNA was evaluated as a workflow. Then, the possible entry of the drug into the organism, which was established as a porous aqueous medium, was modeled.

Finally, a joint simulation was performed to understand the general behavior in the interaction between the outflow of an MNA and the body to which lidocaine is administered. The input parameters to the simulation were set at a velocity of 0.05 m∙s⁻¹, at a pressure of 2000 Pa, the dominant behavior was defined as laminar flow, and a resistive pressure at the inlet of 400 Pa. Our results indicate that the vertical flow exhibits a better fluid distribution across the MNAs and favorable infiltration behavior, representing better delivery of the analgesic to the skin capillaries.

Materials

2.1.1. Analgesic Drug

Among the common anesthetics used in medicine, lidocaine and bupivacaine are normally applied intradermally and both are used as agents that block peripheral nerves and relieve focused pain [17,18]. Lidocaine, depending on its form of administration, can have different problems, ranging from systemic side effects in its intravenous administration [19], to discomfort in the oral intake of pills, especially in the geriatric and pediatric population [20]. This tends to be a major challenge in medical issues and the topical alternative can present an unacceptable response time in many cases [9,21].

From previous studies on the experimental properties of lidocaine hydrochloride in aqueous solution, it is shown that at a temperature of 298.15 K and a concentration of 0.00978 mol·kg⁻¹, a density of 997,944 kg·m⁻³ and a molarity of 0.02578 mol·kg⁻¹ are obtained, plus an apparent molar volume of 236.27 m³·mol⁻¹ for a pressure of 1 atm [17]. The analysis was accompanied by a computational simulation based on CFD that closely approximates the behavior of lidocaine in specific situations.

2.1.2. Microneedle Design

For the MNA design, a hollow microneedle was considered based on an eccentric cone with a height of 600 µm, a basal diameter of 300 µm, and a microchannel of 90 µm in diameter. Those dimensions were found to provide structural stability when breaking the external barrier of human skin [8]. Due to its structural resistance, there is an array of 4 × 4 microneedles with internal microchannels, which seek, through geometric parameters, to ensure a homogeneous distribution of the fluid throughout the array. Therefore, two fluid distribution designs were proposed, a lateral flow (LF) and a vertical flow (VF), as shown in Figure 2 and Figure 3, respectively.

Figure 2. Referential views for the MN 4 × 4 matrix design together with its microchannels. (a) Bottom isometric view, (b) top isometric view, (c) bottom view of microchannels, (d) side view of microneedles.

Figure 3. Views for VF design in a MN 4 × 4 array. (a) Bottom symmetrical view, (b) top isometric view, (c) bottom view, (d) side view of the MN.

For the LF design, a system of rectangular microchannels 100 µm high by 90 µm wide was drawn, this according to the geometric parameters of the hollow MN, which form a branch system whose purpose is to propose a stable distribution of the analgesic along the MNA (Figure 2).

For the VF design, a more robust configuration is observed, which presents microchannels with a more complex geometry when presented as a distribution that uses the three axes as flow directions as shown in Figure 3. This design, like the previous one, aims to achieve a stable distribution based on a symmetrical design.

The epidermis was established as a porous medium system, where the output geometry of the MNA was the input geometry.

Finally, the innermost layers of the skin were defined as porous media, which adopted the specific geometry of the MN considered for this work. With this, the most favorable situation of effective penetration is proposed, leaving the epidermis as shown in Figure 4.

Figure 4. Geometrical design for effective penetration of the 4 × 4 MN array into the epidermis. (a) Isometric view, (b) side view.

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Henriquez, F.; Celentano, D.; Vega, M.; Pincheira, G.; Morales-Ferreiro, J.O. Modeling of Microneedle Arrays in Transdermal Drug Delivery Applications. Pharmaceutics 2023, 15, 358. https://doi.org/10.3390/pharmaceutics15020358

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