Comparison of drug transfer in cone and cone-cylinder microneedles
Comparison of drug transfer in cone and cone-cylinder microneedles
Hajar Moghadas,1,*Mohamad Reza Askari,2
1. Department of Mechanical Engineering, Yasouj University, Yasouj 2. Department of Mechanical Engineering, Yasouj University, Yasouj
Introduction: Today, microneedles (MNs) are widely used for medical applications [1]. They have provided successful results in drug delivery. Improving the performance of MNs requires investigating the effective parameters of designing and manufacturing [3]. Experimental studies are time-consuming and expensive while computer simulation can provide helpful information about various effective parameters with more details and lesser cost [6]. Here, the way of drug diffusion inside a cone and cone-cylinder MN was studied numerically. Currently, due to the small dimensions of MNs and technological limitations, it is not possible to experimentally investigate the drug diffusion inside MN. Simulation makes it possible to model phenomena that are impossible or complex in terms of laboratory and obtain useful information about their effective parameters [8].
Methods: To investigate drug diffusion inside MN, COMSOL software was used to simulate drug transfer as a function of time. 3D geometry of cone and cone-cylinder MN was constructed and then meshed. Grid independence was performed for the computational domains created according to the methods described in previous articles [8]. As seen in Figure 1, the height of the microneedles was 800 µm and their base diameter was 300 µm.
The governing equation of the diffusion is:
(dc_i)/dt- ∇∙〖(D_i ∇c_i)〗_ = R_i. (1)
Where c_i is the drug concentration [mol/m3], t is time [s], Di is the diffusion coefficient [m2/s] and Ri is the mass source [mol/(m3.s)]. The side wall of the microneedle that is in contact with the skin is considered as the drug sink. At t=0 s, a uniform concentration of the drug inside the microneedle is considered as c(0)= 2∙0×〖10〗^(-4) [mol/m3]. For a sample drug with the diffusion coefficient of D=1∙48×〖10〗^(-10) [m2/s], the drug diffusion was simulated over time inside the microneedle applying Transport of Diluted Species under a time-dependent model.
Results: The shape of microneedles 1 and 2 is shown in Figure 1. The result of simulation is demonstrated in Figure 2. The distribution of the drug inside the MNs over time is shown in Figure 2. Initially, there is a uniform concentration of the drug inside the MNs that is shown in red. With the passage of time, the drug is transferred from the side wall of the MNs into the skin, and the contour of the drug concentration inside the MNs changes. At the end of the drug transfer process, the color of the contour changes to blue, indicating that the drug is completely released from the microneedle. Complete transfer of the drug in the cone MN occurs in 64 seconds and in the cone-cylinder ones after 81 seconds. Both microneedles had the same height and diameter, but due to the geometrical difference, they have different volumes of medicine. To make the responses independent of the volume of the MNs, the drug discharge time divide was by the volume (t/V, here t is time and V is the volume of MN). t/V is the time per unit volume. The value of t/V for cone MN is 1.4 times greater than that of the cone-cylinder. That means drug diffusion inside cone shape is faster than cone-cylinder one. The obtained data shows that in addition to the volume of the drug embedded inside the microneedles, their geometry is effective in the complete release of the drug.
Conclusion: Drug penetration inside the microneedle was simulated for different MN shapes. The results show that in addition to the volume of the drug, the geometric shape of the microneedle is effective in releasing the drug from inside the microneedle. In cases where experimental tests cannot be performed due to the complexity of the process or lack of technology, numerical and computer simulations help in understanding various phenomena.
Keywords: Drug delivery, cone microneedles, cone-cylinder microneedles, Simulation