Optimization of Transdermal Drug Delivery with Microcapsules

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Abstract
Research in transdermal drug delivery systems has gained much attention in the past thirty years. One of the biggest challenges in developing an effective system however, is getting past the tightly-structured outermost layer of the skin called the stratum corneum. While many different techniques to safely bypass the stratum corneum have been employed, one promising method of transdermal drug delivery is the use of drug-loaded microcapsules. Encapsulating the drug, as opposed to a non-encapsulated topical application, allows the drug to diffuse into hair follicles where drug release can occur in the deeper layers of the skin. COMSOL was used to model the diffusion of drug through a hair follicle and into the skin layers, via microcapsules of inner radius 300nm and outer radius 350nm. The diffusion of microcapsules through the hair follicle, drug through the microcapsule shell, and drug through the skin layers was modeled using three transient diffusion equations that were solved simultaneously. The drug in microcapsules was modeled as emerging from a source, similar to a patch, above the hair follicle. The COMSOL model was verified by comparing the time for the microcapsules to penetrate into the follicle, the time for the drug to diffuse out of the microcapsules, and the drug concentration in the dermis to literature values. It took 60-70 minutes for the microcapsules to be evenly dispersed throughout the follicle, which is supported by literature values.1 The microcapsule released 75% of its encapsulated drug after 1.25 hours, which is comparable to a literature value of 70% release in 2 hours.1 Additionally, the same source showed that drug release by the microcapsule was complete after 4 hours; almost all of the drug had left the microcapsule in 4 hours in our model. The drug concentration in the dermis in our model after 4 hours (0.0005 ug/mL) was lower than literature sources. However, our design only had drug-containing microcapsules applied directly above the hair follicle, when in reality, much more drug would be applied to the skin surface.2 We showed that a slight variation of our design, using a thin layer of drug over the entire skin surface, greatly improves the value of drug concentration in the dermis. A sensitivity analysis was conducted to determine the significance of parameters on our model. The solution from our design led to a slightly high release rate of the drug and a low final drug concentration in the skin, relative to literature values. This indicated that our model would best reflect the behavior of a potent drug requiring a fast release rate and a low dosage in skin. In order to obtain a more accurate solution, the simplifications in our design could be adjusted and the realistic complexities of actual skin could be added. While we only studied diffusion through one hair follicle, studying several hair follicles in a representative region of the skin could lead to changes in the final drug concentration achieved in the skin. Despite the many simplifications of our model, we were able to show that this microcapsule transdermal system is an effective method for bypassing the highly impermeable outer skin layer.
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2010-05-21T18:46:16Z
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