Numerical Estimation of Drug Diffusion at Dermal Regions of Human Body in Transdermal Drug Delivery System

Khanday, M. A.; Rafiq, Aasma

doi:10.1142/s0219519416500226

Cited by 13 publications

(11 citation statements)

References 8 publications

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“…The current state of the art in mechanistic modeling of TTDS was summarized in Table 1. Such mechanistic modeling provides several advantages compared to the analytical solution of the diffusion-driven drug uptake process [21], [75]. Such analytical solutions enable to calculate drug dose taken up for several drugs, based on their diffusive properties of the skin.…”

Section: Mechanistic Modelingmentioning

confidence: 99%

Predicting transdermal fentanyl delivery using mechanistic simulations for tailored therapy

Defraeye

Bahrami

Ding

et al. 2020

Preprint

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Transdermal drug delivery is a key technology for administering drugs. However, most devices are "one-sizefits-all", even though drug diffusion through the skin varies significantly from person-to-person. For nextgeneration devices, personalization for optimal drug release would benefit from an augmented insight into the drug release and percutaneous uptake kinetics. Our objective was to quantify the changes in transdermal fentanyl uptake with regards to the patient's age and the anatomical location where the patch was placed. We also explored to which extent the drug flux from the patch could be altered by miniaturizing the contact surface area of the patch reservoir with the skin. To this end, we used validated mechanistic modeling of fentanyl diffusion, storage, and partitioning in the epidermis to quantify drug release from the patch and the uptake within the skin. A superior spatiotemporal resolution compared to experimental methods enabled in-silico identification of peak concentrations and fluxes, and the amount of stored drug and bioavailability. The patients' drug uptake showed a 36% difference between different anatomical locations after 72 h, but there was a strong interpatient variability. With aging, the drug uptake from the transdermal patch became slower and less potent. A 70-year-old patient received 26% less drug over the 72-h application period, compared to an 18-year-old patient. Additionally, a novel concept of using micron-sized drug reservoirs was explored in silico. These reservoirs induced a much higher local flux (µg cm -2 h -1 ) than conventional patches. Up to a 200-fold increase in the drug flux was obtained from these small reservoirs. This effect was mainly caused by transverse diffusion in the stratum corneum, which is not relevant for much larger conventional patches. These micronsized drug reservoirs open new ways to individualize reservoir design and thus transdermal therapy. Such computer-aided engineering tools also have great potential for in-silico design and precise control of drug delivery systems. Here, the validated mechanistic models can serve as a key building block for developing digital twins for transdermal drug delivery systems.

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Section: Mechanistic Modelingmentioning

confidence: 99%

Predicting transdermal fentanyl delivery using mechanistic simulations for tailored therapy

Defraeye

Bahrami

Ding

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The current state of the art in mechanistic modeling of TTDS was summarized in Table 1. Such mechanistic modeling provides several advantages compared to the analytical solution of the diffusion-driven drug uptake process (Rim et al, 2005;Khanday and Rafiq, 2016). Such analytical solutions enable to calculate drug dose taken up for several drugs, based on their diffusive properties of the skin.…”

Section: Outlook Mechanistic Modelingmentioning

confidence: 99%

Predicting Transdermal Fentanyl Delivery Using Mechanistic Simulations for Tailored Therapy

et al. 2020

View full text Add to dashboard Cite

Transdermal drug delivery is a key technology for administering drugs. However, most devices are "one-size-fits-all", even though drug diffusion through the skin varies significantly from person-to-person. For next-generation devices, personalization for optimal drug release would benefit from an augmented insight into the drug release and percutaneous uptake kinetics. Our objective was to quantify the changes in transdermal fentanyl uptake with regards to the patient's age and the anatomical location where the patch was placed. We also explored to which extent the drug flux from the patch could be altered by miniaturizing the contact surface area of the patch reservoir with the skin. To this end, we used validated mechanistic modeling of fentanyl diffusion, storage, and partitioning in the epidermis to quantify drug release from the patch and the uptake within the skin. A superior spatiotemporal resolution compared to experimental methods enabled in-silico identification of peak concentrations and fluxes, and the amount of stored drug and bioavailability. The patients' drug uptake showed a 36% difference between different anatomical locations after 72 h, but there was a strong interpatient variability. With aging, the drug uptake from the transdermal patch became slower and less potent. A 70-year-old patient received 26% less drug over the 72-h application period, compared to an 18-year-old patient. Additionally, a novel concept of using micron-sized drug reservoirs was explored in silico. These reservoirs induced a much higher local flux (µg cm-2 h-1) than conventional patches. Up to a 200-fold increase in the drug flux was obtained from these small reservoirs. This effect was mainly caused by transverse diffusion in the stratum corneum, which is not relevant for much larger conventional patches. These micron-sized drug reservoirs open new ways to individualize reservoir design and thus transdermal therapy. Such computer-aided engineering tools also have great potential for in-silico design and precise control of drug delivery systems. Here, the validated mechanistic models can serve as a key building block for developing digital twins for transdermal drug delivery systems.

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“…Consequently, the understanding of drug transport from a TDDS into and through skin is crucial to the development of such systems, in order to achieve an optimal therapeutic effect [3]. Mathematical modeling of skin permeability is an important tool that can aid in the understanding of permeation mechanisms in dermal regions [4][5][6]. For example, modeling can help to predict the rate of penetration of drugs, as well as appropriate doses, exposure times, or sampling intervals.…”

Section: Introductionmentioning

confidence: 99%

Compartmental modeling of skin transport

Amarah

Petlin

Grice

et al. 2018

European Journal of Pharmaceutics and Biopharmaceutics

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The primary objective of this study is to introduce a simple and flexible mathematical approach which models transport processes in skin using compartments. The main feature of the presented approach is that the rate constants for exchange between compartments are derived from physiologically relevant diffusional transport parameters. This allows for better physical interpretation of the rate constants, and limits the number of parameters for the compartmental model. The resulting compartmental solution is in good agreement with previously published solutions for the diffusion model of skin when ten or more compartments are used. It was found that the new compartmental model with three compartments provided a better fit of the previously publish water penetration data than the diffusion model. Two special cases for which it is difficult to implement the diffusion model were considered using our compartmental approach. In both cases the compartmental model predictions agreed well with the diffusion model.

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Numerical Estimation of Drug Diffusion at Dermal Regions of Human Body in Transdermal Drug Delivery System

Cited by 13 publications

References 8 publications

Predicting transdermal fentanyl delivery using mechanistic simulations for tailored therapy

Predicting transdermal fentanyl delivery using mechanistic simulations for tailored therapy

Predicting Transdermal Fentanyl Delivery Using Mechanistic Simulations for Tailored Therapy

Compartmental modeling of skin transport

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