(204y) A Computational Study on the Transport of Actives through Skin Layers | AIChE

(204y) A Computational Study on the Transport of Actives through Skin Layers


Gajula, K. - Presenter, TCS Research
Gupta, R., TCS Research
Balarama Sridhar, D., TCS Research
Rai, B., TCS Research
The accurate prediction of dermal uptake of actives is relevant to both transdermal drug delivery as well as topical application of cosmetics. The current industry standard, however, both in pharma and cosmetics, is to conduct detailed in-vitro and in-vivo trials. These obviously incur huge expenses thereby leading to a very few successful candidates that are finally approved by regulatory authority (FDA). The plasma uptake of drug through skin is limited by the systematic absorption of drugs through distinct layers of skin. The drug permeation through skin mostly happens through passive diffusion. The drug diffusion coefficient and partition coefficient in these layers is mainly responsible for the fate of the drug inside the skin layer.

Skin is composed of many layer in series, mainly SC (stratum corneum), VE (viable epidermis) and dermis. Out of these three layers, the first layer, SC, is responsible for barrier function of the skin. The SC is made up of corneocyte and lipid matrix, which are arranged in brick and mortar fashion respectively. Dermis consists of microscopic blood vessels through which drug enters into systemic circulation.

The detailed modelling of all the skin layers would give an insight into the transport mechanism of drugs in skin layers and would help in obtaining the desired total drug uptake. In this study, we have integrated the models of all the skin layers, and performed finite element simulations to obtain the dermal uptake. The heterogeneity of SC was captured using bricks and mortar model, the diffusion coefficient which governs the transport process in SC was obtained accurately from molecular dynamics simulations1 instead of depending on experiments or from fitted data. The VE layer and subsequent dermis layer were approximated with compartmental models. Diffusion coefficients of the drug in the VE and dermis were obtained from available empirical correlations.2 Finite element method framework was used to predict the time and space dependent concentration profiles of drug in different layers of skin. Permeation of the drug in all these layers were linked in the integrated model. The model was validated with experimentally available release profile.3,4 The concentration depth profiles in VE and dermis layers were also compared with the available experimental data. Our integrated model provides flexibility in analyzing diffusion process in individual skin layers as well as whole skin. This model shall be used as guiding tool for performing targeted experiments in designing a suitable delivery system.


  1. Gupta, Rakesh, D. B. Sridhar, and Beena Rai. "Molecular Dynamics Simulation Study of Permeation of Molecules through Skin Lipid Bilayer." The Journal of Physical Chemistry B 120.34 (2016): 8987-8996.

  2. Bunge, Annette L., and Robert L. Cleek. "A new method for estimating dermal absorption from chemical exposure: 2. Effect of molecular weight and octanol-water partitioning." Pharmaceutical research 12.1 (1995): 88-95.

  3. Kushner, Joseph, et al. "First‐principles, structure‐based transdermal transport model to evaluate lipid partition and diffusion coefficients of hydrophobic permeants solely from stratum corneum permeation experiments." Journal of pharmaceutical sciences 96.12 (2007): 3236-3251.

  4. Dias, M., et al. "Topical delivery of caffeine from some commercial formulations." International journal of pharmaceutics 182.1 (1999): 41-47.