A stepwise protocol for drug permeation assessment that combines heat-separated porcine ear epidermis and vertical diffusion cells

Main Article Content

Ivana Pantelić
Tanja Ilić
Bojan Marković
Sanela Savić
Milica Lukić
Snežana Savić


After decades long absence of an official consensus on the most appropriate evaluation method for in vitro skin performance of topical semisolid drugs, United States Pharmacopoeia (USP 39) finally suggested three types of testing equipment; however, all these provide data on drug release using inert synthetic membranes. Considering the need for a readily available membrane that would be more structurally similar to human skin, this paper provides a detailed protocol of a method for drug permeation assessment that uses heat-separated porcine ear epidermis and modified Franz diffusion cells. Phases that were shown to be critical for variability of the results are identified (e.g. membrane preparation), and process parameters optimized. Applicability of the method was tested on four cream samples loaded with aceclofenac as a model drug. Sample compositions were designed in such a way to provide „large“ variations (variation of the main stabilizer: natural-origin versus synthetic emulsifier) and relatively „minor“ variations (co-solvent variation: none/isopropanol/glycerol). The developed protocol is a straightforward and reliable in vitro test for the evaluation of rate and extent of drug delivery into/through the skin. Moreover, this protocol may be routinely applied even in averagely equipped laboratories during formulation development or preliminary bioequivalence assessment of generic topical semisolids.

Article Details

Chemical Engineering - Pharmaceutical Engineering
Author Biographies

Ivana Pantelić, Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Belgrade

Department of Pharmaceutical Technology and Cosmetology

Tanja Ilić, Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Belgrade

Department of Pharmaceutical Technology and Cosmetology

Bojan Marković, Department of Pharmaceutical Chemistry, University of Belgrade – Faculty of Pharmacy, Belgrade

Department of Pharmaceutical Chemistry

Sanela Savić, Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Belgrade

Department of Pharmaceutical Technology and Cosmetology

Milica Lukić, Department of Pharmaceutical Technology and Cosmetology, University of Belgrade – Faculty of Pharmacy, Belgrade

Department of Pharmaceutical Technology and Cosmetology

Snežana Savić, University of Belgrade - Faculty of Pharmacy

Department of Pharmaceutical Technology and Cosmetology


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