Deuterated Drug in Transdermal Patch

Deuterium involve the replacement of the hydrogen atom in the molecule with the deuterium, which is a heavier isotope of hydrogen. There is plethora of information of use of deuterium in drug discovery to improve metabolism, Pharmacokinetics, reduction in the toxicity (pertaining to the toxic metabolite) od drug molecule. Recent approval of two deuterated drug (AUSTEDO, TEVA;2017 AND DEUCRAVACITINIB, BMS 2022) draws the attention of pharmaceutical companies to this magical atom i.e. Deuterium.

Some reports also discuss the incorporation of deuterium into drug molecules within transdermal patches . Generally, deuterium substitution can impact various physicochemical properties (listed below) of the drug molecule, which may influence it’s behavior during skin absorption.

1.) Altering Molecular size and Shape: Change in the bond length of C-H bond to C-D bond can lead to change in molecular size and shape of the compound which may alter the penetration of drug molecule in the skin.

2.) Hydrogen Bonding: Deuterium has large mass compared to hydrogen which may affect the strength and nature of hydrogen bonding interaction with the molecule. Change in hydrogen bond pattern can influence the solubility and partitioning of the drug in the skin and absorption.

3.) Metabolic stability: Drugs may undergo metabolism in skin before entering in to the systemic circulation. In these drugs metabolism in skin can influence the therapeutic effect and potential side effect of drug. Deuterium substitution can impact the metabolic fate of the drug and could affect the rate of metabolism and subsequent absorption.

4.) Permeability through the stratum Corneum: The Stratum Corneum is the outermost layer of the skin and act as a barrier to the drug penetration. Alteration in physicochemical properties and size may influence its ability to pass through skin layer.

The impact of deuteration will depend upon the drug molecule and formulation. Experimental studies and pharmacokinetic assessments are required to evaluate the effect of deuterium on the skin absorption of a drug molecule for transdermal patch.

References:

1. DE4343838A; Deuterated active ingredients in transdermal application
2. Biotransformation of Drugs in Human Skin; DRUG METABOLISM AND DISPOSITION; Vol. 37, No. 2, :247– 253, 2009