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Cutaneous effects of transdermal levonorgestrel.
D R Friend1, S J Phillips, J R Hill
1Controlled Release and Biomedical Polymers Department, SRI International, Menlo Park, CA 94025.
Summary
Transdermal levonorgestrel devices caused mild to moderate skin irritation in rabbits, primarily erythema. Ethyl acetate and ethanol as enhancers showed similar irritation levels to controls, with reversible effects observed.
Area of Science:
- Pharmacology
- Dermatology
- Materials Science
Background:
- Transdermal drug delivery systems (TDDS) offer advantages over oral administration.
- Skin irritation is a common challenge in TDDS development, potentially limiting drug efficacy.
- Levonorgestrel is a progestin used in various formulations, including transdermal patches.
Purpose of the Study:
- To evaluate the skin irritation potential of transdermal devices delivering levonorgestrel.
- To assess the impact of ethyl acetate and ethanol as permeation enhancers on skin irritation.
- To compare irritation levels between different enhancer formulations and control devices.
Main Methods:
- Transdermal devices containing levonorgestrel and enhancers (ethyl acetate, ethanol, or a mixture) were applied to rabbits for 24 hours.
- Skin irritation (erythema and edema) was assessed visually at multiple time points (24, 48, 72 hours, and 7 days).
- Histological evaluation of skin samples was performed for two formulations.
Main Results:
- Transdermal devices induced mild to moderate skin irritation, with erythema being the predominant sign.
- No significant differences in irritation were observed between devices using pure ethyl acetate, ethyl acetate-ethanol (7:3), or pure ethanol enhancers.
- Control devices (water only) also showed mild irritation, suggesting the vehicle or device itself can be irritating.
Conclusions:
- Ethyl acetate and ethanol, when used as enhancers in transdermal levonorgestrel devices, cause mild to moderate, reversible skin irritation in rabbits.
- The observed irritation is comparable across different enhancer combinations and even to control devices.
- Further research is needed to mitigate skin irritation associated with transdermal drug delivery systems, particularly those utilizing these enhancers.