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Formula optimization based on artificial neural networks in transdermal drug delivery
K Takayama1, J Takahara, M Fujikawa
1Department of Pharmaceutics, Hoshi University, Ebara 2-4-41, Shinagawa-ku, Tokyo, Japan. takayama@hoshi.ac.jp
Summary
O-ethylmenthol (MET) significantly enhances ketoprofen percutaneous absorption from hydrogels. Artificial neural networks optimized formulations for improved drug delivery and safety.
Area of Science:
- Pharmacology
- Drug Delivery Systems
- Materials Science
Background:
- Percutaneous absorption of drugs is crucial for effective topical and transdermal delivery.
- Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) commonly used for pain relief.
- Enhancing drug permeation through the skin can improve therapeutic outcomes.
Purpose of the Study:
- To evaluate the promoting effect of O-ethylmenthol (MET) on ketoprofen percutaneous absorption from alcoholic hydrogels.
- To develop and optimize ketoprofen hydrogel formulations containing MET using artificial neural networks (ANN).
Main Methods:
- In vitro and in vivo studies in rats were conducted to assess drug permeation.
- Formulations were optimized using an ANN model with ethanol and MET as factors.
- Response variables included penetration rate (R(p)), lag time (t(L)), and total irritation score (TIS).
Main Results:
- Low concentrations of MET (0.25-0.5%) markedly increased ketoprofen permeation compared to controls.
- Menthol required higher concentrations (>2%) for comparable permeation enhancement.
- MET improved ketoprofen partitioning into the skin and enhanced drug diffusivity at higher concentrations.
Conclusions:
- O-ethylmenthol is an effective enhancer for ketoprofen percutaneous absorption.
- ANN modeling successfully optimized hydrogel formulations for enhanced efficacy and safety.
- Optimized formulations showed good agreement between predicted and observed penetration rates and irritation scores.