A Comparative Evaluation of Desoximetasone Cream and Ointment Formulations Using Experiments and In Silico Modeling

Area of Science:

• Pharmacology
• Biomedical Engineering
• Computational Modeling

Background:

• Dermal drug delivery offers an alternative to traditional methods but faces challenges in optimizing formulations.
• Physiologically based pharmacokinetic (PBPK) models aid drug development but require efficient calibration methods.
• A research gap exists in accurate PBPK model calibration for dermal drug delivery.

Purpose of the Study:

• To present a novel approach for calibrating PBPK models for dermal drug delivery.
• To develop an integrated dermal drug delivery model using virtual in vitro release (IVRT) and permeation (IVPT) data.
• To optimize and validate the computational model using Desoximetasone formulations.

Main Methods:

• Experimental determination of Desoximetasone release kinetics and permeation profiles.
• Development of a computational model simulating dermal drug delivery.
• Optimization and validation of the model using virtual IVRT and IVPT data.
• Analysis of stratum corneum variability's impact on model performance.

Main Results:

• Experimental data revealed significant differences in lag time and early permeation of Desoximetasone between cream and ointment formulations.
• The computational model demonstrated a good fit with experimental data, accurately predicting Desoximetasone permeation.
• Stratum corneum permeability and partition coefficient variability significantly influenced model differentiation between formulations.
• Virtual IVRT/IVPT data effectively reduced data requirements for model calibration.

Conclusions:

• The novel approach effectively calibrates PBPK models for dermal drug delivery, enhancing accuracy and efficiency.
• Leveraging virtual models accelerates drug development, optimizes dosing, and reduces resource expenditure.
• This method offers a cost-effective and streamlined pathway for developing optimized dermal drug formulations.