Evaluation of progesterone permeability from supercritical fluid processed dispersion systems

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Biomedical Engineering

Background:

• Effective transdermal drug delivery remains a challenge for many active pharmaceutical ingredients.
• Supercritical fluid (SCF) processing offers unique advantages for creating advanced drug delivery systems.
• Bioidentical progesterone (PGN) requires optimized formulations for efficient skin permeation.

Purpose of the Study:

• To investigate the transdermal permeability of PGN using novel dispersion systems prepared by SCF processing.
• To compare the efficacy of SCF-processed dispersions against conventional formulations and a market cream.
• To evaluate the impact of SCF processing on skin integrity and morphology.

Main Methods:

• Preparation of semisolid dispersions of PGN using various excipients (PEG, Gelucire, TPGS, tanscutol P, myritol 318).
• Utilized supercritical carbon dioxide (SC-CO2) for dispersion preparation via gas-saturated suspension method.
• Ex vivo permeation studies using mouse skin, histological examination, and Fourier transform infrared spectroscopy.

Main Results:

• The dispersion system containing TPGS/myritol/transcutol P processed with SC-CO2 demonstrated a two-fold improvement in PGN transdermal permeation over 24 hours compared to controls (245.7 vs. 126 µg cm⁻²).
• SCF-processed systems exhibited significantly improved lag time and flux.
• Histological and spectroscopic analyses indicated no detrimental effects on skin integrity.

Conclusions:

• SCF processing, particularly with SC-CO2 and the TPGS/myritol/transcutol P system, offers a superior method for enhancing PGN transdermal delivery.
• These novel dispersions present a potential advantage over existing market creams for improving drug flux and reducing lag time.
• Further development of SCF-based systems could revolutionize transdermal progesterone therapy.