Investigation of the Compatibility of the Skin PAMPA Model with Topical Formulation and Acceptor Media Additives...

Area of Science:

• Dermatology and Pharmaceutical Sciences
• Biophysical Chemistry
• Formulation Science

Background:

• The stratum corneum (SC) is the primary barrier in topical drug delivery.
• The Skin Parallel Artificial Membrane Permeability Assay (PAMPA) utilizes an artificial membrane to simulate the SC barrier.
• Evaluating formulation excipient compatibility with skin models is crucial for predicting in vivo performance.

Purpose of the Study:

• To assess the compatibility of various lipophilic solvents, penetration enhancers, and topical emulsion components with the Skin PAMPA artificial membrane.
• To compare standard and modified Skin PAMPA assay setups.
• To determine if common formulation ingredients and acceptor media additives compromise the integrity of the artificial membrane.

Main Methods:

• Utilized the Skin PAMPA assay with an artificial membrane mimicking the SC barrier.
• Tested lipophilic solvents (e.g., IPM, DMI, PG, DIPA), topical emulsions with different emulsifiers, and organic acceptor media (DMSO, EtOH).
• Employed methylparaben, ethylparaben, and propylparaben as model permeants and compared standard vs. modified assay configurations.

Main Results:

• The permeation order of parabens (MP > EP > PP) was consistent across different lipophilic solvents.
• Lipophilic solvent rankings were comparable between standard and modified assay setups.
• Pre-incubation with tested solvents, emulsifiers, or acceptor media (≤50% DMSO/EtOH) did not increase paraben permeation, indicating no compromise to membrane integrity.

Conclusions:

• The Skin PAMPA model demonstrates robustness against common lipophilic solvents, non-ionic emulsifiers, and moderate concentrations of organic solvents in acceptor media.
• The assay setup (standard vs. modified) did not significantly alter the relative permeation of model compounds or solvent rankings.
• The Skin PAMPA assay is a valuable pre-screening tool for topical formulation development, provided specific constraints are considered.