Evaluating drug permeability: a comparative study of in vitro permeability models and their regulatory applications

To make oral & transdermal drug products, we want to know a lot about how active pharmaceutical ingredients (APIs) can get through the skin, which is a biological barrier that is very complicated. The very reliable non-clinical technique for quantitatively evaluating drug delivery from semi-solid formulations is the in vitro permeation test (IVPT). IVPT determines how quickly & thoroughly a medication penetrates into skin, gets accessible at the site of action. This technique produces important endpoints like Flux and Cumulative Amount Permeated using serial sampling and physiological circumstances. In order to support the evidence of bioequivalence for complex topical generics, regulatory agencies like the EMA and FDAare increasingly recommending IVPT studies. Drug penetration occurs via the Trans-epidermal (transcellular and intercellular) and Transappendageal routes, with absorption influenced by factors like the Stratum Corneum barrier function, drug properties (e.g., lipophilicity, size), and formulation excipients. Beyond excised skin, other in-vitro permeability models include cell-based systems such as Human Intestinal Cell (Caco-2) and Canine Kidney Cell (MDCK) and non-cell-based high-throughput techniques like parallel artificial membrane permeability assay (PAMPA), and the Franz diffusion cell. Future advancements focus on addressing challenges like membrane variability and sink conditions through technologies such as Raman microspectroscopy, 3D bioprinted skin models, machine learning integration (ML), and Artificial Intelligence