Author: Sam Maher, David J. Brayden, Luca Casettari, and Lisbeth Illum
application of permeation enhancers (PEs) to improve transport of poorly absorbed active pharmaceutical ingredients across the intestinal epithelium is a widely tested approach, permeation enhancers represent a key constituent of conventional oral formulations, permeation enhancer, oral delivery, formulation, permeability, safety, simulated intestinal fluid, hydrophobization, epithelium, a paucity of delivery technologies that address low intestinal epithelial permeability for macromolecules has left pharmaceutical manufacturers with little option but to limit screening of these complex hydrophilic macromolecules or default to parenteral formulation, medicinal chemists in the discovery field should solely focus on safety and efficacy of the active, and rely on formulation and delivery scientists to address sub-optimal solubility, ADME (absorption, distribution, metabolism and excretion), and stability characteristicsor whether medicinal chemists should focus on all of the aforementioned properties to rely less on delivery and formulation scientists, optimizing the molecule and the formulation, improve intestinal permeability in humans, inclusion of an excipient that facilitates transport across the intestinal epithelial barrier, proprietary formulations that attempt to improve oral absorption of macromolecules in humans usually include permeation enhancers (PEs), permeability in oral, nasal, buccal, pulmonary, vaginal, and corneal delivery models. These compounds are broadly categorized as paracellular or transcellular Pes, Transcellular PEs alter epithelial permeability by two contrasting mechanisms, (i) reversible perturbation of the epithelial plasma membrane [9], or (ii) physical interaction with the active to improve passive transcellular permeation (e.g., hydrophobization , surfactant-based PEs are a widely tested category that alter membrane integrity, integrated approach to enabling oral peptide delivery, combining structural engineering and formulation optimization
