Membranes Chemical/Drug Permeation

G. P. Misra and R. A. Siegel. Multipulse drug permeation across a membrane driven by a chemical pH-oscillator. J. Control. Release 79 293—297, 2002. 

In the case of ionized compounds (weak acids and bases), drug permeation depends on the chemical equilibrium between the ionized and the un-ionized form, both in the delivery system itself and in the lacrimal fluid. In general, un-ionized molecules penetrate lipid membranes more readily than ionized ones. 

Gerebtzoff, G., Li-Blatter, X., Fischer, H., Frentzel, A. and Seelig, A. (2004) Halogenation of drugs enhances membrane binding and permeation. Chembiochem A European Journal of Chemical Biology, 5, 676-684. 

Common for all the membrane-, cell- and tissue-based systems used to determine drug permeation, is the need for an incubation solution preserving the viability, functionality and/or integrity of the membranes, cells or tissue. It is also important that the incubation solution does not influence the permeability characteristics of the epithelial membrane or lipid bilayer and that the drug compound is chemically and physically stable and sufficiently soluble in the buffer. In all models, aqueous incubation solutions are used, often with slight modifications depending on the purpose of the study. 

One of the most commonly used methods of modulating tablet drug release is to include it in a matrix system. In addition, the drug release is a function of many factors, including the chemical nature of the membrane, geometry and its thickness, and the particle surface of the drug device, the physico chemical nature of the active substance and the interaction between the membrane and the permeating fluids are also important [116]. 

Most body tissues are protected by lipophilic barriers that serve as the body s primary protection against absorption of chemicals. It is well established that lipophilic chemicals can penetrate lipophilic barriers (including mucous membranes) much more readily than can hydrophilic chemicals by passively diffusing across lipid-rich cell membranes. 2 4l The lipid-rich mucous membranes also serve as barriers to the absorption of hydrophilic species. Lipophilic chemicals, however, promote the permeation of hydrophilic chemicals that are dissolved in the lipophiles. Lipophiles are routinely used, for example, in drug delivery systems (see Section 3.3). 

The range of applications of peptide drugs is very broad, and includes analgesia, cancer therapy, and infection treatment. The processing and delivery of proteins are often challenging, as many protein molecules are physically and chemically unstable. Once administered, proteins can be subject to enzymatic degradation, and present unfavorable permeation through cellular membranes. 

Primary chemical features of a drug and its dosage form that can dictate oral bioavaUability (3) DMSO relationship between pH, ionizable groups and membrane permeation absorption Rule-of-5, active transport (in and out), Pgp, OAT prodrugs and soft drugs. 

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