pH and Drug Delivery

Drug substances used in the treatment of skin diseases have to reach target cells in the skin in order to exert a clinical effect. This makes topical treatment of skin diseases attractive because local drug delivery gives a more direct access to the target cells and reduces potential side effects, as compared to systemic administration. Many drug substances are weak acids or bases, and setting the pH in topical formulations of these types of compounds influence the degree of ionization, which may substantially influence solubility, chemical stability and lipophilicity of the drug substance. According to the pH partition hypothesis, it is generally accepted that the non-ionized species of an acidic or a basic molecule is more permeable across biological barriers than the ionized. Penetration of drug substance into the skin is affected by the physicochemical properties of the drug substance and formulation properties. Several ex vivo studies identify that the degree of ionization of drug substances can change the penetration across the stratum corneum. Setting the pH in the formulation seems to be an important parameter for improving skin penetration together with other parameters such as buffer capacity, nature of counter ions or skin pH. In addition, pH changes give a possibility to design more advanced drug delivery systems, utilizing pH changes for specific targeting of drug substances to diseased tissue.