Physicochemical properties of water and its effect on drug delivery. A commentary

The structure and properties of water are integral to the existence and evolution of life on any number of levels. Consistent with this overarching statement, the unique physiochemical properties of water affect the pharmacological actions and delivery of drugs to the body whether they are administered orally, topically or by injection. This last topic is explored in the current review. While water is a group VIA hydride, it is distinct from other members of the class based on density, dielectric constant, surface tension as well as melting and boiling point. These differences are attributed to the ability of water to hydrogen bond to itself and other substrates resulting in the formation of strongly cohesive systems which molecularly resemble highly dynamic polymeric networks. As a consequence of these properties, hydrophobic compounds tend to aggregate in solution sometimes at the nanoscale. The practical consequence of this aggregation may be observed as spurious results associated with receptor-based high throughput screening assays as well as anomalies in phase-solubility analysis encountered in the study of hydrophobic materials with cyclodextrins. Other insights provided by a knowledge of the structure of water include the actions of excipients. Thus, materials that contribute to the hydrogen-bonding aqueous network (i.e., kosmotropes) will tend to salt more non-polar materials out of solution while material that destabilize the network structures (i.e., chaotropes) will tend to preferentially bind to solutes, reducing unfavorable interactions with water, resulting in solubilization. At membranes, the unique properties of water can affect drug absorption based on resistance in the unstirred water layer (UWL) which resides directly adjacent to the barrier. Depending on the nature of the membrane and the drug, the UWL can effectively reduce drug uptake and penetration. Furthermore, excipients that affect water structure can either contribute to or detract from the ability of a compound to pass the UWL and consequently the membrane. The increasing realization that water influences the actions and interactions drugs and excipients opens a variety of new avenues with regard to the rationale design of useful dosage forms.