Almost all studies on non-invasive topical drug delivery to the eye have emphasized the importance of biological barriers, static membrane barriers such as the cornea and the conjunctiva/sclera and dynamic barriers such as the lacrimal drainage. Hardly any have discussed the importance of the thermodynamic activity of the permeating drug molecules. Most drugs permeate from the eye surface into the eye by passive diffusion where, according to Fick's first law, the drug concentration gradient over the various permeation barriers (e.g., the tear fluid and the lipophilic membrane barriers) is the driving force. At the barrier interphases the dissolved drug molecules must partition from one barrier to another. For example, at the tear-cornea interphase the drug molecules must partition from the aqueous exterior into the lipophilic membrane. The drug partition coefficient between two phases is commonly defined as the equilibrium concentration ratio. However, these are only approximations. The actual driving force in Fick's first law is the gradient of the chemical potential and the equilibrium between two phases is attained when the chemical potential of the drug in one phase is equal to that in the other phase. Here the importance of thermodynamic considerations in topical drug delivery to the eye is reviewed.
Keywords: Chemical potential; Diffusion; Drug delivery; Eye; Partition; Thermodynamics.
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