Applying the Biopharmaceutics Classification System to veterinary pharmaceutical products: Part I: Biopharmaceutics and formulation considerations

The complexity of multiple species approvals continues throughout the life of a product as post-approval manufacturing changes, as well as all generic versions of approved products, are evaluated for each of the approved target animal species. In comparing product bioavailability across animal species, it is not unusual to observe marked interspecies differences. For many compounds, these differences reflect species-specific presystemic metabolism. However, a host of other variables must also be considered, including in vivo drug solubility, gastric transit time, intestinal permeability, diet, and species-by-formulation interactions. To predict potential species-by-formulation interactions, one must consider the solubility and intestinal permeability of the drug entity, the type of formulation, nature of the excipients, and the physiological characteristics of the animal recipient. In this paper, we examine manufacturing and formulation variables that can affect drug bioavailability, and the potential for species-specific differences in the responses to these formulations.