Richard Todd Darrington

Utilization of biopharmaceutical and pharmacokinetic principles in the development of veterinary controlled release drug delivery systems

Publisher Summary In veterinary medicine, the patient populations encapsulate a wide range of species, body sizes, and drug absorption barriers, and therapies generally require long-acting agents that are administered infrequently. The utilization of biopharmaceutical and pharmacokinetic principles in the development of veterinary controlled release drug delivery systems is essential for a rationally designed product. The development of veterinary controlled release drug delivery systems requires the collaboration of several departments of an innovative pharmaceutical company. The aim of this chapter is to provide an overview of biopharmaceutical and pharmacokinetic principles that are essential in meeting the challenges facing innovative producers of veterinary controlled release products. It focuses on two major veterinary markets: livestock, including cattle, swine, sheep, and poultry; and companion animals, including cats, dogs, and horses. The general principles that are applied to pharmaceuticals for these major markets can be applied to pharmaceuticals for other markets.

Dissolution behavior of porcine somatotropin with simultaneous gel formation and lysine Schiff-base hydrolysis.

The primary goal of this work was to develop a reliable in vitro dissolution model to evaluate the effects of Schiff-base hydrolysis and gel formation on the dissolution kinetics of pellets of porcine somatotropin (pST) and pST conjugated with ortho-vanillin (ov-pST) via Schiff-base formation, in an effort to develop an extended-release pST implant. Experimentally, dissolution was investigated as a function of ov concentration in pH 7.4, phosphate buffered saline under sink conditions where steady-state (constant flux) dissolution is typically observed. However, the resulting dissolution profiles displayed variable release rates due to gel formation at the solid-liquid interface, which impeded pST release. Chemical modification of pST with ov reduced gel formation and also resulted in much lower release rates. A mathematical model was developed that quantitatively accounts for changes in dissolution rates due to transient gel formation via irreversible aggregation, along with the effects of reversible Schiff-base hydrolysis involving ov, and predicts dissolution rates in the presence of ov decrease due to the much lower solubility of ov-pST. Our results indicate that although ov-pST is less prone to aggregate, pST/ov-pST equilibration is rapid compared to dissolution and therefore aggregation remains the limiting factor, and ultimately precludes this approach as a viable extended-release delivery system.