Background: Atopica® is the pioneer veterinary cyclosporine capsule product. While there are approved generic versions of Atopica®, human generic products continue to be commonly prescribed by veterinarians. Presently, there is insufficient evidence to substantiate interchangeability of human oral generic cyclosporine and Atopica® in dogs and cats. A potential first step in demonstrating bioequivalence among these products is a dissolution test as described by the U.S Pharmacopeia (USP). This may provide guidance to appropriate products for in vivo bioequivalence studies in dogs.Hypothesis/
Objectives: To determine the dissolution profiles of human generic cyclosporine formulations in comparison to Atopica®. The hypothesis is that human oral generic cyclosporine formulations and Atopica® have different dissolution profiles.Animals: None.
Methods: Dissolution testing was performed in adherence to USP guidelines with Distek 2100 A Tablet Dissolution System with Apparatus II paddles on three human oral generic cyclosporine formulations (Neoral, TEVA, and Apotex) and Atopica®. Capsule rupture time was determined by visual inspection. Cyclosporine concentration in the dissolution medium was measured using high-performance liquid chromatography at 7.5, 15, and 30 minutes.
Results: Capsule rupture times were statistically shorter for Neoral compared to Atopica® and other human generic preparations. Although numerical concentrations of the Neoral capsule were higher at 7.5, 15 and 30 minutes, there was no statistical difference.Conclusions and Clinical Importance: This study suggests a difference in dissolution profiles between Neoral and Atopica® and other human generic preparations, which potentially indicates a variation in vivo. An in vivo pharmacokinetics study is warranted to further substantiate this finding.
