Comparison of the In Vitro Dissolution Profiles for Cyclosporine Formulations

Atopica (formerly Novartis, now Elanco Animal Health) is the pioneer veterinary-approved modified cyclosporine authorized by both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Despite the availability of several veterinary-specific generics, human generics are frequently substituted extra-label in clinical practice. However, therapeutic equivalence in humans does not guarantee equal bioavailability in dogs, whether comparing these products to one another or to Atopica. As a Biopharmaceutics Classification System Class II compound, cyclosporine's oral absorption is primarily determined by its dissolution rate. This study compared the in vivo dissolution profiles of three human cyclosporine products including Neoral (Novartis), TEVA (TEVA Pharmaceuticals), and Apotex (Apotex Inc) with Atopica using a Distek 2100 A system (USP Apparatus 2, 50 rpm, 500 mL deionized water, 37°C). Primary outcomes included visual capsule rupture time and cyclosporine concentration at 7.5, 15, and 30 min, quantified by high-performance liquid chromatography. Neoral exhibited a shorter mean capsule rupture time compared to Atopica, while TEVA and Apotex showed no difference. At the 30-min mark, no significant differences in concentrations were observed among the products. While these in vitro results suggest comparable dissolution at a critical absorption 30-min time point, the shorter capsule rupture time of Neoral highlights formulation-specific differences. Comprehensive in vivo pharmacokinetic studies are warranted to determine if these human generics are truly interchangeable with Atopica or one another in dogs.