Pharmacokinetics of a Taste-Masked Prednisone Oral Microsphere Powder

Abstract

Many active pharmaceutical ingredients (APIs) face the challenge of palatability when administered orally. Taste-masking technologies often utilize coatings to help palatability but these coatings or agglomerations can negatively impact bioavailability. Orbis Biosciences, Inc. (Orbis) has developed a novel taste-masking technology that has previously been demonstrated to have virtually complete taste-masking of the extremely bitter API, prednisone. The next facet of development was to assess the pharmacokinetics (PK) and relative bioequivalence (BE) of prednisone from this new formulation. Presented here is a randomized, open-label, two products, two period and crossover study in fasted adults comparing 10 mg prednisone taste-masked microspheres to a 10 mg prednisone tablet. Fourteen (14) post-dose plasma concentrations obtained over a 12 h period were analyzed for prednisone and its metabolite, prednisolone, using a validated HPLC/MS/MS method. Bioavailability was assessed according to current United States’ Food and Drug Administration (FDA) criteria. Results indicated that for both Cmax (90% CI; 0.81-1.10) and AUCtotal (0.94-1.18), the microsphere formulation met bioavailability criteria for prednisone. For prednisolone, only AUCtotal met criteria for bioavailability. Cmax was lower (90% confidence interval of 0.647-0.938 for log transformed data) and time of Cmax (Tmax) was delayed (2.9 ± 0.5 vs. 1.8 ± 1.0 h, p=0.02) in the microsphere relative to the tablet formulation. In conclusion, the relative bioavailability of the novel microsphere formulation of prednisone was evident as compared to a commercially available tableted formulation of the drug.