The Bioavailability of CHF6563, an Ethanol-Free, Sublingual Neonatal Buprenorphine Formulation: A Bridging Study Conducted in Adults.

Abstract

Objective: Sublingual buprenorphine has demonstrated efficacy for treatment of the neonatal opioid withdrawal syndrome (NOWS), but the current formulation used in clinical practice contains 30% ethanol. Ethanol as a pharmacologically active excipient ideally should be removed from neonatal formulations. The objective of this study was to determine the relative bioavailability of a novel ethanol-free -formulation (CHF6563) compared with the commonly used ethanolic solution in a phase I, open-label, 2-period, -single-dose, crossover study in healthy adults.

Methods: Eighteen adult opioid-naïve volunteers were administered one of the formulations in a randomized crossover treatment. After a 10-day washout period, subjects received the other formulation. Serial blood samples were drawn for pharmacokinetic analysis over 48 hours.

Results: The geometric mean ratio (90% CIs) of the ethanol-free buprenorphine solution AUC_0-last was 0.80 (0.65-0.99) and C_max was 0.81 (0.66-0.99) compared with reference ethanolic formulation. The -ethanol-free formulation had a greater degree of intersubject variability than the ethanol-containing -reference formulation (coefficient of variation of 59% vs 31.5%, respectively, for AUC_0-last).

Conclusions: In an adult population, a novel ethanol-free formulation of buprenorphine containing widely used excipients demonstrated a slight decrease in bioavailability when compared with an ethanolic solution. These results will inform those seeking to develop ethanol-free pediatric drug formulations.