Pharmacokinetic and pharmaceutical properties of a novel buprenorphine/naloxone sublingual tablet for opioid substitution therapy versus conventional buprenorphine/naloxone sublingual tablet in healthy volunteers

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Purpose:A novel sublingual buprenorphine/naloxone rapidly-dissolving tablet (BNX-RDT) for opioid substitution therapy has been developed for improved bioavailability, rapid disintegration and improved taste masking. We compared the bioavailability and pharmaceutical properties of BNX-RDT with conventional buprenorphine/naloxone sublingual tablets (BNX).Methods:Fasting, open-label, randomized, single-dose, two-cohort crossover study in healthy volunteers under naltrexone block. Cohort 1 (high-dose, N = 64) received BNX-RDT 11.4/2.9 mg and BNX 16/4 mg. Cohort 2 (low-dose, N = 61) received BNX-RDT 2.9/0.71 mg and BNX 4/1 mg. Plasma samples were collected over 72 h. Relative systemic exposures of buprenorphine and naloxone were assessed using standard statistical models for bioequivalence analysis. Pharmaceutical assessments included dissolve time, taste and mouthfeel assessments, and overall preference.Results:BNX-RDT 11.4/2.9 mg provided equivalent buprenorphine and naloxone exposure to BNX 16/4 mg. BNX-RDT 2.9/0.71 mg provided ˜20% lower buprenorphine and 35% lower naloxone exposure compared with BNX 4/1 mg. The comparison of BNX-RDT 2.9/0.71 mg with BNX 4/1 mg did not fully meet equivalence criteria. BNX-RDT was associated with improved dose proportionality across strengths compared with BNX (post hoc analysis), resulting in lower exposure from BNX-RDT relative to BNX at the lower strength. Median perceived dissolve times were significantly shorter for BNX-RDT than BNX at high (8.5 versus 16.2 min) and low (7.6 versus 9.1 min) doses. Taste and mouthfeel were rated significantly more pleasant than BNX, with ˜78% of subjects preferring BNX-RDT.Conclusion:BNX-RDT provided improved buprenorphine absorption compared to a conventional sublingual tablet, with shorter dissolve times and improved taste and mouthfeel, resulting in a high preference for the novel formulation.Graphical abstract

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