Buprenorphine in a novel lyophilised instant-melt formulation: Testing safety and pharmacokinetics

First published: 10/05/2019 | Last updated: May 20th, 2019

Aims: To test safety and efficacy of a new freeze-dried, rapidly-dispersing solid formulation (Zydis-bup) compared to standard sublingual buprenorphine (Sub-bup).

Design: Open-label, two-arm randomised (2:1) to Zydis-bup or Sub-bup.   Participants received the randomised treatment for the first 14 days then all were switched to standard Sub-bup for a further 14 days; providing within-subject cross-over for 2/3.   11 subjects also participated in supplementary pharmacokinetic study.

Setting: Specialized clinical trials facility and specialized outpatient addictions treatment facility on same campus.

Participants: 36 male and female opioid dependent patients aged >;18 – <;60 years.

Intervention: Daily dose of standard Sub-bup or novel lyophilised instant-melt Zyd-bup.

Measurements: Retention in treatment; opiate withdrawal; medication hold and dose adequacy; tablet disintegration time; respiratory function; plasma buprenorphine and norbuprenorphine.

Findings: Zydis-bup disintegrated more rapidly than Sub-bup: within 2 minutes in 58% (versus 5% for Sub-bup; p&lt;0.001). Individual tailoring of doses resulted in similar dosing regimens (mean maintenance daily doses of 10.8mg and 9.6mg respectively). No significant between-group differences were detected in retention in treatment, opiate withdrawal phenomena, craving, adequacy of ‘hold’ and measures of respiratory function. No SAEs occurred. PK demonstrated substantial supra-availability of buprenorphine with Zydis-bup although levels of norbuprenorphine were comparable.

Conclusions: Zydis-bup disintegrated more rapidly than Sub-bup, while clinically appearing comparable, but with significant supra-availability. The more rapid disintegration may provide a useful clinical solution to prolonged supervision and risks of diversion, with positive implications for individuals.

Co-Authors

Karolina Bogdanowicz b, James Bell a,b, Rob VanderWaal a, Jenny Keen a,b, Pete Beavan a, Shelagh Baillie c, Alastair Knight d, John Strang a,b a King’s College London, National Addiction Centre (Institute of Psychiatry, Psychology and Neuroscience), Denmark Hill, London SE5 8BB, UK; b Addictions Services, South London & Maudsley NHS Foundation Trust, London; c Martindale Pharma, Buckinghamshire, UK; d Evicom, Twickenham, UK.


Conflicts of interest:

The work was sponsored by Macarthys Laboratories Limited (trading as Martindale Pharma), UK.

EudraCT Number: 2012-003560-49; Sponsor’s Protocol Code Number: MD2012/01XP

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Dr Kylie Reed