Pharmacokinetics of a Calcium Sulfate-Based Extended-Release Buccal Buprenorphine Tablet

Background/Objectives: The prevalence of opioid dependence and abuse is increasing, and the development of novel formulations is essential. Existing extended-release formulations of buprenorphine, such as transdermal patches and subcutaneous injections are available in the market but may have limitations. Using bioceramic technology is a possible approach to provide inherent abuse-deterrent properties, in line with US FDA guidelines on abuse-deterrent formulation, by incorporating the opioid into a ceramic matrix to achieve sustained drug release. The aim of this study was to develop an extended-release formulation, evaluate it in a clinical trial in healthy subjects, and determine the pharmacokinetic profile of the drug, along with its safety and tolerability profile. Methods: A tablet containing 0.8 mg of buprenorphine was developed using calcium sulfate as the matrix (CaS tablet). An in vitro characterization was performed to confirm the controlled release profile of the drug. Thereafter, a single-dose clinical study was conducted including 12 healthy volunteers receiving the CaS tablet and naltrexone hydrochloride. The pharmacokinetic and safety profiles were assessed throughout. Results: The CaS tablet demonstrated an extended-release profile of up to seven hours. No clinically significant trends were observed in terms of safety and tolerability. However, the highest quantifiable plasma concentrations were observed approximately 6 h after administration, coinciding with the end of the dosing period. The quantifiable concentrations ranged from 0.10 to 0.14 ng/mL. Conclusions: In summary, this study suggested the possibility of utilizing bioceramic technology to develop a well-tolerated extended-release formulation using calcium sulfate as a carrier matrix. However, the limited pharmacokinetic data indicates the need for further investigation. Trial registration: ISRCTN12656966.