Stability Study of a Compounded Sublingual Buprenorphine Solution for Neonatal Opioid Withdrawal Syndrome.

Abstract

Objective: Sublingual (SL) buprenorphine is a cornerstone of care in the treatment of adult opioid use disorder. Recent studies have demonstrated its advantages in the management of neonatal opioid withdrawal syndrome (NOWS). Commercially available SL tablets and transdermal patches are not amenable to neonatal use, and published compounding formulas of SL solutions contained undesirable excipients, including ethanol, sugars, and preservatives. The objective of this research is to explore the stability of a novel SL buprenorphine formulation free of alcohol, sugars, and preservatives.

Methods: A 0.075 mg/mL buprenorphine solution was prepared by diluting the commercial injectable solution with normal saline and packaged into polyethylene terephthalate amber prescription bottles and polypropylene amber oral syringes and stored in refrigeration. Quality assessments were conducted by visual, pH, and high-performance liquid chromatography (HPLC) analysis immediately after preparation, and at 7 and 14 days of storage.

Results: There were neither visual nor pH changes detected through 14 days. HPLC analysis indicated that all samples retained >99% initial buprenorphine concentration. Drug concentration increased slightly in the oral syringe after day 7, probably due to moisture loss. No degradation peaks were observed in chromatograms.

Conclusions: This novel buprenorphine is free of alcohol, sugar, and preservatives, and it may offer a significant safety advantage for NOWS patients. Additional clinical studies are recommended to verify the bioavailability and efficacy of this formulation.