Stability Study of Compounded Ethanol-Free Buprenorphine Oral Syringes for the Treatment of Neonatal Opioid...

Buprenorphine (BUP) is advantageous in the management of neonatal opioid withdrawal syndrome (NOWS). A widely used BUP formulation for the treatment of NOWS contains 30% ethanol. This study aimed to investigate the stability of BUP in compounded ethanol-free oral syringes.

A 75-mcg/mL BUP solution was prepared by diluting the commercial injectable solution with water for irrigation, transferred into amber oral syringes, and stored at either room temperature (n = 3) and refrigerated (n = 3) conditions. Microbial testing of the compounded oral syringes was performed to determine microbial growth for 24 and 48 hours at 37°C. The stability of BUP was assessed in the compounded syringes was conducted by pH and liquid chromatography-mass spectrometry (LC-MS) analysis after compounding and at 7, 30, and 60 days of storage.

The concentration of BUP at all time points was between 90% and 110% of the baseline on day 0. Concentration increased slightly in the oral syringes after day 30, likely due to moisture loss, as there were no degradation peaks observed in chromatograms. There was no microbial growth or visual change observed for the compounded ethanol-free BUP oral syringes. The pH of the oral syringes was consistent through 60 days for both room-temperature and refrigerated samples.

Buprenorphine in an ethanol-free formulation is stable and can be easily compounded in pediatric pharmacies. This formulation is appealing for the treatment of NOWS.