Formulation of Buprenorphine for Sublingual Use in Neonates

Abstract

OBJECTIVES The only medication used sublingually in the neonate is buprenorphine for the treatment of neonatal abstinence syndrome (NAS). Compared with morphine, buprenorphine reduces the length of treatment and length of hospitalization in neonates treated for NAS. The objective of this study was to characterize the stability of ethanolic buprenorphine for sublingual administration. METHODS Buprenorphine solution was prepared and stored in amber glass source bottles at either 68°F to 77°F (20°C-25°C) or 36°F to 46°F (2.2°C-7.8°C). Samples were collected from each of these batches on days 0, 3, 7, 14, and 30. Additional samples were withdrawn at baseline from each batch and placed in oral dispensing syringes for 3 and 7 days. Buprenorphine concentration was assessed by liquid chromatography–electrospray ionization–tandem mass spectrometry. RESULTS Neither storage temperature (p=0.65) nor storage time (p=0.24) significantly affected buprenorphine concentrations. All of the mean concentrations, regardless of storage temperature, were above 95% of the labeled concentration, and the potency was maintained for samples stored either in the original amber glass source bottles or in oral syringes. CONCLUSIONS An ethanolic buprenorphine solution is stable at room temperature for 30 days.

Buprenorphine in Neonatal Abstinence Syndrome

“…This formulation is stable at room temperature for at least 30 days and at 7 days in polypropylene-dispensing syringes. 63 Additional advantages included microbiologic asepsis and simplicity of preparation in the context of a clinical trial. Ethanol does not decrease opioid withdrawal and is not expected to have provided any of the efficacy seen in NAS clinical trials.…”

Neonatal opioid withdrawal syndrome: a review of the science and a look toward the use of buprenorphine for affected infants

“…Morphine, methadone and buprenorphine are all available as generic formulations and differences in the costs between drug acquisition or local compounding are negligible. The usual buprenorphine preparation contains 30% ethanol and is stable for 30 days when stored at room temperature [ 42 ]. Ideally, pediatric formulations should be free of ethanol, but when an ethanol free solution is not avaliable the American Academy of Pediatrics recommends that the blood ethanol concentrations not exceed 250 mg/L.…”

Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments

“…16 On the other hand, buprenorphine used in NOWS trials contains a high amount of alcohol, with one reported formulation containing 30% of ethanol. 17 Although there is an increasing number of clinical trials on the comparative efficacy of treatment agents in NOWS, here, we also draw attention to the importance of optimizing the dosing regimen, which can be arguably equally important at identifying the optimal treatment agent. Oftentimes, variations in starting doses, escalation/weaning schemes, and use of adjunctive therapy and nonpharmacological therapy may limit the generalizability of comparative efficacy study results to broader patient populations.…”

“… 16 On the other hand, buprenorphine used in NOWS trials contains a high amount of alcohol, with one reported formulation containing 30% of ethanol. 17 …”

“…Preservative‐free methadone has been compounded for use in clinical trials 16 . On the other hand, buprenorphine used in NOWS trials contains a high amount of alcohol, with one reported formulation containing 30% of ethanol 17 …”