An Ultra-Long-Acting Buprenorphine Prodrug Ion-Pair for Opioid Use Disorder

Abstract Opioid overdose is a significant global public health concern. While buprenorphine (BUP) is a safe and effective treatment for opioid use disorder (OUD), requirements for frequent dosing and patient tolerability to organic solvent based monthly injectables limit its use. These challenges were overcome by the development of a scalable ultra-long-acting (ULA) BUP (NM6BUP-Pamoate). The binding of a lipophilic BUP prodrug to a hydrophobic counterion generated an organic-solvent-free formulation. A single dose of NM6BUP-Pamoate administered to Sprague–Dawley rats at 45 mg/kg produced sustained effective plasma BUP levels for six months. Brain BUP concentrations exceeded the recorded plasma levels. Safety evaluations demonstrated the absence of off-target toxicities, with local and systemic tolerability. NM6BUP-Pamoate simplifies OUD treatment to optimize clinical outcomes.