In vitro and in vivo release of dinalbuphine sebacate extended release formulation: Effect of the oil ratio on drug release.

Nalbuphine is a semi-synthetic opioid indicated for the relief of moderate to severe pain. Dinalbuphine sebacate (DNS) is a prodrug of nalbuphine for which we have developed long-acting lipophilic formulations in a benzyl benzoate/sesame oil mixture for intramuscular (IM) injection. In this study, we found that the in vitro release profile of DNS could be affected by adjusting the weight ratio of benzyl benzoate to sesame oil (the solvent/oil ratio). A longer release period could be attained by increasing the solvent/oil ratio in the formulation. A pharmacokinetic study was conducted in beagle dogs to verify the relationship between the in vitro release and the drug release from the formulations in vivo. The pharmacokinetic study confirmed that the formulation with a higher benzyl benzoate to oil ratio exhibits a longer drug release profile with a lower maximum concentration (Cmax) and a longer time to peak blood concentration level (Tmax) than the formulation with a lower benzyl benzoate to oil ratio.