Development of a sustained release injectable suspension dosage form of buprenorphine.

摘要

A sustained release formulation of buprenorphine that is capable of maintaining analgesia in mice for 3 to 5 days following a single administration of a drug loaded formulation is highly desirable.; To develop a sustained release formulation, the following experiments were conducted and results of these experiments were reported in this investigation: (1) Determining the particle size distribution of buprenorphine free base powder; (2) Developing and validating the buprenorphine HPLC assay that was used for the in vitro studies; (3) Determining the solubility of buprenorphine free base in different plasticizers/solvents, vegetable oils and PBS pH7.4; (4) Determining the partition coefficient of buprenorphine base between PBS pH 7.4 and different vehicles; (5) Evaluating buprenorphine-vehicle compatibility; (6) Formulating buprenorphine suspension formulations; (7) stablishing an appropriate in vivo study method to screen the formulations; (8) Developing and validating the buprenorphine HPLC/MS/MS assay that was used for the in vivo study; (9) Investigating buprenorphine pharmacokinetics in mice following intravenous administration; (10) Evaluating in vivo drug release characteristics of buprenorphine formulations in mice.; In conclusion, sustained-release buprenorphine formulations were successfully developed and analgesic effect was maintained for at least 4 to 5 days (target period of time) in mice following a single subcutaneous injection of these formulations. Thus, the research conducted in this study provides the basis for the development of sustained release injectable parenteral formulation of buprenorphine that is capable of providing prolonged analgesia in mice. The formulation could also be potentially used for the treatment of pain in larger animals and opioid dependence in humans.