Parenteral sustained-release dosage forms of butorphanol for dogs

The objective of this study is to develop a sustained-release parenteral dosage form of butorphanol which can provide an analgesic effect over a 24-h period after subcutaneous administration. Four experimental 24-h butorphanol depot injections, two aqueous suspensions of butorphanol free base (5 and 10 mg/ml), and two oil suspensions of the tartrate salt (10 and 20 mg/ml) have been developed and evaluated in dogs. Each of the formulations was evaluated in a group of three animals; each dog received a 2 mg/kg subcutaneous dose of the depot injection. Butorphanol concentrations in plasma were monitored using HPLC for 72 h after dosing. The drug-plasma concentrations from the experimental depot injections were compared to those obtained from the reference solution injection Torbugesic-SA. It was found that butorphanol absorption from the Torbugesic-SA was significantly faster than that from the aqueous and oil suspensions. Also, the drug-plasma concentration was maintained within the desired therapeutic blood level (5-100 ng/ml) over a 24-h period for all four experimental butorphanol depot injections. Furthermore, the potential side effects of these experimental formulations are expected to be less because of the relatively lower peak concentrations (C-max) as compared to that of the solution injection Torbugesic-SA. (C) 1999 Elsevier Science B.V. All rights reserved.