Parenteral sustained-release dosage forms of butorphanol for dogs

The objective of this study is to develop a sustained-release parenteral do sage form of butorphanol which can provide an analgesic effect over a 24-h period after subcutaneous administration. Four experimental 24-h butorphano l 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 eva luated in a group of three animals; each dog received a 2 mg/kg subcutaneou s dose of the depot injection. Butorphanol concentrations in plasma were mo nitored using HPLC for 72 h after dosing. The drug-plasma concentrations fr om the experimental depot injections were compared to those obtained from t he reference solution injection Torbugesic-SA. It was found that butorphano l absorption from the Torbugesic-SA was significantly faster than that from the aqueous and oil suspensions. Also, the drug-plasma concentration was m aintained within the desired therapeutic blood level (5-100 ng/ml) over a 2 4-h period for all four experimental butorphanol depot injections. Furtherm ore, the potential side effects of these experimental formulations are expe cted to be less because of the relatively lower peak concentrations (C-max) as compared to that of the solution injection Torbugesic-SA. (C) 1999 Else vier Science B.V. All rights reserved.