PREPARATION, CHARACTERIZATION, AND IN-VIVO EVALUATION OF AN OIL SUSPENSION OF A BOVINE GROWTH-HORMONE RELEASING-FACTOR ANALOG

Pharmacia & Upjohn Inc. has discovered a superior bovine growth hormon e releasing factor analog, [Ile(2),Ser(8,28),Ala(15),Leu(27),Hse(30)] bGRF (1-30)-NH-ethyl, acetate salt (U-90699F), for enhancement of anim al growth. This report delineates the preparation, characterization, a nd in vivo evaluation of a U-90699F oil suspension. The oil suspension formulation was selected because of its simplicity, inexpensiveness, and ability to produce sustained U-90699F release. 40% U-90699F monome rs were incorporated into Miglyol oil with acceptable injectability. B oth reversed-phase-high-pressure liquid chromatography (RP-HPLC) and F ourier transform infrared spectroscopy (FTIR) were utilized to evaluat e its chemical and structural stability. This suspension formulation d emonstrated no significant changes in concentration as determined by R P-HPLC for 10 weeks at both 25 and 39 degrees C. The U-90699F disperse d in oil also showed no signs of structural conversion from a-helix to P-sheet as monitored by FTIR. However, there was an increase in alpha -helix/disordered coil structure after initial drug incorporation. The suspension was subcutaneously administered to Holstein steers. Areas under the serum somatotropin concentration curve were used to determin e the duration of action. It was found that the suspension was able to effectively elevate serum somatotropin for at least 14 days.