Lx. Yu et al., PREPARATION, CHARACTERIZATION, AND IN-VIVO EVALUATION OF AN OIL SUSPENSION OF A BOVINE GROWTH-HORMONE RELEASING-FACTOR ANALOG, Journal of pharmaceutical sciences, 85(4), 1996, pp. 396-401
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.