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Pharmacia & Upjohn Inc. has discovered a superior bovine growth hormone releasing factor analog, [IIe2,Ser8,28,Ala15,Leu27,Hse30] bGRF (1-30)-NH-ethyl, acetate salt (U-90699F), for enhancement of animal growth. This report delineates the preparation, characterization, and 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 monomers were incorporated into Miglyol oil with acceptable injectability. Both reversed-phase-high-pressure liquid chromatography (RP-HPLC) and Fourier transform infrared spectroscopy (FTIR) were utilized to evaluate its chemical and structural stability. This suspension formulation demonstrated no significant changes in concentration as determined by RP-HPLC for 10 weeks at both 25 and 39 degrees C. The U-90699F dispersed in oil also showed no signs of structural conversion from alpha-helix to beta-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 determine the duration of action. It was found that the suspension was able to effectively elevate serum somatotropin for at least 14 days.

The powder characteristics of bovine somatotropin and casein spray-dried from laboratory, pilot and production spray-dryers were investigated. The powder characteristics examined included particle size distribution and morphology; bulk density; and flowability as measured by angle of repose, compressibility index and shear cell indices. Morphology classification showed internal voidage, blowholes, expanded, smooth and folding for somatotropin and casein spray-dried from the various spray-dryers. Particle size distributions of the bovine somatotropin and casein were unimodal and skewed. As the drying-chamber size of the spray-dryer increased, the particle sizes of both somatotropin and casein increased from mean volume diameters of 6-8 μ using the laboratory and pilot spray-dryers to 13-24 μ when using the production size spray-dryers. Spray-dried bovine somatotropin and casein had bulk densities of 0.090 to 0.195 g/cm3. Three flowability tests showed casein and somatotropin spray-dried from the di...

Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 microns were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 micrograms of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fisher's paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 micrograms OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freund's adjuvant.

Approximately zero-order release of ephedrine hydrochloride and procaine hydrochloride was obtained from multiple-layered matrixes of hydrogenated castor oil containing various concentrations of the medicinal compound in each layer. For the examples presented, an apparent zero-order release was observed for the release of 50–90% of the medicinal compound.