RESUMEN
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.
Asunto(s)
Hormona Liberadora de Hormona del Crecimiento/administración & dosificación , Hormona Liberadora de Hormona del Crecimiento/química , Hipotálamo/efectos de los fármacos , Animales , Bovinos , Cromatografía Líquida de Alta Presión , Portadores de Fármacos , Estabilidad de Medicamentos , Hormona del Crecimiento/metabolismo , Hipotálamo/metabolismo , Masculino , Espectroscopía Infrarroja por Transformada de Fourier , SuspensionesRESUMEN
The release from matrixes compressed from melts of hydrogenated castor oil and ephedrine hydrochloride or procaine hydrochloride has been studied and is compared with the release from matrixes prepared by compression of physical mixtures. In both, the release is dependent on the square root of time; however, the release is slower from the matrix prepared by the melt process. Parameters that affect the release are compared. The independence of release from stirring speed and the greater tortuosity of the matrix prepared by the melt process indicate that the release is by a matrix diffusion mechanism. In contrast, boundary layer diffusion is operative in the release from the matrixes prepared by compression of physical mixtures. It is demonstrated that for a given formulation, the method of processing may alter the mechanism and rate of release.
Asunto(s)
Aceite de Ricino/química , Efedrina/química , Química Farmacéutica , Difusión , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Procaína/química , SolubilidadRESUMEN
The release from a matrix compressed from a physical mixture of hydrogenated castor oil and ephedrine hydrochloride or procaine hydrochloride has been investigated. The effects on release of the concentration of medicinal compound, particle size of medicinal compound, agitation of dissolution medium, and porosity and tortuosity of the matrix are presented. An attempt is made to fit the experimental data to an acceptable diffusion model.