Abstract
For the purpose of replacement therapy using progesterone, the mixed suppository consisting of Witepsol and ethylene-vinyl acetate copolymer (EVA) was investigated using a computer optimization technique. Witepsol-W35, EVA40Y and EVA250 were employed as the suppository base. Nine formulations were prepared according to a composite experimental designfor two factors; the rate of Witepsol-W35 (X1) and the rate of EVA250 in the EVA phase (X2). Characteristics such as the penetration (Y1), the strength (Y2), DSC peak temperature (Y3), heat of fusion (Y4), the amount dissolved (ADT, Y5) and mean dissolution time (MDT, Y6) were measured. As absorption parameters of progesterone, AUC (Y7) and MRT (Y8) were estimated after vaginal administration of suppositories in rabbits.
After application of multiple regression analysis for each of the characteristics, optimum regression equations were obtained. The best formulation to maximize AUC was sought under the restriction of experimental region. Experimental results obtained for the optimum formulation agreed well with the predictions.
When the mixed suppository which contained 100mg progesterone was administered to voluntary patients, the efficient blood level was maintained for 24 hours.
These results suggested that the progesterone-mixed suppository was quite useful for the treatment of the luteal phase defect.
