[Sustained release double-layered progesterone suppository for luteal support therapy].
A sustained release suppository containing progesterone with a double-layered structure was prepared for the treatment of the luteal phase defect. Hydroxypropylcellulose-H (HPC) and Carbopol-934P (CP) were used as bases of the inner layer and Witepsol W35 was used as a base of the outer layer. The strength of the inner layer (stick) decreased with the increase of the rate of content of HPC component. The strength of the stick which was prepared from a mixture of HPC and CP in a ratio of 1:1, was inverse by proportional to the rate of the addition of crystalline cellulose (CC) and the amount of released drug was proportional to the rate of the addition of CC. The area under the drug release curve of the stick containing 60% of CC in the base was about 12 times of the stick containing no CC (control stick). Furthermore, the mean release time of the stick containing 60% of CC became about a half of the control stick. It was suggested that the drug release of progesterone from the stick could be controlled by changing the rate of the addition of CC. Two types of suppository which containing progesterone in both phases (suppository A) and in the stick alone (suppository B) were prepared. Both suppositories showed a sustained release property and suppository B had a lag time of two hours. When the suppositories were administered in to the vagina of rabbits, they showed a sustained release property and a rapid rise in the serum concentration was more suppressed than an ordinary Witepsol suppository. One hour after the administration of the two layered suppository, some parts of the suppository was identified macroscopically to be remained in the vagina. The usefulness of the double-layered suppository as a hospital preparation should be suggested after the attainment of the optimization of the formulation.
Iwata
M
M
Department of Pharmacy, Yokohama City University Hospital, Kanagawa, Japan.
Takahashi
Y
Y
Shirotake
S
S
Yamamoto
T
T
Takayama
K
K
Machida
Y
Y
Hirahara
F
F
Minaguchi
K
K
Nagai
T
T
D000180:Acrylic Resins; D000277:Adjuvants, Pharmaceutic; D000282:Administration, Intravaginal; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives; D003692:Delayed-Action Preparations; D005260:Female; D007247:Infertility, Female / Q000188:drug therapy; D008183:Luteal Phase; D010570:Pessaries; D011145:Polyvinyls; D011374:Progesterone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D013997:Time Factors
D000180:Acrylic Resins; D000277:Adjuvants, Pharmaceutic; D003692:Delayed-Action Preparations; D011145:Polyvinyls; C006912:carboxypolymethylene; D011374:Progesterone; D002482:Cellulose; C008079:hydroxypropylcellulose