Sustained-release hormonal preparations XV: Release of progesterone from cholesterol pellets in vivo

✍ Scribed by A. A. Joseph; J. L. Hill; J. Patel; S. Patel; Fred A. Kincl

• Publisher: John Wiley and Sons
• Year: 1977
• Tongue: English
• Weight: 536 KB
• Volume: 66
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600660408

✦ Synopsis

Progesterone-sterol pellets were made that porvided a zero-order release of progesterone for 80 days. 4-(14)C-Progesterone was used to measure the release in vitro and in vivo. The dissolution rate in vitro (distilled water as the desorbing medium) for progesterone-cholesterol (59:41 w/w) and the progesterone-beta-sitosterol (47:53 w/w) pellets was 72 microng/100 mm2/24 hr. The average in vivo absorption from subcutaneously implanted pellets in rabbits was 2 +/- 0.1 microng/ml of plasma/cm2 of surface area. Of this amount, 20-25% was progesterone; the remainder was progesterone metabolites and conjugates. Zero-order release (plasma levels) was obtained for approximately 80 days or until about 70% of the available progesterone was exhausted. During this time, the level of excreted radioactivity in urine continuously decreased, indicating that monitoring only this parameter would lead to erroneous conclusions. A long-term effect and increased effectiveness were obtained with a 5-20-mg progesterone equivalent dose, using gel prepared from 2% methylcellulose as the suspending medium.