[Preparation and physicochemical evaluation of progesterone suppository]

ABSTRACT

Progesterone, the most important progestin in humans, is indicated in several conditions. Progesterone suppresses menstruation and uterine contractility that is very important for the maintenance of pregnancy. After oral administration, it is almost completely metabolized in the first passage through the liver and its intramuscular injection causes local irritation and pain. Therefore rectal or vaginal suppositories of progesterone are used in the treatment of premenstrual syndrome, puerperal depression [Cyclogest [R], 200-800 mg/day] and luteal phase defects[25 mg/12h] in patients with infertility and sterility. The main objectives of this study were to prepare different formulations of progesterone suppository in hydrophilic and lipophilic bases and to select the suitable formulation based on drug release from the bases. Hydrophilic [PEGs], hydrophobic [Witepsol H[35]] bases and additive ingredients were used to manufacture the suppositories. The replacement factor was determined and suppositories were prepared by using the fusion method. In order to control the physicochemical characteristics, various parameters such as weight variation, liquefaction time [Krowczynski method] and content uniformity were determined. Dissolution testing was done by dialysis cell method in dissolution apparatus [Pharmatest, PTSW3-Germany]. The amount of drug released during dissolution test was determined by using UV spectrophotometer at 241 nm. Content uniformity, weight variation and liquefaction times of manufactured bases were acceptable according to official pharmacopoeia [BP and USP]. Releasing profiles in normal saline containing 0.1% Sodium Lauryl Sulfate showed that the rate of release from PEGs formulations is faster than Witepsol bases. PEGs and Witepsol bases could be successfully used to prepare progesterone suppositories. In vivo bioavailability of progesterone after rectal and vaginal administration and the clinical assessment of the selected formulations are future plans