Progesterone Vaginal Suppositories
» Progesterone Vaginal Suppositories contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of progesterone (C21H30O2).
suppositories compounded in fatty acid base
Prepare Progesterone Vaginal Suppositories in fatty acid base as follows (see Pharmaceutical Compounding—Nonsterile Preparations 795):
Progesterone (micronized) 25 mg to 600 mg
Fatty acid base, a sufficient quantity to make one suppository  
Calibrate the actual molds with the fatty acid base that is used for preparing the suppositories, and adjust the formula accordingly. Heat the fatty acid base slowly and evenly until melted. Slowly add the Progesterone powder to the melted base, with stirring. Mix thoroughly, and pour into molds. Cool in a refrigerator until solidified, trim, and wrap.
Packaging and storage— Preserve in well-closed, light-resistant containers. Store in a refrigerator.
Labeling— Label Suppositories to state that they are Progesterone Vaginal Suppositories in a Fatty Acid Base and to state the content, in mg, of progesterone per suppository. Label Suppositories to state that they are to be stored in a refrigerator (2 to 8). Label them to state that they are to be used only as directed, and that wrappers are to be removed prior to use.
USP Reference standards 11
USP Methyltestosterone RS Click to View Structure
USP Progesterone RS Click to View Structure
Uniformity of dosage units 905: meet the requirements for Weight Variation.
Beyond-use date— Ninety days after the day on which they were compounded.
Assay for suppositories compounded in fatty acid base—
Alcohol mixture— Prepare a mixture of dehydrated alcohol, isopropyl alcohol, and methanol (90:5:5).
Mobile phase— Prepare a filtered and degassed mixture of Alcohol mixture and water (55:45). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluted alcohol mixture— Prepare a mixture of Alcohol mixture and water (7:3).
Resolution solution— Dissolve an accurately weighed quantity of USP Methyltestosterone RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.4 mg per mL. Separately and similarly prepare a solution in Mobile phase having a known concentration of about 0.4 mg of USP Progesterone RS per mL. Transfer 2.0 mL of each solution to a 10-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Standard preparation 1— Dissolve an accurately weighed quantity of USP Progesterone RS in n-propyl alcohol, and dilute quantitatively, and stepwise if necessary, with n-propyl alcohol to obtain a solution having a known concentration of about 0.25 mg per mL. Mix 5.0 mL of this solution with 10.0 mL of Diluted alcohol mixture.
Standard preparation 2— Dissolve an accurately weighed quantity of USP Progesterone RS in n-propyl alcohol, and dilute quantitatively, and stepwise if necessary, with n-propyl alcohol to obtain a solution having a known concentration of about 3 mg per mL. Transfer 3.0 mL of this solution to a 100-mL volumetric flask, dilute with Diluted alcohol mixture to volume, and mix.
Assay preparation 1— Transfer 1 Suppository, containing not more than 100 mg of progesterone, to a 100-mL volumetric flask, dissolve in about 90 mL of n-propyl alcohol, heat at 45 for 4 minutes, sonicate for 10 minutes, cool, dilute with n-propyl alcohol to volume, and mix. Dilute quantitatively, and stepwise if necessary, with n-propyl alcohol, sonicating if necessary, to obtain a solution containing about 0.25 mg of progesterone per mL. Transfer 5.0 mL of this solution to a 50-mL centrifuge tube, add 10.0 mL of Diluted alcohol mixture, mix, sonicate for 1 minute, and centrifuge for 10 minutes at 2000 rpm. Pass the supernatant through a filter having a 0.45-µm or finer porosity, discarding the first 4 mL of the filtrate.
Assay preparation 2— Transfer 1 Suppository, containing more than 100 mg of progesterone, to a 200-mL volumetric flask, dissolve in about 180 mL of n-propyl alcohol, heat at 45 for 8 minutes, sonicate for 5 minutes, cool, dilute with n-propyl alcohol to volume, and mix. Dilute quantitatively, with n-propyl alcohol, stepwise if necessary, sonicating each dilution for 1 minute, to obtain a solution containing about 0.09 mg of progesterone per mL. Transfer about 15 mL of this solution to a 50-mL centrifuge tube, and centrifuge for 10 minutes at 2000 rpm. Pass the supernatant through a filter having a 0.45-µm or finer porosity, discarding the first 4 mL of the filtrate.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 245-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The column temperature is maintained at 40. The flow rate is about 1.0 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for methyltestosterone and 1.0 for progesterone; the resolution, R, between methyltestosterone and progesterone is not less than 2.0; the tailing factor is not more than 2.0 for the progesterone peak; and the relative standard deviation for replicate injections is not more than 2.0% for progesterone.
Procedure— Separately inject equal volumes (about 10 µL) of Standard preparation 1 and Assay preparation 1, or of Standard preparation 2 and Assay preparation 2, into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of progesterone (C21H30O2) in the Suppository taken by the formula:
300CD(rU / rS)
in which C is the concentration, in mg per mL, of USP Progesterone RS in the Standard preparation; D is the dilution factor for obtaining the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
suppositories compounded in polyethylene glycol base
Prepare Progesterone Vaginal Suppositories in polyethylene glycol base as follows (see Pharmaceutical Compounding—Nonsterile Preparations 795):
Progesterone (micronized) 25 mg to 600 mg
Polyethylene glycol base, a sufficient quantity to make one suppository  
Calibrate the actual molds with polyethylene glycol base that is used for preparing the Suppositories, and adjust the formula accordingly. Heat the polyethylene glycol base slowly and evenly until melted. Slowly add the Progesterone powder to the melted base, with stirring. Mix thoroughly, and pour into molds. Cool, trim, and wrap.
Packaging and storage— Preserve in tight, light-resistant containers. Do not dispense or store polyethylene glycol–base suppositories in polystyrene containers. Store in a refrigerator.
Labeling— Label Suppositories to state that they are Progesterone Vaginal Suppositories in a Polyethylene Glycol Base and to state the content, in mg, of progesterone per suppository. Label Suppositories to state that they are to be stored in a refrigerator (2 to 8). Label them to state that they are to be used only as directed, that wrappers are to be removed prior to use, and that, if necessary, they may be moistened prior to insertion.
USP Reference standards 11
USP Methyltestosterone RS Click to View Structure
USP Progesterone RS Click to View Structure
Uniformity of dosage units 905: meet the requirements for Weight Variation.
Beyond-use date— Ninety days after the day on which they were compounded.
Assay for suppositories compounded in polyethylene glycol base—
Alcohol mixture, Mobile phase, Resolution solution, and Chromatographic system— Proceed as directed in the compliance Assay for suppositories compounded in fatty acid base.
Standard preparation— Dissolve an accurately weighed quantity of USP Progesterone RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase, to obtain a solution having a known concentration of about 0.1 mg per mL.
Assay preparation— Dissolve 1 Suppository in 200 mL of Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution containing about 0.1 mg of progesterone per mL. Pass a 10-mL portion of the mixture through a filter having a 0.45-µm or finer porosity, discarding the first 4 mL of the filtrate.
Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of progesterone (C21H30O2) in the Suppository taken by the formula:
200CD(rU / rS)
in which C is the concentration, in mg per mL, of USP Progesterone RS in the Standard preparation; D is the dilution factor for obtaining the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Jeanne H. Sun
Assistant Scientific Liaison
1-301-816-3361
(CMP2010) Compounding
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 4435
Pharmacopeial Forum: Volume No. 33(1) Page 82