Progesterone Intrauterine Contraceptive System
»Progesterone Intrauterine Contraceptive System contains not less than 90.0percent and not more than 110.0percent of the labeled amount of C21H30O2.It is sterile.
Packaging and storage— Preserve in sealed,single-unit containers.
Identification— Cut off and discard the sealed ends of the drug-containing cores of 2Systems,and force the contents of the tubes into a small centrifuge tube.Add 3mLof methanol,insert the stopper in the tube,mix,centrifuge,and transfer the clear,supernatant to a small beaker.Evaporate the methanol to dryness,wash the residue with two 4-mLportions of cyclohexane,and discard the washings.Dry the residue in vacuum at 50to constant weight:the IRabsorption spectrum of a mineral oil dispersion of the dried residue so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Progesterone RS.
Sterility á71ñ: meets the requirements.
Uniformity of dosage units á905ñ: meets the requirements.
Chromatographic purity—
Test preparation— Remove the drug-containing core from 1System,as directed in the Assay,transferring it to a small flask with 25mLof methanol.Shake vigorously for several minutes,and allow the insoluble portion to settle.The resulting supernatant is the Test preparation.
Procedure— Divide a 20-×20-cm thin-layer chromatographic plate,coated with a 0.25-mm layer of chromatographic silica gel mixture,into sections 2cm apart.In successive sections of the plate,on a line 2cm from the lower edge of the plate and parallel to it,apply 1µL,2µL,3µL,and 100µLof the Test preparation.Develop the plate in a suitable pre-equilibrated chromatographic chamber with a solvent system consisting of a mixture of chloroform and ethyl acetate (2:1)until the solvent front has moved 10cm above the point of application of the spots.Remove the plate,and allow to air-dry.Observe the dried plate under short-wavelength UVlight (254nm).If spots other than the principal spot are observed in the lane of the 100-µLspecimen,estimate the concentration of each by comparison with the 1-µL(1%),2-µL(2%),and 3-µL(3%)spots.The requirement is met if the sum of impurities in the 100-µLspecimen does not exceed 3%.
Drug release pattern— Remove the attached sutures from 10Systems,and secure each system to a corrosion-resistant wire of sufficient length such that the systems are completely immersed during the shaking operation but do not touch the bottoms of the flasks.Suspend each system by the attached wire from the arm of a mechanical shaker designed to travel 2.5cm in each direction in a vertically reciprocating cycle,at a speed of 2.5cycles per second,so that each system is immersed in a separate 250-mLvolumetric flask containing 230mLof water,pre-equilibrated to 60±0.1.Immerse the volumetric flasks in an insulated constant-temperature water bath,maintained at 60±0.1and having a suitable means of maintaining the water level,so that the water level of the bath is above the water level in the flasks.Employ a rack or other suitable means of support for the flasks in the water bath.
Operate the shaker under the conditions described above for 23.5hours,then remove the flasks and the systems from the bath.Remove the systems from the flasks,and immerse each system in a different flask containing 230mLof water,pre-equilibrated to 60±0.1,and immerse these flasks in the water bath.Repeat this shaking operation daily for 12days,using different flasks each day.
Determine the quantity of progesterone in the solutions from each of the twelve days of testing as follows.Immediately add 15mLof methanol to each solution,allow to cool to room temperature,dilute with water to volume,and mix.Concomitantly determine the UVabsorbances of each test solution and of a solution of USP Progesterone RSin the same medium,having a known concentration of about 7µg per mL,in 2-cm cells at the wavelength of maximum absorbance at about 248nm,with a suitable spectrophotometer,against a blank of water and methanol (47:3).Calculate the progesterone release rate,in mg per day,in the solutions taken by the formula:
(AU/AS)(24/23.5)0.25C,
in which AUand ASare the absorbances of the test solution and the Standard solution,respectively,and Cis the concentration,in µg per mL,of USP Progesterone RSin the Standard solution.For the time points specified,the drug-release pattern conforms to Acceptance Table 4under Drug Release á724ñ.
Day Release Rate
(mg per day)
6
9
12		 1.05-1.45
0.95-1.35
0.90-1.30
Assay— Cut off the lower sealed end of the drug-containing core of a number of Progesterone Intrauterine Contraceptive Systems,sufficient to provide about 400mg of progesterone,forcing the viscous liquid core into a 1000-mLvolumetric flask.Cut the core sections in half lengthwise,using a sharp blade,taking precautions not to contaminate either the core material or the outside of the membranes.Transfer all of these sections of the systems to the flask containing the core material.Add about 500mLof methanol to the flask,shake vigorously for 5to 10minutes,dilute with methanol to volume,and centrifuge a portion of the solution.Dilute 10.0mLof the clear,supernatant with methanol to 250mL,and mix.Concomitantly determine the absorbances of this solution and of a Standard solution of USP Progesterone RS,previously dried and accurately weighed,in methanol having a known concentration of about 16µg of progesterone per mL,in 1-cm cells at the wavelength of maximum absorbance at about 241nm,with a suitable spectrophotometer,using methanol as the blank.Calculate the quantity,in mg,of C21H30O2in each System taken by the formula:
25(C/N)(AU/AS),
which Cis the concentration,in µg per mL,of USP Progesterone RSin the Standard solution,Nis the number of Systems taken,and AUand ASare the absorbances of the test solution and the Standard solution,respectively.
Auxiliary Information— Staff Liaison:Clydewyn M.Anthony,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28–NF23Page 1636
Phone Number:1-301-816-8139