title: Dissolution testing of norethindrone:ethinyl estradiol, norethindrone:mestranol, and norethindrone acetate:ethinyl estradiol combination tablets.
abstract: Dissolution of oral contraceptive combination products from six manufacturing firms was studied utilizing the rotating basket method at 100 rpm in 600 mL of 0.1 M HCl and 0.02% sodium lauryl sulfate (SLS). Most of the combination products of norethindrone (NE):ethinyl estradiol (EE) dissolved satisfactorily in water using the paddle method which was first proposed by U.S.P., whereas three of 18 tested products showed better dissolution in acidic aqueous medium containing SLS. Acidic medium with surfactant was also found to be suitable for combination products of norethindrone (NE):mestranol (ME) and norethindrone acetate (NEAc):ethinyl estradiol (EE). A modified U.S.P. assay procedure, a reversed-phase high-performance liquid chromatographic (HPLC) method with a mobile phase of acetonitrile and phosphate buffer, was used to analyze NE and EE concurrently. The NEAc and ME were analyzed separately in these combination products. The NEAc was found to hydrolyze to some extent (approximately 20% in 8 h) in acidic dissolution medium at room temperature, but less so at 4 degrees C. The NE was identified as the sole degradation product of NEAc hydrolysis and was also measured to account for the total amount of NEAc dissolved. A simple dissoluting testing method which utilizes a single dissolution medium was applicable for all oral contraceptive combination tablets surveyed.
authors.affiliation: Biopharmaceutics Research Branch, Food and Drug Administration, Washington, DC 20204.
authors.forename: H T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: G K
authors.initials: GK
authors.lastname: Shiu
authors.forename: W N
authors.initials: WN
authors.lastname: Worsley
authors.forename: J P
authors.initials: JP
authors.lastname: Skelly
mesh_terms: D000433:1-Propanol; D002851:Chromatography, High Pressure Liquid; D003278:Contraceptives, Oral, Hormonal / Q000032:analysis*; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000032:analysis*; D007202:Indicators and Reagents; D008656:Mestranol / Q000032:analysis*; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000032:analysis*; D000077563:Norethindrone Acetate; D012967:Sodium Dodecyl Sulfate; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
chemical_list: D003278:Contraceptives, Oral, Hormonal; D004338:Drug Combinations; D007202:Indicators and Reagents; D012967:Sodium Dodecyl Sulfate; D004997:Ethinyl Estradiol; D000433:1-Propanol; D000077563:Norethindrone Acetate; D008656:Mestranol; D009640:Norethindrone