Preformulation for Tabletting Natural Mixtures of Conjugated Estrogens

A method of producing a pharmaceutical preformulation in the form of a uniform, tabletable, solid, free-flowing, dry pharmaceutical extract, said method comprising:

• spraying an aqueous solution consisting essentially of an extract of a mixture of natural conjugated equine estrogens from pregnant mares' urine containing conjugated estrogens in the following proportions relative to total estrogen content:
• 52.5 to 61.5% estrone;
• 22.5 to 30.5% equilin;
• 13.5 to 19.5% 17-α-dihydroequilin;
• 2.5 to 9.5% estradiol, and
• 0.5 to 4.0% 17-β-dihydroequilin;
• onto a powdered or granular pharmaceutical support material consisting essentially of material selected from the group consisting of microcrystalline celluloses and mixtures of microcrystalline cellulose with lactose and having a mean particle size in the range from 50 to 130 μm,
• in an amount corresponding to an estrogen content including free estrogens and other solids calculated as dry matter relative to the amount of the pharmaceutical support material in the range from 0.25 to 0.70 gram of dry matter per gram of support material,
• in a fluidized bed so as to obtain particles containing a uniform amount of said mixture of conjugated estrogens per amount of support material;
• and
• drying the resulting particles to obtain estrogen-containing particles in which the ratio of said mixture of natural equine conjugated estrogens relative to the amount of the pharmaceutical support material lies in the range from 35 to 100 mg of conjugated estrogens per gram of support material, and the proportion of free hormones relative to the total hormone content is less than 5% by weight, and which have a particle-size distribution corresponding to the following sieve analysis:
• 100% by weight of the particles pass through a sieve mesh size of 500 μm;
• at least 98% by weight of the particles pass through a sieve mesh size of 250 μm;
• about 65 to 99.5% by weight of the particles pass through a sieve mesh size of 160 μm;
• about 35 to 87% by weight of the particles pass through a sieve mesh size of 125 μm;
• and
• fines of less than 23% by weight passing through a sieve mesh size of 63 μm.