Preformulation for tabletting natural mixtures of conjugated estrogens

A pharmaceutical preformulation in the form of a tabletable, solid, free-flowing, dry extract;

• (a) wherein said solid extract contains a uniform amount of a mixture of natural conjugated equine estrogens per amount of support material, defined relative to the main hormone constituents;
• (b) wherein the uniform active-substance content is applied by spraying an aqueous solution consisting essentially of an extract of said mixture of natural conjugated equine estrogens from pregnant mares' urine 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 thereafter drying,
• (c) wherein said preformulation has the active-substance content including free estrogens and other solids calculated as dry matter relative to the amount of the pharmaceutical support material in the preformulation lying in the range from 0.25 to 0.70 gram of dry matter per gram of support material;
• (d) wherein said preformulation has the active-substance content calculated as the ratio of said mixture of natural equine conjugated estrogens relative to the amount of the pharmaceutical support material lying in the range from 35 to 100 mg of conjugated estrogens per gram of support material;
• (e) wherein said preformulation contains conjugated estrogens in the following proportions:
• 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;
• (f) wherein in said preformulation the proportion of free hormones relative to the total hormone content in the active substance is less than 5% by weight;
• and
• (g) wherein the preformulation has 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.