|Inventors||Oliver Krebs, Stephane Dubuis|
|Original Assignee||Intervet International B.V.|
Methods for making zilpaterol are known in the art. For example, in U.S. Pat. No. 4,585,770, Fréchet et al. describe compounds encompassed by a genus characterized as 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-jk]-benzazepin-2[1H]-one derivatives and pharmaceutically acceptable acid addition salts thereof. The derivatives correspond in structure to the following formula:
Example 7 First Illustration of a Contemplated Suitable Dosage FormA tablet is prepared containing 2.5 or 5 mg of the HCl salt of Example 6, and sufficient excipient of lactose, wheat starch, treated starch, rice starch, talc, and magnesium stearate for a final weight of 100 mg.
Example 8 Second Illustration of a Contemplated Suitable Dosage FormGranules are prepared containing 12.5 or 25 of the HCl salt of Example 6 in each daily dose of granules.
Example 9 Third Illustration of a Contemplated Suitable Dosage FormThe HCl salt of Example 6 is crystallized using the methodology discussed U.S. Pat. No. 5,731,028 for making crystalline racemic trans zilpaterol. Less than 5% of the crystals have a size of less than 15 μm, and at least 95% of the crystals have a size of less than 250 μm. A premix of the crystalline HCl salt secured to a 300-800 μm corn cob support is then obtained using the methodology discussed in European Patent 0197188 (incorporated by reference into this patent). The concentration of the HCl salt in the premix is 3% (by weight).
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