Crystalline micronisate, process for the manufacture thereof and use thereof for the preparation of a medicament
AssigneeBoehringer Ingelheim Pharma GmbH & Co. KG
InventorsHelmut Bender, Hagen Graebner, Konrad Schindler, Michael Trunk, Michael Walz
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Abstract
The invention relates to a crystalline micronisate of (1α,2β,4β,5α,7β)-7-[(hydroxydi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane-bromide, processes for preparing it and its use for preparing a pharmaceutical composition, particularly for preparing a pharmaceutical composition with an anticholinergic activity.
Claims18
1) Crystalline tiotropium bromide micronisate, characterised by a particle size X50 of between 1.0 μm and 3.5 μm at a Q(5.8) value of more than 60%, by a specific surface value in the range between 2 m2/g and 5 m2/g, by a specific heat of solution of more than 65 Ws/g and by a water content from about 1 % to about 4.5%.
6) A process for preparing crystalline tiotropium bromide micronisate which comprises the steps of:
- a) obtaining crystalline tiotropium bromide monohydrate, which crystalline tiotropium bromide monohydrate when thermally analysed by DSC has an endothermic maximum at 230±5° C. at a heating rate of 10K/min, has an IR spectrum which has bands inter alia at wavelengths 3570, 3410, 3105, 1730, 1260, 1035 and 720 cm−1 and which is characterised by a simple monoclinic cell with the following dimensions:
- a=18.0774 Å, b=11.9711 Å, c=9.9321 Å, β=102.691°, V=2096.96 Å3,
- b) micronizing the crystalline tiotropium bromide monohydrate so obtained and,
- c) exposing the resulting micronized crystalline tiotropium bromide at a temperature of about 15 to about 40° C. to water vapour with a relative humidity of at least about 40% for a period of at least about 6 hours.
Dependencies are inferred from the claim text.