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PREPARATION OF MICRONIZED CRYSTALLINE 1α, 2β, 4β, 5α, 7β)-7-[(HYDROXYDI-2-THIENYLACETYL) OXY]-9, 9-DIMETHYL-3-OXA-9- AZONIATRICYCLO [3.3.1.0] NONANE BROMIDE.

IP.com Disclosure Number: IPCOM000238312D
Publication Date: 2014-Aug-17
Document File: 3 page(s) / 306K

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PREPARATION OF MICRONIZED CRYSTALLINE 1α, 2β, 4β, 5α, 7β)-7- [(HYDROXYDI-2-THIENYLACETYL) OXY]-9, 9-DIMETHYL-3-OXA-9-

AZONIATRICYCLO [3.3.1.0] NONANE BROMIDE.

    1α, 2β, 4β, 5α, 7β)-7-[(hydroxydi-2-thienylacetyl) oxy]-9, 9-dimethyl-3-oxa-9- azoniatricyclo[3.3.1.0]nonane bromide, referred to as 'Compound I', has the following structure:

    Described herein after, is a process for the preparation of micronized crystalline form of Compound I.

Micronized monohydrate form of Compound I, characterized by a particle size d(0.5) of between 1.0 µm and 3.5 µm; by a water content from about 1.5 to about 4.5%; and/or by a powder XRD Pattern as depicted on Figure 2 with peaks at about 12.0, 14.9, 15.7, 16.9, 17.5,
17.6, 18.8, 19.4, 20.3 and 23.7 ± 0.2 degrees 2-theta, was prepared by using micronized methanol solvate form of Compound I, characterized by a particle size d (0.9) of less than 20 µm and a powder XRD Pattern as depicted on Figure 1 with peaks at about 9.9, 11.0, 13.5,
13.7, 15.3, 15.5, 18.0, 19.8, 19.9, 20.5 and 21.5±0.2 degrees 2-theta, as a starting material. Crystalline methanol solvate form of Compound I can be prepared according to any suitable method known in the art, e.g. according to the procedure disclosed in example 3 of WO2006117300. Upon micronization, done e.g. by using jet mill technology and nitrogen as carrier gas, the material was exposed to water either in a closed chamber (under atmospheric pressure or static vacuum) with a relative humi...