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Crystalline Form of 1-{[(α-isobutanoyloxyethoxy)carbonyl]-aminomethyl}-1-cyclohexane acetic acid

IP.com Disclosure Number: IPCOM000188134D
Publication Date: 2009-Sep-23
Document File: 4 page(s) / 139K

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The IP.com Prior Art Database

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Crystalline Form of 1-{[(α-isobutanoyloxyethoxy)carbonyl]-aminomethyl}-1-cyclohexane acetic acid

1-{[(α-isobutanoyloxyethoxy)carbonyl]-aminomethyl}-1-cyclohexane acetic acid ("GBPE") is a transported prodrug of 1-(aminomethyl)cyclohexane acetic acid ("GBP") and is described according to the following formula:

C16H27NO6

M.W. 329.39


Provided is a crystalline form of GBPE characterized by data selected from the group consisting of: an X-Ray Powder Diffraction ("XRPD") pattern having peaks at about 7.1, 8.4, 9.0, 10.7 and
13.0 degrees two theta ± 0.2 degrees two theta; an XRPD pattern as substantially depicted in Figure 1; and a combination thereof. This crystalline form of GBPE can be further characterized by data selected from the group consisting of an XPRD pattern having peaks at about 11.4, 16.5,
17.8 and 19.5 degrees two theta ± 0.2 degrees two theta; a Differential Scanning Calorimetry ("DSC") thermogram having a peak at about 67°C to about 70°C; a DSC thermogram as depicted in Figure 2; and a combination thereof. This new crystalline form GBPE possesses a high crystallinity level, having sharp XPRD peaks and higher melting point than the prior art forms. The high crystallinity is advantageous in properties such as processability, flowability, and physical and chemical stability.

This crystalline form can be prepared by a process comprising: dissolving GBPE in solvent A to provide a solution; and adding an anti-solvent B to the solution to obtain a precipitate, wherein solvent A and anti-solvent B are described in the following Table 1. Preferably, the starting GBPE is GBPE form I. Preferably, the process is done while stirring. Preferably, the stirring is done for a period of time as described in Table 1. Preferably, the reaction is done at a specific temperature, as described in Table 1, found in the description of example 1 below. The precipitate is then isolated, preferably, by vacuum filtration.

An additional process for preparing this crystalline form of GBPE comprising slurrying GBPE Form I in dibutyl-ether. Preferably, the slurrying is for about 12 hours to about 24 hours, more preferably, for about 16 hours. Preferably, the slurrying is at about room temperature. The obtained crystalline form is further isolated. The isolation may be done by vacuum filtration. As used herein, the term "room temperature" or "RT" refers to a temperature of about 15°C to about 30°C, more preferably, refers to a temperature of about 25°C.

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The Powder X-ray diffraction analysis above was performed using a Philips X'Per...