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Solid state forms of (N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)methanesulfonamide hydrochloride

IP.com Disclosure Number: IPCOM000193200D
Publication Date: 2010-Feb-14
Document File: 6 page(s) / 154K

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The IP.com Prior Art Database

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         Solid state forms of (N-(2-butyl-3-(4-(3- (dibutylamino)propoxy)benzoyl)benzofuran-5-yl)methanesulfonamide hydrochloride

    N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)benzofuran-5-yl)methanesulfonamide hydrochloride (referred to as DRD HCl) of the following structure:

DRD HCl

is a potassium channel antagonist marketed for the treatment of atrial fibrillation and atrial flutter.

Solid state forms were found and are described below.

Amorphous DRD hydrochloride:

The amorphous form of DRD HCl is characterized by a PXRD pattern as depicted in Figure
1.

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Fig. 1 shows a PXRD pattern of amorphous DRD HCl:

ntensity (counts)

I225

100

25

0

5 10 15 20 25 30 35

2Theta (°)

Crystalline DRD HCl:

    The crystalline DRD HCl form is characterized by data selected from a group consisting of: a powder XRD pattern having peaks at about 7.7, 8.1, 13.9, 15.8, 21.5, 23.4, 26.2, 26.9 0.2 degrees 2-theta; a powder XRD pattern as depicted in figure 2; and any combination thereof.

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Fig. 2 shows a PXRD pattern of crystalline DRD HCl:

    The above crystalline form can be further characterized by a DSC thermogram as depicted in figure 3; and a combination thereof.

Figure 3 shows a DSC thermogram of crystalline DRD Hydrochloride:

145.57°C

Comment: hermeti ka s rupicom

Instrument: DSC Q1000 V9.8 Build 296

3.0

2.5

2.0

Heat Flow (W/g)

1.5

1.0

0.5

139.50°C
86.91J/g

0.0

0 50 100 150 200 250 300 350

Temperature (°C)

Exo Down Universal V4.2E TA Instruments

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Examples:

Experimental

PXRD - amorphous DRD HCl

    Analysis (XRPD) of DRD was measured with a Philips X'Pert PRO powder diffractometer with the following parameters:

Sample holder preparation Sample is applied directly on silicon

PW1817/32 "zero background" holder

Instrument Philips X'Pert PRO

Goniometer PW3050/60

Generator PW3040; 45 kV, 40 mA

X-Ray tube PW3373/00; Cu anode LFF

X-ray radiation (CuK 1) = 1.540598 Å Temperature 295±5K

PXRD - Crystalline DRD HCl

    Analysis (XRPD) of DRD was measured with a Philips X'Pert PRO powder diffractometer with the above described parameters.

The described peak positions were determined by using a silicon powder as an internal standard in an admixture with the sample measured. The position of the silicon(Si) peak was corrected to silicone theoretical peak: 28.45 degrees two theta, and the positions of the measured peaks were corrected respectively. No correction was performed on the presented diffractograms in the figure.

Differential scanning calorimetry (DSC)

Analysis of DRD HCl from I was measured using a TA Q 1000 DSC, scanning from 20 oC to

350 oC at a scan rate of 10 oC/minute with nitrogen flow 40 mL/min. A sample was placed in a standard aluminium pan and the reference pan was prepared the same.

Example 1: Preparation of DRD base according to IPCOM000190391D

    Step a: preparation of (5-amino-2-butylbenzofuran-3-yl)(4-(3- (dibutylamino)propoxy)phenyl)methanone:

    A 10% water solution of sodi...