Crystalline carbazole derivative and preparation method thereof

Abstract

Provided herein are crystalline carbazole derivatives, pharmaceutical compositions and methods of treatment thereof.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 382,608, filed on November 7, 2022, which is incorporated herein by reference in its entirety. Background Art

[0003] Fat-related conditions present numerous aesthetic and health-related problems. Despite recent progress, new treatments for fat-related conditions are still needed. Summary of the Invention

[0004] In one aspect, provided herein is anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A):

[0005]

[0006] The anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having:

[0007] (a) An X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0008] Changwei

[0009] (b) with Figure 8 substantially the same X-ray powder diffraction pattern as shown; or

[0010] (c) combinations thereof.

[0011] In one aspect, provided herein is a mixture of anhydrous crystalline forms of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A):

[0012]

[0013] In some embodiments, the mixture comprises anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 4.8±0.2° 2-θ, 22.3±0.2° 2-θ, 24.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the anhydrous crystalline form of Compound A is formed by a process comprising exposing Compound A to elevated temperature. In some embodiments, the anhydrous crystalline form of Compound A is formed by a process comprising drying Compound A to a lower water content.

[0014] In one aspect, provided herein is a method for preparing anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A), the method comprising reducing the water content of a sample of Compound A and maintaining the sample at low relative humidity. In some embodiments, reducing the water content comprises heating the sample of Compound A. In some embodiments, the low relative humidity is less than about 30%.

[0015] In one aspect, provided herein is a method for preparing Form 1 of crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A Form 1), the method comprising exposing a sample of Compound A to a moist environment. In some embodiments, the sample of Compound A is an unstable crystalline form. In some embodiments, the sample of Compound A is anhydrous.

[0016] Incorporation by reference

[0017] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The novel features of the present invention are particularly set forth in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by referring to the following detailed description of illustrative embodiments utilizing the principles of the invention and the accompanying drawings, in which:

[0019] Figure 1 Shown is an X-ray powder diffraction (XRPD) pattern of Form 1 of crystalline Compound A.

[0020] Figure 2 Shown is a differential scanning calorimetry (DSC) thermogram of Form 1 of crystalline Compound A.

[0021] Figure 3 Shown is a thermogravimetric analysis (TGA) graph of Form 1 of crystalline Compound A.

[0022] Figure 4 The X-ray powder diffraction (XRPD) pattern of crystalline Form 2 of Compound A is shown.

[0023] Figure 5Shown is a differential scanning calorimetry (DSC) thermogram of Form 2 of crystalline Compound A.

[0024] Figure 6 Shown is a thermogravimetric analysis (TGA) graph of Form 2 of crystalline Compound A.

[0025] Figure 7 Shown is an X-ray powder diffraction (XRPD) pattern of Form 3 of crystalline Compound A.

[0026] Figure 8 Shown is an X-ray powder diffraction (XRPD) pattern of Form 4 of crystalline Compound A. DETAILED DESCRIPTION

[0027] Although small molecule inhibitors are typically initially evaluated for their activity when dissolved in solution, solid-state characteristics (e.g., polymorphism) are also important. Polymorphic forms of drug substances can have different physical properties, including melting points, apparent solubility, dissolution rates, optical and mechanical properties, vapor pressure, and density. These properties can directly affect the ability to process or manufacture drug substances and drug products. In addition, the differences in these properties can and often lead to different pharmacokinetic characteristics of different polymorphic forms of drugs. Therefore, polymorphism is often an important factor in regulatory review of the "sameness" of drug products from different manufacturers. For example, polymorphism has been evaluated in many multi-million dollar or even multi-billion dollar drugs, such as warfarin sodium, famotidine, and ranitidine. Polymorphism can affect the quality, safety, and / or efficacy of drug products. Therefore, there is still a need for polymorphs of drug products. The present disclosure addresses this need and also provides related advantages.

[0028] Compound A

[0029] As used herein, Compound A refers to 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride, which has the chemical structure shown below:

[0030]

[0031] Compound A, 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride, has been prepared previously (see, WO 2013 / 072915 and US Pat. No. 9,447,040).

[0032] In some embodiments disclosed herein, Compound A is amorphous. In some embodiments disclosed herein, Compound A is crystalline.

[0033] I. Crystalline Form of Compound A

[0034] Compound A exhibits polymorphism, and the crystalline form of Compound A prepared according to the methods described herein can be characterized by any method known in the art. For example, crystalline Compound A is characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot stage microscopy, and other analytical methods (e.g., Raman spectroscopy, solid-state nuclear magnetic resonance (ssNMR) spectroscopy, and infrared (IR) spectroscopy). In some embodiments, the crystallinity of the solid form is determined by X-ray powder diffraction (XRPD).

[0035] XRPD: The crystalline form of Compound A according to the present invention can be characterized by XRPD, e.g. Figure 1 、 Figure 4 or Figure 7 As shown. The relative intensities of XRPD peaks can vary depending on particle size, sample preparation technique, sample installation procedure, and the specific instrument used. In addition, instrument variations and other factors can affect 2-θ values. Thus, XRPD peak assignments can vary, for example, by plus or minus about 0.2 degrees.

[0036] DSC: The crystalline form of Compound A according to the present invention can also be identified by its characteristic DSC thermogram, e.g. Figure 2 or Figure 5 As shown. For DSC, it is known that the observed temperature will depend on the rate of temperature change as well as the sample preparation technique and the specific instrument employed. Therefore, the values ​​reported herein relating to DSC thermograms may vary, for example, by plus or minus about 4°C.

[0037] TGA: The crystalline form of Compound A of the present invention may also give rise to thermal behavior that is different from that of the amorphous material or another polymorphic form. Thermal behavior can be measured in the laboratory by thermogravimetric analysis (TGA), which can be used to distinguish some polymorphic forms from other polymorphic forms. In one aspect, the crystalline form of Compound A can be characterized by thermogravimetric analysis. Crystalline Compound A can be identified by its characteristic TGA thermogram, e.g. Figure 3 or Figure 6 shown.

[0038] The crystalline form of Compound A can be used to prepare pharmaceutical preparations and can be obtained by a crystallization method. Semi-crystalline forms can also be obtained. In some embodiments, the semi-crystalline form of Compound A comprises one or more crystalline forms and / or amorphous Compound A as described herein. In some embodiments, amorphous forms are obtained using a solidification method. In various embodiments, crystallization is performed by generating the desired compound (e.g., Compound A) in a reaction mixture and separating the desired crystalline form from the reaction mixture, or by dissolving the crude compound in a solvent, optionally accompanied by heating, followed by cooling (including active cooling) and / or adding an anti-solvent to crystallize / solidify the product for a period of time to perform crystallization. After crystallization or solidification, drying can be performed under controlled conditions until the desired water content of the desired crystalline form is reached.

[0039] In various embodiments, the crystalline compound A disclosed herein is stable at room temperature. In some instances, the crystalline compound A is stable and can be stored at room temperature for a long time without chemical degradation or change in crystalline form. In some instances, the crystalline compound A is stable and can be stored at room temperature for a long time without significant chemical degradation or change in crystalline form. In some instances, the crystalline compound A is stable and can be stored at room temperature for a period of at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days. In some instances, the crystalline compound A is stable and can be stored at room temperature for a period of more than about 7 days. In some instances, the crystalline compound A is stable and can be stored at room temperature for a period of 10-20 days. In some instances, the crystalline compound A is stable and can be stored at room temperature for a period of 10-15 days. In some instances, the crystalline compound A is stable and can be stored at room temperature for a period of 15-20 days. In some instances, the crystalline compound A is stable and can be stored at room temperature for a period of 10-12 days. In some instances, the crystalline compound A is stable and can be stored at room temperature for a period of 12-14 days. In some instances, crystalline compound A is stable and can be stored at room temperature for a period of 14-16 days. In some instances, crystalline compound A is stable and can be stored at room temperature for a period of 16-18 days. In some instances, crystalline compound A is stable and can be stored at room temperature for a period of 18-20 days. In some instances, crystalline compound A is stable and can be stored at room temperature for a period of 1-2 days, 1-3 days, 1-4 days, 1-5 days, 1-6 days, 1-7 days, 2-3 days, 2-4 days, 2-5 days, 2-6 days, 2-7 days, 3-4 days, 3-5 days, 3-6 days, 3-7 days, 4-5 days, 4-6 days, 4-7 days, 5-6 days, 5-7 days or 6-7 days. In some instances, crystalline compound A can be stored at room temperature for a period of at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days. In some embodiments, crystalline Compound A is stable and can be stored at room temperature for a period of at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, or at least 12 months. In some embodiments, crystalline Compound A is stable and can be stored at room temperature for more than 1 year without chemical degradation or change in crystalline form. In some embodiments, crystalline Compound A is stable and can be stored at room temperature for more than 1 year without significant chemical degradation or change in crystalline form. In some embodiments, crystalline Compound A is stable and can be stored at room temperature for a period of at least 12 months, at least 14 months, at least 16 months, at least 18 months, at least 20 months, at least 22 months, or at least 24 months.In some embodiments, crystalline compound A is stable and can be stored at room temperature for 1 to 2 years without chemical degradation or change in crystalline form. In some embodiments, crystalline compound A is stable and can be stored at room temperature for 1 to 2 years without significant chemical degradation or change in crystalline form. In some embodiments, crystalline compound A is stable and can be stored at room temperature for more than 2 years. In some embodiments, crystalline compound A is stable and can be stored at room temperature for a period of at least 24 months, at least 30 months, or at least 36 months. In some embodiments, crystalline compound A is stable and can be stored at room temperature for 36 months. In some embodiments, crystalline compound A is stable and can be stored at room temperature for a period of 12-18 months, 14-20 months, 16-22 months, 18-24 months, 20-26 months, 22-38 months, or 24-40 months.

[0040] In various embodiments, crystalline compound A disclosed herein is stable at a temperature higher than room temperature and / or at high relative humidity (RH). In some instances, crystalline compound A is stable and can be stored for a long time at about 40 ° C, about 75% RH without chemical degradation or crystalline form changes. In some instances, crystalline compound A is stable and can be stored for a long time at about 40 ° C, about 75% RH without significant chemical degradation or crystalline form changes. In some instances, crystalline compound A is stable and can be stored for at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days at about 40 ° C and about 75% RH. In some instances, crystalline compound A is stable and can be stored for more than about 7 days at about 40 ° C and about 75% RH. In some examples, crystalline Compound A is stable and can be stored at about 40° C. and about 75% RH for a period of 1-2 days, 1-3 days, 1-4 days, 1-5 days, 1-6 days, 1-7 days, 2-3 days, 2-4 days, 2-5 days, 2-6 days, 2-7 days, 3-4 days, 3-5 days, 3-6 days, 3-7 days, 4-5 days, 4-6 days, 4-7 days, 5-6 days, 5-7 days, or 6-7 days. In some examples, crystalline Compound A is stable and can be stored at about 40° C. and about 75% RH for a period of at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0041] In various embodiments, the crystalline compound A disclosed herein is stable at high temperatures. In some instances, the crystalline compound A is stable and can be stored at about 80°C for a long period of time without chemical degradation or change in crystalline form. In some instances, the crystalline compound A is stable and can be stored at about 80°C for a long period of time without significant chemical degradation or change in crystalline form. In some instances, the crystalline compound A is stable and can be stored at about 80°C for a period of at least about 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days. In some instances, the crystalline compound A is stable and can be stored at about 80°C for a period of more than about 7 days. In some examples, crystalline Compound A can be stored at about 80° C. for a period of 1-2 days, 1-3 days, 1-4 days, 1-5 days, 1-6 days, 1-7 days, 2-3 days, 2-4 days, 2-5 days, 2-6 days, 2-7 days, 3-4 days, 3-5 days, 3-6 days, 3-7 days, 4-5 days, 4-6 days, 4-7 days, 5-6 days, 5-7 days, or 6-7 days. In some examples, crystalline Compound A is stable and can be stored at about 80° C. for a period of at least 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days.

[0042] Crystalline Compound A Form 1

[0043] Figure 1 Shown is an X-ray powder diffraction (XRPD) pattern of Form 1 of crystalline Compound A.

[0044] Figure 2 Shown is a differential scanning calorimetry (DSC) thermogram of Form 1 of crystalline Compound A.

[0045] Figure 3 Shown is a thermogravimetric analysis (TGA) graph of Form 1 of crystalline Compound A.

[0046] In one aspect, provided herein is crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A). Some embodiments provide compositions comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride. In some embodiments, crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride Form 1 (Compound A Form 1) is characterized as having:

[0047] (a) An X-ray powder diffraction pattern comprising peaks at 4.0±0.2° 2-θ, 16.5±0.2° 2-θ, and 15.5±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0048] (b) with Figure 1 The X-ray powder diffraction pattern shown is essentially the same as that of Cu

[0049] The wavelength of the X-rays is measured by Kα1 radiation.

[0050] (c) Differential Scanning Calorimetry (DSC) thermogram, including:

[0051] i) an endotherm in the range of about 260-270°C; and

[0052] ii) an endotherm in the range of about 175-195°C;

[0053] (d) Differential Scanning Calorimetry (DSC) thermogram, including:

[0054] i) an endotherm with an onset of about 265°C and a peak at about 266°C; and

[0055] ii) an endotherm with an onset of about 180°C and a peak at about 190°C;

[0056] (e) with Figure 2 substantially the same differential scanning calorimetry (DSC) thermograms as shown;

[0057] (f) with Figure 3 substantially the same thermogravimetric analysis (TGA) thermograms as shown;

[0058] (g) XRPD unchanged after storage at 40°C and 75% relative humidity (RH) for 7 days;

[0059] (h) XRPD unchanged after storage at 80°C for 7 days;

[0060] or

[0061] (i) combinations thereof.

[0062] In some embodiments, Form 1 of crystalline Compound A is characterized by Figure 1 shows substantially the same X-ray powder diffraction pattern as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0063] In some embodiments, Form 1 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 4.0±0.2° 2-θ, 16.5±0.2° 2-θ, and 15.5±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 1 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 4.0 ± 0.1° 2-θ, 16.5 ± 0.1° 2-θ, and 15.5 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 1 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at about 4.0° 2-θ, about 16.5° 2-θ, and about 15.5° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0064] In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A further comprises at least one selected from the group consisting of 24.1 ± 0.2° 2-θ, 26.0 ± 0.2° 2-θ, and The 2-theta peak, as measured using Cu Kα1 radiation, has an X-ray wavelength of 1.54060 In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A further comprises at least one selected from the group consisting of 24.1 ± 0.1° 2-θ, 26.0 ± 0.1° 2-θ, and The peak of θ, as measured using Cu Kα1 radiation, where the X-ray wavelength is 1.54060 In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A further comprises at least one peak selected from about 24.1° 2-θ, about 26.0° 2-θ, and about 26.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0065] In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A further comprises at least one peak selected from 19.9 ± 0.2° 2-θ, 23.8 ± 0.2° 2-θ, and 26.5 ± 0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A further comprises at least one peak selected from 19.9 ± 0.1° 2-θ, 23.8 ± 0.1° 2-θ, and 26.5 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A further comprises at least one peak selected from about 19.9° 2-θ, about 23.8° 2-θ, and about 26.5° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0066] In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least one peak selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least two peaks selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least three peaks selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least four peaks selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least five peaks selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least six peaks selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least seven peaks selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 1 of crystalline Compound A comprises at least eight peaks selected from 4.0±0.2°2-θ, 15.5±0.2°2-θ, 16.5±0.2°2-θ, 19.9±0.2°2-θ, 23.8±0.2°2-θ, 24.1±0.2°2-θ, 26.0±0.2°2-θ, 26.1±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 1 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 4.0±0.2° 2-θ, 15.5±0.2° 2-θ, 16.5±0.2° 2-θ, 19.9±0.2° 2-θ, 23.8±0.2° 2-θ, 24.1±0.2° 2-θ, 26.0±0.2° 2-θ, 26.1±0.2° 2-θ, and 26.5±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 1 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 4.0±0.1° 2-θ, 15.5±0.1° 2-θ, 16.5±0.1° 2-θ, 19.9±0.1° 2-θ, 23.8±0.1° 2-θ, 24.1±0.1° 2-θ, 26.0±0.1° 2-θ, 26.1±0.1° 2-θ, and 26.5±0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 1 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at about 4.0° 2-θ, about 15.5° 2-θ, about 16.5° 2-θ, about 19.9° 2-θ, about 23.8° 2-θ, about 24.1° 2-θ, about 26.0° 2-θ, about 26.1° 2-θ, and about 26.5° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0067] In some embodiments, Form 1 of crystalline Compound A is prepared by Figure 2 In some embodiments, Form 1 of crystalline Compound A is characterized by a differential scanning calorimetry (DSC) thermogram comprising: an endotherm in the range of about 260-270°C; and an endotherm in the range of about 175-195°C. In some embodiments, Form 1 of crystalline Compound A is characterized by a differential scanning calorimetry (DSC) thermogram comprising: an endotherm with an onset of about 265°C and a peak at about 266°C; and an endotherm with an onset of about 180°C and a peak at about 190°C.

[0068] In some embodiments, Form 1 of crystalline Compound A is characterized by an endotherm in the DSC thermogram within the range of about 260-270° C., e.g., about 260-270° C., 260-268° C., 260-266° C., 260-264° C., 260-262° C., 262-270° C., 262-268° C., 262-266° C., 262-264° C., 264-270° C., 264-268° C., 264-266° C., 266-270° C., 266-268° C., or 26-270° C. In some examples, Form 1 of crystalline Compound A is characterized by an endotherm at about 266° C. in the DSC thermogram.

[0069] In some embodiments, Form 1 of crystalline Compound A is further characterized by an endotherm in a DSC thermogram within the range of about 175-195° C., e.g., about 175-195° C., 175-190° C., 175-185° C., 175-180° C., 180-195° C., 180-190° C., 180-185° C., 185-195° C., 185-190° C., or 190-195° C. In some examples, Form 1 of crystalline Compound A is further characterized by an endotherm at about 190° C. in a DSC thermogram.

[0070] In some embodiments, Form 1 of crystalline Compound A is prepared by Figure 3In various embodiments, Form 1 of crystalline Compound A decomposes at temperatures above about 150° C., about 200° C., about 250° C., about 300° C., about 350° C., about 400° C., about 450° C., about 500° C., about 550° C., or above 600° C. In some instances, Form 1 of crystalline Compound A decomposes at temperatures above about 250° C.

[0071] Crystalline Compound A Form 2

[0072] Figure 4 Shown is an X-ray powder diffraction (XRPD) pattern of Form 2 of crystalline Compound A.

[0073] Figure 5 Shown is a differential scanning calorimetry (DSC) thermogram of Form 2 of crystalline Compound A.

[0074] Figure 6 Shown is a thermogravimetric analysis (TGA) graph of Form 2 of crystalline Compound A.

[0075] In one aspect, provided herein is crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A). Some embodiments provide compositions comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride. In some embodiments, crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride Form 2 (Compound A Form 2) is characterized as having:

[0076] (a) An X-ray powder diffraction pattern comprising peaks at 4.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 24.8±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0077] (b) with Figure 4 shows substantially the same X-ray powder diffraction pattern as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0078] (c) Differential Scanning Calorimetry (DSC) thermogram, including:

[0079] i) an endotherm in the range of about 260-270°C;

[0080] (d) Differential Scanning Calorimetry (DSC) thermogram, including:

[0081] i) an endotherm with an onset of about 265°C and a peak at about 266°C;

[0082] (e) with Figure 5 substantially the same differential scanning calorimetry (DSC) thermograms as shown;

[0083] (f) with Figure 6 substantially the same thermogravimetric analysis (TGA) thermograms as shown;

[0084] (g) XRPD unchanged after storage at 80°C for 7 days;

[0085] or

[0086] (h) combinations thereof.

[0087] In some embodiments, Form 2 of crystalline Compound A is characterized by Figure 4 The X-ray powder diffraction patterns shown are essentially the same.

[0088] In some embodiments, Form 2 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 4.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 24.8±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 2 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 4.8 ± 0.1° 2-θ, 26.5 ± 0.1° 2-θ, and 24.8 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 2 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at about 4.8° 2-θ, about 26.5° 2-θ, and about 24.8° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0089] In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A further comprises at least one peak selected from 17.5 ± 0.2° 2-θ, 17.9 ± 0.2° 2-θ, and 21.0 ± 0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A further comprises at least one peak selected from 17.5 ± 0.1° 2-θ, 17.9 ± 0.1° 2-θ, and 21.0 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A further comprises at least one peak selected from about 17.5° 2-θ, about 17.9° 2-θ, and about 21.0° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0090] In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A further comprises at least one peak selected from 19.6 ± 0.2° 2-θ, 25.5 ± 0.2° 2-θ, and 20.4 ± 0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A further comprises at least one peak selected from 19.6 ± 0.1° 2-θ, 25.5 ± 0.1° 2-θ, and 20.4 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A further comprises at least one peak selected from about 19.6° 2-θ, about 25.5° 2-θ, and about 20.4° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0091] In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least one peak selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least two peaks selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least three peaks selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least four peaks selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least five peaks selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least six peaks selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least seven peaks selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 2 of crystalline Compound A comprises at least eight peaks selected from 4.8±0.2°2-θ, 17.5±0.2°2-θ, 17.9±0.2°2-θ, 19.6±0.2°2-θ, 20.4±0.2°2-θ, 21.0±0.2°2-θ, 24.8±0.2°2-θ, 25.5±0.2°2-θ, and 26.5±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 2 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 4.8±0.2° 2-θ, 17.5±0.2° 2-θ, 17.9±0.2° 2-θ, 19.6±0.2° 2-θ, 20.4±0.2° 2-θ, 21.0±0.2° 2-θ, 24.8±0.2° 2-θ, 25.5±0.2° 2-θ, and 26.5±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 2 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 4.8±0.1° 2-θ, 17.5±0.1° 2-θ, 17.9±0.1° 2-θ, 19.6±0.1° 2-θ, 20.4±0.1° 2-θ, 21.0±0.1° 2-θ, 24.8±0.1° 2-θ, 25.5±0.1° 2-θ, and 26.5±0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 2 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at about 4.8° 2-θ, about 17.5° 2-θ, about 17.9° 2-θ, about 19.6° 2-θ, about 20.4° 2-θ, about 21.0° 2-θ, about 24.8° 2-θ, about 25.5° 2-θ, and about 26.6° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0092] In some embodiments, Form 2 of crystalline Compound A is prepared by Figure 5 In some embodiments, Form 2 of crystalline Compound A is characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm in the range of about 260-270° C. In some embodiments, Form 2 of crystalline Compound A is characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm with an onset at about 265° C. and a peak at about 266° C.

[0093] In some embodiments, Form 2 of crystalline Compound A is characterized by an endotherm in the DSC thermogram within the range of about 260-270° C., e.g., about 260-270° C., 260-268° C., 260-266° C., 260-264° C., 260-262° C., 262-270° C., 262-268° C., 262-266° C., 262-264° C., 264-270° C., 264-268° C., 264-266° C., 266-270° C., 266-268° C., or 268-270° C. In some embodiments, Form 2 of crystalline Compound A is characterized by an endotherm at about 266° C. in the DSC thermogram.

[0094] In some embodiments, Form 2 of crystalline Compound A is prepared by Figure 6 Thermogravimetric analysis (TGA) thermograms characterizing substantially the same are shown.

[0095] In some embodiments, Form 1 of crystalline Compound A is formed by exposing Form 2 of crystalline Compound A to ambient conditions. In some embodiments, Form 1 of crystalline Compound A is formed by exposing Form 2 of crystalline Compound A to moist conditions. In some embodiments, moist conditions include a RH greater than about 25%. In some embodiments, moist conditions include a RH greater than about 30%. In some embodiments, moist conditions include a RH greater than about 35%. In some embodiments, moist conditions include a RH greater than about 40%. In some embodiments, moist conditions include a RH greater than about 45%. In some embodiments, moist conditions include a RH greater than about 50%. In some embodiments, moist conditions include a RH greater than about 55%. In some embodiments, moist conditions include a RH greater than about 60%. In some embodiments, moist conditions include a RH greater than about 65%. In some embodiments, moist conditions include a RH greater than about 70%. In some embodiments, moist conditions include a RH greater than about 75%. In some embodiments, moist conditions include a RH greater than about 80%. In some embodiments, moist conditions include a RH between about 30% and about 70%. In some embodiments, moist conditions include a RH of less than about 90%. In some embodiments, moist conditions include a RH of less than about 80%. In some embodiments, moist conditions include a RH of less than about 70%. In some embodiments, moist conditions include a RH of less than about 60%. In some embodiments, moist conditions include a RH of less than about 50%. In some embodiments, moist conditions include a RH of less than about 40%. In some embodiments, moist conditions include a RH of less than about 30%. In some embodiments, in some embodiments, Form 1 of crystalline Compound A is formed by a method comprising the steps of: (i) exposing Form 2 of crystalline Compound A to a first humidity; and (ii) exposing the compound from step (i) to a second humidity. In some embodiments, the first humidity is higher than the second humidity. In some embodiments, the first humidity is greater than about 80% RH. In some embodiments, the first humidity is greater than about 90% RH. In some embodiments, the first humidity is between about 80% and about 90% RH. In some embodiments, the second humidity is less than about 80% RH. In some embodiments, the second humidity is less than 70% RH. In some embodiments, the second humidity is between about 30% and about 70% RH. In some embodiments, forming further comprises allowing the crystalline Form 2 of Compound A to be at a temperature between about 15°C and about 80°C. In some embodiments, the temperature is between about 20°C and about 80°C. In some embodiments, the temperature is between about 20°C and about 75°C. In some embodiments, the temperature is between about 25°C and about 80°C. In some embodiments, the temperature is between about 25°C and about 75°C.In some embodiments, the temperature is between about 25°C and about 70°C. In some embodiments, the temperature is between about 25°C and about 65°C. In some embodiments, the temperature is between about 20°C and about 60°C. In some embodiments, the temperature is greater than about 20°C. In some embodiments, the temperature is greater than about 25°C. In some embodiments, the temperature is greater than about 35°C. In some embodiments, the temperature is greater than about 50°C. In some embodiments, the temperature is greater than about 60°C. In some embodiments, the temperature is greater than about 70°C. In some embodiments, the temperature is less than about 80°C. In some embodiments, the temperature is less than about 70°C. In some embodiments, the temperature is less than about 65°C. In some embodiments, the temperature is less than about 55°C. In some embodiments, the temperature is less than about 45°C. In some embodiments, the temperature is less than about 35°C.

[0096] Crystalline Compound A Form 3

[0097] Figure 7 Shown is an X-ray powder diffraction (XRPD) pattern of crystalline Form 3 of crystalline Compound A.

[0098] In one aspect, provided herein is crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A). Some embodiments provide compositions comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride. In some embodiments, crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride Form 3 (Compound A Form 3) is characterized as having:

[0099] (a) An X-ray powder diffraction pattern comprising peaks at 28.4±0.2° 2-θ, 18.5±0.2° 2-θ, and 12.1±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0100] (b) with Figure 7 shows substantially the same X-ray powder diffraction pattern as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0101] or

[0102] (c) combinations thereof.

[0103] In some embodiments, Form 3 of crystalline Compound A is characterized as having Figure 7 The X-ray powder diffraction patterns shown are essentially the same.

[0104] In some embodiments, Form 3 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 28.4±0.2° 2-θ, 18.5±0.2° 2-θ, and 12.1±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 3 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 28.4 ± 0.1° 2-θ, 18.5 ± 0.1° 2-θ, and 12.1 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 3 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at about 28.4° 2-θ, about 18.5° 2-θ, and about 12.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0105] In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A further comprises at least one peak selected from 26.8 ± 0.2° 2-θ, 31.7 ± 0.2° 2-θ, and 23.3 ± 0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A further comprises at least one peak selected from 26.8 ± 0.1° 2-θ, 31.7 ± 0.1° 2-θ, and 23.3 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is 1.54060 In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A further comprises at least one peak selected from about 26.8° 2-θ, about 31.7° 2-θ, and about 23.3° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0106] In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A further comprises at least one peak selected from 20.7±0.2° 2-θ, 30.8±0.2° 2-θ, and 21.8±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A further comprises at least one peak selected from 20.7±0.1° 2-θ, 30.8±0.1° 2-θ, and 21.8±0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A further comprises at least one peak selected from about 20.7° 2-θ, about 30.8° 2-θ, and about 21.8° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0107] In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least one peak selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least two peaks selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least three peaks selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least four peaks selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least five peaks selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least six peaks selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least seven peaks selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 3 of crystalline Compound A comprises at least eight peaks selected from 12.1±0.2°2-θ, 18.5±0.2°2-θ, 20.7±0.2°2-θ, 21.8±0.2°2-θ, 23.3±0.2°2-θ, 26.8±0.2°2-θ, 28.4±0.2°2-θ, 30.8±0.2°2-θ, and 31.7±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 3 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 12.1±0.2° 2-θ, 18.5±0.2° 2-θ, 20.7±0.2° 2-θ, 21.8±0.2° 2-θ, 23.3±0.2° 2-θ, 26.8±0.2° 2-θ, 28.4±0.2° 2-θ, 30.8±0.2° 2-θ, and 31.7±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 3 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 12.1±0.1° 2-θ, 18.5±0.1° 2-θ, 20.7±0.1° 2-θ, 21.8±0.1° 2-θ, 23.3±0.1° 2-θ, 26.8±0.1° 2-θ, 28.4±0.1° 2-θ, 30.8±0.1° 2-θ, and 31.7±0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 3 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at about 12.1° 2-θ, about 18.5° 2-θ, about 20.7° 2-θ, about 21.8° 2-θ, about 23.3° 2-θ, about 26.8° 2-θ, about 28.4° 2-θ, about 30.8° 2-θ, and about 31.7° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is Crystalline Compound A Form 4

[0108] Figure 8 Shown is an X-ray powder diffraction (XRPD) pattern of Form 4 of crystalline Compound A.

[0109] In one aspect, provided herein is crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A). Some embodiments provide compositions comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride. In some embodiments, crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride Form 4 (Compound A Form 4) is characterized as having:

[0110] (a) An X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0111] (b) with Figure 8 substantially the same X-ray powder diffraction pattern as shown;

[0112] or

[0113] (c) combinations thereof.

[0114] In some embodiments, Form 4 of crystalline Compound A is characterized by Figure 8 The X-ray powder diffraction patterns shown are essentially the same.

[0115] In some embodiments, Form 4 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0 ± 0.2° 2-θ, 22.3 ± 0.2° 2-θ, and 31.2 ± 0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0 ± 0.1° 2-θ, 22.3 ± 0.1° 2-θ, and 31.2 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at about 3.0° 2-θ, about 22.3° 2-θ, and about 31.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0116] In some embodiments, Form 4 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 4.0±0.2° 2-θ, 5.0±0.2° 2-θ, and 15.3±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at 4.0±0.1° 2-θ, 5.0±0.1° 2-θ, and 15.3±0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A is characterized by having an X-ray powder diffraction pattern comprising peaks at about 4.0° 2-θ, about 5.0° 2-θ, and about 15.3° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0117] In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A further comprises at least one peak selected from 3.0 ± 0.2° 2-θ, 25.6 ± 0.2° 2-θ, and 31.2 ± 0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A further comprises at least one peak selected from 3.0 ± 0.1° 2-θ, 25.6 ± 0.1° 2-θ, and 31.2 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A further comprises at least one peak selected from about 3.0° 2-θ, about 25.6° 2-θ, and about 31.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0118] In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A further comprises at least one peak selected from 17.6±0.2° 2-θ, 20.6±0.2° 2-θ, and 22.3±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A further comprises at least one peak selected from 17.6 ± 0.1° 2-θ, 20.6 ± 0.1° 2-θ, and 22.3 ± 0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A further comprises at least one peak selected from about 17.6° 2-θ, about 20.6° 2-θ, and about 22.3° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0119] In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A comprises at least one peak selected from 3.0±0.2°2-θ, 4.0±0.2°2-θ, 5.0±0.2°2-θ, 15.3±0.2°2-θ, 17.6±0.2°2-θ, 20.6±0.2°2-θ, 22.3±0.2°2-θ, 25.6±0.2°2-θ, and 31.2±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A comprises at least two peaks selected from 3.0±0.2°2-θ, 4.0±0.2°2-θ, 5.0±0.2°2-θ, 15.3±0.2°2-θ, 17.6±0.2°2-θ, 20.6±0.2°2-θ, 22.3±0.2°2-θ, 25.6±0.2°2-θ, and 31.2±0.2°2-θ, as measured using CuKα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A comprises at least three peaks selected from 3.0±0.2°2-θ, 4.0±0.2°2-θ, 5.0±0.2°2-θ, 15.3±0.2°2-θ, 17.6±0.2°2-θ, 20.6±0.2°2-θ, 22.3±0.2°2-θ, 25.6±0.2°2-θ, and 31.2±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A comprises at least four peaks selected from 3.0±0.2°2-θ, 4.0±0.2°2-θ, 5.0±0.2°2-θ, 15.3±0.2°2-θ, 17.6±0.2°2-θ, 20.6±0.2°2-θ, 22.3±0.2°2-θ, 25.6±0.2°2-θ, and 31.2±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A comprises at least five peaks selected from 3.0±0.2°2-θ, 4.0±0.2°2-θ, 5.0±0.2°2-θ, 15.3±0.2°2-θ, 17.6±0.2°2-θ, 20.6±0.2°2-θ, 22.3±0.2°2-θ, 25.6±0.2°2-θ, and 31.2±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A comprises at least six peaks selected from 3.0±0.2°2-θ, 4.0±0.2°2-θ, 5.0±0.2°2-θ, 15.3±0.2°2-θ, 17.6±0.2°2-θ, 20.6±0.2°2-θ, 22.3±0.2°2-θ, 25.6±0.2°2-θ, and 31.2±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A has an X-ray powder diffraction pattern comprising at least seven peaks selected from 3.0±0.2° 2-θ, 4.0±0.2° 2-θ, 5.0±0.2° 2-θ, 15.3±0.2° 2-θ, 17.6±0.2° 2-θ, 20.6±0.2° 2-θ, 22.3±0.2° 2-θ, 25.6±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, the X-ray powder diffraction pattern of Form 4 of crystalline Compound A comprises at least eight peaks selected from 3.0±0.2°2-θ, 4.0±0.2°2-θ, 5.0±0.2°2-θ, 15.3±0.2°2-θ, 17.6±0.2°2-θ, 20.6±0.2°2-θ, 22.3±0.2°2-θ, 25.6±0.2°2-θ, and 31.2±0.2°2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 4.0±0.2° 2-θ, 5.0±0.2° 2-θ, 15.3±0.2° 2-θ, 17.6±0.2° 2-θ, 20.6±0.2° 2-θ, 22.3±0.2° 2-θ, 25.6±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at 3.0±0.1° 2-θ, 4.0±0.1° 2-θ, 5.0±0.1° 2-θ, 15.3±0.1° 2-θ, 17.6±0.1° 2-θ, 20.6±0.1° 2-θ, 22.3±0.1° 2-θ, 25.6±0.1° 2-θ, and 31.2±0.1° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is In some embodiments, Form 4 of crystalline Compound A has an X-ray powder diffraction pattern comprising peaks at about 3.0° 2-θ, about 4.0° 2-θ, about 5.0° 2-θ, about 15.3° 2-θ, about 17.6° 2-θ, about 20.6° 2-θ, about 22.3° 2-θ, about 25.6° 2-θ, and about 31.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0120] In some embodiments, Form 1 of crystalline Compound A is formed by exposing Form 4 of crystalline Compound A to moist conditions. In some embodiments, moist conditions include a RH greater than about 25%. In some embodiments, moist conditions include a RH greater than about 30%. In some embodiments, moist conditions include a RH greater than about 35%. In some embodiments, moist conditions include a RH greater than about 40%. In some embodiments, moist conditions include a RH greater than about 45%. In some embodiments, moist conditions include a RH greater than about 50%. In some embodiments, moist conditions include a RH greater than about 55%. In some embodiments, moist conditions include a RH greater than about 60%. In some embodiments, moist conditions include a RH greater than about 65%. In some embodiments, moist conditions include a RH greater than about 70%. In some embodiments, moist conditions include a RH greater than about 75%. In some embodiments, moist conditions include a RH greater than about 80%. In some embodiments, moist conditions include between about 30% and about 70% RH. In some embodiments, moist conditions include less than about 90%. In some embodiments, the humid conditions include a RH of less than about 80%. In some embodiments, the humid conditions include a RH of less than about 70%. In some embodiments, the humid conditions include a RH of less than about 60%. In some embodiments, the humid conditions include a RH of less than about 50%. In some embodiments, the humid conditions include a RH of less than about 40%. In some embodiments, the humid conditions include a RH of less than about 30%. In some embodiments, forming further comprises allowing the crystalline Form 4 of Compound A to be at a temperature between about 15°C and about 80°C. In some embodiments, the temperature is between about 20°C and about 80°C. In some embodiments, the temperature is between about 20°C and about 75°C. In some embodiments, the temperature is between about 25°C and about 80°C. In some embodiments, the temperature is between about 25°C and about 75°C. In some embodiments, the temperature is between about 25°C and about 70°C. In some embodiments, the temperature is between about 25°C and about 65°C. In some embodiments, the temperature is between about 20°C and about 60°C. In some embodiments, the temperature is between about 25°C and about 40°C. In some embodiments, the temperature is greater than about 20°C. In some embodiments, the temperature is greater than about 25°C. In some embodiments, the temperature is greater than about 35°C. In some embodiments, the temperature is greater than about 50°C. In some embodiments, the temperature is greater than about 60°C. In some embodiments, the temperature is greater than about 70°C. In some embodiments, the temperature is less than about 80°C. In some embodiments, the temperature is less than about 70°C. In some embodiments, the temperature is less than about 65°C. In some embodiments, the temperature is less than about 55°C. In some embodiments, the temperature is less than about 45°C. In some embodiments, the temperature is less than about 35°C.II. Methods for preparing Compound A and its polymorphic forms.

[0121] In one aspect, the present invention provides a method for preparing a crystalline form of Compound A:

[0122]

[0123] In some embodiments, Compound A is prepared according to the Examples herein.

[0124] The crystalline compound A according to the present invention is not limited by the raw materials used to prepare the compound A.

[0125] In one aspect, the present invention relates to a process for preparing a crystalline form of Compound A, or a pharmaceutically acceptable salt and / or solvate thereof, by isolating the desired crystalline form as a first solid form after synthesis of Compound A, or alternatively, by isolating the desired crystalline form as a transition from a previous solid form of Compound A. Transitions from one form to another are within the scope of the present invention, as they may be alternative preparation methods for obtaining the desired form for preparing a pharmaceutical formulation.

[0126] If desired, the separation and purification of chemical entities and intermediates described herein can be carried out by any suitable separation or purification procedure, for example, filtration, extraction, crystallization, column chromatography, thin layer chromatography or thick layer chromatography or a combination of these procedures. Specific descriptions of suitable separation and isolation procedures can be found by reference to the following examples. However, other equivalent separation or isolation procedures can also be used. Prior to crystallization, Compound A can be isolated at about 50% chemical purity, 55% chemical purity, 60% chemical purity, 65% chemical purity, 70% chemical purity, 75% chemical purity, 80% chemical purity, 90% chemical purity, 91% chemical purity, 92% purity, 93% chemical purity, 94% chemical purity, 95% chemical purity, 96% chemical purity, 97% chemical purity, 98% chemical purity, 99% chemical purity, about 98% chemical purity or about 100% chemical purity.

[0127] In some embodiments, the crystalline forms disclosed herein are obtained by crystallizing Compound A with a chemical purity of less than about 98%, less than about 97%, less than about 96%, less than about 95%, less than about 94%, less than about 93%, less than about 92%, less than about 91%, less than about 90%, less than about 89%, less than about 88%, less than about 87%, less than about 86%, less than about 85%, less than about 84%, less than about 83%, less than about 82%, less than about 81%, less than about 80%, less than about 78%, less than about 76%, less than about 74%, less than about 72%, or less than about 70%. In some embodiments, the crystalline form is obtained by crystallizing Compound A with a chemical purity ranging from about 70% to about 99%, 80% to about 96%, about 85% to about 96%, about 90% to about 96%, about 80% to 98%, about 85% to about 98%, about 90% to about 98%, about 92% to about 98%, about 94% to 98%, or about 96% to about 98%.

[0128] In some embodiments, isolating the desired crystalline form of Compound A involves crystallizing the crude reaction product from a single solvent system. In various embodiments, isolating the desired crystalline form of Compound A involves crystallizing the crude product from a binary, ternary, or higher solvent system (collectively, a multi-solvent system).

[0129] In some embodiments, crystallization is performed by generating the desired compound A in a reaction mixture and isolating the desired crystalline form from the reaction mixture. In some embodiments, a reaction mixture is formed by adding (5-bromopentyl)-trimethylammonium bromide and potassium carbonate to a solution of 3,6-dibromocarbazole to form dissolved 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A). In other embodiments, a reaction mixture is formed by dissolving Compound A in a solvent. In some embodiments, brine and HCl are also added to the reaction mixture. In some embodiments, brine and HCl are added to the reaction mixture after the reaction is complete.

[0130] Preparation of crystalline compound A

[0131] In some embodiments, crystalline Compound A is obtained from a solution formed by adding a solvent to Compound A. In some embodiments, the solvent is selected from 1-butanol, 2-propanol, acetone, acetonitrile, benzyl alcohol, dichloromethane, dimethyl sulfoxide, ethanol, ethyl acetate, isopropyl acetate, methanol, methyl ethyl ketone, propylene glycol, methyl isobutyl ketone, tert-butyl methyl ether, tetrahydrofuran, toluene, Tween 80, water, and combinations thereof.

[0132] In some embodiments, crystalline Compound A is obtained by temperature cycling of a solution of Compound A. In some embodiments, temperature cycling comprises cycling the temperature between 0° C. and 80° C., e.g., 0° C. to 80° C., 0° C. to 70° C., 0° C. to 60° C., 0° C. to 50° C., 5° C. to 80° C., 5° C. to 70° C., 5° C. to 60° C., 5° C. to 50° C., 10° C. to 80° C., 10° C. to 70° C., 10° C. to 60° C., 10° C. to 50° C., 15° C. to 80° C., 15° C. to 70° C., 15° C. to 60° C., 15° C. to 50° C., 20° C. to 80° C., 20° C. to 70° C., 20° C. to 60° C., or 20° C. to 50° C. In some embodiments, temperature cycling comprises cycling the temperature between 5° C. and 50° C. In some embodiments, temperature cycle is included in and keeps between 0.5 to 10 hours at low temperature and high temperature, for example 0.5 to 10 hours, 0.5 to 8 hours, 0.5 to 6 hours, 0.5 to 4 hours, 0.5 to 2 hours, 1 to 10 hours, 1 to 8 hours, 1 to 6 hours, 1 to 4 hours, 1 to 2 hours, 2 to 10 hours, 2 to 8 hours, 2 to 6 hours, 2 to 4 hours, 4 to 10 hours, 4 to 8 hours, 4 to 6 hours, 6 to 10 hours, 6 to 8 hours, or between 8 to 10 hours. In some embodiments, temperature cycle is included in and keeps 1 hour at low temperature and high temperature. In some embodiments, temperature cycle further includes adding antisolvent. In some embodiments, antisolvent is tert-butyl methyl ether.

[0133] In some embodiments, crystalline Compound A is obtained by rapidly cooling a solution of Compound A. In some embodiments, rapid cooling comprises rapidly cooling the solution to a temperature between 0°C and 10°C, such as 0°C to 10°C, 0°C to 8°C, 0°C to 6°C, 0°C to 4°C, 0°C to 2°C, 1°C to 10°C, 1°C to 8°C, 1°C to 6°C, 1°C to 4°C, 1°C to 2°C, 2°C to 10°C, 2°C to 8°C, 2°C to 6°C, 2°C to 4°C, 4°C to 10°C, 4°C to 8°C, 4°C to 6°C, 6°C to 10°C, 6°C to 8°C, or between 8°C and 10°C. In some embodiments, rapid cooling comprises rapidly cooling the solution to a temperature of 6°C. In some embodiments, rapid cooling further comprises rapidly cooling the solution to a temperature between 0°C and -20°C, e.g., 0°C to -20°C, 0°C to -18°C, 0°C to -16°C, 0°C to -14°C, 0°C to -12°C, 0°C to -10°C, 0°C to -8°C, 0°C to -6°C, 0°C to -4°C, 0°C to -2°C, -2°C to -20°C, -2°C to -18°C, ℃, -2℃ to -16℃, -2℃ to -14℃, -2℃ to -12℃, -2℃ to -10℃, -2℃ to -8℃, -2℃ to -6℃, -2℃ to -4℃, -4℃ to -20℃, -4℃ to -18℃, -4℃ to -16℃, -4℃ to -14℃, -4℃ to -12℃, -4℃ to -10℃, -4℃ to -8℃, -4℃ to -6℃, -6 ℃ to -20℃, -6℃ to -18℃, -6℃ to -16℃, -6℃ to -14℃, -6℃ to -12℃, -6℃ to -10℃, -6℃ to -8℃, -8℃ to -20℃, -8℃ to -18℃, -8℃ to -16℃, -8℃ to -14℃, -8℃ to -12℃, -8℃ to -10℃, -10℃ to -20℃, -10℃ to -18℃ , -10°C to -16°C, -10°C to -14°C, -10°C to -12°C, -12°C to -20°C, -12°C to -18°C, -12°C to -16°C, -12°C to -14°C, -14°C to -20°C, -14°C to -18°C, -14°C to -16°C, -16°C to -20°C, -16°C to -18°C, or between -18°C and -20°C. In some embodiments, the rapid cooling further comprises rapidly cooling the solution to a temperature of -18°C. In some embodiments, the rapid cooling further comprises adding an antisolvent. In some embodiments, the antisolvent is added before cooling. In some embodiments, the antisolvent is added after cooling. In some embodiments, the antisolvent is added after the first cooling and before the second cooling. In some embodiments, the antisolvent is tert-butyl methyl ether.

[0134] In various embodiments, crystallization further involves filtering the solution containing the resulting crystals of crystalline Compound A. In some embodiments, crystallization optionally involves washing the resulting crystals with a solvent, for example, one or more times with a recrystallization solvent. In some embodiments, crystallization optionally involves drying the resulting crystals, for example, under vacuum at a temperature of about 20-30°C.

[0135] In some embodiments, the chemical purity of crystalline Compound A is greater than 60%, 70%, 80%, 90%, 95%, or 99%. In some embodiments, the chemical purity of crystalline Compound A is greater than about 90%. In some embodiments, the chemical purity of crystalline Compound A is greater than about 95%. In some embodiments, the chemical purity of crystalline Compound A is greater than about 99%. The chemical purity of crystalline Compound A can be measured by any available analytical technique, such as by HPLC analysis.

[0136] In various embodiments, crystalline compound A is solvated. In some embodiments, crystalline compound A is anhydrous (i.e., unhydrated). In various embodiments, crystalline compound A is hydrated. In some embodiments, crystalline compound A is hydrated and is characterized by having 1 to 2 water molecules associated with the hydrate. In some embodiments, crystalline compound A is hydrated, and the average number of water molecules associated with the hydrate is about 1.5. In some embodiments, compound A is multiply hydrated. In various embodiments, crystalline compound A is a dihydrate. In some embodiments, crystalline compound A comprises a water content. In some embodiments, crystalline compound A comprises a water content of about 1 to about 10% (weight / weight %). In some embodiments, crystalline compound A comprises a water content of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% (w / w %). In some embodiments, crystalline compound A comprises a water content of 2 to about 8% (w / w %). In some embodiments, crystalline Compound A comprises a water content (w / w %) of 3 to about 6%. In some embodiments, crystalline Compound A comprises a water content (w / w %) of 3.5 to about 5.5%. In some embodiments, the water content is determined by Karl Fischer coulometric titration.

[0137] III. Additional Definitions

[0138] As used herein, "active agent" is used to refer to a chemical entity that has biological activity. In certain embodiments, an "active agent" is a compound that has pharmaceutical utility.

[0139] As used herein, "modulate" refers to a change in activity relative to the activity in the absence of the chemical entity, as a direct or indirect response to the presence of a chemical entity as described herein. The change can be an increase or decrease in activity and can be due to a direct interaction of the compound with the target or due to an interaction of the compound with one or more other factors that in turn affect the activity of the target. For example, the presence of a chemical entity can increase or decrease the activity of a target, for example, by directly binding to the target, by producing (directly or indirectly) another factor that increases or decreases the activity of the target, or by (directly or indirectly) increasing or decreasing the amount of the target present in a cell or organism.

[0140] As used herein, a "therapeutically effective amount" of a chemical entity described herein refers to an amount that, when administered to a human or non-human subject, provides a therapeutic benefit (e.g., improvement of symptoms), slows disease progression, or prevents disease.

[0141] "Treatment" encompasses the administration of Compound A or a pharmaceutically acceptable salt, solvate or hydrate thereof to a mammalian subject, particularly a human subject, in need of such administration, and includes (i) arresting the development of clinical symptoms of the disease, (ii) causing regression of clinical symptoms of the disease, and / or (iii) prophylactic treatment for preventing the onset of the disease.

[0142] As used herein, a "pharmaceutically acceptable" component is one that is suitable for use in humans and / or animals without undue adverse side effects (eg, toxicity, irritation, and allergic response), commensurate with a reasonable benefit / risk ratio.

[0143] "Pharmaceutically acceptable salts" include, but are not limited to, salts formed with inorganic acids, such as hydrochlorides, carbonates, phosphates, hydrogenphosphates, diphosphates, hydrobromides, sulfates, sulfinates, nitrates, and the like; and salts formed with organic acids, such as malate, malonate, maleate, fumarate, tartrate, succinate, citrate, acetate, lactate, gluconate, methanesulfonate, tris(hydroxymethyl-aminomethane), p-toluenesulfonate, propionate, 2-hydroxyethylsulfonate, benzoate, salicylate, stearate, oxalate, pamoate, and alkanoates, such as acetate, HO2C-(CH2) n -CO2H (wherein n is 0-4), etc. Other salts include sulfate, methanesulfonate, chloride, bromide, trifluoroacetate, picrate, sorbate, benzyl alcoholate, salicylate, nitrate, phthalate or morpholine.

[0144] As used herein, a "subject" refers to a mammal that has been or will be the subject of treatment, observation, or experiment. The methods described herein can be used for human therapy and veterinary applications. In some embodiments, the subject is a human.

[0145] The term "mammal" is intended to have its standard meaning, and encompasses, for example, humans, dogs, cats, sheep, and cattle.

[0146] The compounds disclosed herein may be used in different isotopically enriched forms, e.g. 2 H. 3 H. 11 C. 13 C and / or 14 In a specific embodiment, the compound is deuterated at at least one position. Such deuterated forms can be prepared by the procedures described in U.S. Patents 5,846,514 and 6,334,997. As described in U.S. Patents 5,846,514 and 6,334,997, deuteration can improve efficacy and increase the duration of drug action.

[0147] Deuterium-substituted compounds can be synthesized using various methods, for example, as described in: Dean, Dennis C., ed. Recent Advances in the Synthesis and Applications of Radiolabeled Compounds for Drug Discovery and Development. [In Curr., Pharm. Des., 2000; 6(10)] 2000, p. 110; George W.; Varma, Rajender S. The Synthesis of Radiolabeled Compounds via Organometallic Intermediates, Tetrahedron, 1989, 45(21), 6601-21; and Evans, E. Anthony. Synthesis of radiolabeled compounds, J. Radioanal. Chem., 1981, 64(1-2), 9-32.

[0148] In one aspect, a compound having the structure:

[0149]

[0150] in,

[0151] Each R is independently selected from hydrogen or deuterium, and

[0152] X is an anion.

[0153] In some embodiments, X is halogen (Cl, Br, or I). In some embodiments, X is Cl.

[0154] "Solvates" are formed by the interaction of a solvent and a compound. The term "compound" is intended to include solvates of the compound. Similarly, "pharmaceutically acceptable salts" include solvates of pharmaceutically acceptable salts. Suitable solvates are pharmaceutically acceptable solvates, such as hydrates, including monohydrates and hemihydrates. Also included are solvates formed with one or more solvents of crystallization.

[0155] Pharmaceutically acceptable forms of the compounds recited herein include pharmaceutically acceptable salts, chelates, non-covalent complexes, prodrugs, and mixtures thereof.

[0156] A "chelate" is formed by the coordination of a compound to a metal ion at two (or more) points. The term "compound" is intended to include chelates of the compound. Similarly, a "pharmaceutically acceptable salt" includes chelates of pharmaceutically acceptable salts.

[0157] A "non-covalent complex" is formed by the interaction of a compound and another molecule, wherein no covalent bond is formed between the compound and the molecule. For example, complexation can occur through van der Waals interactions, hydrogen bonding, and electrostatic interactions (also known as ionic bonding). Such non-covalent complexes are included in the term "compound." Similarly, pharmaceutically acceptable salts include "non-covalent complexes" of pharmaceutically acceptable salts.

[0158] When ranges are used herein for physical properties (eg, molecular weight) or chemical properties (eg, chemical formula), all combinations and subcombinations of ranges and specific embodiments therein are intended to be included.

[0159] When referring to a quantity or a numerical range, the term "about" means that the quantity or numerical range mentioned is an approximation within the range of experimental variability (or within the range of statistical experimental error), so that the quantity or numerical range can vary from, for example, 1% to 15% of the stated quantity or numerical range. In some examples of numerical ranges, "about" means ±10%.

[0160] As used herein, "significant" refers to any detectable change that is statistically significant in a standard parametric test of statistical significance, such as Student's T-test, where p < 0.05.

[0161] IV. How to use

[0162] In another aspect, provided herein is a method of treating a disease or condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof provided herein, or a pharmaceutical composition provided herein.

[0163] In some embodiments, the disease or condition is a fat-related condition. In some embodiments, the fat-related condition is obesity, abnormal fat distribution, diabetes, cardiovascular disease, obstructive sleep apnea, lipoma, cancer, osteoarthritis, endocrine disease, reproductive disease, neurological disease, psychiatric disease, rheumatic disease, or orthopedic disease. In some embodiments, the fat-related condition is cellulite, excess fat in various body regions, lipoma, fatty tumor disease, a fat accumulation-related condition, Derken's disease, lipedema, or dormant lipoma. In some embodiments, the fat-related condition is cellulite. In some embodiments, the fat-related condition is excess fat in various body regions. In some embodiments, the fat-related condition is lipoma. In some embodiments, the fat-related condition is fatty tumor disease. In some embodiments, the fat-related condition is a fat accumulation-related condition. In some embodiments, the fat-related condition is Derken's disease. In some embodiments, the fat-related condition is lipedema. In some embodiments, the fat-related condition is dormant lipoma.

[0164] In some embodiments, the disease or condition is fibrosis associated with a second disease or condition. In some embodiments, the second disease or condition is pulmonary fibrosis, cirrhosis of the liver, endomyocardial fibrosis, old myocardial infarction, atrial fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, nephrogenic systemic fibrosis, carpal tunnel syndrome, arthrofibrosis, Crohn's disease, keloids, scleroderma, arthrofibrosis, Peyronie's disease, Dupuytren's contracture, or adhesive capsulitis.

[0165] In some embodiments, the disease or condition is a liposarcoma or a solid tumor. In some embodiments, the disease or condition is a liposarcoma. In some embodiments, the disease or condition is a solid tumor.

[0166] In some embodiments, the disease or condition is angiolipoma.

[0167] In another aspect, provided herein is a use of crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof provided herein, or a pharmaceutical composition provided herein, in the preparation of a medicament for treating a disease or condition in a subject in need thereof.

[0168] In some embodiments, the disease or condition is a fat-related condition. In some embodiments, the fat-related condition is obesity, abnormal fat distribution, diabetes, cardiovascular disease, obstructive sleep apnea, lipoma, cancer, osteoarthritis, endocrine disease, reproductive disease, neurological disease, psychiatric disease, rheumatic disease, or orthopedic disease. In some embodiments, the fat-related condition is cellulite, excess fat in various body regions, lipoma, fatty tumor disease, a fat accumulation-related condition, Derken's disease, lipedema, or dormant lipoma. In some embodiments, the fat-related condition is cellulite. In some embodiments, the fat-related condition is excess fat in various body regions. In some embodiments, the fat-related condition is lipoma. In some embodiments, the fat-related condition is fatty tumor disease. In some embodiments, the fat-related condition is a fat accumulation-related condition. In some embodiments, the fat-related condition is Derken's disease. In some embodiments, the fat-related condition is lipedema. In some embodiments, the fat-related condition is dormant lipoma.

[0169] In some embodiments, the disease or condition is fibrosis associated with a second disease or condition. In some embodiments, the second disease or condition is pulmonary fibrosis, cirrhosis of the liver, endomyocardial fibrosis, old myocardial infarction, atrial fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, nephrogenic systemic fibrosis, carpal tunnel syndrome, arthrofibrosis, Crohn's disease, keloids, scleroderma, arthrofibrosis, Peyronie's disease, Dupuytren's contracture, or adhesive capsulitis.

[0170] In some embodiments, the disease or condition is a liposarcoma or a solid tumor. In some embodiments, the disease or condition is a liposarcoma. In some embodiments, the disease or condition is a solid tumor.

[0171] In some embodiments, the disease or condition is angiolipoma.

[0172] As used herein, a therapeutically effective amount of crystalline Compound A refers to an amount sufficient to achieve the intended application (including but not limited to disease treatment as defined herein). The use of subtherapeutic amounts of crystalline Compound A for treating the intended disease condition is also contemplated in the subject methods.

[0173] The amount of crystalline Compound A administered can vary depending on the intended application (in vitro or in vivo) or the subject and disease condition to be treated (e.g., the weight and age of the subject, the severity of the disease condition, the mode of administration, etc.), which can be readily determined by one of ordinary skill in the art.

[0174] Measuring the biological effect of crystalline Compound A can include performing an assay on a biological sample (e.g., a sample from a subject). Any of a variety of samples can be selected according to the assay. Examples of samples include, but are not limited to, blood samples (e.g., plasma or serum), breath condensate samples, bronchoalveolar lavage fluid, sputum samples, urine samples, and tissue samples.

[0175] The subject treated with crystalline Compound A can be monitored to determine the effectiveness of the treatment, and the treatment regimen can be adjusted based on the subject's physiological response to the treatment. For example, if the inhibition of the biological effect is above or below a threshold, the dosage or frequency of administration can be reduced or increased, respectively. The method may further include continuing the therapy if it is determined that the therapy is effective. The method may include maintaining, gradually reducing, reducing or stopping the amount of the compound administered in the therapy if it is determined that the therapy is effective. The method may include increasing the amount of the compound administered in the therapy if it is determined that the therapy is ineffective. Alternatively, the method may include stopping the therapy if it is determined that the therapy is ineffective. In some embodiments, if the inhibition of the biological effect is above or below a threshold, such as in the absence of a response or an adverse reaction, treatment with crystalline Compound A is stopped. The biological effect can be a change in any one of a variety of physiological indicators.

[0176] V. Compositions and Formulations

[0177] The present disclosure provides compositions, including pharmaceutical compositions, comprising one or more crystalline forms of the present invention.

[0178] In some embodiments, crystalline compound A is formulated into a pharmaceutical composition. In specific embodiments, the pharmaceutical composition is formulated in a conventional manner using one or more physiologically acceptable carriers, which include excipients and adjuvants that assist in processing the active compound / crystalline active compound into a pharmaceutically usable preparation. Suitable formulations depend on the selected route of administration. Any pharmaceutically acceptable techniques, carriers, and excipients are suitable for preparing the pharmaceutical compositions described herein: Remington: The Science and Practice of Pharmacy, 19th Edition (Easton, Pa.: Mack Publishing Company, 1995); Hoover, John E., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pennsylvania 1975; Liberman, HA and Lachman, L., eds., Pharmaceutical Dosage Forms, Marcel Decker, New York, NY, 1980; and Pharmaceutical Dosage Forms and Drug Delivery Systems, 7th Edition (Lippincott Williams & Wilkins 1999).

[0179] Provided herein is a pharmaceutical composition comprising crystalline compound A and a pharmaceutically acceptable diluent, excipient, or carrier. In certain embodiments, crystalline compound A is administered as a pharmaceutical composition in which crystalline compound A is mixed with other active ingredients, such as in a combination therapy. All combinations of active substances described in the combination therapy section below and throughout this disclosure are contemplated herein. In a specific embodiment, the pharmaceutical composition comprises crystalline compound A. In some embodiments, crystalline compound A is crystalline form 1. In some embodiments, crystalline compound A is crystalline form 2. In some embodiments, crystalline compound A is crystalline form 3. In some embodiments, crystalline compound A is crystalline form 4. In some embodiments, crystalline compound A is a mixture of crystalline form 1 and crystalline form 2. In some embodiments, crystalline compound A is a mixture of crystalline form 1 and crystalline form 3. In some embodiments, crystalline compound A is a mixture of crystalline form 1 and crystalline form 4. In some embodiments, crystalline compound A is a mixture of crystalline form 2 and crystalline form 3. In some embodiments, crystalline compound A is a mixture of crystalline form 2 and crystalline form 4. In some embodiments, crystalline compound A is a mixture of crystalline form 3 and crystalline form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 2, and crystalline Form 3. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 2, and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 3, and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 2, crystalline Form 3, and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 2, crystalline Form 3, and crystalline Form 4.

[0180] As used herein, a pharmaceutical composition refers to a mixture of crystalline compound A and other chemical components (e.g., carriers, stabilizers, diluents, dispersants, suspending agents, thickeners, and / or excipients). In certain embodiments, the pharmaceutical composition facilitates the administration of crystalline compound A to an organism. In some embodiments, when practicing the methods of treatment or uses provided herein, a therapeutically effective amount of crystalline compound A is administered to a mammal suffering from a disease or condition to be treated in the form of a pharmaceutical composition. In a specific embodiment, the mammal is a human. In certain embodiments, the therapeutically effective amount varies according to the severity of the disease, the age and relative health of the subject, and other factors. Crystalline compound A as described herein is used alone or in combination with one or more therapeutic agents as a mixture component.

[0181] In one embodiment, crystalline Compound A is formulated in an aqueous solution. In specific embodiments, by way of example only, the aqueous solution is selected from a physiologically compatible buffer, such as Hank's solution, Ringer's solution, or a physiological saline buffer. In other embodiments, crystalline Compound A is formulated for transmucosal administration. In specific embodiments, the transmucosal formulation includes a penetrant suitable for the barrier to be permeated. In other embodiments in which the crystalline Compound A described herein is formulated for other parenteral injections, suitable formulations include aqueous or non-aqueous solutions. In specific embodiments, such solutions include physiologically compatible buffers and / or excipients. In some embodiments, the aqueous solution comprises propylene glycol. In some embodiments, the aqueous solution comprises water and 5-95% propylene glycol (v / v%). In some embodiments, the aqueous solution comprises water and 10-90% propylene glycol (v / v%). In some embodiments, the aqueous solution comprises water and 20-80% propylene glycol (v / v%). In some embodiments, the aqueous solution comprises water and 40-70% propylene glycol (v / v%). In some embodiments, the aqueous solution comprises water and 55-65% propylene glycol (v / v%). In some embodiments, the aqueous solution comprises water and 60% propylene glycol (v / v%).

[0182] In another embodiment, the crystalline Compound A described herein is formulated for oral administration. Crystalline Compound A is formulated by combining crystalline Compound A with, for example, a pharmaceutically acceptable carrier or excipient. In various embodiments, the crystalline Compound A described herein is formulated into oral dosage forms, including, by way of example only, tablets, powders, pills, dragees, capsules, liquids, gels, syrups, elixirs, ointments, suspensions, and the like.

[0183] In certain embodiments, the pharmaceutical preparation for oral use is obtained by mixing one or more solid excipients with the crystalline compound A described herein, optionally grinding the resulting mixture, and, if desired, processing the mixture of granules after adding suitable auxiliary agents to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers, such as sugars, including lactose, sucrose, mannitol or sorbitol; cellulose preparations, such as corn starch, wheat starch, rice starch, potato starch, gelatin, tragacanth gum, methylcellulose, microcrystalline cellulose, hydroxypropyl methylcellulose, sodium hydroxymethylcellulose; or others, such as polyvinylpyrrolidone (PVP or povidone) or calcium phosphate. In a specific embodiment, a disintegrant is optionally added. By way of example only, disintegrants include cross-linked croscarmellose sodium, polyvinylpyrrolidone, agar, or alginic acid or a salt thereof, such as sodium alginate.

[0184] In one embodiment, dosage form (for example dragee core and tablet) has one or more suitable coatings.In a specific embodiment, concentrated sugar solution is used for coated dosage form.Sugar solution optionally contains additional components, for example only as an example, gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol and / or titanium dioxide, lacquer solution and suitable organic solvent or solvent mixture.Dye and / or pigment also can be optionally added in the coating for identification.In addition, dye and / or pigment are optionally used to characterize the different combinations of active compound dosage.

[0185] In certain embodiments, a therapeutically effective amount of crystalline Compound A described herein is formulated into other oral dosage forms. Oral dosage forms include push-fit capsules made of gelatin, and sealed soft capsules made of gelatin and a plasticizer (e.g., glycerol or sorbitol). In specific embodiments, the push-fit capsules contain the active ingredient mixed with one or more fillers. By way of example only, fillers include lactose, binders (e.g., starch) and / or lubricants (e.g., talc or magnesium stearate) and, optionally, stabilizers. In other embodiments, soft capsules contain one or more active compounds dissolved or suspended in a suitable liquid. By way of example only, suitable liquids include one or more fatty oils, liquid paraffin, or liquid polyethylene glycol. In addition, stabilizers are optionally added.

[0186] In other embodiments, a therapeutically effective amount of crystalline compound A as described herein is formulated for buccal or sublingual administration. By way of example only, formulations suitable for buccal or sublingual administration include tablets, lozenges, or gels. In other embodiments, crystalline compound A as described herein is formulated for parenteral injection, including formulations suitable for push injection or continuous infusion. In specific embodiments, the formulation for injection is in unit dosage form (e.g., ampoule) or in a multidose container. Preservatives are optionally added to the injection formulation. In other embodiments, the pharmaceutical composition of crystalline compound A is formulated into a form suitable for parenteral injection, such as a sterile suspension, solution, or emulsion in an oily or aqueous vehicle. Parenteral injection formulations optionally contain formulation agents, such as suspending agents, stabilizers, and / or dispersants. In specific embodiments, pharmaceutical formulations for parenteral administration include aqueous solutions of active crystalline compound A in water-soluble form. In some embodiments, pharmaceutical formulations for parenteral administration include propylene glycol. In some embodiments, pharmaceutical formulations for parenteral administration include propylene glycol and water. In additional embodiments, the suspension of active crystalline compound A is prepared as a suitable oily injection suspension. As examples only, suitable lipophilic solvents or vehicles for use in pharmaceutical compositions described herein include fatty oils (e.g., sesame oil) or synthetic fatty acid esters (e.g., ethyl oleate or triglycerides) or liposomes. In certain specific embodiments, aqueous injection suspensions contain substances that increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension contains a suitable stabilizer or increases the solubility of crystalline compound A to allow the preparation of a reagent for a highly concentrated solution. Alternatively, in other embodiments, the active ingredient is in powder form for combination with a suitable vehicle (e.g., sterile pyrogen-free water) before use.

[0187] In other embodiments, crystalline Compound A is administered topically. Crystalline Compound A described herein is formulated into a variety of topically administrable compositions, such as solutions, suspensions, lotions, gels, pastes, medicated sticks, balms, creams, or ointments. Such pharmaceutical compositions optionally contain solubilizers, stabilizers, tonicity enhancing agents, buffers, and preservatives.

[0188] In other embodiments, crystalline compound A is formulated for transdermal administration. In a specific embodiment, the transdermal formulation adopts a transdermal delivery device and a transdermal delivery patch, and can be a lipophilic emulsion or a buffered aqueous solution dissolved and / or dispersed in a polymer or adhesive. In various embodiments, this patch is constructed for continuous, pulsed or on-demand delivery of pharmaceutical agents. In an additional embodiment, the transdermal delivery of crystalline compound A is achieved by an iontophoresis patch, etc. In certain embodiments, a transdermal patch provides controlled delivery of crystalline compound A. In a specific embodiment, the absorption rate is slowed down by using a rate-controlling membrane or by trapping the compound in a polymer matrix or gel. In an alternative embodiment, absorption enhancers are used to increase absorption. Absorption enhancers or carriers include absorbable pharmaceutically acceptable solvents that help pass through the skin. For example, in one embodiment, the transdermal device is in the form of a bandage, comprising a backing portion, a reservoir containing the compound and an optional carrier, an optional rate-controlling barrier for delivering the compound to the host's skin at a controlled and predetermined rate over a long period of time, and an instrument for fixing the device to the skin.

[0189] In other embodiments, crystalline Compound A is formulated for administration by inhalation. Various forms suitable for administration by inhalation include, but are not limited to, aerosols, mists, or powders. Pharmaceutical compositions of crystalline Compound A are conveniently delivered in the form of an aerosol spray from a pressurized bag or nebulizer using a suitable propellant (e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, or other suitable gas). In specific embodiments, the dosage unit of the pressurized aerosol is determined by providing a valve that delivers a metered amount. In certain embodiments, for example, by way of example only, gelatin capsules and cartridges for use in an inhaler or insufflator are formulated to contain a powder mixture of the compound and a suitable powder base (e.g., lactose or starch).

[0190] In other embodiments, crystalline Compound A is formulated into rectal compositions such as enemas, rectal gels, rectal foams, rectal aerosols, suppositories, jelly suppositories or retention enemas, containing conventional suppository bases such as cocoa butter or other glycerides, as well as synthetic polymers such as polyvinylpyrrolidone and PEG, etc. In suppository forms of the compositions, a low melting wax such as, but not limited to, a mixture of fatty acid glycerides, optionally in combination with cocoa butter, is first melted.

[0191] In certain embodiments, the pharmaceutical composition is formulated in any conventional manner using one or more physiologically acceptable carriers, which include excipients and adjuvants that assist in processing the active crystalline Compound A into a pharmaceutically usable formulation. Suitable formulations depend on the chosen route of administration. Any pharmaceutically acceptable technique, carrier, and excipient are optionally used as appropriate. Pharmaceutical compositions comprising crystalline Compound A are prepared in a conventional manner, for example, by conventional mixing, dissolving, granulating, making dragees, grinding, emulsifying, encapsulating, entrapping, or compression methods.

[0192] The pharmaceutical composition comprises at least one pharmaceutically acceptable carrier, diluent or excipient and crystalline compound A described herein as an active ingredient. The active ingredient is in the form of a free acid or free base, or in the form of a pharmaceutically acceptable salt. All tautomers of the compounds described herein are included within the scope of the compounds provided herein. In addition, the compounds described herein encompass unsolvated forms and solvated forms with pharmaceutically acceptable solvents (e.g., water, ethanol, etc.). The solvated forms of the compounds provided herein are also considered to be disclosed herein. In addition, the pharmaceutical composition optionally comprises other medicinal or pharmaceutical agents, carriers, adjuvants, such as preservatives, stabilizers, wetting agents or emulsifiers, solution promoters, salts for regulating osmotic pressure, buffers and / or other therapeutically valuable substances.

[0193] Methods for preparing compositions comprising crystalline Compound A described herein include formulating crystalline Compound A with one or more inert pharmaceutically acceptable excipients or carriers to form a solid, semisolid, or liquid. Solid compositions include, but are not limited to, powders, tablets, dispersible granules, capsules, cachets, and suppositories. Liquid compositions include solutions in which the compound is dissolved, emulsions containing the compound, or solutions containing liposomes, micelles, or nanoparticles containing the compound disclosed herein. Semisolid compositions include, but are not limited to, gels, suspensions, and creams. The pharmaceutical compositions described herein may be in the form of liquid solutions or suspensions, solid forms suitable for dissolution or suspension in a liquid prior to use, or as emulsions. These compositions optionally also contain small amounts of non-toxic auxiliary substances, such as wetting agents or emulsifiers, pH buffers, and the like.

[0194] In some embodiments, the pharmaceutical composition comprising crystalline Compound A illustratively takes the form of a liquid, wherein the agent is present in solution, suspension, or both. Typically, when the composition is administered as a solution or suspension, a first portion of the agent is present in solution, and a second portion of the agent is present in suspension in the form of particles in a liquid matrix. In some embodiments, the liquid composition comprises a gel formulation. In other embodiments, the liquid composition is aqueous.

[0195] In certain embodiments, useful aqueous suspensions contain one or more polymers as suspending agents. Useful polymers include water-soluble polymers (e.g., cellulosic polymers, e.g., hydroxypropyl methylcellulose) and water-insoluble polymers (e.g., cross-linked carboxyl-containing polymers). Certain pharmaceutical compositions described herein contain mucoadhesive polymers selected from, for example, carboxymethylcellulose, carbomer (acrylic acid polymer), poly(methyl methacrylate), polyacrylamide, polycarbophil, acrylic acid / butyl acrylate copolymer, sodium alginate, and dextran.

[0196] Useful pharmaceutical compositions optionally further comprise a solubilizing agent that aids in the dissolution of crystalline Compound A. The term "solubilizing agent" generally includes agents that result in the formation of micellar or true solutions of the agent. Certain acceptable nonionic surfactants (e.g., polysorbate 80) can be used as solubilizing agents, as can ophthalmologically acceptable glycols, polyglycols (e.g., polyethylene glycol 400), and glycol ethers.

[0197] In addition, useful pharmaceutical compositions optionally contain one or more pH adjusters or buffers, including acids such as acetic acid, boric acid, citric acid, lactic acid, phosphoric acid, and hydrochloric acid; bases such as sodium hydroxide, sodium phosphate, sodium borate, sodium citrate, sodium acetate, sodium lactate, and tris; and buffers such as citrate / dextrose, sodium bicarbonate, and ammonium chloride. Such acids, bases, and buffers are included in amounts necessary to maintain the pH of the composition within an acceptable range.

[0198] In addition, useful compositions optionally further comprise one or more salts in an amount required to bring the osmolality of the composition into an acceptable range. Such salts include those having sodium, potassium, or ammonium cations and chloride, citrate, ascorbate, borate, phosphate, bicarbonate, sulfate, thiosulfate, or bisulfite anions; suitable salts include sodium chloride, potassium chloride, sodium thiosulfate, sodium bisulfite, and ammonium sulfate.

[0199] Other useful pharmaceutical compositions optionally contain one or more preservatives to inhibit microbial activity. Suitable preservatives include mercury-containing substances such as phenylmercuric borate and thimerosal; stabilized chlorine dioxide; and quaternary ammonium compounds such as benzalkonium chloride, cetyltrimethylammonium bromide, and cetylpyridinium chloride.

[0200] Other useful compositions contain one or more surfactants to enhance physical stability or for other purposes. Suitable nonionic surfactants include polyoxyethylene fatty acid glycerides and vegetable oils, for example, polyoxyethylene (60) hydrogenated castor oil; and polyoxyethylene alkyl ethers and alkylphenyl ethers, for example, octoxynol 10, octoxynol 40.

[0201] Other useful compositions include one or more antioxidants to enhance chemical stability where desired. By way of example only, suitable antioxidants include ascorbic acid and sodium metabisulfite.

[0202] In certain embodiments, aqueous suspension compositions are packaged in single-dose non-reclosable containers. Alternatively, multiple-dose reclosable containers are used, in which case a preservative is typically included in the composition.

[0203] In alternative embodiments, other delivery systems for hydrophobic pharmaceutical compounds are employed. Liposomes and emulsions are examples of delivery vehicles or carriers useful herein. In certain embodiments, organic solvents, such as N-methylpyrrolidone, are also employed. In additional embodiments, the crystalline forms described herein are delivered using a sustained release system, such as a semipermeable matrix of a solid hydrophobic polymer containing the therapeutic agent. Various sustained release materials are available herein. In some embodiments, sustained release capsules release the crystalline form for a period of several weeks to more than 100 days. Depending on the chemical properties and biological stability of the therapeutic agent, additional strategies are employed to stabilize the protein.

[0204] In certain embodiments, the formulations described herein comprise one or more antioxidants, metal chelators, sulfhydryl-containing compounds, and / or other general stabilizers. Examples of such stabilizers include, but are not limited to: (a) about 0.5% to about 2% w / v glycerol, (b) about 0.1% to about 1% w / v methionine, (c) about 0.1% to about 2% w / v monothioglycerol, (d) about 1 mM to about 10 mM EDTA, (e) about 0.01% to about 2% w / v ascorbic acid, (f) 0.003% to about 0.02% w / v polysorbate 80, (g) 0.001% to about 0.05% w / v polysorbate 20, (h) arginine, (i) heparin, (j) dextran sulfate, (k) cyclodextrin, (l) pentosan polysulfate and other heparinoids, (m) divalent cations (e.g., magnesium and zinc); or (n) combinations thereof.

[0205] VI. Route of Administration

[0206] Suitable routes of administration include, but are not limited to, oral, intravenous, rectal, aerosol, parenteral, subcutaneous, ocular, pulmonary, transmucosal, transdermal, vaginal, otic, nasal, and topical administration. In addition, parenteral delivery includes, by way of example only, intramuscular, subcutaneous, intravenous, intramedullary injection, as well as intrathecal, direct intraventricular, intraperitoneal, intralymphatic, and intranasal injection.

[0207] In certain embodiments, crystalline compound A is applied in a local rather than systemic manner, for example, via crystalline compound A being injected directly into an organ, typically a depot preparation or a sustained release preparation. In a specific embodiment, the long-acting preparation is applied by implantation (e.g., subcutaneous or intramuscular) or intramuscular injection. In addition, in other embodiments, the drug is delivered in a targeted drug delivery system, for example, delivered in a liposome coated with an organ-specific antibody. In this embodiment, the liposome is targeted to an organ and selectively absorbed by the organ. In other embodiments, crystalline compound A is provided in the form of a rapid release preparation, in the form of a delayed release preparation, or in the form of an intermediate release preparation. In other embodiments, crystalline compound A is applied topically. In some embodiments, crystalline compound A is applied subcutaneously.

[0208] VII. Kits / Products

[0209] For use in therapeutic applications as described herein, kits and articles are also provided. In some embodiments, such kits include carriers, packaging, or containers that are separated to accommodate one or more containers, such as vials, tubes, etc., each of which includes one of the individual elements used in the methods described herein. Suitable containers include, for example, bottles, vials, syringes, and test tubes. The container is formed from a variety of materials (e.g., glass or plastic).

[0210] The articles provided herein contain packaging materials. The packaging materials used to package pharmaceutical products are included in, for example, those found in U.S. Patent Nos. 5,323,907, 5,052,558, and 5,033,252. Examples of pharmaceutical packaging materials include, but are not limited to, blister packs, bottles, tubes, inhalers, pumps, bags, vials, containers, syringes, bottles, and any packaging materials suitable for the selected formulation and intended administration and treatment mode. For example, the container comprises crystalline compound A as described herein, optionally in a composition or in combination with another agent disclosed herein. The container optionally has a sterile inlet (e.g., the container is an intravenous solution bag or a vial with a stopper that can be pierced by a hypodermic needle). This kit optionally includes a compound and an identification description or label or instructions associated with its use in the methods described herein.

[0211] The kit described herein can include one or more of the crystalline forms provided in the present disclosure and a pharmaceutically acceptable excipient, carrier, diluent, solution or buffer for redissolving the crystalline form into a pharmaceutical product suitable for administration to an individual. The diluent, solution or buffer can include, for example, water for injection, normal saline or another suitable isotonic buffer solution. In some embodiments, the pharmaceutically acceptable excipient, carrier, diluent, solution or buffer can include one or more of the following: propylene glycol, polyoxyl hydrogenated castor oil, ethanol, glycerol, sorbitol, mannitol, benzyl alcohol, lauryl glucoside, ammonium lauryl sulfate, sodium lauryl sulfate, sodium lauryl (polyoxyethylene) ether sulfate, sodium myrethiocyanate (polyoxyethylene) ether sulfate, sulfate), docusate, perfluorooctane sulfonate, perfluorobutane sulfonate, sodium stearate, sodium lauroyl sarcosinate, perfluorononanoate, perfluorooctanoate, cetyltrimethylammonium bromide, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, dimethyldioctadecylammonium chloride, dimethyldioctadecylammonium bromide, 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate, cocamidopropyl hydroxysulfobetaine, cocamidopropyl betaine, phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, sphingomyelin, octaethylene glycol monododecyl ether, pentaethylene glycol monododecyl ether, nonaethylene glycol, polyethylene glycol nonylphenyl ether, 2-[4-(2,4,4-Trimethylpentan-2-yl)phenoxy]ethanol, polyethylene glycol-35 castor oil, polyethoxylated tallow amine, cocamide monoethanolamine, cocamide diethanolamine, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl monolaurate, glyceryl dilaurate, glyceryl trilaurate, sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, decyl glucoside, lauryl glucoside, octyl glucoside, lauryl dimethylamine oxide, propionic acid, butyric acid, valeric acid, caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, pearly acid, stearic acid, nonadecanoic acid, arachidic acid, heneisosylic acid acid), behenic acid, tricosyl acid, lignoceric acid, pentacosyl acid, cerotic acid, heptacosyl acid, montanic acid, nonacosylic acid, melissic acid, hentriacontylic acid, lacceric acid, pedic acid, geddic acid, pentacosyl acid, hexadecanoic acid, heptacosyl acid, octadecanoic acid, nonacosyl acid, tetratriacontylic acid, crotonic acid, myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaccenic acid, cis-9-eicosenoic acid, eicosenoic acid, erucic acid, nervonic acid, linoleic acid, eicosadienoic acid, docosadienoic acid, linolenic acid, pinolenic acid, eleostearic acid, mead acid, dihomo-γ-linolenic acid, eicosatrienoic acid acid)、6,9,12,1,5-octadecatalonic acid, arachidonic acid, eicosatetraenoic acid, adrenic acid, bosseopentaenoic acid, eicosapentaenoic acid, ozubondo acid, sardine acid, tetracosanolpentaenoic acid, cervonic acid, herring acid, arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, tryptophan, vitamin E, ascorbyl palmitate, butylated hydroxytoluene, triethyl citrate, citric acid, or a combination thereof. In some embodiments, the pharmaceutically acceptable excipient, carrier, diluent, solution or buffer may comprise one or more of the following: propylene glycol, polyethylene glycol hydrogenated castor oil, ethanol, glycerol, sorbitol, mannitol, benzyl alcohol, lauryl glucoside, ammonium lauryl sulfate, sodium lauryl sulfate, sodium lauryl (polyoxyethylene) ether sulfate, sodium myristyl (polyoxyethylene) ether sulfate, sodium stearate, sodium lauroyl sarcosinate, benzalkonium chloride, benzethonium chloride, phosphatidylcholine, sphingomyelin, 2-[4-(2,4,4-Trimethylpentan-2-yl)phenoxy]ethanol, polyethylene glycol-35 castor oil, glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl monolaurate, glyceryl dilaurate, glyceryl trilaurate, sorbitan monolaurate, sorbitan monostearate, sorbitan tristearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, lauric acid, tridecanoic acid, myristic acid, palmitic acid, stearic acid , myristoleic acid, palmitoleic acid, hexadecenoic acid, oleic acid, elaidic acid, vaccenic acid, cis-9-eicosenoic acid, arginine, histidine, lysine, aspartic acid, glutamic acid, serine, threonine, asparagine, glutamine, cysteine, glycine, proline, alanine, valine, isoleucine, leucine, methionine, phenylalanine, tyrosine, tryptophan, vitamin E, ascorbyl palmitate, butylated hydroxytoluene, triethyl citrate, citric acid, or a combination thereof. In some embodiments, the pharmaceutically acceptable excipient, carrier, diluent, solution, or buffer may comprise one or more of the following: ethanol, glycerol, propylene glycol, sorbitol, mannitol, benzyl alcohol, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or a combination thereof. In some embodiments, the pharmaceutically acceptable excipient, carrier, diluent, solution, or buffer may comprise polysorbate 80, propylene glycol, benzyl alcohol, and water for injection. The pharmaceutically acceptable excipient, carrier, diluent, solution, or buffer may be provided in the same or separate containers. In some embodiments, the pharmaceutically acceptable excipient, carrier, diluent, solution, or buffer may be provided in the same container. In some embodiments, the pharmaceutically acceptable excipient, carrier, diluent, solution, or buffer may be provided in separate containers.

[0212] For example, kits typically include one or more additional containers, each containing one or more of the various materials (e.g., reagents, optionally in concentrated form, and / or devices) required for commercial and user use of the compounds described herein. Non-limiting examples of such materials include, but are not limited to, buffers, diluents, filters, needles, syringes; carriers, packaging, container, vial, and / or tube labels listing the contents and / or instructions for use, and package inserts with instructions for use. A set of instructions is also typically included. The label is optionally located on or associated with the container. For example, when letters, numbers, or other characters forming the label are affixed, molded, or etched into the container itself, the label is on the container; when the label is present within a container or carrier that also houses the container, e.g., as a package insert, the label is associated with the container. Furthermore, the label serves to indicate that the contents are to be used for a specific therapeutic application. Furthermore, the label indicates instructions for use of the contents, e.g., in the methods described herein. In certain embodiments, the pharmaceutical composition is present in a package or dispenser device that contains one or more unit dosage forms containing a compound provided herein. The package, for example, comprises metal or plastic foil, such as a blister pack. Alternatively, the package or dispenser device is accompanied by instructions for administration. Alternatively, the package or dispenser is accompanied by a notice associated with the container in a form prescribed by a governmental agency regulating the preparation, use, or sale of drugs, which notice reflects the agency's approval of the drug form for human or veterinary administration. Such notices, for example, are labeling approved by the U.S. Food and Drug Administration for prescription drugs, or approved product inserts. In some embodiments, a composition containing crystalline Compound A formulated in a compatible pharmaceutical carrier is prepared, placed in an appropriate container, and labeled for treatment of the indicated condition.

[0213] In some embodiments, disclosed herein is a kit comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A) and one or more pharmaceutically acceptable excipients. In some embodiments, crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A) is anhydrous. In some embodiments, crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A) is hydrated. In some embodiments, crystalline Compound A is crystalline Compound A Form 1. In some embodiments, crystalline Compound A is crystalline Compound A Form 2. In some embodiments, crystalline Compound A is crystalline Compound A Form 3. In some embodiments, crystalline Compound A is crystalline Compound A Form 4. In some embodiments, Compound A is Compound A Form 1. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1 and crystalline Form 2. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1 and crystalline Form 3. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1 and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 2 and crystalline Form 3. In some embodiments, crystalline Compound A is a mixture of crystalline Form 2 and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 3 and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 2, and crystalline Form 3. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 2, and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 3, and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 2, crystalline Form 3, and crystalline Form 4. In some embodiments, crystalline Compound A is a mixture of crystalline Form 1, crystalline Form 2, crystalline Form 3, and crystalline Form 4.

[0214] In some embodiments, provided herein is a kit comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A) and one or more pharmaceutically acceptable excipients for treating a disease or condition. In some embodiments, the disease or condition is a fat-related disease or condition, a fibrosis-related disease or condition, a liposarcoma, a solid tumor, or an angiolipoma. In some embodiments, the disease or condition is a fat-related condition. In some embodiments, the fat-related condition is obesity, abnormal fat distribution, diabetes, cardiovascular disease, obstructive sleep apnea, lipoma, cancer, osteoarthritis, endocrine disease, reproductive disease, neurological disease, mental illness, rheumatism, or orthopedic disease. In some embodiments, the fat-related condition is cellulite, excess fat in various areas of the body, lipoma, fatty tumor disease, fat accumulation-related condition, Delken's disease, lipedema, or dormant lipoma. In some embodiments, the fat-related condition is cellulite. In some embodiments, the fat-related condition is excess fat in various areas of the body. In some embodiments, the fat-related condition is a lipoma. In some embodiments, the fat-related condition is a fatty tumor disease. In some embodiments, the fat-related condition is a fat accumulation-related condition. In some embodiments, the fat-related condition is Derken's disease. In some embodiments, the fat-related condition is lipedema. In some embodiments, the fat-related condition is a dormant lipoma. In some embodiments, the disease or condition is fibrosis associated with a second disease or condition. In some embodiments, the second disease or condition is pulmonary fibrosis, cirrhosis of the liver, endomyocardial fibrosis, old myocardial infarction, atrial fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, nephrogenic systemic fibrosis, carpal tunnel syndrome, arthrofibrosis, Crohn's disease, keloids, scleroderma, arthrofibrosis, Peyronie's disease, Dupuytren's contracture, or adhesive capsulitis. In some embodiments, the disease or condition is a liposarcoma or a solid tumor. In some embodiments, the disease or condition is a liposarcoma. In some embodiments, the disease or condition is a solid tumor. In some embodiments, the disease or condition is angiolipoma.

[0215] Example

[0216] The following examples are provided to more fully describe the manner of using the present invention. These examples are for illustrative purposes only and should not be used to limit the true scope of the present invention.

[0217] In some embodiments, 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A) is prepared as described in WO 2013 / 072915 and U.S. Patent No. 9,447,040, which are incorporated herein by reference for this synthesis. In some embodiments, Compound A is prepared as described herein.

[0218] Example 1: Preparation of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A)

[0219] 3,6-Dibromocarbazole (1.00 g, 3.0 mM) was dissolved in dimethylformamide (100 mL). (5-Bromopentyl)-trimethylammonium bromide (0.57 g, 3.0 mM) was immediately added. After magnetic stirring for 10 minutes, potassium carbonate (1.40 g, 10 mM) was added. After stirring for another 10 minutes, the temperature was raised to 50°C and the mixture was stirred for 4 hours. After cooling to room temperature, the solution was transferred to a separatory funnel and water (200 mL) and dichloromethane (200 mL) were added. The solvent mixture was shaken and the lower phase was collected. The upper aqueous phase was extracted four times with 3:1 dichloromethane / methanol (50 mL). The combined organics were washed with brine (100 mL), dried over magnesium sulfate, filtered and concentrated. The obtained residue was crystallized from water to obtain 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A) (1.28 g). 1 H NMR(CD3OD,400MHz)δ8.21(d,J=0.4Hz,2H),7.54(dd,J=2.0,0.4Hz,2H),7.47(d,J=2.0,2 H), 4.39 (t, J = 0.6, 2H), 3.16 (m, 2H), 3.01 (s, 9H), 1.93 (m, 2H), 1.70 (m, 2H), 1.31 (m, 2H). MS: m / z=451,453,455(M + , symmetrical 2Br triplet) and 452,454,456 (M+H + , symmetrical 2Br triplet).

[0220] Example 2: Temperature Cycling Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium Chloride Form 1 (Compound A Form 1)

[0221] To a known mass of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A) was added a 0.5 mL aliquot of a solvent (selected from 1-butanol, 2-propanol, acetone, acetonitrile, benzyl alcohol, dichloromethane, dimethyl sulfoxide, ethanol, ethyl acetate, isopropyl acetate, methanol, methyl ethyl ketone, propylene glycol, methyl isobutyl ketone, tert-butyl methyl ether, tetrahydrofuran, toluene, Tween 80, water, tert-butyl methyl ether / water (2:9)). 8 v / v%), acetonitrile / 1-butanol / tert-butyl methyl ether / water (2:2:2:94 v / v%), acetonitrile / 1-butanol / tert-butyl methyl ether (25:25:50 v / v%), Tween 80 / propylene glycol / benzyl alcohol / water (10:60:3:27 w / w%), Tween 80 / propylene glycol / benzyl alcohol (14:81:5 w / w%), methanol / water (40:60 v / v%), and methanol / water (80:00 v / v%) were added until a mobile slurry was observed. During the solvent addition, the reaction mixture was maintained at 50°C with stirring and then temperature cycled between 5°C and 50°C for 1 hour, at both low and high temperatures. After 18 hours of cycling, if the reaction mixture was still a clear solution, tert-butyl methyl ether was added; the addition was continued until a slurry was observed or the total volume reached 1.8 mL. The reaction mixture was then allowed to continue temperature cycling for a total of 72 hours. The saturated solution was extracted, needle filtered, and stored at ambient temperature for further screening experiments. The gained solid was vacuum dried for 3 days at ambient temperature. 1-Butanol, 2-propanol, acetone, acetonitrile, benzyl alcohol, dichloromethane, dimethyl sulfoxide, ethanol, ethyl acetate, isopropyl acetate, methanol, methyl ethyl ketone, methyl isobutyl ketone, tert-butyl methyl ether, tetrahydrofuran, toluene, Tween 80, tert-butyl methyl ether / water (2: 98 v / v%), acetonitrile / 1-butanol / tert-butyl methyl ether (25: 25: 50 v / v%), Tween 80 / propylene glycol / benzyl alcohol (14: 81: 5 w / w%) and methanol / water (40: 60 v / v%) solutions provide crystalline Compound A (Form 1).

[0222] Example 3: Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium Chloride Form 1 (Compound A Form 1) by Rapid Cooling

[0223] The solution obtained in Example 2 was rapidly cooled to 6°C. After 4 days, the ethanol solution provided crystalline Compound A. The remaining solution was rapidly cooled to -18°C. After 48 hours, 1-butanol, 2-propanol, acetonitrile, Tween 80 / propylene glycol / benzyl alcohol (14:81:5 w / w%), methanol / water (40:60 v / v%), and methanol / water (80:20 v / v%) provided crystalline Form 1 of Compound A. The remaining solution was treated with tert-butyl methyl ether. After 18 hours, a benzyl alcohol and dimethyl sulfoxide solution provided crystalline Compound A (Form 1).

[0224] Example 4: Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium Chloride Form 1 (Compound A Form 1) by Evaporation

[0225] At room temperature, the solution obtained in Example 2 was added to an open vial. After 4 days, 1-butanol, 2-propanol, acetonitrile, methanol, acetonitrile / 1-butanol / tert-butyl methyl ether / water (2:2:2:94 v / v%), acetonitrile / 1-butanol / tert-butyl methyl ether (25:25:50 v / v%), Tween 80 / propylene glycol / benzyl alcohol (14:81:5 w / w%), methanol / water (40:60 v / v%), and methanol / water (80:00 v / v%) solutions provided crystalline Compound A (Form 1).

[0226] Example 5: Antisolvent Addition Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium Chloride Form 1 (Compound A Form 1)

[0227] The solution obtained in Example 2 was added to a vial and tert-butyl methyl ether was added in 50 μL aliquots at ambient temperature until precipitation was observed or a total of 1.8 mL of antisolvent had been added. The solid was isolated by centrifugation. The remaining solution was cooled to 6° C. and stored for 72 hours, cooled to −18° C., and stored for 48 hours. 1-Butanol, benzyl alcohol, dimethyl sulfoxide, ethanol, methanol, acetonitrile / 1-butanol / tert-butyl methyl ether (25:25:50 v / v%) and methanol / water (80:00 v / v%) solutions provided crystalline Compound A (Form 1).

[0228] Example 6: Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium Chloride Form 2 (Compound A Form 2) from Compound A Form 1

[0229] A known mass of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride Form 1 (Compound A Form 1) was added to a pre-tared open aluminum pan and loaded into a TA Instruments Discovery SDT 650 Auto-Simultaneous DSC and maintained at room temperature. The sample was then heated from 30°C to 200°C at a rate of 10°C / min. The sample was held at 200°C for 10 minutes and then cooled to 30°C. This method provided crystalline Compound A (Form 2).

[0230] Example 7: Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium Chloride Form 3 (Compound A Form 3)

[0231] synthesis

[0232] 3,6-Dibromocarbazole was dissolved in MeCN / MeTHF. (5-Bromopentyl)-trimethylammonium bromide was immediately added. After magnetic stirring for 10 minutes, potassium carbonate was added. After stirring for an additional 10 minutes, the temperature was raised to 50°C, and the mixture was stirred for 4 hours. After cooling to room temperature, the solution was transferred to a separatory funnel and water and dichloromethane were added. The solvent mixture was shaken and the lower phase was collected. The upper aqueous phase was extracted four times with 3:1 dichloromethane / methanol. The combined organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated. A portion of the resulting 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A) was bead milled (6 cycles at 6000 rpm for 60 seconds each, with a 10-second rest period between cycles). The ground and unground samples were placed in a crystallizing dish, protected from dust, and exposed to air at 20-25% relative humidity at ambient temperature for 15 days. Both the ground and unground samples afforded crystalline Compound A (Form 3).

[0233] Temperature Cycle

[0234] To a known mass of 5-(3,6-dibromo-9H-carbazole-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A) was added water until a mobile slurry was observed. The slurry was gradually heated until the compound dissolved at about 56°C. The solution was further heated to 85°C, quickly cooled to 65°C, and then slowly cooled to 20°C over 9 hours. The slurry was stirred at 140 RPM for 7 days. A lower stirring rate of 110 RPM was applied for two additional heating / cooling cycles. The slurry was reheated to about 56°C to form a very dilute slurry, aged for 1 hour, and cooled to 20°C over 8 hours. The slurry was then cooled at 20°C for 5 hours, at which time the solid was separated by filtration using a polypropylene felt filter (2 microns) to obtain a wet cake. The cake was rinsed with water, washed twice with MTBE, and vacuum dried for 1 hour. Drying was continued for another hour to obtain crystalline Compound A (Form 3).

[0235] Example 8: Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium Chloride Form 4 (Compound A Form 4) from Compound A

[0236] A known mass of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride was dried until the water content reached ≤1% (w / w). The dried sample was kept under low humidity conditions. This method yielded crystalline Compound A (Form 4).

[0237] Example 9: Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium Chloride Form 1 (Compound A Form 1) from Compound A Form 2

[0238] A known mass of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride Form 2 (Compound A Form 2) was analyzed by variable humidity X-ray powder diffraction (VH-XRPD) on a Philips X'Pert Pro multipurpose diffractometer equipped with a humidity chamber. The diffractometer was operated with a 40 kV / 40 mA generator setting in Bragg-Brentano geometry (step size 0.008° 2θ) using Cu K radiation ( The sample was scanned between 4 and 35.99° 2θ (α1:α2 ratio = 0.5). Measurements were performed between 7–90% RH, with XRPD scans collected at each humidity step. VH-XRPD analysis was performed during an absorption period between ambient and 90% RH, a desorption period between 90% RH and 7% RH, and a second absorption period between 20% and 40% RH. Crystalline Form 1 of Compound A was observed during the desorption period between 90% RH and 20% RH and during the second absorption period at 40% RH.

[0239] Example 10: Preparation of Crystalline 5-(3,6-Dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium Chloride Form 1 (Compound A Form 1) from Compound A Form 4

[0240] A known mass of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride Form 4 (Compound A Form 4) was converted to crystalline Form 1 of Compound A after exposure to 25°C and 40°C and >30% RH.

[0241] Example 11: X-ray powder diffraction (XRPD)

[0242] Although the following diffractometer is used, other types of diffractometers may be used. Additionally, other wavelengths may be used and converted to Cu Ka. In some embodiments, synchrotron radiation X-ray powder diffraction (SR-XRPD) may be used to characterize the crystalline form.

[0243] "Characteristic peaks," to the extent they are present, are a subset of the observed peaks and are used to distinguish one crystalline polymorph from another (a polymorph is a crystalline form having the same chemical composition). Characteristic peaks are determined by evaluating which observed peaks, if any, are present in one crystalline polymorph of a compound relative to all other known crystalline polymorphs of the compound within ±0.2° 2-theta.

[0244] XRPD analysis was performed on a PANalyticalX'pert Pro with a PIXcel detector (128 channels), scanning the samples between 3 and 35° 2θ. The material was gently ground (if necessary) to release any agglomerates and loaded onto a porous plate with Kapton or Mylar polymer film to support the sample. The porous plate was then placed in the diffractometer and analyzed using Cu K radiation ( α1:α2 ratio = 0.5), using a 40 kV / 40 mA generator setting in transmission mode (step size 0.0130° 2θ, step time 18.87 s). Data were visualized and images were generated using the HighScore Plus 4.7 desktop application (PANalytical, 2017).

[0245] A representative XRPD pattern obtained for crystalline Compound A (Form 1) is shown in Figure 1 Representative XRPD peaks obtained for crystalline Compound A (Form 1) are listed in Table 1.

[0246] Table 1.

[0247]

[0248] In some embodiments, representative XRPD peaks obtained for crystalline Compound A (Form 1) are listed in Table 1-1.

[0249] Table 1-1.

[0250] Angle (°2-θ) strength(%) 4.0 100 15.4 32.32 16.4 35.53 19.9 12.18 23.8 17.45 24.1 30.26 24.5 11.61 26.0 26.84 26.0 30.75 26.4 22.16

[0251] A representative XRPD pattern obtained for crystalline Compound A (Form 2) is shown in Figure 4 Representative XRPD peaks obtained for crystalline Compound A (Form 2) are listed in Table 2.

[0252] Table 2.

[0253] Angle (°2-θ) strength(%) 4.8 100 15.0 37.46 17.5 63.57 17.9 56.62 19.6 43.09 20.4 37.98 21.0 43.18 24.8 88.6 25.5 40.01 26.5 89.07

[0254] A representative XRPD pattern obtained for crystalline Compound A (Form 3) is shown in Figure 7 Representative XRPD peaks obtained for crystalline Compound A (Form 3) are listed in Table 3.

[0255] Table 3.

[0256]

[0257]

[0258] *Where 1 is the peak with the largest signal intensity, and 30 is the peak with the smallest signal intensity.

[0259] A representative XRPD pattern obtained for crystalline Compound A (Form 4) is shown in Figure 8 Representative XRPD peaks obtained for crystalline Compound A (Form 4) are listed in Table 4.

[0260] Table 4.

[0261] Angle (°2-θ) strength* 3.0 5 4.0 3 5.0 1 15.3 2 17.6 9 20.6 8 22.3 7 24.1 10 25.6 4 31.2 6

[0262] *Where, among the representative peaks listed, 1 is the peak with the greatest signal intensity, and 10 is the peak with the least signal intensity.

[0263] Example 12: Thermogravimetric Analysis / Differential Scanning Calorimetry (TGA / DSC)

[0264] 5-10 mg of material was added to a pre-tared open aluminum pan and loaded into a TA Instruments Discovery SDT 650 Auto-Simultaneous DSC and maintained at room temperature. The sample was then heated from 30°C to 400°C at a rate of 10°C / min, during which the change in sample weight and the heat flow response (DSC) were recorded. Nitrogen was used as the sample purge gas at a flow rate of 200 c m 3 / min. The TGA graph obtained for crystalline Compound A (Form 1) is shown in Figure 3 and the TGA pattern obtained for crystalline Compound A (Form 2) is shown in Figure 6 middle.

[0265] Example 13: Differential Scanning Calorimetry (DSC)

[0266] 1-5 mg of material was weighed into an aluminum DSC pan and sealed non-hermetically with an aluminum lid. The sample pan was then loaded into a TA Instruments Discovery DSC 2500 differential scanning calorimeter equipped with an RC90 cooler. The sample and reference were heated to 300°C at a scan rate of 10°C / min, and the resulting heat flow reaction was monitored. The sample was then cooled to 20°C and then heated again to 300°C at 10°C / min. Nitrogen was used as the purge gas with a flow rate of 50 cm 3 / min. The DSC thermogram obtained for crystalline Compound A (Form 1) is shown in Figure 2 The DSC thermogram obtained for crystalline Compound A (Form 2) is shown in Figure 5 middle.

[0267] Example 14: Stability Testing of Crystalline Compound A Form 1

[0268] Crystalline Compound A (Form 1) was unchanged after storage for 7 days at room temperature, 7 days at 40° C. / 75% RH, or 7 days at 80° C. The results of the accelerated stability testing of crystalline Compound A (Form 1) are shown in Table 5. Purity was determined by HPLC analysis.

[0269] Table 5.

[0270] condition Time point purity XRPD Room temperature (open vial) 7 days 99.93％ No change 40℃ / 75%RH (open vial) 7 days 99.93％ No change 80℃ (sealed vial) 7 days 99.93％ No change

[0271] After storage for 36 months at 25°C / 60% RH or 6 months at 40°C / 75% RH, crystalline Compound A (Form 1) was unchanged. The results of the long-term stability testing of crystalline Compound A (Form 1) are shown in Table 6. Purity was determined by HPLC analysis.

[0272] Table 6.

[0273]

[0274]

[0275] Example 15: Karl Fischer (KF) coulometric titration

[0276] The water content of crystalline Compound A was determined using KF coulometric titration by direct addition or liquid extraction.

[0277] Add directly

[0278] 10-20 mg of crystalline Compound A was weighed into a vial. The solid was then manually introduced into the titration cell of a Mettler Toledo C30 compact titrator. The vial was reweighed after the addition of the solid, and the weight of the added solid was entered into the instrument. Once the sample was completely dissolved in the cell, the titration was started. The water content was automatically calculated as a percentage by the instrument, and the data was printed. The analysis was performed in duplicate.

[0279] Liquid extraction

[0280] Weigh 10-20 mg of crystalline Compound A into a vial. Extract 10-15 mL of Coulomat from the cell of a Mettler Toledo C30 compact titrator and add to the vial containing the sample. Dissolve the solid by manual shaking or using an ultrasonic bath. When complete dissolution is achieved, inject the solution back into the titrator cell and enter the added sample weight on the instrument. The water content is automatically calculated as a percentage by the instrument and the data is printed. Analyze in duplicate.

[0281] The KF titration results obtained for crystalline Compound A are summarized in Table 7.

[0282] Table 7.

[0283]

[0284] Although preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that these embodiments are provided as examples only. Without departing from the present invention, those skilled in the art will appreciate that many variations, changes, and replacements may be employed. It should be understood that in practicing the present invention, various alternatives to the embodiments of the present invention described herein may be employed. The following claims are intended to define the scope of the present invention, and methods and structures within the scope of these claims and their equivalents will be encompassed thereby.

[0285] The following list of embodiments further illustrates the disclosure of the present application, which are given for illustrative purposes only and are not intended to limit the disclosure in any way:

[0286] Embodiment 1: Crystallization of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A):

[0287]

[0288] or a hydrate thereof, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having:

[0289] (a) An X-ray powder diffraction pattern comprising peaks at 4.0±0.2° 2-θ, 16.5±0.2° 2-θ, and 15.5±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0290] (b) with Figure 1 The X-ray powder diffraction pattern shown is essentially the same as that of Cu

[0291] The wavelength of the X-rays is measured by Kα1 radiation.

[0292] (c) Differential Scanning Calorimetry (DSC) thermogram, including:

[0293] i) an endotherm in the range of about 260-270°C; and

[0294] ii) an endotherm in the range of about 175-195°C;

[0295] (d) Differential Scanning Calorimetry (DSC) thermogram, including:

[0296] i) an endotherm with an onset of about 265°C and a peak at about 266°C; and

[0297] ii) an endotherm with an onset of about 180°C and a peak at about 190°C;

[0298] (e) with Figure 2 substantially the same differential scanning calorimetry (DSC) thermograms as shown;

[0299] (f) with Figure 3 substantially the same thermogravimetric analysis (TGA) thermograms as shown;

[0300] (g) XRPD unchanged after storage at 40°C and 75% relative humidity (RH) for 7 days;

[0301] (h) XRPD unchanged after storage at 80°C for 7 days;

[0302] or

[0303] (i) combinations thereof.

[0304] Embodiment 2: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof according to Embodiment 1, characterized by having an X-ray powder diffraction pattern comprising peaks at 4.0±0.2° 2-θ, 16.5±0.2° 2-θ, and 15.5±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0305] Embodiment 3: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride or a hydrate thereof according to embodiment 1 or 2, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having Figure 1 shows substantially the same X-ray powder diffraction pattern as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0306] Embodiment 4: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof according to any one of Embodiments 1 to 3, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride is characterized by a differential scanning calorimetry (DSC) thermogram comprising:

[0307] i) an endotherm in the range of about 260-270°C; and

[0308] ii) an endotherm in the range of about 175-195°C.

[0309] Embodiment 5: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof according to any one of Embodiments 1 to 4, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride is characterized by a differential scanning calorimetry (DSC) thermogram comprising:

[0310] i) an endotherm with an onset of about 265°C and a peak at about 266°C; and

[0311] ii) An endotherm starting at about 180°C and peaking at about 190°C.

[0312] Embodiment 6: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride or a hydrate thereof according to any one of Embodiments 1 to 5, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is obtained by reacting with Figure 2 The samples were characterized by differential scanning calorimetry (DSC) thermograms.

[0313] Embodiment 7: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride or a hydrate thereof according to any one of Embodiments 1 to 6, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is obtained by reacting with Figure 3 Thermogravimetric analysis (TGA) thermograms characterizing substantially the same are shown.

[0314] Embodiment 8: Crystallization of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A):

[0315]

[0316] or a hydrate thereof, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having:

[0317] (a) An X-ray powder diffraction pattern comprising peaks at 28.4±0.2° 2-θ, 18.5±0.2° 2-θ, and 12.1±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0318] (b) with Figure 7 The X-ray powder diffraction pattern shown is essentially the same as that of Cu

[0319] The wavelength of the X-rays is measured by Kα1 radiation.

[0320] or

[0321] (c) combinations thereof.

[0322] Embodiment 9: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof according to Embodiment 8, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride is characterized by having an X-ray powder diffraction pattern comprising peaks at 28.4±0.2° 2-θ, 18.5±0.2° 2-θ, and 12.1±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0323] Embodiment 10: Crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride or a hydrate thereof according to embodiment 8 or 9, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having Figure 7 shows substantially the same X-ray powder diffraction pattern as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0324] Embodiment 11: A pharmaceutical composition comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof according to any one of Embodiments 1 to 10 and at least one pharmaceutically acceptable excipient.

[0325] Embodiment 12: The pharmaceutical composition according to embodiment 11, wherein the pharmaceutical composition is formulated for administration to a mammal by parenteral administration.

[0326] Embodiment 13: A method of treating a disease or condition in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride or a hydrate thereof of any one of Embodiments 1 to 10 or a pharmaceutical composition of Embodiment 11 or 12.

[0327] Embodiment 14: The method according to embodiment 13, wherein the disease or disorder is a fat-related disorder.

[0328] Embodiment 15: The method according to embodiment 14, wherein the fat-related disorder is obesity, abnormal fat distribution, diabetes, cardiovascular disease, obstructive sleep apnea, lipoma, cancer, osteoarthritis, endocrine disease, reproductive disease, neurological disease, psychiatric disease, rheumatic disease or orthopedic disease.

[0329] Embodiment 16: The method according to embodiment 14, wherein the fat-related disorder is cellulite, excess fat in various areas of the body, lipoma, adipose tumor disease, a fat accumulation-related disorder, Derken's disease, lipedema, or dormant lipoma.

[0330] Embodiment 17: The method according to embodiment 13, wherein the disease or condition is fibrosis associated with a second disease or condition.

[0331] Embodiment 18: The method of embodiment 17, wherein the second disease or condition is pulmonary fibrosis, cirrhosis of the liver, endomyocardial fibrosis, old myocardial infarction, atrial fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, nephrogenic systemic fibrosis, carpal tunnel syndrome, arthrofibrosis, Crohn's disease, keloid, scleroderma, arthrofibrosis, Peyronie's disease, Dupuytren's contracture, or adhesive capsulitis.

[0332] Embodiment 19: The method according to claim 13, wherein the disease or condition is a liposarcoma or a solid tumor.

[0333] Embodiment 20: The method according to embodiment 13, wherein the disease or condition is lipoma.

[0334] Embodiment 21: The method according to embodiment 13, wherein the disease or condition is angiolipoma.

[0335] Embodiment 22: Use of crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride or a hydrate thereof according to any one of Embodiments 1 to 10 or the pharmaceutical composition of Embodiment 11 or 12 in the preparation of a medicament for treating a disease or condition in a subject in need thereof.

[0336] Embodiment 23: The use according to embodiment 22, wherein the disease or disorder is a fat-related disorder.

[0337] Embodiment 24: The use according to embodiment 23, wherein the fat-related disorder is obesity, abnormal fat distribution, diabetes, cardiovascular disease, obstructive sleep apnea, lipoma, cancer, osteoarthritis, endocrine disease, reproductive disease, neurological disease, psychiatric disease, rheumatic disease or orthopedic disease.

[0338] Embodiment 25: The use according to embodiment 23, wherein the fat-related disorder is cellulite, excess fat in various areas of the body, lipoma, adipose tumor disease, a fat accumulation-related disorder, Derken's disease, lipedema, or dormant lipoma.

[0339] Embodiment 26: The use according to embodiment 22, wherein the disease or condition is fibrosis associated with a second disease or condition.

[0340] Embodiment 27: The use according to embodiment 26, wherein the second disease or condition is pulmonary fibrosis, cirrhosis of the liver, endomyocardial fibrosis, old myocardial infarction, atrial fibrosis, mediastinal fibrosis, myelofibrosis, retroperitoneal fibrosis, progressive massive fibrosis, nephrogenic systemic fibrosis, carpal tunnel syndrome, arthrofibrosis, Crohn's disease, keloid, scleroderma, arthrofibrosis, Peyronie's disease, Dupuytren's contracture, or adhesive capsulitis.

[0341] Embodiment 28: The use according to embodiment 22, wherein the disease or disorder is liposarcoma or a solid tumor.

[0342] Embodiment 29: The use according to embodiment 22, wherein the disease or disorder is angiolipoma.

[0343] Embodiment 30: Anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A):

[0344]

[0345] The anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having:

[0346] (a) An X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0347] (b) with Figure 8 substantially the same X-ray powder diffraction pattern as shown;

[0348] or

[0349] (c) combinations thereof.

[0350] Embodiment 31: An anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride according to Embodiment 30, characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0351] Embodiment 32: Anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride according to embodiment 30 or embodiment 31, wherein the anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having Figure 8 shows substantially the same X-ray powder diffraction pattern as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0352] Embodiment 33: A mixture of anhydrous crystalline forms of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A):

[0353]

[0354] Embodiment 34: A mixture according to Embodiment 33, wherein the mixture comprises anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 4.8±0.2° 2-θ, 22.3±0.2° 2-θ, 24.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0355] Embodiment 35: A mixture according to Embodiment 33 or Embodiment 34, wherein the anhydrous crystalline form of Compound A is formed by a process comprising exposing Compound A to an elevated temperature.

[0356] Embodiment 36: The mixture of Embodiment 35, wherein the elevated temperature is greater than about 90°C.

[0357] Embodiment 37: The mixture of Embodiment 35, wherein the elevated temperature is greater than about 100°C.

[0358] Embodiment 38: The mixture of Embodiment 35, wherein the elevated temperature is greater than about 150°C.

[0359] Embodiment 39: The mixture of Embodiment 35, wherein the elevated temperature is greater than about 200°C.

[0360] Embodiment 40: A mixture according to any one of Embodiments 33-39, wherein the anhydrous crystalline form of Compound A is formed by a process comprising drying Compound A to a lower water content.

[0361] Embodiment 41: The mixture of Embodiment 40, wherein the water content is less than about 5% (w / w).

[0362] Embodiment 42: The mixture of embodiment 40, wherein the water content is less than about 2.5% (w / w).

[0363] Embodiment 43: The mixture of embodiment 40, wherein the water content is less than about 1% (w / w).

[0364] Embodiment 44: A method for preparing anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A), the method comprising reducing the water content of a sample of Compound A and maintaining the sample at a low relative humidity.

[0365] Embodiment 45: The method of Embodiment 44, wherein reducing the water content comprises heating the Compound A sample.

[0366] Embodiment 46: The method according to claim 44 or 45, wherein reducing the water content comprises heating the sample of Compound A to a temperature greater than about 90°C.

[0367] Embodiment 47: The method of Embodiment 44 or 45, wherein reducing the water content comprises heating the sample of Compound A to a temperature greater than about 100°C.

[0368] Embodiment 48: The method of Embodiment 44 or 45, wherein reducing the water content comprises heating the sample of Compound A to a temperature greater than about 150°C.

[0369] Embodiment 49: The method of Embodiment 44 or 45, wherein reducing the water content comprises heating the sample of Compound A to a temperature greater than about 200°C.

[0370] Embodiment 50: The method of any one of Embodiments 44-49, wherein the low relative humidity is less than about 30%.

[0371] Embodiment 51: The method of any one of Embodiments 44-49, wherein the low relative humidity is less than about 20%.

[0372] Embodiment 52: The method of any one of Embodiments 44-49, wherein the low relative humidity is less than about 10%.

[0373] Embodiment 53: The method according to any one of embodiments 44-49, wherein the water content of the sample is reduced to less than about 5% (w / w).

[0374] Embodiment 54: The method according to any one of embodiments 44-49, wherein the water content of the sample is reduced to less than about 2.5% (w / w).

[0375] Embodiment 55: The method according to any one of Embodiments 44-49, wherein the water content of the sample is reduced to less than about 1% (w / w).

[0376] Embodiment 56: A method for preparing crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride Form 1 (Compound A Form 1), the method comprising exposing a sample of Compound A to a moist environment.

[0377] Embodiment 57: The method of Embodiment 56, wherein the sample of Compound A is in an unstable crystalline form.

[0378] Embodiment 58: The method according to Embodiment 56 or 57, wherein the sample of Compound A is anhydrous.

[0379] Embodiment 59: The method of Embodiment 58, wherein the sample of Compound A is anhydrous and is characterized by having:

[0380] (a) An X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0381] (b) with Figure 8 substantially the same X-ray powder diffraction pattern as shown; or

[0382] (c) combinations thereof.

[0383] Embodiment 60: The method of Embodiment 58, wherein the sample of Compound A is anhydrous and is characterized by:

[0384] (a) An X-ray powder diffraction pattern comprising peaks at 4.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 24.8±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0385] (b) with Figure 4 The X-ray powder diffraction pattern shown is essentially the same as that of Cu

[0386] The wavelength of the X-rays is measured by Kα1 radiation. or

[0387] (c) combinations thereof.

[0388] Embodiment 61. The method of Embodiment 58, wherein the sample of Compound A comprises a mixture of anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride.

[0389] Embodiment 62: The method of embodiment 61, wherein the mixture of anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride is characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 4.8±0.2° 2-θ, 22.3±0.2° 2-θ, 24.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is

[0390] Embodiment 63: The method of any one of Embodiments 56-62, wherein the humid environment comprises a relative humidity greater than about 30%.

[0391] Embodiment 64: The method of any one of Embodiments 56-62, wherein the humid environment comprises a relative humidity greater than about 40%.

[0392] Embodiment 65: The method of any one of Embodiments 56-62, wherein the humid environment comprises a relative humidity greater than about 50%.

[0393] Embodiment 66: The method of any one of Embodiments 56-62, wherein the humid environment comprises a relative humidity greater than about 60%.

[0394] Embodiment 67: The method of any one of Embodiments 56-62, wherein the humid environment comprises a relative humidity greater than about 70%.

[0395] Embodiment 68: The method of any one of Embodiments 56-62, wherein the humid environment comprises a relative humidity of about 30% to about 70%.

[0396] Embodiment 69: The method of any one of Embodiments 56-68, wherein the humid environment further comprises a temperature of from about 15°C to about 50°C.

[0397] Embodiment 70: The method of any one of Embodiments 56-68, wherein the humid environment further comprises a temperature of from about 15°C to about 40°C.

[0398] Embodiment 71: The method of any one of Embodiments 56-68, wherein the humid environment further comprises a temperature of from about 20°C to about 40°C.

Claims

1. Anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride (Compound A): The anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having: (a) An X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is (b) an X-ray powder diffraction pattern substantially the same as that shown in FIG8 ; or (c) combinations thereof.

2. The anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride according to claim 1, characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is 3. The anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride of claim 1 , wherein the anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-ammonium chloride is characterized by having an X-ray powder diffraction pattern substantially the same as that shown in FIG8 , as measured using Cu Kα1 radiation, wherein the X-ray wavelength is 4. A mixture of anhydrous crystalline forms of 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A):

5. The mixture of claim 4, wherein the mixture comprises anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 4.8±0.2° 2-θ, 22.3±0.2° 2-θ, 24.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is 6. The mixture of claim 4, wherein the anhydrous crystalline form of Compound A is formed by a process comprising exposing Compound A to an elevated temperature.

7. The mixture of claim 6, wherein the elevated temperature is greater than about 90°C.

8. The mixture of claim 6, wherein the elevated temperature is greater than about 100°C.

9. The mixture of claim 6, wherein the elevated temperature is greater than about 150°C.

10. The mixture of claim 6, wherein the elevated temperature is greater than about 200°C.

11. The mixture of claim 4, wherein the anhydrous crystalline form of Compound A is formed by a process comprising drying Compound A to a lower water content.

12. The mixture of claim 11, wherein the water content is less than about 5% (w / w).

13. The mixture of claim 11, wherein the water content is less than about 2.5% (w / w).

14. The mixture of claim 11, wherein the water content is less than about 1% (w / w).

15. A method for preparing anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A), the method comprising reducing the water content of a sample of Compound A and maintaining the sample at low relative humidity.

16. The method of claim 15, wherein reducing the water content comprises heating the Compound A sample.

17. The method of claim 15, wherein reducing the water content comprises heating the Compound A sample to a temperature greater than about 90°C.

18. The method of claim 15, wherein reducing the water content comprises heating the Compound A sample to a temperature greater than about 100°C.

19. The method of claim 15, wherein reducing the water content comprises heating the Compound A sample to a temperature greater than about 150°C.

20. The method of claim 15, wherein reducing the water content comprises heating the Compound A sample to a temperature greater than about 200°C.

21. The method of claim 15, wherein the low relative humidity is less than about 30%.

22. The method of claim 15, wherein the low relative humidity is less than about 20%.

23. The method of claim 15, wherein the low relative humidity is less than about 10%.

24. The method of claim 15, wherein the water content in the sample is reduced to less than about 5% (w / w).

25. The method of claim 15, wherein the water content in the sample is reduced to less than about 2.5% (w / w).

26. The method of claim 15, wherein the water content in the sample is reduced to less than about 1% (w / w).

27. A method for preparing Form 1 of crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A Form 1), the method comprising exposing a sample of Compound A to a moist environment.

28. The method of claim 27, wherein the sample of Compound A is in an unstable crystalline form.

29. The method of claim 27, wherein the Compound A sample is anhydrous.

30. The method of claim 29, wherein the Compound A sample is anhydrous and is characterized by: (a) An X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 22.3±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is (b) an X-ray powder diffraction pattern substantially the same as that shown in FIG8 ; or (c) combinations thereof.

31. The method of claim 29, wherein the Compound A sample is anhydrous and is characterized by: (a) An X-ray powder diffraction pattern comprising peaks at 4.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 24.8±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is (b) An X-ray powder diffraction pattern substantially the same as that shown in FIG4 , as measured using Cu Kα1 radiation, wherein the X-ray wavelength is or (c) combinations thereof.

32. The method of claim 29, wherein the sample of Compound A comprises a mixture of anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride.

33. The method of claim 32, wherein the mixture of anhydrous crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride is characterized by having an X-ray powder diffraction pattern comprising peaks at 3.0±0.2° 2-θ, 4.8±0.2° 2-θ, 22.3±0.2° 2-θ, 24.8±0.2° 2-θ, 26.5±0.2° 2-θ, and 31.2±0.2° 2-θ, as measured using Cu Kα1 radiation, wherein the X-ray wavelength is 34. The method of claim 27, wherein the humid environment comprises a relative humidity greater than about 30%.

35. The method of claim 27, wherein the humid environment comprises a relative humidity greater than about 40%.

36. The method of claim 27, wherein the humid environment comprises a relative humidity greater than about 50%.

37. The method of claim 27, wherein the humid environment comprises a relative humidity greater than about 60%.

38. The method of claim 27, wherein the humid environment comprises a relative humidity greater than about 70%.

39. The method of claim 27, wherein the humid environment comprises a relative humidity of about 30% to about 70%.

40. The method of claim 27, wherein the humid environment further comprises a temperature from about 15°C to about 50°C.

41. The method of claim 27, wherein the humid environment further comprises a temperature from about 15°C to about 40°C.

42. The method of claim 27, wherein the humid environment further comprises a temperature of from about 20°C to about 40°C.

43. A kit comprising crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A) and one or more pharmaceutically acceptable excipients.

44. The kit of claim 43, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A) is anhydrous.

45. The kit of claim 43, wherein the crystalline 5-(3,6-dibromo-9H-carbazol-9-yl)-N,N,N-trimethylpentan-1-aminium chloride (Compound A) is hydrated.

46. ​​A kit according to any one of claims 43 to 45 for use in treating a disease or disorder.

47. The kit of claim 46, wherein the disease or condition is a fat-related disease or condition, a fibrosis-related disease or condition, a liposarcoma, a solid tumor, or an angiolipoma.

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