Forms and Compositions of Sodium Chenodeoxycholate

Abstract

The present disclosure provides solid forms of sodium chenodeoxycholate (NaCDC), as well as compositions thereof, and methods of use and preparation thereof. In some embodiments, the provided solid forms are useful for treating gastrointestinal disorders, such as constipation (e.g., IBS-C). In some embodiments, the provided solid forms are useful for preparing new formulations of NaCDC, such as formulations uniquely designed to address certain problems of prior formulations of CDCA or salts thereof.

Description

[Technical field]

[0001] Related Applications This application claims priority to and the benefit of Italian Application No. 102022000006161 (filed March 29, 2022) and Italian Application No. 102022000019725 (filed September 26, 2022), the entire contents of each of which are incorporated herein by reference. [Background technology]

[0002] Chenodeoxycholic acid (CDCA), a type of bile acid, has been used as a treatment for patients suffering from cholelithiasis, for example, but it has a side effect of causing diarrhea. In addition, sodium chenodeoxycholate (NaCDC) has been investigated for use as a treatment for constipation. See, for example, Rao, AS, et al., Gastroenterology, 2010 Nov; 139(5): 1549-1558.e.1. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Rao,AS,et al.,Gastroenterology,2010 Nov;139(5):1549-1558.e.1 Summary of the Invention [Means for solving the problem]

[0004] The present disclosure recognizes the need for new formulations of chenodeoxycholic acid (CDCA) or its salts, and provides such formulations and related technology (e.g., methods, compositions, etc.). Specifically, a formulation of CDCA salt (sodium chenodeoxycholic acid, NaCDC) coated with Eudragit S100 in a capsule was shown to be effective for symptoms of irritable bowel syndrome with constipation (IBS-C), but nearly half of the patients suffered from abdominal pain and cramps. See Rao, AS, et al., Gastroenterology, 2010 Nov;139(5):1549-1558.e.1. Steiger et al. hypothesized that such side effects may be driven by high local concentrations of chenodeoxycholic acid (CDC) as it is released into the intestinal tract, but further recognized that effective release of CDC from a controlled release system may be difficult due to reduced water content along the colon. Therefore, they preliminarily evaluated a coated bilayer tablet formulation containing an immediate release layer and a sustained release layer and showed promising in vitro release patterns and reduced occurrence of large contractions when the tablets were administered rectally to pigs. See Steiger, C., et al., Clin. Transl. Gastroenterology 2020;11:e00229. This disclosure provides insight that the development of formulations comprising CDCA or a salt thereof continues to be an important aspect in establishing novel treatments for gastrointestinal disorders (e.g., IBS-C).

[0005] The present disclosure provides solid forms of sodium chenodeoxycholate (NaCDC), as well as compositions thereof, and methods of use and preparation thereof, and related art. In some embodiments, the provided solid forms are useful for treating gastrointestinal disorders, such as constipation (e.g., IBS-C). In some embodiments, the provided solid forms are useful for preparing new formulations of NaCDC, such as formulations uniquely designed to address certain problems of prior formulations of CDCA or salts thereof. [Brief description of the drawings]

[0006] [Figure 1] 1 is a powder X-ray diffraction (XRPD) pattern of NaCDC form A.

[0007] [Diagram 2] 1 is a differential scanning calorimetry (DSC) curve of NaCDC form A.

[0008] [Diagram 3] 1 is a thermogravimetric analysis (TGA) curve of NaCDC form A.

[0009] [Figure 4] A series of XRPD patterns showing NaCDC Form A before (bold line) and after (thin line) exposure to RH 95% at room temperature for 15 hours.

[0010] [Diagram 5] 1 is a powder X-ray diffraction (XRPD) pattern of NaCDC form B.

[0011] [Figure 6] 1 is a differential scanning calorimetry (DSC) curve of NaCDC form B.

[0012] [Figure 7] 1 is a thermogravimetric analysis (TGA) curve of NaCDC form B.

[0013] [Figure 8] A series of XRPD patterns showing NaCDC form B before (bold line) and after (thin line) exposure to RH 95% at room temperature for 15 hours.

[0014] [Figure 9] 1 is a dynamic vapor sorption (DVS) plot of NaCDC form A.

[0015] [Figure 10] 1 is a DVS plot of NaCDC form B.

[0016] [Figure 11] 1 shows the intrinsic dissolution profiles of NaCDC Form A and NaCDC Form B.

[0017] [Figure 12] 1 shows a linear regression analysis of the intrinsic dissolution profiles of NaCDC Form A and NaCDC Form B.

[0018] [Figure 13] 1 shows the solubility curves of NaCDC form A and NaCDC form B.

[0019] [Figure 14] 1 is a DSC curve of NaCDC form B.

[0020] [Figure 15] 1 is a plot of TG (top) / DSC (bottom) analysis of NaCDC form B.

[0021] [Figure 16] 1 is a series of XRPD patterns showing material obtained after heating NaCDC form B at 315° C. (bottom) and 360° C. (top).

[0022] [Figure 17] A series of XRPD patterns showing the material obtained after exposure of NaCDC form B to UV 254 nm light under various conditions: starting material, clear vial, amber vial, and control (bottom to top).

[0023] [Figure 18] 1 is a series of XRPD patterns showing NaCDC form B (bottom) and material obtained from experiments ST19 (middle) and ST20 (top).

[0024] [Figure 19A] 1 is an XRPD pattern of form S1 from experiment ST19.

[0025] [Figure 19B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S1.

[0026] [Figure 20] A series of XRPD patterns from one particular solubility experiment, from bottom to top: NaCDC form B, NaCDC form B after heating at 315° C., ST19, SAS03, SAS07, SAS08, SAS24, SAS33, SAS39, SAS46, SAS47, and SAS48.

[0027] [Figure 21A] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S2.

[0028] [Figure 21B] 1 is an XRPD pattern of form S3 from experiment SAS07.

[0029] [Figure 22] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S4.

[0030] [Figure 23A] 1 is a series of XRPD patterns showing material from experiments SAS47 (bottom) and FAS08 (top).

[0031] [Figure 23B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S5.

[0032] [Figure 24A] 1 is a series of XRPD patterns showing material from experiments ST19, SL13, SL39, and RAS11 (ordered from bottom to top).

[0033] [Figure 24B] 1 is a plot of TG (top) / DSC (bottom) analysis of Form S1 (or forms similar and / or isomorphous to Form S1).

[0034] [Diagram 25] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S2.

[0035] [Figure 26A] 1 is a series of XRPD patterns showing material from experiments SL27 (bottom) and SL56 (top).

[0036] [Figure 26B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S7.

[0037] [Figure 27] 1 is a plot of TG (top) / DSC (bottom) analysis of Form S1 (or forms similar and / or isomorphous to Form S1).

[0038] [Figure 28] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S5.

[0039] [Figure 29] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S6.

[0040] [Diagram 30] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S2.

[0041] [Figure 31A] 1 is the XRPD pattern of form S4.

[0042] [Figure 31B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S4.

[0043] [Figure 32A] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S5.

[0044] [Figure 32B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S5.

[0045] [Diagram 33]1 is the XRPD pattern of form S2.

[0046] [Figure 34A] 1 is a series of XRPD patterns showing material obtained from experiment VDS012 (top) and NaCDC form B (bottom).

[0047] [Figure 34B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S8.

[0048] [Diagram 35] A series of XRPD patterns showing material from experiments ASDS17, ASDS21, ST19, ASDS03, ASDS03 stored for approximately 3 weeks, and SDGR03 (in order from bottom to top).

[0049] [Diagram 36] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of form S14.

[0050] [Figure 37] 1 is a series of XRPD patterns showing material from experiments ASDS04, ASDS04 stored for 22 days, ASDS08 stored for 23 days, NaCDC monohydrate, ASDS08, and NaCDC hemihydrate (ordered from bottom to top).

[0051] [Figure 38] 1 is a plot of TG (top) / DSC (bottom) analysis of form S9-a obtained from a sample from experiment ASDS04 stored for 22 days.

[0052] [Figure 39] 1 is a plot of TG (top) / DSC (bottom) analysis of form S9-a obtained from a sample from experiment ASDS08 stored for 23 days.

[0053] [Figure 40A] 1 is an XRPD spectrum of form S10.

[0054] [Figure 40B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of form S10.

[0055] [Diagram 41] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of form S11.

[0056] [Diagram 42] A series of XRPD patterns showing experiment ASDS19 (bottom), a sample from experiment ASDS19 stored for 22 days (middle), and material from experiment RAS36.

[0057] [Diagram 43] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of form S12.

[0058] [Diagram 44] 1 is a series of XRPD patterns showing material from experiment ASDS16 before (bottom) and after (top) storage for 22 days.

[0059] [Diagram 45] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of form S13.

[0060] [Figure 46A] 1 is an XRPD spectrum of form S14.

[0061] [Figure 46B] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of form S14.

[0062] [Figure 47] 1 is a plot of TG analysis (top) / DSC analysis (bottom) of Form S5.

[0063] [Figure 48] 1 is a series of XRPD patterns showing material from experiment RAS11 before (bottom) and after (top) storage at room temperature for two weeks.

[0064] [Figure 49] 1 is a plot of TG (top) / DSC (bottom) analysis of Form S1 (or forms similar and / or isomorphous to Form S1).

[0065] [Figure 50A] A series of XRPD patterns showing material from experiments SAS07, RAS34, RAS33, and ASDS18 (in order from bottom to top).

[0066] [Figure 50B] 1 is a plot of TG (top) / DSC (bottom) analysis of Form S3 (or forms similar and / or isomorphous to Form S3).

[0067] [Figure 51] A series of XRPD patterns showing material from experiment RAS33 before (bottom) and after (middle) storage at room temperature for two weeks, as well as Form S1 (top; from experiment RAS11).

[0068] [Figure 52] 1 is a plot of TG (top) / DSC (bottom) analysis of Form S6 (or a form similar and / or isomorphous to Form S6).

[0069] [Figure 53] 1 is an XRPD pattern of material from experiment RAS037.

[0070] [Figure 54A] A series of XRPD patterns showing material from experiment RAS36 before (bottom) and after (middle) storage at room temperature in solution for 2 weeks, as well as form S14 (top; obtained from experiment ASDS17).

[0071] [Figure 54B] 1 is a plot of TG (top) / DSC (bottom) analysis of material from experiment RAS36 after two weeks of storage at room temperature. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0072] Chenodeoxycholic acid Chenodeoxycholic acid (CDCA) is a bile acid with the following structure: [ka] There remains a need to identify salts and / or solid forms of CDCA (e.g., those described herein) that are useful for various therapeutic applications. It would be desirable to provide forms of CDCA (e.g., salts and / or solid forms) that impart improved properties, such as stability, solubility, hygroscopicity (e.g., the provided forms may be less hygroscopic than another form), bioavailability, pharmacokinetics, and / or ease of formulation, as compared to another form of CDCA (e.g., an amorphous form).

[0073] Sodium chenodeoxycholate In some embodiments, the disclosure provides a salt form of CDCA (e.g., a sodium salt form of CDCA, also known as sodium chenodeoxycholate or NaCDC). In some embodiments, the disclosure provides a crystalline solid form of sodium chenodeoxycholate (NaCDC). In some embodiments, the disclosure provides one or more polymorphic solid forms of NaCDC. As used herein, the term "polymorph" refers to the ability of a compound to exist in one or more different crystal structures. For example, one or more polymorphs may differ in pharma- ceutical relevant physical properties (e.g., solubility, stability, and / or hygroscopicity) between one form and another.

[0074] It will be understood that the crystalline solid forms of NaCDC can exist in neat or nonsolvated forms, hydrated forms, solvated forms, and / or heterosolvated forms. In some embodiments, the crystalline solid forms of NaCDC do not have any water or solvent incorporated into the crystal structure (i.e., are "nonsolvated" or "anhydrous"). In some embodiments, the crystalline solid forms of NaCDC include water and / or solvent in the crystal structure (i.e., are hydrated and / or solvated, respectively). As used herein, the term "solvate" refers to a solid form in which a stoichiometric or nonstoichiometric amount of one or more solvents is incorporated into the crystal structure. For example, a solvated or heterosolvated polymorph can independently include 0.05, 0.1, 0.2, 0.5, 1.0, 1.5, 2.0, etc. equivalents of one or more solvents incorporated into the crystal lattice. As used herein, the term "hydrate" refers to a solvate in which the solvent incorporated into the crystal structure is water. It will be appreciated that solvates containing only certain solvents, particularly water, may be suitable for development as a drug. See Zhang, C., et al., J. Pharm. Sci., 2018, 107(10):2731-34. Solvates containing other solvents may be useful, inter alia, for manufacturing and / or testing, even if they are not acceptable for use in an approved pharmaceutical product.

[0075] In some embodiments, the disclosure provides NaCDC as a hydrate (e.g., sesquihydrate). In some embodiments, the disclosure provides NaCDC as an anhydrate.

[0076] In some embodiments, the disclosure provides NaCDC as a solvate (eg, a solvate of ethanol, ethyl acetate, methanol, methyl tert-butyl ether, trifluoroethanol, or water, or any combination thereof).

[0077] It will be further understood that the term "salt" or "salt form" encompasses complexes of CDCA with an acid or base, including those resulting from ionic interactions between CDCA and an acid or base, as well as non-ionic bonds between CDCA and a neutral species. In some embodiments, the salt forms provided result from ionic interactions between CDCA and a base (e.g., a sodium base, such that the resulting form is NaCDC).

[0078] As used herein, the term "about" when used in reference to degree 2 theta values ​​refers to the stated value ±0.2 degree 2 theta. In other embodiments, the degree 2 theta values ​​provided refer to the stated value ±0.1 degree 2 theta.

[0079] Form A In some embodiments, the disclosure provides sodium chenodeoxycholate as Form A. In some embodiments, Form A is a hydrate (e.g., a sesquihydrate).

[0080] In some embodiments, Form A is characterized by one or more peaks in its XRPD pattern selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees 2-theta. In some embodiments, Form A is characterized by two or more peaks in its XRPD pattern selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees 2-theta. In some embodiments, Form A is characterized by three or more peaks in its XRPD pattern selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees 2-theta. In some embodiments, Form A is characterized by four or more peaks in its XRPD pattern selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees 2-theta. In some embodiments, Form A is characterized by five or more peaks in its XRPD pattern selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees 2-theta. In some embodiments, Form A is characterized by six or more peaks in its XRPD pattern selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees 2-theta.

[0081] In some embodiments, Form A is characterized by peaks selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees 2-theta in its XRPD pattern. In some embodiments, Form A is characterized by substantially all of the following peaks in its XRPD pattern: [Table 17]

[0082] In some embodiments, Form A is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 1; (ii) a DSC pattern showing loss of water from slightly above ambient temperature up to about 150°C; (iii) a DSC pattern substantially similar to that shown in FIG. (iv) a TGA pattern showing a weight loss of 4.3% up to 150°C; and (v) A TGA pattern substantially similar to that shown in FIG.

[0083] Form B In some embodiments, the disclosure provides sodium chenodeoxycholate as Form B. In some embodiments, Form B is anhydrous.

[0084] In some embodiments, form B is characterized in its XRPD pattern by one or more peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees 2-theta. In some embodiments, form B is characterized in its XRPD pattern by two or more peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees 2-theta. In some embodiments, form B is characterized in its XRPD pattern by three or more peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees 2-theta. In some embodiments, form B is characterized in its XRPD pattern by four or more peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees 2-theta. In some embodiments, form B is characterized in its XRPD pattern by five or more peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees 2-theta.

[0085] In some embodiments, Form B is characterized in its XRPD pattern by peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees 2-theta. In some embodiments, Form B is characterized in its XRPD pattern by substantially all of the following peaks: [Table 18]

[0086] In some embodiments, Form B is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 5; (ii) a DSC pattern showing no thermal events from room temperature to approximately 288°C; (iii) a DSC pattern substantially similar to that shown in FIG. (iv) a TGA pattern that exhibits less than 0.1% weight loss up to 150° C.; and (v) TGA pattern substantially similar to that shown in FIG.

[0087] In some embodiments, Form B is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 5; (ii) a DSC pattern showing no thermal events from room temperature to approximately 288°C; (iii) a DSC pattern substantially similar to that shown in FIG. (iv) a TGA pattern showing less than 0.1% weight loss up to 150° C.; (v) a TGA pattern substantially similar to that shown in FIG. (vi) a DSC pattern substantially similar to that shown in FIG. (vii) A TGA pattern substantially similar to that shown in FIG. (viii) A DSC pattern substantially similar to that shown in FIG.

[0088] Form S1 In some embodiments, the disclosure provides sodium chenodeoxycholate as Form S1. In some embodiments, Form S1 is a solvate. In some embodiments, Form S1 is a methyl ethyl ketone solvate. In some embodiments, Form S1 is a methyl tert-butyl ether solvate. In some embodiments, Form S1 is a trifluoroethanol solvate. In some embodiments, Form S1 is an acetone solvate. In some embodiments, Form S1 is a hydrate.

[0089] In some embodiments, "Form S1" refers to one or more similar and / or identical forms characterized by the feature(s) described herein.

[0090] In some embodiments, Form S1 is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees 2-theta. In some embodiments, Form S1 is characterized in its XRPD pattern by two or more peaks selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees 2-theta. In some embodiments, Form S1 is characterized in its XRPD pattern by three or more peaks selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees 2-theta. In some embodiments, Form S1 is characterized by four or more peaks in its XRPD pattern selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees 2-theta. In some embodiments, Form S1 is characterized by five or more peaks in its XRPD pattern selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees 2-theta. In some embodiments, Form S1 is characterized by six or more peaks in its XRPD pattern selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees 2-theta.

[0091] In some embodiments, Form S1 is characterized in its XRPD pattern by peaks selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees 2-theta. In some embodiments, Form S1 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S1-A. In some embodiments, Form S1 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S1-B.

[0092] In some embodiments, Form S1 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 19A, Figure 24A, and / or Figure 48; (ii) a DSC pattern showing thermal events at about 96.0° C., about 142.5° C., and / or about 313.4° C.; (iii) a DSC pattern substantially similar to that shown in Figure 19B, Figure 24B, Figure 27, and / or Figure 49; (iv) a TGA pattern showing a weight loss of about 2.177% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in Figure 19B, Figure 24B, Figure 27, and / or Figure 49.

[0093] Form S2 In some embodiments, the present disclosure provides sodium chenodeoxycholate as Form S2. In some embodiments, Form S2 is a solvate. In some embodiments, Form S2 is an ethanol solvate.

[0094] In some embodiments, Form S2 is characterized in its XRPD pattern by one or more peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees 2-theta. In some embodiments, Form S2 is characterized in its XRPD pattern by two or more peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees 2-theta. In some embodiments, Form S2 is characterized in its XRPD pattern by three or more peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees 2-theta. In some embodiments, Form S2 is characterized in its XRPD pattern by four or more peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees 2-theta. In some embodiments, Form S2 is characterized in its XRPD pattern by five or more peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees 2-theta.

[0095] In some embodiments, Form S2 is characterized in its XRPD pattern by peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees 2-theta, hi some embodiments, Form S2 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S2.

[0096] In some embodiments, Form S2 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 33; (ii) a DSC pattern showing thermal events at about 112.9° C., about 177.8° C., and / or about 334.1° C.; (iii) a DSC pattern substantially similar to that shown in Figure 21A, Figure 25, and / or Figure 30; (iv) a TGA pattern showing a weight loss of about 3.95% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in Figure 21A, Figure 25, and / or Figure 30.

[0097] Form S3, Form S6, and Form S11 In some embodiments, the present disclosure provides sodium chenodeoxycholate as Form S3, Form S6, and / or Form S11. In some embodiments, Form S3 and / or Form S11 are anhydrous. In some embodiments, Form S6 is a solvate. In some embodiments, Form S6 is an ethyl acetate solvate. In some embodiments, Form S3, Form S6, and Form S11 are similar and / or isomorphous to one another. Thus, in some embodiments, Form S3, Form S6, and / or Form S11 share one or more characteristics described herein.

[0098] In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by one or more peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees 2 theta. In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by two or more peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees 2 theta. In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by three or more peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees 2 theta. In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by four or more peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees 2-theta. In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by five or more peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees 2-theta.

[0099] In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees 2-theta. In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by substantially all of the peaks listed in Table S3. In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by substantially all of the peaks listed in Table S6. In some embodiments, Form S3, Form S6, and / or Form S11 are characterized in their XRPD patterns by substantially all of the peaks listed in Table S11.

[0100] In some embodiments, Form S3, Form S6, and / or Form S11 are characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 21B and / or Figure 50A; (ii) a DSC pattern showing thermal events at about 50.6° C., about 199.8° C., and / or about 331.5° C.; (iii) a DSC pattern substantially similar to that shown in Figure 29 and / or Figure 41; (iv) a TGA pattern showing a weight loss of about 2.456% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 29 and / or FIG. 41.

[0101] Form S4 In some embodiments, the present disclosure provides sodium chenodeoxycholate as Form S4. In some embodiments, Form S4 is a solvate. In some embodiments, Form S4 is a 2,2,2-trifluoroethanol (TFE) solvate.

[0102] In some embodiments, Form S4 is characterized by one or more peaks in its XRPD pattern selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees 2-theta. In some embodiments, Form S4 is characterized by two or more peaks in its XRPD pattern selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees 2-theta. In some embodiments, Form S4 is characterized by three or more peaks in its XRPD pattern selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees 2-theta. In some embodiments, Form S4 is characterized by four or more peaks in its XRPD pattern selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees 2-theta. In some embodiments, Form S4 is characterized by five or more peaks in its XRPD pattern selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees 2-theta. In some embodiments, Form S4 is characterized by six or more peaks in its XRPD pattern selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees 2-theta.

[0103] In some embodiments, Form S4 is characterized in its XRPD pattern by peaks selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees 2-theta, hi some embodiments, Form S4 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S4.

[0104] In some embodiments, Form S4 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 31A; (ii) a DSC pattern showing thermal events at about 146.5° C. and / or about 333.9° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 22 and / or FIG. 31B ; (iv) a TGA pattern showing a weight loss of about 14.23% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 22 and / or FIG. 31B.

[0105] Form S5 In some embodiments, the present disclosure provides sodium chenodeoxycholate as Form S5. In some embodiments, Form S5 is a solvate. In some embodiments, Form S5 is a methanol solvate.

[0106] In some embodiments, Form S5 is characterized in its XRPD pattern by one or more peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2-theta. In some embodiments, Form S5 is characterized in its XRPD pattern by two or more peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2-theta. In some embodiments, Form S5 is characterized in its XRPD pattern by three or more peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2-theta. In some embodiments, Form S5 is characterized in its XRPD pattern by four or more peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2 theta. In some embodiments, Form S5 is characterized in its XRPD pattern by five or more peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2 theta. In some embodiments, Form S5 is characterized in its XRPD pattern by six or more peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2 theta.

[0107] In some embodiments, Form S5 is characterized in its XRPD pattern by peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2-theta. In some embodiments, Form S5 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S5-A. In some embodiments, Form S5 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S5-B.

[0108] In some embodiments, Form S5 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 23A; (ii) a DSC pattern showing thermal events at about 82° C., about 183.9° C., and / or about 331.5° C.; (iii) a DSC pattern substantially similar to that shown in Figures 23B, 28, 32A, 32B, and / or 47; (iv) a TGA pattern showing a weight loss of about 4.79% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in Figure 23B, Figure 28, Figure 32A, Figure 32B, and / or Figure 47.

[0109] Form S7 In some embodiments, the present disclosure provides sodium chenodeoxycholate as Form S7. In some embodiments, Form S7 is a solvate. In some embodiments, Form S7 is an isopropanol solvate.

[0110] In some embodiments, Form S7 is characterized by one or more peaks in its XRPD pattern selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees 2-theta. In some embodiments, Form S7 is characterized by two or more peaks in its XRPD pattern selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees 2-theta. In some embodiments, Form S7 is characterized by three or more peaks in its XRPD pattern selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees 2-theta. In some embodiments, Form S7 is characterized in its XRPD pattern by four or more peaks selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees 2-theta. In some embodiments, Form S7 is characterized in its XRPD pattern by five or more peaks selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees 2-theta.

[0111] In some embodiments, Form S7 is characterized in its XRPD pattern by peaks selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees 2-theta, hi some embodiments, Form S7 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S7.

[0112] In some embodiments, Form S7 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 26A; (ii) a DSC pattern showing thermal events at about 109.2° C., about 324.5° C., and / or about 335.3° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 26B; (iv) a TGA pattern showing a weight loss of about 10.04% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 26B.

[0113] Form S9-a In some embodiments, the present disclosure provides sodium chenodeoxycholate as Form S9-a. In some embodiments, Form S9-a is a solvate. In some embodiments, Form S9-a is a solvate of acetonitrile, water, or a combination thereof.

[0114] In some embodiments, form S9-a is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees 2-theta. In some embodiments, form S9-a is characterized in its XRPD pattern by two or more peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees 2-theta. In some embodiments, form S9-a is characterized in its XRPD pattern by three or more peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees 2-theta. In some embodiments, form S9-a is characterized in its XRPD pattern by four or more peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees 2-theta. In some embodiments, form S9-a is characterized in its XRPD pattern by five or more peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees 2-theta.

[0115] In some embodiments, Form S9-a is characterized in its XRPD pattern by peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees 2-theta, hi some embodiments, Form S9-a is characterized in its XRPD pattern by substantially all of the peaks listed in Table S9-a.

[0116] In some embodiments, form S9-a is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 37 (bottom spectrum); (ii) a DSC pattern showing thermal events at about 99.9° C. and / or about 328° C.; (iii) a DSC pattern substantially similar to that shown in Figure 38 and / or Figure 39; (iv) a TGA pattern showing a weight loss of about 8.635% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 38 and / or FIG. 39.

[0117] Form S9-b In some embodiments, the disclosure provides sodium chenodeoxycholate as form S9-b.

[0118] In some embodiments, form S9-b is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees 2-theta. In some embodiments, form S9-b is characterized in its XRPD pattern by two or more peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees 2-theta. In some embodiments, form S9-b is characterized in its XRPD pattern by three or more peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees 2-theta. In some embodiments, form S9-b is characterized in its XRPD pattern by four or more peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees 2-theta. In some embodiments, form S9-b is characterized in its XRPD pattern by five or more peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees 2-theta.

[0119] In some embodiments, form S9-b is characterized in its XRPD pattern by peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees 2-theta. In some embodiments, form S9-b is characterized in its XRPD pattern by substantially all of the peaks listed in Table S9-b. In some embodiments, form S9-b is characterized by an XRPD pattern substantially similar to that shown in Figure 37 (second spectrum from the top).

[0120] Form S10 In some embodiments, the disclosure provides sodium chenodeoxycholate as Form S10. In some embodiments, Form S10 is a solvate. In some embodiments, Form S10 is a solvate of 2,2,2-trifluoroethanol (TFE), ethyl acetate, or a combination thereof.

[0121] In some embodiments, Form S10 is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta. In some embodiments, Form S10 is characterized in its XRPD pattern by two or more peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta. In some embodiments, Form S10 is characterized in its XRPD pattern by three or more peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta. In some embodiments, Form S10 is characterized in its XRPD pattern by four or more peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta. In some embodiments, Form S10 is characterized in its XRPD pattern by five or more peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta. In some embodiments, Form S10 is characterized in its XRPD pattern by six or more peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta.

[0122] In some embodiments, Form S10 is characterized in its XRPD pattern by peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta, hi some embodiments, Form S10 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S10.

[0123] In some embodiments, Form S10 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 40A; (ii) a DSC pattern showing thermal events at about 141.3° C., about 324° C., and / or about 336° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 40B; (iv) a TGA pattern showing a weight loss of about 16% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in Figure 40B.

[0124] Form S12 and Form S15 In some embodiments, the present disclosure provides sodium chenodeoxycholate as form S12 and / or form S15. In some embodiments, form S12 and / or form S15 is a solvate. In some embodiments, form S12 and / or form S15 is a methyl tert-butyl ether (MTBE) solvate. In some embodiments, form S12 and form S15 are similar and / or isomorphous to each other. Thus, in some embodiments, form S12 and / or form S15 share one or more characteristics described herein.

[0125] In some embodiments, Form S12 and / or Form S15 is characterized in its XRPD pattern by one or more peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees 2-theta. In some embodiments, Form S12 and / or Form S15 is characterized in its XRPD pattern by two or more peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees 2-theta. In some embodiments, Form S12 and / or Form S15 is characterized in its XRPD pattern by three or more peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees 2-theta. In some embodiments, Form S12 and / or Form S15 is characterized in its XRPD pattern by four or more peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees 2-theta. In some embodiments, Form S12 and / or Form S15 is characterized in its XRPD pattern by five or more peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees 2-theta. In some embodiments, Form S12 and / or Form S15 is characterized in its XRPD pattern by six or more peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees 2-theta.

[0126] In some embodiments, Form S12 and / or Form S15 are characterized in their XRPD patterns by peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees 2-theta. In some embodiments, Form S12 and / or Form S15 are characterized in their XRPD patterns by substantially all of the peaks listed in Table S12. In some embodiments, Form S12 and / or Form S15 are characterized in their XRPD patterns by substantially all of the peaks listed in Table S15.

[0127] In some embodiments, Form S12 and / or Form S15 are characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 42; (ii) a DSC pattern showing thermal events at about 80.8° C., about 180° C., and / or about 332° C.; (iii) a DSC pattern substantially similar to that shown in FIG. (iv) a TGA pattern showing a weight loss of about 4.448% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in FIG.

[0128] Form S13 In some embodiments, the present disclosure provides sodium chenodeoxycholate as Form S13. In some embodiments, Form S13 is a solvate. In some embodiments, Form S13 is a solvate of 2,2,2-trifluoroethanol (TFE), diisopropyl ether, or a mixture thereof.

[0129] In some embodiments, Form S13 is characterized in its XRPD pattern by one or more peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees 2-theta. In some embodiments, Form S14 is characterized in its XRPD pattern by two or more peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees 2-theta. In some embodiments, Form S14 is characterized in its XRPD pattern by three or more peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees 2-theta. In some embodiments, Form S14 is characterized in its XRPD pattern by four or more peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees 2-theta. In some embodiments, Form S14 is characterized in its XRPD pattern by five or more peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees 2-theta.

[0130] In some embodiments, Form S13 is characterized in its XRPD pattern by peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees 2-theta, hi some embodiments, Form S13 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S13.

[0131] In some embodiments, Form S13 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 44 and / or Figure 53; (ii) a DSC pattern showing thermal events at about 55.4° C., about 148.8° C., about 191.8° C., and / or about 335° C.; (iii) a DSC pattern substantially similar to that shown in Figure 45; (iv) a TGA pattern showing a weight loss of about 6.162% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in FIG.

[0132] Form S14 In some embodiments, the present disclosure provides sodium chenodeoxycholate as form S14. In some embodiments, form S14 is a solvate. In some embodiments, form S14 is a 2,2,2-trifluoroethanol (TFE) solvate.

[0133] In some embodiments, Form S14 is characterized by one or more peaks in its XRPD pattern selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees 2-theta. In some embodiments, Form S14 is characterized by two or more peaks in its XRPD pattern selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees 2-theta. In some embodiments, Form S14 is characterized by three or more peaks in its XRPD pattern selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees 2-theta. In some embodiments, Form S14 is characterized in its XRPD pattern by four or more peaks selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees 2-theta. In some embodiments, Form S14 is characterized in its XRPD pattern by five or more peaks selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees 2-theta.

[0134] In some embodiments, Form S14 is characterized in its XRPD pattern by peaks selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees 2-theta, hi some embodiments, Form S14 is characterized in its XRPD pattern by substantially all of the peaks listed in Table S14.

[0135] In some embodiments, Form S14 is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 46A; (ii) a DSC pattern showing thermal events at about 143.7° C. and / or about 331° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 46B; (iv) a TGA pattern showing a weight loss of about 15.84% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in Figure 46B.

[0136] Preparation of the provided solid forms In some embodiments, the present disclosure provides a method of preparing a crystalline solid form of sodium chenodeoxycholate (NaCDC).

[0137] In some embodiments, solid forms of NaCDC are prepared by contacting CDCA (e.g., amorphous CDCA, crystalline CDCA, or mixtures thereof) with a suitable base (e.g., sodium hydroxide). In some embodiments, the present disclosure provides a method of preparing NaCDC, comprising providing CDCA and combining CDCA with a suitable base (e.g., sodium hydroxide), optionally in a suitable solvent, to provide NaCDC. In some embodiments, about 1.0, about 2.0, about 3.0, about 4.0, about 5.0, or more equivalents of a suitable base (e.g., sodium hydroxide) are added.

[0138] In some embodiments, the solid form of NaCDC is prepared by dissolving NaCDC (e.g., amorphous NaCDC, crystalline NaCDC, or a mixture thereof) in a suitable solvent and then converting NaCDC back into a solid phase. In some embodiments, the solid form of NaCDC is prepared by combining NaCDC (e.g., amorphous NaCDC, crystalline NaCDC, or a mixture thereof) in a suitable solvent under suitable conditions and isolating the solid form of NaCDC. In some embodiments, the solid form of NaCDC is prepared according to the methods described herein (e.g., according to slurry, sonication slurry, slow evaporation, solvent drop milling, vapor diffusion into solid, antisolvent vapor diffusion into solution, rapid cooling, forward antisolvent addition method, or reverse antisolvent addition method, as described in the Examples herein).

[0139] In some embodiments, the suitable solvent is methyl isobutyl ketone (MIBK), n-butanol, water, or a mixture thereof. In some embodiments, the suitable solvent is selected from acetone, acetonitrile, n-butyl acetate, diisopropyl ether, ethanol, 2-ethoxyethanol, ethyl acetate, ethyl ether, n-heptane, isopropyl acetate, methanol, methyl ethyl ketone, methyl tert-butyl ether, 2-propanol, 2,2,2-trifluoroethanol, toluene, water, or a mixture thereof.

[0140] In some embodiments, the method of preparing a solid form of NaCDC comprises heating a mixture containing NaCDC to a suitable temperature. In some embodiments, the method of preparing a solid form of NaCDC comprises stirring a mixture containing NaCDC at ambient temperature. In some embodiments, the method of preparing a solid form of NaCDC comprises cooling a mixture containing NaCDC to a suitable temperature.

[0141] In some embodiments, the solid form of NaCDC precipitates from a mixture (e.g., a solution, suspension, or slurry). In some embodiments, the solid form of NaCDC crystallizes from a solution. In some embodiments, the solid form of NaCDC crystallizes from a solution after seeding the solution (e.g., adding crystals of NaCDC to the solution). In some embodiments, the solid form of NaCDC precipitates or crystallizes from a mixture after cooling, addition of an anti-solvent, and / or removal of all or part of the solvent by methods such as evaporation, distillation, filtration, reverse osmosis, absorption, or reaction.

[0142] In some embodiments, the method of preparing a solid form of NaCDC includes isolating the solid form. It will be appreciated that the solid form of NaCDC can be isolated by any suitable means. In some embodiments, the solid form of NaCDC is separated from the supernatant by filtration. In some embodiments, the solid form of NaCDC is separated from the supernatant by decantation. In some embodiments, the solid form of NaCDC is separated from the supernatant by centrifugation.

[0143] In some embodiments, the isolated solid form of NaCDC is dried (eg, in air or under reduced pressure, optionally at elevated temperature).

[0144] In some embodiments, a solid form of NaCDC is prepared by converting one solid form of NaCDC to another solid form of NaCDC. For example, in some embodiments, a solid form of NaCDC (e.g., any one of forms S1, S2, S3, S4, S5, S6, S7, S9-a, S9-b, S10, S11, S12, S13, S14, and / or S15) is prepared by converting NaCDC form B as described in the Examples herein.

[0145] In some embodiments, the solid form of NaCDC is prepared by a process comprising combining CDCA in a suitable solvent (e.g., methyl isobutyl ketone). In some embodiments, the combining step comprises stirring the mixture at a suitable temperature (e.g., ambient temperature). In some embodiments, the process further comprises adding a suitable base (e.g., sodium hydroxide (e.g., as an aqueous solution)). In some embodiments, the process further comprises heating the mixture to reflux (e.g., azeotropic reflux). In some embodiments, the process further comprises distilling off a portion of the solvent, for example, until a vapor temperature of about 117° C. is observed. In some embodiments, the process further comprises cooling the mixture to a suitable temperature (e.g., ambient temperature). In some embodiments, the process further comprises shaking or stirring the mixture (e.g., at ambient temperature). In some embodiments, the process further comprises isolating the solid form of NaCDC (e.g., Form A) by a suitable method (e.g., filtration). In some embodiments, the process includes obtaining a mixture of chenodeoxycholic acid in methyl isobutyl ketone, adding aqueous sodium hydroxide to the mixture, heating the mixture, and removing the solvent to obtain NaCDC Form A.

[0146] In some embodiments, the disclosure provides a method of preparing a solid form of NaCDC, comprising combining CDCA in a suitable solvent (e.g., methyl isobutyl ketone). In some embodiments, the combining step comprises stirring the mixture at a suitable temperature (e.g., ambient temperature). In some embodiments, the method further comprises adding a suitable base (e.g., sodium hydroxide (e.g., as an aqueous solution)). In some embodiments, the method further comprises heating the mixture to reflux (e.g., azeotropic reflux). In some embodiments, the method further comprises distilling off a portion of the solvent, for example, until a vapor temperature of about 117° C. is observed. In some embodiments, the method further comprises cooling the mixture to a suitable temperature (e.g., ambient temperature). In some embodiments, the method further comprises shaking or stirring the mixture (e.g., at ambient temperature). In some embodiments, the method further comprises isolating the solid form of NaCDC (e.g., Form A) by a suitable method (e.g., filtration). In some embodiments, the method includes obtaining a mixture of chenodeoxycholic acid in methyl isobutyl ketone, adding aqueous sodium hydroxide to the mixture, heating the mixture, and removing the solvent to obtain NaCDC Form A.

[0147] In some embodiments, the solid form of NaCDC is prepared by a process comprising combining CDCA in a suitable solvent (e.g., n-butanol). In some embodiments, the combining step comprises stirring the mixture at a suitable temperature (e.g., ambient temperature). In some embodiments, the process further comprises adding a suitable base (e.g., sodium hydroxide (e.g., as an aqueous solution)). In some embodiments, the process further comprises heating the mixture to reflux (e.g., azeotropic reflux). In some embodiments, the process further comprises distilling off a portion of the solvent, for example, until a vapor temperature of about 117° C. is observed. In some embodiments, the process further comprises cooling the mixture to a suitable temperature (e.g., ambient temperature). In some embodiments, the process further comprises shaking or stirring the mixture (e.g., at ambient temperature). In some embodiments, the process further comprises isolating the solid form of NaCDC (e.g., Form B) by a suitable method (e.g., filtration). In some embodiments, the process includes obtaining a mixture of chenodeoxycholic acid in n-butanol, adding aqueous sodium hydroxide to the mixture, heating the mixture, and removing the solvent to obtain NaCDC Form B.

[0148] In some embodiments, the disclosure provides a method of preparing a solid form of NaCDC, comprising combining CDCA in a suitable solvent (e.g., n-butanol). In some embodiments, the combining step comprises stirring the mixture at a suitable temperature (e.g., ambient temperature). In some embodiments, the method further comprises adding a suitable base (e.g., sodium hydroxide (e.g., as an aqueous solution)). In some embodiments, the method further comprises heating the mixture to reflux (e.g., azeotropic reflux). In some embodiments, the method further comprises distilling off a portion of the solvent, for example, until a vapor temperature of about 117° C. is observed. In some embodiments, the method further comprises cooling the mixture to a suitable temperature (e.g., ambient temperature). In some embodiments, the method further comprises shaking or stirring the mixture (e.g., at ambient temperature). In some embodiments, the method further comprises isolating the solid form of NaCDC (e.g., Form B) by a suitable method (e.g., filtration). In some embodiments, the method includes obtaining a mixture of chenodeoxycholic acid in n-butanol, adding aqueous sodium hydroxide to the mixture, heating the mixture, and removing the solvent to obtain NaCDC Form B.

[0149] composition In some embodiments, the present disclosure also provides compositions comprising one or more solid forms of CDCA and / or NaCDC. In some embodiments, the compositions provided comprise amorphous CDCA, crystalline CDCA, amorphous NaCDC, crystalline NaCDC (e.g., Form A or Form B, or any other form provided herein), or mixtures thereof. In some embodiments, the compositions provided comprise NaCDC Form A. In some embodiments, the compositions provided comprise NaCDC Form B.

[0150] In some embodiments, the provided compositions comprising a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) are substantially free of impurities. As used herein, the term "substantially free of impurities" means that the composition does not contain significant amounts of extraneous substances. Such extraneous substances may include starting materials, residual solvents, or any other impurities that may result from the preparation and / or isolation of the crystalline solid form. In some embodiments, the compositions comprise at least about 90% by weight of the crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein). In some embodiments, the compositions comprise at least about 95% by weight of the crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein). In some embodiments, the compositions comprise at least about 99% by weight of the crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein).

[0151] In some embodiments, the provided compositions comprising a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) are substantially pure (e.g., comprising at least about 95%, 97%, 97.5%, 98%, 98.5%, 99%, 99.5%, or 99.8% by weight of the crystalline solid form, based on the total weight of the composition). In some embodiments, the compositions comprising a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) comprise about 5.0 percent or less of total organic impurities. In some embodiments, the compositions comprising a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) comprise about 3.0 percent or less of total organic impurities. In some embodiments, the compositions comprising a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) comprise about 1.5 percent or less of total organic impurities. In some embodiments, a composition comprising a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) comprises about 1.0 percent or less of total organic impurities. In some embodiments, a composition comprising a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) comprises about 0.5 percent or less of total organic impurities. In some embodiments, the percent of total organic impurities is measured by HPLC.

[0152] In some embodiments, the composition comprises a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein) as well as an amorphous solid form (e.g., amorphous CDCA and / or amorphous NaCDC). In some embodiments, the composition comprising a crystalline solid form is substantially free of amorphous solid form. As used herein, the term "substantially free of amorphous solid form" means that the composition does not comprise a significant amount of amorphous solid form. In some embodiments, the composition comprises at least about 90% by weight of a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein). In some embodiments, the composition comprises at least about 95% by weight of a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein). In some embodiments, the composition comprises at least about 99% by weight of a crystalline solid form (e.g., NaCDC Form A or NaCDC Form B, or any other form provided herein). In some embodiments, the composition comprises about 10% by weight or less of the amorphous solid form (e.g., amorphous CDCA and / or amorphous NaCDC). In some embodiments, the composition comprises about 5% by weight or less of the amorphous solid form (e.g., amorphous CDCA and / or amorphous NaCDC). In some embodiments, the composition comprises about 1% by weight or less of the amorphous solid form (e.g., amorphous CDCA and / or amorphous NaCDC).

[0153] In some embodiments, the composition comprises a free acid form (e.g., CDCA) and a salt form (e.g., NaCDC). In some such embodiments, the free acid form is crystalline, amorphous, or a mixture thereof, and in some such embodiments, the salt form is crystalline, amorphous, or a mixture thereof.

[0154] In some embodiments, the compositions include a mixture of crystalline solid forms (eg, a mixture of one or more crystalline forms of CDCA and / or NaCDC).

[0155] Pharmaceutical Compositions In some embodiments, the disclosure provides a pharmaceutical composition comprising NaCDC (e.g., a crystalline form, e.g., Form A or Form B, or any other form provided herein) and a pharma- ceutically acceptable carrier. In some embodiments, the disclosure provides a pharmaceutical composition comprising a solid form of NaCDC (e.g., a solid form described herein) and a pharma- ceutically acceptable carrier. In some embodiments, the pharmaceutical composition provided comprises NaCDC (i.e., in a suitable form, e.g., a crystalline form described herein), and one or more fillers, disintegrants, lubricants, anti-adherents, and / or anti-tackifiers, etc.

[0156] The pharmaceutical compositions of the present disclosure can be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, bucally, vaginally, intraperitoneally, intracisternally, or via an implanted reservoir. In some embodiments, provided pharmaceutical compositions are administered orally, intraperitoneally, or intravenously. In some embodiments, provided pharmaceutical compositions are administered orally.

[0157] In some embodiments, the pharmaceutical compositions provided are in an oral dosage form (e.g., a capsule or tablet). In some embodiments, the pharmaceutical compositions provided are tablets. In some embodiments, the pharmaceutical compositions provided are bilayer tablets (e.g., those described herein). In some embodiments, the pharmaceutical compositions provided are capsules.

[0158] In some embodiments, the pharmaceutical composition provided is a solid pharmaceutical composition (eg, a solid dosage form such as a capsule or tablet).

[0159] In some embodiments, the solid forms of NaCDC provided are useful for preparing pharmaceutical compositions comprising CDCA or a salt thereof as previously reported. For example, PCT Publication No. WO2021 / 030474 (the entire contents of which are incorporated herein by reference) describes certain articles and compositions for delivering therapeutic agents (including CDCA or a salt thereof) to the colon of a subject. Thus, in some embodiments, the solid forms provided can be used to prepare the articles and compositions described herein.

[0160] In some embodiments, the pharmaceutical composition provided is an article, (e.g., a tablet), comprising a first portion comprising a secretion inducer (e.g., CDCA or a salt thereof, e.g., NaCDC, e.g., in a solid form as described herein), a second portion adjacent to the first portion comprising a therapeutic agent (e.g., CDCA or a salt thereof, e.g., NaCDC, e.g., in a solid form as described herein), and a degradable coating associated with the article. In some embodiments, the secretion inducer is configured to increase water content in the colon of the subject. In some embodiments, the local concentration of the secretion inducer is at least 3 mM. In some embodiments, the secretion inducer is configured to increase the amount of intestinal fluid present in the intestine of the subject. In some embodiments, the secretion inducer is configured to completely dissolve within one-fifth of the distance between the ileocecal valve and the right colonic flexure. In some embodiments, the secretion inducer is configured to increase motility of the gastrointestinal tract of the subject. In some embodiments, the article comprises an amount of the secretion inducer of 5 mg to 5 g. In some embodiments, the article comprises a wt% of the secretion inducer of 10 wt% to 95 wt% based on the total weight of the article. In some embodiments, the article is configured to release the therapeutic agent in the colon of the subject. In some embodiments, the article comprises an amount of the therapeutic agent of 10 mg to 10 g. In some embodiments, the article comprises a therapeutic agent of 10 wt % to 95 wt % wt % based on the total weight of the article. In some embodiments, the mass ratio of the secretion inducer:therapeutic agent is 10:90 to 90:10. In some embodiments, the mass ratio of the first part:second part is 1:1 to 1:99. In some embodiments, the degradable coating comprises Eudragit S100, Phloral, HPMC, or Duocoat. In some embodiments, the article further comprises hydroxypropyl methylcellulose (HPMC). In some embodiments, the article further comprises magnesium stearate.

[0161] In some embodiments, the pharmaceutical composition provided is an article (e.g., a tablet) that includes a first component configured to increase the amount of intestinal fluid present in the intestine of a subject, and a second component associated with the first component and configured to release a therapeutic agent in the intestine of the subject. In some embodiments, the first component includes CDCA or a salt thereof (e.g., NaCDC, e.g., a solid form described herein). In some embodiments, the second component includes CDCA or a salt thereof (e.g., NaCDC, e.g., a solid form described herein). In some embodiments, the article is configured to release a therapeutic agent in a portion of the intestine of the subject (e.g., the colon).

[0162] In some embodiments, the pharmaceutical composition provided is an article (e.g., a tablet) comprising a first portion comprising a bile acid or a salt thereof (e.g., CDCA or a salt thereof, e.g., NaCDC, e.g., a solid form described herein), the first portion configured for immediate release in the colon of the subject, a second portion adjacent to the first portion, the second portion comprising a bile acid or a salt thereof (e.g., CDCA or a salt thereof, e.g., NaCDC, e.g., a solid form described herein), the second portion configured for sustained release in the colon of the subject, and a degradable or erodible coating associated with the article. In some embodiments, the article is a pill, tablet, or capsule. In some embodiments, the first portion is configured to completely dissolve within one-fifth of the distance between the ileocecal valve and the right colonic flexure of the subject. In some embodiments, the first portion is configured to provide a local colonic concentration of the bile acid of at least 3 mM. In some embodiments, the second portion further comprises hydroxypropyl methylcellulose (HPMC). In some embodiments, the coating is configured such that the bile acid or salt thereof is released from the first portion in the colon of the subject, hi some embodiments, the coating is or comprises Eudragit S100.

[0163] In some embodiments, the ratio (e.g., weight or height ratio) of the first portion or component and the second portion or component is 1:1 or more, 1:2 or more, 1:3 or more, 1:4 or more, 1:5 or more, 1:10 or more, 1:20 or more, 1:30 or more, 1:40 or more, 1:50 or more, 1:60 or more, 1:70 or more, 1:75 or more, 1:80 or more, 1:85 or more, 1:90 or more, 1:95 or more, 1:96 or more, 1:97 or more, 1:98 or more, or 1:99 or more. In some embodiments, the ratio (e.g., weight ratio or height ratio) of the first portion or component to the second portion or component is 1:1 or less, 1:2 or less, 1:3 or less, 1:4 or less, 1:5 or less, 1:10 or less, 1:20 or less, 1:30 or less, 1:40 or less, 1:50 or less, 1:60 or less, 1:70 or less, 1:75 or less, 1:80 or less, 1:85 or less, 1:90 or less, 1:95 or less, 1:96 or less, 1:97 or less, 1:98 or less, or 1:99 or less. Combinations of the above ranges are also possible (e.g., 1:1 or less and 1:99 or more).

[0164] In some embodiments, the ratio (e.g., weight ratio or height ratio) of the second portion or component and the first portion or component is 1:1 or more, 1:2 or more, 1:3 or more, 1:4 or more, 1:5 or more, 1:10 or more, 1:20 or more, 1:30 or more, 1:40 or more, 1:50 or more, 1:60 or more, 1:70 or more, 1:75 or more, 1:80 or more, 1:85 or more, 1:90 or more, 1:95 or more, 1:96 or more, 1:97 or more, 1:98 or more, or 1:99 or more. In some embodiments, the ratio (e.g., weight ratio or height ratio) of the second portion or component to the first portion or component is 1:1 or less, 1:2 or less, 1:3 or less, 1:4 or less, 1:5 or less, 1:10 or less, 1:20 or less, 1:30 or less, 1:40 or less, 1:50 or less, 1:60 or less, 1:70 or less, 1:75 or less, 1:80 or less, 1:85 or less, 1:90 or less, 1:95 or less, 1:96 or less, 1:97 or less, 1:98 or less, or 1:99 or less. Combinations of the above ranges are also possible (e.g., 1:1 or less and 1:99 or more).

[0165] In some embodiments, the pharmaceutical compositions provided include a secretion inducer. In some embodiments, the secretion inducer is a chemical species that stimulates an increased release of intestinal fluid along the gastrointestinal tract (e.g., relative to the basal release of intestinal fluid and / or the basal release of intestinal fluid in response to a foreign body (e.g., food) present in the gastrointestinal tract). In this way, the increased amount of intestinal fluid enhances the solubility and / or absorption of the therapeutic agent. In some embodiments, the secretion inducer is a bile acid (e.g., CDCA) or a salt thereof. In some embodiments, the secretion inducer is NaCDC. In some embodiments, the secretion inducer includes bisacodyl, senna, sennoside, linaclotide, plecanatide, lubiprostone, 30 methylnaltrexone, naloxegol, polyethylene glycol, lactulose, or prucalopride. In some embodiments, the secretion inducer can be a salt, such as magnesium citrate, magnesium hydroxide, or a bile salt, as non-limiting examples. Other secretion inducers are possible, as any chemical species that stimulates the release of intestinal fluid along the gastrointestinal tract can function as a secretion inducer.

[0166] In some embodiments, the wt% of the secretion inducer relative to the article or composition (e.g., tablet, capsule, etc.) is 10 wt% or more, 15 wt% or more, 20 wt% or more, 25 wt% or more, 30 wt% or more, 40 wt% or more, 50 wt% or more, 60 wt% or more, 70 wt% or more, 75 wt% or more, 80 wt% or more, 90 wt% or more, or 95 wt% or more. In some embodiments, the wt% of the secretion inducer relative to the article or composition (e.g., tablet, capsule, etc.) is 95 wt% or less, 90 wt% or less, 80 wt% or less, 75 wt% or less, 70 wt% or less, 60 wt% or less, 50 wt% or less, 40 wt% or less, 30 wt% or less, 25 wt% or less, 20 wt% or less, 15 wt% or less, or 10 wt% or less. Combinations of the above ranges are also possible (eg, greater than or equal to 10 wt % and less than or equal to 50 wt %). Other ranges are also possible.

[0167] In some embodiments, the amount (e.g., mass) of secretory inducer present in the article or composition (e.g., tablet, capsule, etc.) is 5 mg or more, 10 mg or more, 20 mg or more, 20 mg or more, 30 mg or more, 50 mg or more, 60 mg or more, 70 mg or more, 75 mg or more, 80 mg or more, 90 mg or more, 95 mg or more, 100 mg or more, 250 mg or more, 500 mg or more, 750 mg or more, 1 g or more, 2 g or more, 3 g or more, 4 g or more, or 5 g or more. In some embodiments, the amount of secretion inducer present in the article or composition (e.g., tablet, capsule, etc.) is 5g or less, 4g or less, 3g or less, 2g or less, 1g or less, 750mg or less, 500mg or less, 250mg or less, 100mg or less, 95mg or less, 90mg or less, 80mg or less, 75mg or less, 70mg or less, 60mg or less, 50mg or less, 40mg or less, 30mg or less, 25mg or less, 20mg or less, 10mg or less, or 5mg or less. Combinations of the above ranges are also possible (e.g., 5mg or more and 5g or less). Other ranges are also possible.

[0168] In some embodiments, the provided pharmaceutical compositions include a therapeutic agent. In some embodiments, the therapeutic agent can be one or a combination of therapeutic agents, diagnostic agents, and / or enhancing agents (e.g., drugs, nutrients, microorganisms, in vivo sensors, and tracers). In some embodiments, the therapeutic agent is a nutritional supplement, a prophylactic agent, or a diagnostic agent. Therapeutic agents can include, but are not limited to, any synthetic or natural biologically active compound or composition of matter that, when administered to a subject (e.g., a human or non-human animal), induces a desired pharmacological, immunogenic, and / or physiological effect (e.g., an increase in the amount of intestinal fluid present in the colon of the subject) through local and / or systemic action. For example, in some embodiments, therapeutic agents include chemicals traditionally considered to be drugs, vaccines, and biopharmaceuticals. Lists of examples of known therapeutic agents can be found, e.g., in the United States Pharmacopeia (USP); Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Ed., McGraw Hill, 2017; Katzung, B. and Vanderah, TW (eds.) Basic and Clinical Pharmacology, McGraw-Hill; 15th edition (December 5, 2020); Prescriber's Digital Reference (pdr.net); The Merck Manual 20 th ed. (2018), Porter, RE (ed.), Wiley; or for animals, The Merck Veterinary Manual, 11th ed., Kahn, CA (ed.), Merck Manuals, 2016; and “Approved Drug Products with Therapeutic Equivalence and Evaluations,” (published by the U.S. Food and Drug Administration (FDA)) (“Orange Book”).

[0169] In some embodiments, the therapeutic agent is a bile acid (e.g., CDCA) or a salt thereof. In some embodiments, the therapeutic agent is NaCDC. Non-limiting examples of bile acids include chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, taurocholic acid, glycocholic acid, cholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, deoxycholic acid, and lithocholic acid. Thus, in some embodiments, the therapeutic agent is selected from the group consisting of chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, taurocholic acid, glycocholic acid, cholic acid, taurochenodeoxycholic acid, glycochenodeoxycholic acid, deoxycholic acid, and lithocholic acid, or salts thereof.

[0170] In some embodiments, the wt% of the therapeutic agent relative to the total weight of the article or composition (e.g., tablet, capsule, etc.) is 10 wt% or more, 15 wt% or more, 20 wt% or more, 25 wt% or more, 30 wt% or more, 40 wt% or more, 50 wt% or more, 60 wt% or more, 70 wt% or more, 75 wt% or more, 80 wt% or more, 90 wt% or more, or 95 wt% or more. In some embodiments, the wt% of the therapeutic agent relative to the total weight of the article or composition (e.g., tablet, capsule, etc.) is 95 wt% or less, 90 wt% or less, 80 wt% or less, 75 wt% or less, 70 wt% or less, 60 wt% or less, 50 wt% or less, 40 wt% or less, 30 wt% or less, 25 wt% or less, 20 wt% or less, 15 wt% or less, or 10 wt% or less. Combinations of the above ranges are also possible (eg, greater than or equal to 10 wt % and less than or equal to 50 wt %). Other ranges are also possible.

[0171] In some embodiments, the amount (e.g., mass) of therapeutic agent present in the article or composition (e.g., tablet, capsule, etc.) is 10 mg or more, 20 mg or more, 25 mg or more, 60 mg or more, 70 mg or more, 75 mg or more, 80 mg or more, 90 mg or more, 95 mg or more, 100 mg or more, 250 mg or more, 300 mg or more, 400 mg or more, 500 mg or more, 750 mg or more, 1 g or more, 2 g or more, 3 g or more, 4 g or more, 5 g or more, 6 g or more, 7 g or more, 8 g or more, 9 g or more, or 10 g or more. In some embodiments, the amount (e.g., mass) of therapeutic agent present in an article or composition (e.g., tablet, capsule, etc.) is 10 mg or less, 20 mg or less, 25 mg or less, 60 mg or less, 70 mg or less, 75 mg or less, 80 mg or less, 90 mg or less, 95 mg or less, 100 mg or less, 250 mg or less, 300 mg or less, 400 mg or less, 500 mg or less, 750 mg or less, 1 g or less, 2 g or less, 3 g or less, 4 g or less, 5 g or less, 6 g or less, 7 g or less, 8 g or less, 9 g or less, or 10 g or less. Combinations of the above ranges are also possible (e.g., 10 mg or more and 10 g or less). Other ranges are also possible.

[0172] In some embodiments, the mass ratio of secretion inducer:therapeutic agent is 10:90 or more, 20:80 or more, 30:70 or more, 40:60 or more, 50:50 or more, 60:40 or more, 70:30 or more, 80:20 or more, or 90:10 or more. In some embodiments, the mass ratio of secretion inducer:therapeutic agent is 90:10 or less, 80:20 or less, 70:30 or less, 60:40 or less, 50:50 or less, 40:60 or less, 30:70 or less, 20:80 or less, or 10:90 or less. Combinations of the above ranges are also possible (e.g., 10:90 or more to 30:70 or less). Other ranges are also possible.

[0173] In some embodiments, the pharmaceutical compositions provided include a coating. In some embodiments, the coating is degradable and / or erodible (e.g., by gastrointestinal fluids under physiological conditions). In some embodiments, the coating is or includes Eudragit S100. Any suitable coating configured to release the secretion-inducing agent in the desired portion of the gastrointestinal tract (e.g., non-limiting examples include the distal ileum or distal colon) can be used. Non-limiting examples of suitable degradable coatings include Eudragit S, Phloral, CODES, and Duocoat. In some embodiments, the coating is or includes, for example, hydroxypropyl methylcellulose (HPMC). Other coatings are possible.

[0174] In some embodiments, the pharmaceutical composition provided includes one or more additional components (e.g., excipients). In some embodiments, the additional components can contribute to the stability of the composition, the solubility of the composition, and / or the ability of the composition to deliver a therapeutic agent to a desired portion of the gastrointestinal tract. In some embodiments, the additional component is magnesium stearate. In some embodiments, the additional component is hydroxypropyl methylcellulose. In some embodiments, the additional component is Aerosil® 200 Pharma. In some embodiments, the additional component is selected from microcrystalline cellulose (e.g., Avicel PH102), croscarmellose sodium, copovidone, magnesium stearate, calcium hydrogen phosphate dihydrate, sodium starch glycolate, sodium stearyl fumarate, poly(ethylene oxide) (e.g., PolyOX WSR1105), and hydroxypropyl methylcellulose (e.g., HPMC K4M). In some embodiments, the additional component can form a matrix around or within the composition. In some embodiments, the additional component can control the release of one or more other components of the composition (e.g., the secretion inducer or the therapeutic agent). Non-limiting examples of suitable matrix-forming and / or release-controlling agents include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, alginates, plant-derived gums, chitosan, gelatin, pectin, carrageenan, polyacrylates, polyethylene oxide, and starch. Examples of hydrophobic matrix-forming and / or release-controlling agents include waxes, fatty acids, fatty alcohols and esters, glycerin esters, polyesteramides, ethylcellulose, polyethylene, polypropylene, polythiourethanes, polyvinyl butyral, polylactic acid, poly(lactide-coglycolide), cellulose acetate, and cellulose acetate butyrate. Other additional components that aid in the delivery of the secretion inducer or therapeutic agent are also possible.

[0175] In some embodiments, the pharmaceutical composition provided can include hydrophilizing agent.Non-limiting examples of suitable hydrophilizing agent include cyclodextrin, surfactant, solid buffer (e.g., sodium citrate / citric acid).Other examples of hydrophilizing agent are possible, since the present disclosure is not so limited.

[0176] In some embodiments, the pharmaceutical compositions provided are configured such that when administered to a subject, the secretion inducer is present at a local concentration of at least 3 mM along the gastrointestinal tract. In some embodiments, the local concentration is at least 5 mM. In some embodiments, a local concentration of at least 3 mM, at least 5 mM, at least 10 mM, at least 15 mM, at least 20 mM, at least 30 mM, or at least 50 mM is provided. In some embodiments, a local concentration of 100 mM or less, 50 mM or less, 30 mM or less, 20 mM or less, 15 mM or less, 10 mM or less, or 5 mM or less is provided. As described herein, "local concentration" refers to the amount of a substance per unit volume at a location near the article. For example, the concentration of the secretion inducer along the entire gastrointestinal tract may be substantially less than 3 mM, while the concentration of the secretion inducer in the vicinity of the provided composition or article may be 3 mM or more.

[0177] In some embodiments, the maximum cross-sectional dimension (e.g., diameter) of the provided pharmaceutical compositions is at least 10 mm, at least 12 mm, at least 14 mm, at least 15 mm, at least 18 mm, at least 19 mm, at least 21 mm, at least 23 mm, or at least 26 mm. In some embodiments, the maximum cross-sectional dimension of the provided pharmaceutical compositions is up to 27 mm, up to 24 mm, up to 22 mm, up to 20 mm, up to 18 mm, up to 16 mm, up to 15 mm, or up to 10 mm.

[0178] In some embodiments, the pharmaceutical composition provided is a bilayer tablet coated with Eudragit S100, the bilayer tablet comprising a first layer comprising 81% NaCDC, 17% hydroxypropylmethylcellulose (HPMC) (MW: 120,000), and 2% magnesium stearate, and a second layer comprising 98% NaCDC and 2% magnesium stearate. In some such embodiments, the bilayer tablet comprises 400 mg of NaCDC in the first layer. In some such embodiments, the bilayer tablet comprises 98 mg of NaCDC in the second layer.

[0179] In some embodiments, the pharmaceutical composition provided is a bilayer tablet coated with Eudragit S100, the bilayer tablet comprising a first layer comprising 87.5% NaCDC, 10% HPMC (MW: 120,000), 2% magnesium stearate, and 0.5% Aerosil 200, and a second layer comprising 97.5% NaCDC, 2% magnesium stearate, and 0.5% Aerosil 200. In some such embodiments, the bilayer tablet comprises 400 mg of NaCDC in the first layer. In some such embodiments, the bilayer tablet comprises 100 mg of NaCDC in the second layer.

[0180] In some embodiments, the provided pharmaceutical compositions are prepared by (i) obtaining NaCDC in any suitable form (e.g., a crystalline form described herein) and (ii) formulating the NaCDC with suitable excipients to obtain a pharmaceutical composition.

[0181] use The present disclosure provides uses of the solid forms and compositions described herein. In some embodiments, the provided solid forms and compositions thereof are useful in the pharmaceutical field (e.g., as therapeutic agents). In some embodiments, the provided solid forms and compositions described herein are useful in research (e.g., as analytical tools and / or controls).

[0182] In some embodiments, the present disclosure provides a method of administering the provided solid forms and compositions thereof to a subject in need thereof. In some embodiments, the present disclosure provides a method of administering the provided solid forms and compositions thereof to a subject suffering from a gastrointestinal disorder (e.g., constipation, e.g., IBS-C). In some embodiments, the present disclosure provides a method of administering the provided solid forms and compositions thereof to a subject suffering from a systemic disorder (e.g., a subject in whom treatment, e.g., administration of the provided solid forms or compositions thereof to the gastrointestinal tract, may be effective in treating the systemic disorder). In some embodiments, the present disclosure provides a method of administering the provided solid forms and compositions thereof to a subject in need of a colonoscopy (e.g., a test for diagnosing a colonic lesion). In some embodiments, the present disclosure provides a method of administering the provided solid forms and compositions thereof to a subject suffering from constipation, ulcerative colitis, Crohn's disease, diabetes, metabolic disorders, obesity, traveler's diarrhea, hepatic encephalopathy, or a disease associated with biome regulation. In some embodiments, such a method comprises orally administering the provided solid forms or compositions thereof to a subject.

[0183] As used herein, it will be understood that a "subject" refers to an organism, typically a mammal (e.g., a human, a non-human mammal, a non-human primate, a primate, a mouse, a rat, a hamster, a gerbil, a cat, a dog, etc.). In some embodiments, the subject is a human.

[0184] In some embodiments, the present disclosure provides a method of delivering a therapeutic agent (e.g., a bile acid, e.g., CDCA or a salt thereof) to the intestine (e.g., colon) of a subject in need thereof. In some embodiments, such methods include administering a solid form or composition described herein (e.g., a composition comprising or prepared from one or more solid forms provided herein). In some embodiments, such methods include orally administering a provided solid form or composition thereof to a subject.

[0185] In some embodiments, the disclosure provides a method of treating a disease, disorder, or condition, comprising administering a provided solid form or composition thereof to a subject in need thereof. As used herein, "treat", "treatment", or "treating" refers to any administration of a therapeutic agent that partially or completely relieves, improves, alleviates, inhibits, delays the onset of, reduces the severity of, and / or reduces the incidence of one or more symptoms, characteristics, and / or causes of a particular disease, disorder, and / or condition. In some embodiments, such treatment may be treatment of a subject who does not show signs of the relevant disease, disorder, and / or condition, and / or treatment of a subject who shows only early signs of the disease, disorder, and / or condition. Alternatively or additionally, such treatment may be treatment of a subject who shows one or more established signs of the relevant disease, disorder, and / or condition. In some embodiments, treatment may be treatment of a subject who has been diagnosed as suffering from the relevant disease, disorder, and / or condition. In some embodiments, the treatment may be treatment of a subject known to have one or more susceptibility factors that are statistically correlated with an increased risk of developing the relevant disease, disorder, and / or condition. Thus, in some embodiments, the treatment may be prophylactic, and in some embodiments, the treatment may be therapeutic.

[0186] In some embodiments, the present disclosure provides a method of treating a gastrointestinal disorder (e.g., constipation, e.g., IBS-C), comprising administering a provided solid form or composition thereof to a subject in need thereof. In some embodiments, the provided method achieves a certain desired outcome, such as improved efficacy (e.g., compared to another formulation of CDCA or its salt) and / or reduced incidence of abdominal pain and / or cramping. In some embodiments, such a method comprises orally administering a provided solid form or composition thereof to a subject.

[0187] In some embodiments, the disclosure provides a method of treating a systemic disorder (e.g., one in which administration of a therapeutic agent (e.g., a provided solid form or composition thereof) to the gastrointestinal tract may be effective in treating the systemic disorder), comprising administering a provided solid form or composition thereof to a subject in need thereof. In some embodiments, the disclosure provides a method of treating a disease, disorder, or condition selected from the group consisting of constipation, ulcerative colitis, Crohn's disease, diabetes, metabolic disorders, obesity, traveler's diarrhea, hepatic encephalopathy, and diseases associated with biome regulation, comprising administering a provided solid form or composition thereof to a subject in need thereof. In some embodiments, such a method comprises orally administering a provided solid form or composition thereof to a subject.

[0188] In some embodiments, the present disclosure provides a method of diagnosing a colonic pathology, comprising administering a provided solid form or composition thereof to a subject in need thereof. In some such embodiments, the subject has undergone or will undergo a colonoscopy. In some embodiments, such a method comprises orally administering a provided solid form or composition thereof to the subject.

[0189] Exemplary embodiments The following numbered embodiments are illustrative, though non-limiting, of certain aspects of the present disclosure. 1. A crystalline solid form of sodium chenodeoxycholate, said solid form being selected from form A and form B. 2. The solid form of embodiment 1, wherein said solid form is Form A. 3. The solid form of embodiment 2, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees two-theta. 4. The solid form of embodiment 2, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 6.07, about 6.55, about 10.72, about 14.64, about 15.06, about 17.58, and about 18.34 degrees two-theta. 5. The solid form of embodiment 2, wherein the solid form is characterized by substantially all of the following peaks in its XRPD pattern: [Table 19] 6. The solid form of embodiment 2, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 1; (ii) a DSC pattern showing loss of water from slightly above ambient temperature up to about 150°C; (iii) a DSC pattern substantially similar to that shown in FIG. (iv) a TGA pattern showing a weight loss of 4.3% up to 150°C; and (v) A TGA pattern substantially similar to that shown in FIG. 7. The solid form of embodiment 1, wherein said solid form is form B. 8. The solid form of embodiment 7, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees two-theta. 9. The solid form of embodiment 7, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 6.75, about 8.14, about 9.79, about 14.02, about 16.10, and about 18.63 degrees two-theta. 10. The solid form of embodiment 7, wherein the solid form is characterized by substantially all of the following peaks in its XRPD pattern: [Table 20] 11. The solid form according to embodiment 7, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 5; (ii) a DSC pattern showing no thermal events from room temperature to approximately 288°C; (iii) a DSC pattern substantially similar to that shown in FIG. (iv) a TGA pattern that exhibits less than 0.1% weight loss up to 150° C.; and (v) TGA pattern substantially similar to that shown in FIG. 12. A crystalline solid form of sodium chenodeoxycholate obtainable from the methods described herein. 13. A crystalline solid form of sodium chenodeoxycholic acid, prepared by a process comprising obtaining a mixture of chenodeoxycholic acid in methyl isobutyl ketone, adding aqueous sodium hydroxide to the mixture, heating the mixture (and, for example, azeotropically refluxing), and removing the solvent to obtain the crystalline solid form of sodium chenodeoxycholic acid. 14. A crystalline solid form of sodium chenodeoxycholic acid, prepared by a process comprising obtaining a mixture of chenodeoxycholic acid in n-butanol, adding aqueous sodium hydroxide to the mixture, heating the mixture (e.g., to azeotropic reflux), and removing the solvent to obtain the crystalline solid form of sodium chenodeoxycholic acid. 15. A crystalline solid form of sodium chenodeoxycholate, said solid form being selected from form S1, form S2, form S3, form S4, form S5, form S6, form S7, form S9-a, form S9-b, form S10, form S11, form S12, form S13, form S14, and form S15. 16. The solid form of embodiment 15, wherein said solid form is form S1. 17. The solid form of embodiment 16, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees two-theta. 18. The solid form of embodiment 16, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 5.45, about 5.80, about 7.46, about 9.76, about 12.40, about 14.88, and about 20.02 degrees two-theta. 19. The solid form of embodiment 16, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S1-A or Table S1-B. 20. The solid form according to embodiment 16, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 19A, Figure 24A, and / or Figure 48; (ii) a DSC pattern showing thermal events at about 96.0° C., about 142.5° C., and / or about 313.4° C.; (iii) a DSC pattern substantially similar to that shown in Figure 19B, Figure 24B, Figure 27, and / or Figure 49; (iv) a TGA pattern showing a weight loss of about 2.177% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in Figure 19B, Figure 24B, Figure 27, and / or Figure 49. 21. The solid form of embodiment 15, wherein the solid form is form S2. 22. The solid form of embodiment 21, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees two theta. 23. The solid form of embodiment 21, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 7.11, about 7.78, about 9.81, about 12.58, about 12.96, and about 13.54 degrees two theta. 24. The solid form of embodiment 21, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S2. 25. The solid form according to embodiment 21, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 33; (ii) a DSC pattern showing thermal events at about 112.9° C., about 177.8° C., and / or about 334.1° C.; (iii) a DSC pattern substantially similar to that shown in Figure 21A, Figure 25, and / or Figure 30; (iv) a TGA pattern showing a weight loss of about 3.95% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in Figure 21A, Figure 25, and / or Figure 30. 26. The solid form according to embodiment 15, wherein the solid form is form S3, form S6, and / or form S11. 27. The solid form of embodiment 26, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees two theta. 28. The solid form of embodiment 26, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 5.00, about 7.56, about 10.56, about 11.45, about 11.93, and about 12.46 degrees two theta. 29. The solid form of embodiment 26, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S3, Table S6, or Table S11. 30. The solid form according to embodiment 26, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 21B and / or Figure 50A; (ii) a DSC pattern showing thermal events at about 50.6° C., about 199.8° C., and / or about 331.5° C.; (iii) a DSC pattern substantially similar to that shown in Figure 29 and / or Figure 41; (iv) a TGA pattern showing a weight loss of about 2.456% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 29 and / or FIG. 41. 31. The solid form of embodiment 15, wherein the solid form is form S4. 32. The solid form of embodiment 31, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees two-theta. 33. The solid form of embodiment 31, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 7.07, about 7.65, about 9.70, about 13.43, about 15.02, about 16.52, and about 16.96 degrees two theta. 34. The solid form of embodiment 31, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S4. 35. The solid form according to embodiment 31, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 31A; (ii) a DSC pattern showing thermal events at about 146.5° C. and / or about 333.9° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 22 and / or FIG. 31B ; (iv) a TGA pattern showing a weight loss of about 14.23% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 22 and / or FIG. 31B. 36. The solid form of embodiment 15, wherein the solid form is form S5. 37. The solid form of embodiment 36, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2-theta. 38. The solid form of embodiment 36, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 7.11, about 8.63, about 12.08, about 12.75, about 13.46, about 14.25, and about 16.68 degrees 2-theta. 39. The solid form of embodiment 36, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S5. 40. The solid form according to embodiment 36, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 23A; (ii) a DSC pattern showing thermal events at about 82° C., about 183.9° C., and / or about 331.5° C.; (iii) a DSC pattern substantially similar to that shown in Figures 23B, 28, 32A, 32B, and / or 47; (iv) a TGA pattern showing a weight loss of about 4.79% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in Figure 23B, Figure 28, Figure 32A, Figure 32B, and / or Figure 47. 41. The solid form of embodiment 15, wherein the solid form is form S7. 42. The solid form of embodiment 41, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees two theta. 43. The solid form of embodiment 41, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 8.47, about 9.90, about 14.36, about 15.26, about 17.00, and about 17.72 degrees two theta. 44. The solid form of embodiment 41, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S7. 45. The solid form according to embodiment 41, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 26A; (ii) a DSC pattern showing thermal events at about 109.2° C., about 324.5° C., and / or about 335.3° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 26B; (iv) a TGA pattern showing a weight loss of about 10.04% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 26B. 46. ​​The solid form of embodiment 15, wherein the solid form is form S9-a. 47. The solid form of embodiment 46, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees two theta. 48. The solid form of embodiment 46, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 5.10, about 7.00, about 13.52, about 14.23, about 15.46, and about 18.78 degrees two theta. 49. The solid form of embodiment 46, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S9-a. 50. The solid form according to embodiment 46, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 37 (bottom spectrum); (ii) a DSC pattern showing thermal events at about 99.9° C. and / or about 328° C.; (iii) a DSC pattern substantially similar to that shown in Figure 38 and / or Figure 39; (iv) a TGA pattern showing a weight loss of about 8.635% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 38 and / or FIG. 39. 51. The solid form of embodiment 15, wherein the solid form is form S9-b. 52. The solid form of embodiment 51, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees two theta. 53. The solid form of embodiment 51, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 5.47, about 7.48, about 9.82, about 12.66, and about 15.07 degrees two theta. 54. The solid form of embodiment 51, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S9-b. 55. The solid form of embodiment 51, wherein said solid form is characterized by an XRPD pattern substantially similar to that shown in Figure 37 (bottom spectrum). 56. The solid form according to embodiment 15, wherein said solid form is form S10. 57. The solid form of embodiment 56, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta. 58. The solid form of embodiment 56, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 5.13, about 7.01, about 8.69, about 9.11, about 13.55, about 14.91, and about 15.53 degrees 2-theta. 59. The solid form of embodiment 56, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S10. 60. The solid form according to embodiment 56, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 40A; (ii) a DSC pattern showing thermal events at about 141.3° C., about 324° C., and / or about 336° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 40B; (iv) a TGA pattern showing a weight loss of about 16% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in Figure 40B. 61. The solid form according to embodiment 15, wherein the solid form is form S12 and / or form S15. 62. The solid form of embodiment 61, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees two theta. 63. The solid form of embodiment 61, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 4.82, about 5.22, about 5.89, about 10.81, about 13.00, about 15.00, and about 18.94 degrees two theta. 64. The solid form of embodiment 61, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S12 or Table S15. 65. The solid form according to embodiment 61, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in FIG. 42; (ii) a DSC pattern showing thermal events at about 80.8° C., about 180° C., and / or about 332° C.; (iii) a DSC pattern substantially similar to that shown in FIG. (iv) a TGA pattern showing a weight loss of about 4.448% up to about 150° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 66. The solid form of embodiment 15, wherein the solid form is form S13. 67. The solid form of embodiment 66, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees two theta. 68. The solid form of embodiment 66, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 4.95, about 7.53, about 9.85, about 11.55, about 12.12, and about 15.01 degrees two-theta. 69. The solid form of embodiment 66, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S13. 70. The solid form according to embodiment 66, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 44 and / or Figure 53; (ii) a DSC pattern showing thermal events at about 55.4° C., about 148.8° C., about 191.8° C., and / or about 335° C.; (iii) a DSC pattern substantially similar to that shown in Figure 45; (iv) a TGA pattern showing a weight loss of about 6.162% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in FIG. 71. The solid form according to embodiment 15, wherein the solid form is form S14. 72. The solid form of embodiment 71, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees two theta. 73. The solid form of embodiment 71, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at about 5.15, about 5.50, about 7.05, about 12.04, about 14.90, and about 16.56 degrees two theta. 74. The solid form of embodiment 71, wherein the solid form is characterized in its XRPD pattern by substantially all of the peaks listed in Table S14. 75. The solid form according to embodiment 71, wherein the solid form is characterized by one or more of the following: (i) an XRPD pattern substantially similar to that shown in Figure 46A; (ii) a DSC pattern showing thermal events at about 143.7° C. and / or about 331° C.; (iii) a DSC pattern substantially similar to that shown in FIG. 46B; (iv) a TGA pattern showing a weight loss of about 15.84% up to about 180° C.; and (v) A TGA pattern substantially similar to that shown in Figure 46B. 76. A pharmaceutical composition comprising a solid form according to any one of embodiments 1 to 75 and a pharma- ceutically acceptable carrier. 77. The pharmaceutical composition according to embodiment 76, wherein the pharmaceutical composition is a solid. 78. The pharmaceutical composition of embodiment 76 or 77, wherein the pharmaceutical composition is formulated for oral administration. 79. A pharmaceutical composition, prepared by a method comprising obtaining a solid form according to any one of embodiments 1 to 75, and formulating said solid form with suitable excipients to obtain said pharmaceutical composition. 80. A pharmaceutical composition comprising: a first portion comprising a bile acid or a salt thereof, the first portion being configured for immediate release in the colon of the subject; a second portion adjacent to the first portion, the second portion comprising a bile acid or a salt thereof and configured for sustained release in the colon of the subject; and a degradable or erodible coating associated with said pharmaceutical composition. The pharmaceutical composition, wherein at least one of the first and second parts comprises a solid form according to any one of embodiments 1 to 75. 81. A pharmaceutical composition comprising: a first portion comprising a bile acid or a salt thereof, the first portion being configured for immediate release in the colon of the subject; a second portion adjacent to the first portion, the second portion comprising a bile acid or a salt thereof and configured for sustained release in the colon of the subject; and a degradable or erodible coating associated with said pharmaceutical composition. Obtaining a solid form according to any one of embodiments 1 to 75; and b. formulating said solid form with suitable excipients to obtain said pharmaceutical composition. 82. The pharmaceutical composition according to embodiment 80 or 81, wherein the pharmaceutical composition is a tablet. 83. The pharmaceutical composition of any one of embodiments 80-82, wherein the bile acid or salt thereof in the first and second moieties is chenodeoxycholic acid or a salt thereof. 84. The pharmaceutical composition of embodiment 83, wherein the first part and the second part comprise a solid form as described in any one of embodiments 1 to 75. 85. A pharmaceutical composition according to any one of embodiments 80-84, wherein the coating is or comprises Eudragit S100. 86. A method comprising administering a solid form according to any one of embodiments 1 to 75 or a pharmaceutical composition according to any one of embodiments 76 to 85 to a subject in need thereof. 87. The method according to embodiment 86, comprising orally administering a solid form according to any one of embodiments 1 to 75 or a pharmaceutical composition according to any one of embodiments 76 to 85. 88. A method for treating a disease, disorder, or condition, comprising administering to a subject in need thereof a solid form described in any one of embodiments 1 to 75 or a pharmaceutical composition described in any one of embodiments 76 to 85. 89. The method of any one of embodiments 86-88, wherein the subject is suffering from a gastrointestinal disease, disorder, or condition. 90. The method of any one of embodiments 86-88, wherein the subject suffers from constipation. 91. The method of any one of embodiments 86-88, wherein the subject suffers from irritable bowel syndrome with constipation (IBS-C). 92. A method for preparing a solid form according to any one of embodiments 1 to 75, according to a method described herein. 93. A method for preparing a solid form according to any one of embodiments 1 to 14, comprising: obtaining chenodeoxycholic acid; contacting chenodeoxycholic acid with a suitable base in a suitable solvent to obtain said solid form; The method comprising: 94. The method of embodiment 93, wherein the suitable base is sodium hydroxide. 95. The method of embodiment 93, wherein the suitable solvent is selected from methyl isobutyl ketone, n-butanol, and water. 96. A method for preparing a solid form according to any one of embodiments 2 to 6, comprising: obtaining a mixture of chenodeoxycholic acid in methyl isobutyl ketone; adding aqueous sodium hydroxide to the mixture; heating the mixture; removing the solvent to obtain said solid form; The method comprising: 97. A method for preparing a solid form according to any one of embodiments 7 to 11, comprising: obtaining a mixture of chenodeoxycholic acid in n-butanol; adding aqueous sodium hydroxide to the mixture; heating the mixture; and removing the solvent to obtain the solid form. 98. The method of embodiment 96 or 97, wherein the mixture is heated to azeotropic reflux. 99. A method for preparing a pharmaceutical composition according to any one of embodiments 76 to 85, comprising: Obtaining a solid form according to any one of embodiments 1 to 75; formulating said solid form with suitable excipients to obtain said pharmaceutical composition; The method comprising: EXAMPLES

[0190] The examples provided herein document and support certain aspects of the present disclosure, but are not intended to limit the scope of any claims. The following non-limiting examples are provided to further illustrate certain teachings provided by the present disclosure. Those skilled in the art will appreciate that, in light of this application, various modifications can be made to the specific embodiments illustrated in the examples without departing from the spirit and scope of the present teachings.

[0191] Materials and Methods: Examples 1-4 X-ray powder diffraction (XRPD) XRPD analysis was performed on a Bruker D8 Advance diffractometer (goniometer radius 280 mm, working in Bragg-Brentano geometry). The radiation used was Ni filtered CuKα (1.54 Å) and the detector used was a silicon strip (LynxEye) detector. The analysis range was 3–40° in 2θ (in 0.02° increments). The sample holder used was a zero-background silicon single crystal. The acquired data were analyzed with Diffrac.Eva software (version 4.3.0.1, Bruker AXS).

[0192] Differential Scanning Calorimetry (DSC) Differential scanning calorimetry (DSC) analysis was performed in a Mettler-Toledo DSC-3 cell. Accurately weighed samples of 3–7 mg were placed in aluminum pans with perforated lids and heated from 30°C to 300°C at 10°C / min under nitrogen flow. The data were analyzed with Stare software (version 16.00).

[0193] Thermogravimetric analysis (TGA) Thermogravimetric analysis (TGA) was performed on a Mettler-Toledo TGA2. Accurately weighed samples of 15–30 mg were heated from 25°C to 300°C at 10°C / min under a nitrogen stream. The data were analyzed with Stare software (version 16.20).

[0194] Dynamic Vapor Sorption (DVS) DVS measurements were performed with an SMS-DVS Intrinsic. Sample size was approximately 50 mg and was accurately weighed. Measurements were performed at 25°C. The relative humidity (RH) ranges investigated were 40-90 and 0-90% RH (in 10% RH increments). After each RH change, the sample mass was stabilized (waiting time 10-60 min, stabilization criterion ≦0.002 g, 10 min).

[0195] The moisture absorption of the samples was calculated as follows: Weight change % = (W2-W1)W1 / 100 During the ceremony, W1: weight of the sample at the start of the experiment (25°C, 40% RH) W2: weight of the sample at 25°C and 80% RH in the first adsorption cycle

[0196] High Pressure Liquid Chromatography (HPLC) In the intrinsic dissolution test, the following HPLC method was used. [Table 21]

[0197] Example 1. Preparation and characterization of provided solid forms Chenodeoxycholate Sodium Form A NaCDC Form A was prepared according to the following exemplary procedure. A 1 liter reactor equipped with a Dean-Stark apparatus was charged with CDCA (50 g) and methyl isobutyl ketone (2500 mL, 5 volumes) at 20° C.±5° C. The mixture was stirred and then 18.7 g of a solution of NaOH 30% p / p in water was added. Once dissolution was complete, a slight exothermic reaction was observed. The solution was heated to azeotropic reflux for 2-3 hours to distill off the water. Once crystallization began to occur, the mixture was stirred at 115-117° C. for an additional hour, then cooled at 20° C.±5° C. and stirred at 20° C.±5° C. for 2 hours. The mixture was filtered by washing the panel with 50 mL of methyl isobutyl ketone. The wet product (51.6 g) was dried under vacuum at 50° C. to give NaCDC Form A (47.8 g, 85.2% yield).

[0198] The XRPD pattern of Form A is shown in Figure 1 and the corresponding data is summarized below. [Table 22]

[0199] As shown in Figure 2, DSC analysis of Form A showed that water loss started just above room temperature and continued up to about 150°C. Karl Fischer analysis showed a water content of 6.0 w / w% in Form A. TGA analysis of Form B (Figure 3) showed a weight loss of 4.3% up to 150°C. Form A was determined to be a sesquihydrate.

[0200] DVS of Form A showed that this form was hygroscopic (14.1% weight change in the first adsorption cycle, Figure 9).

[0201] Upon exposure to humid air, the water content of Form A increased, eventually becoming partially amorphous and losing crystallinity after 15–20 h at 95% humidity (Figure 4).

[0202] Chenodeoxycholate Sodium Form B NaCDC form B was prepared according to the following exemplary procedure: A 1 liter reactor equipped with a Dean-Stark apparatus was charged with CDCA (50 g) and n-butanol (300 mL) at 20° C.±5° C. The mixture was stirred and then aqueous NaOH (18.7 g, 30% p / p in water) was added. The solution was heated to azeotropic reflux for 3-4 hours. Once crystallization started, approximately 200 mL (4 volumes) of solvent was distilled in about 3-4 hours until a vapor temperature of 117° C. was reached. The resulting suspension was cooled to 20° C.±5° C. and shaken at 20° C.±5° C. for 1 hour. The solid was filtered and washed with n-butanol (50 mL). The wet solid was dried under vacuum at 75° C. to obtain NaCDC form B (46.7 g, 88.5% yield).

[0203] The XRPD pattern of Form B is shown in Figure 5 and the corresponding data is summarized below. [Table 23]

[0204] As shown in Figure 6, DSC analysis of Form B showed no thermal events from room temperature to a broad melting event (starting at approximately 288°C). Karl Fischer analysis showed a water content of less than 0.1 w / w% in Form B. TGA analysis of Form B (Figure 7) showed less than 0.1% weight loss up to 150°C. Form B was determined to be anhydrous.

[0205] DVS of form B showed that this form was slightly hygroscopic (0.8% weight change in the first adsorption cycle, Figure 10).

[0206] Exposure to moist air resulted in eventual amorphization after 15–20 h at 95% humidity ( Figure 8 ), although the loss of crystallinity was significantly slower than for form A.

[0207] Example 2. Stability test The in-process stability of NaCDC Form B was evaluated under two conditions at reflux as listed in Table 1 below. No changes in the HPLC impurity profile were observed under either condition, indicating that the product is stable under these conditions. [Table 1]

[0208] Example 3. Intrinsic dissolution test The intrinsic dissolution profiles of NaCDC Forms A and B were measured from drug discs of constant surface area using a USP spinning disc apparatus in phosphate buffer (pH 7.4) at 37° C. After compression (see below), no changes in solid state form based on XRPD were observed.

[0209] A typical apparatus consisted of a punch and a die, the base of which was attached to a platen. The die had a cavity into which a defined amount of the material for which the intrinsic dissolution rate was to be determined was placed. The punch was then inserted into the cavity of the die, and the test material was compressed in a hydraulic press. A non-collapsible compact of the material was formed in the cavity of the die, with a single surface of the basal area exposed to the bottom surface of the die. The die assembly was then attached to a shaft by a holder, and the platen was removed. The shaft holding the die assembly was placed in the dissolution liquid at a distance of 1.0 cm or more from the bottom of the container. In this procedure, the flow of liquid was generated by the rotation of the die. The amount of dissolved material was measured as a function of time. In particular, the cumulative amount dissolved at each time point was corrected for losses due to sampling. If the amount vs. time profile showed curvature, only the first linear portion was used to determine the dissolution rate. The method parameters are summarized below. [Table 24]

[0210] The intrinsic dissolution profiles of NaCDC Forms A and B are shown in Figure 11. A linear regression analysis of the profiles is shown in Figure 12, and the intrinsic dissolution rates are summarized in Table 2. Notably, Form B had a higher intrinsic dissolution rate than Form A while being less hygroscopic. [Table 2]

[0211] Example 4. Measurement of solubility curve The solubility curve measurements of NaCDC Form A and Form B were carried out using a Crystal16 automated crystallizer (Technobis Crystallization Systems) with an array of 16 microreactors equipped with a turbidimeter for determining the clearing and clouding points. Four different concentrations of samples for each crystal form were prepared by accurately weighing different amounts of each sample and adding 1000 μL of phosphate buffer (pH 7.4) to each vial. The suspensions thus obtained were stirred using a magnetic stirrer and heated from 0° C. to 90° C. at 0.5° C. / min. The clearing points of each sample were determined and plotted to obtain the crystallization curves (FIG. 13). NaCDC Form B showed slightly higher solubility than NaCDC Form A.

[0212] Materials and Methods: Examples 5-10 X-ray powder diffraction (XRPD) XRPD analysis was performed in transmission mode using a Bruker D8 Discover diffractometer in DAVINCI configuration (scan type: TwoTheta or Offset Coupled TwoTheta / Theta), scanning the samples from 2θ angles of 1.5 to 45°, using an acquisition time of 7.58 min (step increment of 0.01°, time per step of 0.1 s, generator voltage / generator amperage of 40 mA / 40 kV (reaching a power output of 1.6 kW)). Approximately 2-3 mg of each sample was used. Detection limits in XRPD vary based on the crystallinity of the sample. In general, for crystalline compounds, detection limits in XRPD are estimated to be approximately 2% wt or even lower.

[0213] Differential Scanning Calorimetry (DSC) Approximately 3.9 mg of sample was weighed into an aluminum DSC pan and non-hermetically sealed with an aluminum lid. The sample pan was then loaded into a Setaram DSC131 EVO (equipped with a chiller). Once a stable heat flow response was obtained, the sample and reference material were heated to 450°C at a rate of 10°C / min and the resulting heat flow response was monitored. Nitrogen was used as the purge gas with a flow rate of 40 cm 3 / min. Prior to analysis, the instrument was temperature and heat flow calibrated using lead and indium reference standards. Sample analysis was performed using CALISTO software and the temperature of the thermal event was quoted as the onset temperature (measured according to the manufacturer's specifications).

[0214] Thermogravimetric analysis and DSC combined (TG / DSC) Approximately 1.56-5.78 mg of sample was weighed into an open aluminum pan and simultaneously loaded into a Setaram LABSYS EVO thermogravimetric / differential scanning calorimeter (TG-DTA / DSC) and held at 30 °C for 15 min. The sample was then heated from 30 °C to 550 °C at a rate of 10 °C / min, during which the change in sample weight was recorded along with any differential thermal events. Nitrogen was used as the purge gas, with a flow rate of approximately 180 cm 3 The heating rate was 10° C. / min. Prior to analysis, the instrument was calibrated for mass loss and temperature using copper sulfate pentahydrate and indium and lead reference standards. Sample analysis was performed using CALISTO software and the corresponding mass loss and thermal event temperatures were quoted as onset temperatures (measured according to manufacturer's specifications). All analyses were performed at a heating rate of 10° C. / min and background subtracted.

[0215] High-performance liquid chromatography (HPLC) HPLC analysis was performed on an Agilent 1260 Infinity chromatograph using a Hichrom C18 column 100 x 4.6 mm, 3.5 μm, 40°C. Method details are as follows: [Table 25]

[0216] Example 5. Further characterization of NaCDC form B Additional standalone DSC analysis of NaCDC form B was performed as shown in FIG. 14. This analysis revealed two endothermic events. One was believed to be a melt accompanied by a phase transformation (T オンセット = 291.9 °C), and the other is melting (T オンセット =331.6°C).

[0217] TG / DSC analysis of NaCDC form B was also performed. The results are shown in FIG. 15. This analysis revealed two endothermic events. One was believed to be a melt accompanied by a phase transformation (T オンセット = 291.8 °C and heat = 35 J / g), and the other melting (T オンセット = 336.4 °C and heat = 51.2 J / g). オンセット The difference was due to the different types of crucibles used (100 μL open aluminum crucibles were used for the TG / DSC, whereas 30 μL closed hole aluminum crucibles were used for the standalone DSC).

[0218] Based on the results obtained from the TG / DSC analysis, a sample of NaCDC form B was heated at 315° C. and another sample was heated at 360° C. After heating, the samples were cooled to room temperature and analyzed by XRPD (FIG. 16). The sample heated at 315° C. had a different diffractogram than the starting material. The material obtained after heating the sample at 360° C. was amorphous. HPLC analysis indicates that the purity of the sample heated at 315° C. was 66.9%.

[0219] Example 6. Photostability test The photostability of NaCDC form B was evaluated in the solid state and in MeOH solutions in clear, amber and aluminum foil wrapped vials by exposure to UV 254 nm light for 48 hours. The solutions were prepared by weighing approximately 10 mg of NaCDC form B and mixing it with 500 μL of MeOH. After 48 hours, the solids and solutions were sampled and analyzed by HPLC to assess degradation. In parallel, XRPD analysis was performed on the recovered solids. A summary of the experimental results is summarized in Table 3. [Table 3]

[0220] In experiments performed in the solid state, no form conversion was observed by XRPD, indicating that NaCDC form B is stable (Figure 17). In solution, HPLC analysis indicated that the compound was stable, as evidenced by minimal purity loss (see Table 3).

[0221] Example 7. Stability testing in slurry / solution Approximately 10 mg of NaCDC form B was weighed into a clear HPLC vial and the selected solvent (500 μL) was added to the vial. Experiments ST07, 09, 11, 13, 15, 17, 19, and 21 were continued to stir at 30°C and 60°C for 24 hours and samples were taken for HPLC analysis after 4 and 24 hours. The same experiments were subsequently evaporated under reduced pressure (21-22 mbar) at 30°C for 24 hours and the solids were evaluated by HPLC and XRPD. Separately, solutions and slurries of ST10, 12, 14, 16, 18, 20, and 22 were stirred at 30°C and 60°C for 24 hours (no samples were taken) and evaporated under reduced pressure (20-21 mbar) at 60°C for 24 hours. The recovered material was sampled for HPLC and XRPD analysis. A summary of the experimental results is summarized in Table 4. [Table 4-1] [Table 4-2]

[0222] XRPD analysis showed that NaCDC form B was stable as no form transformation was observed in most of the slurry experiments, with two exceptions observed: ST19 and ST20 (in MEK evaporated at 30° C. and 60° C., respectively), which gave rise to a new form, S1 (FIG. 18).

[0223] In general, the starting material remained stable in solution and / or slurry under the test conditions. HPLC analysis performed throughout the stability study revealed purity of 86.1% or higher at 212 nm, except for experiments ST08 and ST16 (evaporated at 60° C.) where the purity dropped to approximately 84.5%. Additionally, experiments ST19 and ST21 (using MEK and evaporated at 30° C.) showed lower purity (74.1% and 55.9%), which may suggest the presence of amorphous impurities not detectable by XRPD.

[0224] Characterization of Form S1 Form S1 was obtained from experiments ST19 and ST20 (24 hours at room temperature in MEK slurry, evaporated at 30° C. and 60° C., respectively).

[0225] Samples from ST19 were characterized by XRPD as shown in Figure 19A, and the corresponding data are summarized in Table S1-A. [Table 26-1] [Table 26-2]

[0226] The sample from ST20 was characterized by TG / DSC as shown in FIG. 19B. Three endothermic events were identified in the DSC trace. The first event was at T オンセット= 96.0 °C and a mass loss of 2.177% (theoretical mass of 3.704% corresponds to 0.25 MEK molecules). Therefore, the mass loss could be due to physical adsorption or residual. The second event was associated with a desolvation process with a T オンセット = 142.5 °C, a heat measurement of 3.29 J / g. Considering the preferred orientation of the sample, this corresponded to either an artifact or a phase transformation. The third event was T オンセット = 313.4 °C. The sample from ST19 showed a similar TG / DSC trace but did not show the second endotherm observed from ST20.

[0227] Example 8. Solubility test Approximately 10 mg of NaCDC form B was weighed into a 1.6 mL HPLC vial. A 3-5 mm PTFE covered cylindrical magnetic stir bar was added to the vial. Qualitative solubility evaluation tests were performed by adding small successive aliquots of each selected solvent system to the corresponding vial at approximately 15 min intervals under stirring at room temperature (50 μL volumes added at 500 rpm up to 200 μL, 100 μL volumes added at 700 rpm for a total volume of 200-1000 μL). The vial was visually inspected before each addition to confirm dissolution of the starting material, and solvent addition was stopped when complete dissolution was observed. The clear solution was allowed to stand at room temperature. If no dissolution had occurred by the time a total volume of 1 mL was reached (concentration of approximately 10 mg / mL at room temperature), the vial was heated under stirring, first at 40 °C (with the exception of experiment SAS23 with ethyl ether, which was heated at 30 °C only for 1 h) and then at 50 °C. The experiments were held at each temperature for 1 hour and then visually inspected to see if dissolution had occurred. At the end of the experiment period, the magnetic stir bar was removed and all slurries or solutions were dried at different temperatures depending on the boiling point of each solvent used (i.e., 30°C, 20-21 mbar or 50°C, 21 mbar for 21 hours, with the exception of experiments SAS07, SAS33, SAS34, SAS35, SAS36, and SAS45, which were dried at 50°C for 43 hours). All of the resulting solids were analyzed by XRPD. For some selected experiments, HPLC analysis was performed. Solids that yielded new XRPD patterns were examined by TGA / DSC. The results are summarized in Table 6. Explanations of the qualitative solubility terms are provided in Table 5. [Table 5] [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4] [Table 6-5] [Table 6-6] [Table 6-7] [Table 6-8] [Table 6-9]

[0228] Most of the solids tested showed good purity by HPLC, with the exception of experiments using 2-ethoxyethanol, 3-methyl-1-butanol, benzonitrile, DMAc, NMP, DMSO, and HO:DMSO (1:1 v / v), where purity decreased from 99.2% to 1.2–68.0%.

[0229] XRPD analysis revealed the formation of several novel morphologies as shown in FIG.

[0230] Characterization of Form S2 Form S2 was identified from experiments using EtOH (SAS03) or mixtures of equal volumes of EtOH with MeCN (SAS39) and n-heptane (SAS48). Based on the TG / DSC analysis of experiment SAS39 (FIG. 21A), form S2 was assigned as a solvated form with a first endothermic event at 112.9° C. (suggesting desolvation) and a mass loss of 3.95% due to 0.5 EtOH molecules (corresponding to 5% theoretical mass). The second event was a T オンセット This corresponds to a phase transformation with a subsequent recrystallization event at approximately 195 °C and finally a crystallization event at 334.1 °C (T オンセット ) and melt.

[0231] Characterization of morphology S3 Form S3 was identified from a single experiment (SAS07) with 2-ethoxyethanol. Form S3 was determined to be a mixture of NaCDC with a predominately crystalline degradant based on HPLC analysis (38% purity at 212 nm). XRPD analysis of the material from experiment SAS07 is shown in FIG. 21B and the corresponding data are summarized in Table S3. [Table 27-1] [Table 27-2]

[0232] Characterization of Form S4 Form S4 was identified from a single experiment with 2,2,2-trifluoroethanol (SAS08). Based on the TG / DSC analysis of experiment SAS08 (FIG. 22), Form S4 was assigned as a solvated form with a first endothermic event at 146.5° C. (suggesting desolvation) and a mass loss of 14.23% due to one TFE molecule (corresponding to a theoretical mass of 19.44%). The second event was at 333.9° C. (T オンセット ) corresponds to melting at

[0233] Characterization of Form S5 Form S5 was identified from two experiments using equal volumes of MeOH with EtOAc (SAS46) and n-heptane (SAS47). The XRPD spectrum of the material from experiment SAS47 is shown in Figure 23A and the corresponding data are summarized in Table S5-A. [Table 28-1] [Table 28-2]

[0234] Based on the TG / DSC analysis of experiment SAS47 (FIG. 23B), Form S5 was assigned as a solvated form with a first endothermic event at approximately 82° C. (suggesting desolvation) and a mass loss of 4.79% due to 0.5 MeOH molecules (corresponding to 3.59% theoretical mass). The second event was a T オンセット Finally, the temperature reaches 331.5°C (T オンセット ) and melt.

[0235] Example 9. Polymorphism Screening slurry Approximately 15 mg of NaCDC Form B was weighed into an HPLC vial and an appropriate volume of solvent was added at room temperature. The slurry was aged under stirring (500 rpm) for 7 days at multiple temperatures: 5°C, 25-30°C, 40°C, and 50°C. All solids were air-dried on filter paper and then analyzed by XRPD. Depending on the results obtained by XRPD and the availability of materials, some experiments were analyzed by HPLC and TG / DSC. The results from the slurry experiments are summarized in Table 7. [Table 7-1] [Table 7-2] [Table 7-3] [Table 7-4] [Table 7-5] [Table 7-6] [Table 7-7] [Table 7-8] [Table 7-9] [Table 7-10] [Table 7-11] [Table 7-12]

[0236] Based on the XRPD data, the majority of the material recovered from the slurry experiments returned the same crystalline phase as the starting material (NaCDC Form B). In some experiments, three different forms were identified: Form S1 (or a form isomorphous to Form S1), Form S2, and Form S7.

[0237] Characterization of Form S1 Form S1 (or a similar and / or isomorphous form to Form S1) was obtained from run SL13 using tert-butyl methyl ether at 5° C. and run SL39 using tert-butyl methyl ether at 25-30° C. HPLC analysis of both materials showed good purity at 212 nm of 87.2% (SL13) and 84.0% (SL39). XRPD analyses of these samples are shown in FIG. 24A and corresponding data for samples from run SL39 are summarized in Table S1-B. [Table 29-1] [Table 29-2]

[0238] Based on the TG / DSC analysis of SL39 (air-dried on filter paper for at least 2 hours before using in thermal analysis), two endothermic events were shown ( FIG. 24B ). The first event was at T オンセット = 93.2 °C and a mass loss of 1.241% (theoretical mass of 2.19% corresponds to 0.125 MTBE molecules). Therefore, the observed mass loss can be attributed to physical adsorption or residual. The second event is T オンセット= 312.8 °C.

[0239] Characterization of Form S2 Form S2 was obtained from all slurry experiments with ethanol (i.e., experiments SL01, SL26, and SL52 at 5°C, 25-30°C, and 40°C, respectively) or from mixtures with ethanol at 5°C, 25-30°C, and 50°C (experiments SL22, SL48, and SL74 with EtOH:MeCN 1:1 v / v, and experiments SL23, SL49, and SL75 with EtOH:n-heptane 1:1 v / v, respectively).

[0240] TG / DSC analysis of the material from experiment SL26 (FIG. 25) showed two endothermic events. The first event was at T オンセット = 113.4 °C and a mass loss of 7.013% (5% theoretical mass corresponds to 0.75 molecules of EtOH). オンセット = 324.6 °C. The presence of two maxima associated with melting may be due to the non-homogeneity of the material (e.g., a possible mixture of large and small particles). Based on the data obtained, Form S2 was assigned as a solvate of NaCDC.

[0241] Characterization of Form S7 Form S7 was obtained from experiments SL27 and SL56, which used 2-PrOH at 25-30° C. and 50° C., respectively. XRPD spectra of materials obtained from experiments SL27 and SL56 are shown in FIG. 26A, and the corresponding data for experiment SL56 are summarized in Table S7. [Table 30-1] [Table 30-2]

[0242] Based on the TG / DSC analysis of the material obtained from experiment SL56 (air-dried on filter paper for at least 2 hours prior to thermal analysis), three endothermic events were observed ( FIG. 26B ). The first event was at T オンセット = 109.2 °C and a mass loss of 10.037% (12.66% of the theoretical mass corresponds to one molecule of 2-PrOH). The second event is a phase transformation (T オンセット = 324.5 °C, corresponding to heat of 2.65 J / g. The third event is T オンセット = 335.3 °C. The melting temperature of Form S7 corresponds to the melting temperature of NaCDC Form B (T オンセット Form S7 was assigned as a solvate of anhydrous NaCDC form B based on similarity to the Solubility Test (SDS) of 1.0 mM NaCl, 1.0 mM MgCl, and 1.0 mM NaCl.

[0243] Slurry with ultrasonic treatment Approximately 15 mg of NaCDC Form B was weighed into an HPLC vial and 0.4 mL of the corresponding solvent was added at room temperature. The slurry was sonicated for 15 minutes and then allowed to cool at 5° C. for 30 minutes. This cycle was repeated six times. At the end of the sixth cycle, all the runs were air-dried on a filter paper and the collected solids were analyzed by XRPD. Based on the XRPD data, some runs were analyzed by HPLC. The results of the slurries from sonication at 5° C. and thermal cycling experiments (SLS) are shown in Table 8. [Table 8]

[0244] Based on the XRPD data, the majority of the material recovered from the slurry experiments returned the same crystalline phase as the starting material (NaCDC Form B). Form S2 was obtained from the SLS08 and SLS09 experiments (using EtOH:MeCN 1:1 v / v and EtOH:n-heptane 1:1 v / v, respectively). HPLC analysis of both materials showed good purity, 79.2% (SLS08) and 89.7% (SLS09) at 212 nm.

[0245] Slow Evaporation Five stock solutions (with MeOH, water, 2,2,2-trifluoroethanol, MeOH:EtOAc (1:1 v / v), and MeOH:acetone (1:1 v / v)) were prepared with NaCDC form B at room temperature. The final concentration of each solution was close to the concentration obtained from the solubility study described in Example 8. Approximately 19-23 mg of NaCDC form B was weighed into a 1.6 mL HPLC vial (or an 8 mL flask for MeOH:EtOAc and MeOH:acetone stock solutions) and dissolved in the appropriate solvent at room temperature. For the water stock solution, approximately 40 mg of NaCDC form B was used. The experiment was kept at room temperature for 1 h with stirring (500 rpm), and then the solution was filtered through a 0.45 μm PTFE filter. A foaming phenomenon was observed when filtering the stock solution with water. Therefore, the filtration was performed slowly and in several steps. The filtered solution was then slowly evaporated at atmospheric pressure at 25 °C (experiment EV01-05) or 50 °C (experiment EV06-09). After complete evaporation of the solvent, the solids were collected and analyzed by XRPD. Depending on the results obtained from the XRPD analysis and also on the availability of materials, some experiments were analyzed by HPLC and TG / DSC. The results of slow evaporative crystallization (EV) are summarized in Table 9. [Table 9-1] [Table 9-2]

[0246] Based on the XRPD data, the majority of the material recovered from these experiments was in an amorphous phase. In some experiments, four different forms were identified: Form S1 (or forms isomorphous to Form S1), Form S4, Form S5, and Form S6.

[0247] Characterization of Form S1 Form S1 (or a similar and / or isomorphous form to Form S1) was obtained from experiment EV03 using 2,2,2-trifluoroethanol at 25-30° C. HPLC analysis of this material showed good purity, 88.3% at 212 nm. TG / DSC analysis of the material from experiment EV03 showed three endothermic events (FIG. 27). The first two events were at T オンセット = 94.4℃ and T オンセット = 144.7 °C and was due to desolvation with a cumulative mass loss of 5.487% (4.86% of the theoretical mass corresponds to 0.25 TFE molecules). オンセット = 335.9 °C.

[0248] Characterization of Form S4 Form S4 (mixture with SM, preferred orientation) was obtained from experiment EV07 with TFE after slow evaporation at 50° C. The purity of this material was 91.7% at 212 nm as determined by HPLC. The results from the TFE experiment suggest that Form S4 is a solvate.

[0249] Characterization of Form S5 Form S5 was obtained from experiment EV09 using MeOH:acetone 1:1 v / v at 50° C. Based on the TG / DSC analysis of the material obtained from experiment EV09, two events were observed ( FIG. 28 ). Prior to the first event, a mass loss of 5.642% was observed on the TG curve, which was not attributed to a well-defined desolvation process. This could be due to physically adsorbed solvent (theoretical mass is calculated to be 7.17% for one molecule of MeOH). T オンセット A possible recrystallization event was observed with T = 195.3 °C (as well as two maxima at 198.9 °C and 212.5 °C). オンセット A melting event was observed with a melting temperature of 332.9°C.

[0250] Characterization of Form S6 Form S6 was obtained from experiment EV08 using MeOH:EtOAc 1:1 v / v at 50° C. Form S6 was similar to Form S3 from the SAS07 experiment. The HPLC purity of this material was determined to be 71.4% at 212 nm (18% major impurity with a retention time of 3.81 min). Based on the TG / DSC analysis of the material obtained from experiment EV08, three events were observed (FIG. 29). The first broad endothermic event was at T オンセット = 50.6 °C and a mass loss of 2.456% (theoretical mass of 2.191% corresponds to 0.125 EtOAc molecules). The second exothermic event was associated with recrystallization (T オンセット =199.8 °C), while the third endothermic event is associated with T オンセット = 331.5°C.

[0251] Solvent Drop Grinding Approximately 20 mg of NaCDC Form B was ground with a 10 μL aliquot of the corresponding solvent for 10 minutes at room temperature using an agate mortar and pestle. Once complete evaporation of the solvent was observed, an additional 10 μL aliquot of solvent was added and the procedure was repeated until the completion time of the experiment. All solids were analyzed by XRPD. For experiments where a phase transformation was observed by XRPD, additional analysis by TG / DSC and / or HPLC was performed. The results of the solvent drop grinding experiments (SDGR) are shown in Table 10. [Table 10]

[0252] Based on the XRPD data, four new forms were identified: Form S1 (or isomorphous with Form S1) (mixture with NaCDC form B), Form S2, Form S4, and Form S5.

[0253] Characterization of Form S1 Form S1 (or a similar and / or isomorphous form to Form S1) was obtained from experiment SDGR02 using 2-PrOH as a mixture with NaCDC Form B. The purity of this material was 81.3% as judged by HPLC at 212 nm.

[0254] Characterization of Form S2 Form S2 was obtained from three experiments using ethanol (SDGR01) or mixtures with ethanol (SDGR07: EtOH:MeCN 1:1 v / v, SDGR08: EtOH:n-heptane 1:1 v / v). The purity of the tested materials was 86.5% or higher at 212 nm as determined by HPLC, except for the material from experiment SDGR01, which was 83.4% pure.

[0255] Based on the TG / DSC analysis of the material from experiment SDGR01 (FIG. 30), Form S2 was オンセット The compound was assigned as an EtOH-solvated form with a first endothermic event at T = 105.3 °C (suggesting desolvation) and a mass loss of 7.677% that can be attributed to 0.75 EtOH molecules (corresponding to 5% theoretical mass). The second event was an endothermic event at T = 180.7 °C (suggesting desolvation) and a mass loss of 7.677% that can be attributed to 0.75 EtOH molecules (corresponding to 5% theoretical mass). オンセット This corresponds to a phase transformation involving a recrystallization event at approximately 200°C, and finally a crystallization event at 334.6°C (T オンセット ) a melting event occurs. These results are similar to those obtained with material from experiments SAS48 and SDGR07.

[0256] Characterization of Form S4 Form S4 was obtained from experiment SDGR03 using TFE. The material showed good HPLC purity of 90.9% at 212 nm. The results suggested that Form S4 is a solvated form of TFE. The XRPD spectrum of the material from experiment SDGR03 is shown in Figure 31A and the corresponding data is summarized in Table S4. [Table 31]

[0257] Based on the TG / DSC analysis of the material (FIG. 31B), Form S4 may be solvated with TFE, オンセットThe first endothermic event at T = 117.6 °C (suggesting desolvation) was accompanied by a mass loss of 14.620% (attributable to one molecule of TFE (corresponding to 19.44% of theoretical mass)). The second event was accompanied by a T オンセット This corresponds to a phase transformation involving a recrystallization event at approximately 200°C, and finally a crystallization event at 335.6°C (T オンセット ) the melting event occurs. These results are similar to those obtained from experiment SAS08.

[0258] Characterization of Form S5 Form S5 was obtained from two experiments: SDGR05 using MeOH:EtOAc 1:1 v / v and SDGR06 using MeOH:acetone 1:1 v / v. The HPLC purity of this material was 87% at 212 nm. Based on the TG / DSC analysis of the material obtained from experiment SDGR05 (FIG. 32A), Form S5 is a solvated form with a first endothermic event at approximately 101° C. (suggesting desolvation) and a mass loss of 4.426% that can be attributed to 0.5 MeOH molecules (corresponding to 3.59% theoretical mass). The second event was a T オンセット Finally, at 333°C (T オンセット ) a melting event occurs.

[0259] Vapor diffusion into solids Approximately 20 mg of NaCDC Form B was weighed into a 1.6 mL HPLC vial. Each of the above vials was individually placed into a 40 mL container that initially contained 0.5 mL of the corresponding solvent. The container was isolated from light and air and placed in a closed cabinet at 25° C. or in an oven at 50° C. for 12 days. After the experimental time, most of the samples remained solid / wet solid (experiments VDS02-12). They were collected and analyzed by XRPD. Experiment VDS01 gave a fine suspension after 12 days, which was dried overnight at 30° C. and 21 mbar. All solids were analyzed by XRPD and some experiments were also analyzed by HPLC and TG / DSC depending on the results obtained. The results of vapor diffusion into solids (VDS) are summarized in Table 11. [Table 11-1] [Table 11-2]

[0260] Based on the XRPD data, the majority of the material recovered from these experiments was in the same crystalline phase as the starting material (NaCDC form B). Additionally, four different forms were identified: Form S2, Form S4, Form S5, and Form S8 (mixture with SM).

[0261] Characterization of Form S2 Form S2 was obtained from experiment VDS05 after diffusion with EtOH for 12 days at 50° C. (remained stable under storage conditions at room temperature). The HPLC purity of the tested material was 92.1% at 212 nm. The TG / DSC analysis of this material was consistent with that obtained from experiments SAS48, SDGR01, and SDGR07. The XRPD analysis of this material is shown in FIG. 33 and the corresponding data are summarized in Table S2. [Table 32-1] [Table 32-2] [Table 32-3]

[0262] Characterization of Form S4 Form S4 was obtained from experiment VDS09 with TFE after diffusion for 12 days at 50° C. (the suspension formed redissolved under storage conditions at room temperature.) The HPLC purity of this material was 90.9% at 212 nm.

[0263] Characterization of Form S5 Form S5 was obtained from experiment VDS01 with MeOH after vacuum drying of a fine suspension obtained after 12 days of diffusion at room temperature. The HPLC purity of this material was approximately 90% at 212 nm. Based on the TG / DSC analysis of VDS01 (FIG. 32B), Form S5 was assigned as a solvated form with a first endothermic event at approximately 101° C. (suggesting desolvation) and a mass loss of 4.426% that can be attributed to 0.5 MeOH molecules (corresponding to 3.59% theoretical mass). The second event was a T of 190.9° C. オンセット Finally, the recrystallization event at 333°C (T オンセット ) a melting event was observed.

[0264] Characterization of Form S8 Form S8 was obtained after diffusion as a mixture with starting material from experiment VDS12 (NaCDC Form B) with MEK for 12 days at 50° C. (remained stable under storage conditions at room temperature). The HPLC purity of the tested material was 93.7% at 212 nm. The XRPD spectrum of the material from experiment VDS12 compared to NaCDC Form B is shown in FIG. 34A and the corresponding data are summarized in Table S8. [Table 33-1] [Table 33-2] [Table 33-3]

[0265] Based on the TG / DSC analysis of experiment VDS12, three endothermic events were observed (FIG. 34B). The first event was at T オンセット = 292.6 °C. A small secondary event, which may indicate a phase transformation or the presence of an impurity (or may be due to inhomogeneity of the material), occurs at T オンセット = 322.4 °C. Finally, T オンセットA melting event was observed at C = 337.0 °C. Considering that no mass loss was observed on the TG curve, S8 was assigned as the anhydrous form of NaCDC.

[0266] Antisolvent vapor diffusion into solution Based on the solubilities determined at room temperature in the solubility study in Example 8, three solutions were prepared using NaCDC Form B (water: 203.41 mg / mL, MeOH: 100.37 mg / mL, and TFE: 50.66 mg / mL). The experiments were kept at room temperature for 1 hour under stirring (500 rpm) until the starting materials were completely dissolved, and then the solutions were filtered through 0.45 μm PTFE filters (with the exception of the water stock solution, which was filtered through a 0.2 μm nylon filter to avoid the foaming phenomenon encountered during the EV experiments).

[0267] A set volume of concentrated solution was pipetted into a clear HPLC vial, which was then individually placed into a 40 mL container that initially contained 2 mL of anti-solvent. Each of the corresponding solvents was added as detailed in Table 12 below. The diffusion systems were left to stand in a closed cabinet at 25° C. or in an oven at 50° C. for 12 days. After the experimental time, solids were obtained from many samples, which were collected and analyzed by XRPD. The remaining solutions (ASDS01, 02, 05, 14, 17, 18, and 21) or suspensions (ASDS06) were dried overnight at 30° C. and 21 mbar. All collected solids were analyzed by XRPD. Based on the results obtained, the experiments were analyzed by HPLC. Depending on the availability of materials, some were selected for TG / DSC. The results of anti-solvent vapor diffusion into solution (ASDS) are summarized in Table 12. [Table 12-1] [Table 12-2] [Table 12-3] [Table 12-4] [Table 12-5]

[0268] Based on the XRPD results, eight different forms were identified from these experiments: Form S1 (or isomorphous to Form S1), Form S5, Form S9-a, Form S9-b, Form S10, Form S11 (or isomorphous to Form S3), Form S12 (as a mixture with an amorphous phase), Form S13, and Form S14.

[0269] Characterization of forms S1 and S14 Form S1 (or a similar and / or isomorphous form to Form S1) was obtained from experiments ASDS03 and ASDS07 using water (and acetone as antisolvent) after diffusion for 12 days at 25° C. and 50° C., respectively. The HPLC purity of these materials was determined to be ≧89.1% at 212 nm.

[0270] The precipitate formed in aqueous solution in the presence of acetone (anti-solvent) was stored for up to 3 weeks and then subjected to thermal analysis. In this case, the bulk of the ASDS03 solid was dried on a filter paper for up to 2 hours at room temperature, after which the recovered material was analyzed by XRPD. The results showed that the material was converted to form S14 (or a similar and / or isomorphous form to form S14) (Figure 35). This material was assigned as a mixed solvate of acetone and water based on TG / DSC analysis (Figure 36). Therefore, the first endothermic event indicated that the T オンセット = 42.8 °C and a mass loss of 3.888%, which can be attributed to 0.25 acetone molecules (corresponding to 3.07% theoretical mass). A second endothermic event suggested a desolvation event with T オンセット = 103.6 °C and a mass loss of 1.982%, which could be attributed to 0.5 molecules of water (corresponding to a theoretical mass of 2.08%). Also, what appears to be recrystallization was observed in the DSC trace at approximately 190 °C and finally at approximately 332 °C (T オンセット A melting event was observed at T オンセットwas different from the starting material (NaCDC form B), implying that form S14 (or a similar and / or isomorphous form to form S14) may be a solvate of another anhydrous form.

[0271] Characterization of Form S5 Form S5 was obtained from experiments ASDS09 and ASDS12 using MeOH (and acetone as anti-solvent) after 12 days of diffusion at 25° C. or 50° C., respectively, and from experiment ASDS10 using MeOH (and ethyl ether as anti-solvent) after 12 days of diffusion at 25° C. Form S5 with additional peaks and preferred orientation was also obtained from experiments ASDS11 and ASDS13 using MeOH (and MTBE as anti-solvent) at 25° C. or 50° C., respectively. HPLC purity of the tested material indicated high purity, greater than 93.3% at 212 nm.

[0272] Characterization of forms S9-a and S9-b Form S9-a (with preferred orientation) was obtained from experiment ASDS04 using water (and acetonitrile as antisolvent) after 12 days of diffusion at 25° C. Form S9-b (with preferred orientation, but similar to NaCDC monohydrate) was obtained from experiment ASDS08 using the same solvent / antisolvent system after 12 days of diffusion at 50° C. The HPLC purity of both materials was good (>86.9%) (212 nm).

[0273] Precipitates formed in aqueous solutions in the presence of acetonitrile (as antisolvent) from experiments ASDS04 and ASDS08 were stored at room temperature for up to 24 days and then subjected to thermal analysis. In this case, most of the solids from experiments ASDS04 and ASDS08 were dried on filter paper at room temperature for 1-2 hours, after which the recovered material was analyzed by XRPD. The results showed that the material from experiment ASDS04 remained unchanged after storage (but with lower crystallinity), while the material from experiment ASDS08 transformed with a morphology similar to form S9-a (and with lower crystallinity) (Figure 37). The corresponding data for the initial material from experiments ASDS04 and ASDS08 are summarized below (Tables S9-a and S9-b, respectively). [Table 34-1] [Table 34-2] [Table 34-3] [Table 34-4] [Table 35-1] [Table 35-2] [Table 35-3]

[0274] Based on TG / DSC analysis, the sample from experiment ASDS04 stored for 22 days (FIG. 38) was assigned as a solvate with water or MeCN, or a mixed solvate. Therefore, the first endothermic event indicates that T オンセット = 99.9 °C and a desolvation event with a mass loss of 8.635% (which could be attributed to two molecules of water (corresponding to 8.32% of theoretical mass) or one molecule of MeCN (corresponding to 9.01% of theoretical mass)) was suggested. Finally, a T オンセットA melting event accompanied by

[0275] Based on TG / DSC analysis, the sample from experiment ASDS08 stored for 23 days (FIG. 39) was assigned as a solvate with water or MeCN, or a mixed solvate. Therefore, the first endothermic event indicates that T オンセット = 94.8 °C and a desolvation event was suggested with a mass loss of 2.298%, which could be attributed to 0.5 molecules of water (corresponding to 2.08% of theoretical mass) or 0.25 molecules of MeCN (corresponding to 2.25% of theoretical mass). Finally, a T of approximately 336 °C was observed. オンセット A melting event accompanied by

[0276] Characterization of Forms S10 and S11 Form S10 was obtained from experiment ASDS14 using TFE (and EtOAc as anti-solvent) after 12 days of diffusion at 25° C. Form S11 (or similar and / or isomorphous to Form S3) was obtained from experiment ASDS18 using the same system of solvents / anti-solvents after 12 days of diffusion at 50° C. Both samples were evaporated overnight at 30° C. and 21 mbar. The HPLC purity of the material from experiment ASDS14 was 91.4%, while for the material from experiment ASDS18 the purity decreased to 75.6% (212 nm).

[0277] The XRPD spectrum of the material from experiment ASDS14 is shown in FIG. 40A and the corresponding data is summarized in Table S10. [Table 36-1] [Table 36-2]

[0278] The XRPD spectrum of the material from experiment ASDS18 is shown in FIG. 50A and the corresponding data is summarized in Table S11. [Table 37-1] [Table 37-2]

[0279] Based on the TG / DSC analysis (FIG. 40B), the material from experiment ASDS14 was assigned as a solvate with TFE or EtOAc, or a mixed solvate. Therefore, the first endothermic event indicates that T オンセット = 141.3 °C and a desolvation event with a mass loss of 16% (which can be attributed to one molecule of TFE (corresponding to 19.44% of theoretical mass) or one molecule of EtOAc (corresponding to 17.53% of theoretical mass)) was suggested. オンセット The first melting step was observed at approximately T オンセット A possible recrystallization followed by a final melting step was observed.

[0280] Based on the TG / DSC analysis (Figure 41), the material obtained from experiment ASDS18 was assigned as an anhydrous form with some residual solvent or physical adsorption of solvent. Therefore, although a mass loss of 3.799% was observed on the TG curve, it was not attributable to a clearly defined event. The T at approximately 328 °C オンセット A melting event accompanied by

[0281] Characterization of Form S12 Form S12 (mixture with amorphous phase) was obtained from experiment ASDS19 using TFE (and MTBE as antisolvent) after diffusion for 12 days at 50° C. The HPLC purity of this sample was determined to be 97.1% at 212 nm.

[0282] The precipitate formed in TFE solution in the presence of MTBE (anti-solvent) was stored at room temperature for 22 days and then subjected to thermal analysis. In this case, most of the material from experiment ASDS19 was dried on a filter paper at room temperature for up to 2 hours, after which the recovered material was analyzed by XRPD. The results showed that the material stored for 22 days was converted to form S15 (also identified in experiment RAS36) (Figure 42). Considering that form S12 was obtained as a mixture of amorphous phase and low crystallinity, form S12 may be the same as form S15. The XRPD data of experiment ASDS19 before 22 days of storage are summarized in Table S12 and the XRPD data of experiment ASDS19 after 22 days of storage are summarized in Table S15. [Table 38] [Table 39-1] [Table 39-2]

[0283] Based on TG / DSC analysis (Figure 43), the material from experiment ASDS19 stored for 22 days was assigned as a solvate with MTBE. オンセット = 80.8 °C and suggests desolvation with a mass loss of 4.448%, which can be attributed to 0.25 molecules of MTBE (corresponding to a theoretical mass of 4.38%). An inflection point is observed at approximately 180 °C, which may suggest recrystallization. Finally, a T オンセット A melting event accompanied by

[0284] Characterization of Form S13 Form S13 (showing broad peaks and a tendency towards amorphousness) was obtained from experiment ASDS16 using TFE (and diisopropyl ether as antisolvent) after diffusion for 12 days at 25° C. The HPLC purity of this sample was 92.4% at 212 nm.

[0285] The precipitate formed in TFE solution in the presence of DIPE (anti-solvent) was stored at room temperature for 22 days and then subjected to thermal analysis. In this case, most of the material from experiment ASDS16 was dried on a filter paper at room temperature for up to 2 hours, after which the recovered material was analyzed by XRPD. The results showed that the material stored for 22 days remained unchanged and a less crystalline phase with some additional peaks or preferred orientation was obtained (Figure 44).

[0286] Based on TG / DSC analysis (Figure 45), form S13 was assigned as a mixed solvate of DIPE and TFE. Therefore, from the first endothermic event, T オンセット = 55.4 °C and a mass loss of 2.358%, which can be attributed to 0.125 molecules of DIPE (corresponding to 2.47% of theoretical mass). A second endothermic event indicated desolvation with T オンセット = 148.8 °C and a mass loss of 3.804%, which can be attributed to 0.25 molecules of TFE (corresponding to 4.86% theoretical mass). A third exothermic event suggested another desolvation with T オンセット = 191.8 °C. Finally, a recrystallization event with T オンセット A melting event accompanied by

[0287] Characterization of Form S14 Form S14 was obtained from two experiments, ASDS17 using TFE (and acetone as anti-solvent) after 12 days of diffusion at 25° C., and ASDS21 using the same system of solvent / anti-solvent after 12 days of diffusion at 50° C. Both samples were evaporated overnight at 30° C. and 21 mbar. The HPLC purity of the material from experiment ASDS17 was 89.3%, while the HPLC purity of the material from experiment ASDS21 was approximately 70% (212 nm). The XRPD analysis of the material obtained from experiment ASDS21 is shown in FIG. 46A, and the corresponding data are summarized in Table S14. [Table 40-1] [Table 40-2]

[0288] Based on the TG / DSC analysis of the material from experiment ASDS17 (FIG. 46B), Form S14 was assigned as a solvated form with a first endothermic event at 143.7° C. suggesting desolvation and a mass loss of 15.84% that can be attributed to one TFE molecule (corresponding to 19.44% of the theoretical mass). The second event was at 331° C. (T オンセット ) corresponds to the melting event at T オンセット is similar to form S4, but the melting T オンセット This means that Form S14 is a monosolvate with TFE, but may be an anhydrous form other than NaCDC Form B.

[0289] rapid cooling Stock solutions of 10 (using water, HO:THF 1:1 v / v; HO:EtOH 1:1 v / v; HO:2-PrOH 1:1 v / v; HO:MeCN 1:1 v / v; HO:acetone 1:1 v / v; methanol; 2,2,2-trifluoroethanol; MeOH:EtOAc 1:1 v / v; and MeOH:acetone 1:1 v / v) were prepared at 1.5x solubility (determined from the solubility study in Example 8) at room temperature under stirring at 700 rpm and heated at 40° C. for 1 h. Mixtures that were not dissolved at 40° C. were heated at 50° C. for additional stirring time or solvent volume. The exact concentrations of each stock solution are shown in Table 13. After the above times the solutions were completely dissolved and the hot solutions were filtered through a 0.45 μm PTFE filter (or a 0.2 μm nylon filter in the case of water stock solutions) and kept at the working temperature.

[0290] After filtration, a predetermined volume of each solution (finally containing 196.91–65.72 mg of NaCDC per experiment) was added to the appropriate vial, which was further placed at 25 °C (experiments CL01–10), 5 °C (experiments CL11–19), or -20 °C (experiments CL20–23) and aged for 7 days and checked periodically. No precipitate occurred after the time had passed. The solutions were vacuum evaporated at 30 °C and low pressure (final pressure = 20–21 mbar) for approximately 18 h (experiments CL01, 02, 05, 06, 10, 11, 13, 14, 15, 16, 19, 20, 22, and 23), or approximately 41 h (experiments CL03, 04, 08, 09, 12, 17, and 18), or 4.5 days (experiments CL07 and 21), and analyzed by XRPD. Based on the results obtained, some experiments were also analyzed by HPLC or TG / DSC. The results of fast cooling crystallization (CL) are summarized in Table 14. [Table 13-1] [Table 13-2] [Table 14-1] [Table 14-2] [Table 14-3] [Table 14-4] [Table 14-5]

[0291] Based on the XRPD data, most experiments yielded amorphous phase material, with one distinct form (form S5) being identified from the majority of experiments using MeOH as the solvent.

[0292] Characterization of Form S5 Form S5 was obtained with preferred orientation from run CL16 using MeOH after cooling for 7 days at 5° C. and drying the residual solution under vacuum, or from runs CL10 and CL23 using MeOH:acetone 1:1 v / v after cooling for 7 days at 25° C. and drying the residual solution under vacuum. Form S5 was also obtained with low crystallinity in a mixture with an amorphous phase from runs CL19 (using MeOH:acetone 1:1 v / v; after cooling for 7 days at 5° C. and drying the residual solution under vacuum) and CL22 (using MeOH:EtOAc 1:1 v / v; after cooling for 7 days at −20° C. and drying the residual solution under vacuum). The HPLC purity of these samples was generally good (88.5% or higher) at 212 nm, except for CL22, which was 84.8%.

[0293] Based on the TG / DSC analysis of the material from experiment CL16 (FIG. 47), Form S5 was オンセット The compound was assigned as a solvated form with a first endothermic event at T = 120.3 °C (suggesting desolvation) and a mass loss of 5.867% that can be attributed to 0.5 MeOH molecules (corresponding to 3.59% of the theoretical mass). The second event was オンセット = 188.1 °C (possible phase transformation). オフセット A third exothermic event was observed, corresponding to recrystallization with a melting event at approximately 336° C. (T オンセット ) was observed.

[0294] Forward antisolvent addition method Three stock solutions (using water, methanol, and 2,2,2-trifluoroethanol) were prepared at room temperature with stirring at 700 rpm at 1.5 times solubility (determined from the solubility test in Example 8) and heated at 40° C. for 1 hour. Not all mixtures dissolved at 40° C., some were heated at 50° C. with additional stirring time or volume. The exact concentration of each stock solution is shown in Table 13. After the above times, the solutions were completely dissolved and the hot solutions were filtered through a 0.45 μm PTFE filter (or a 0.2 μm nylon filter in the case of water stock solutions) and kept at working temperature. The appropriate anti-solvent was added in three steps at 25° C. (500 rpm) with a delay of approximately 10 minutes in between, resulting in a total solvent / anti-solvent volume ratio of 0.5, 1, and 5, respectively. After complete addition of the anti-solvent, the experiments were stirred at 25° C. for 1 day and the resulting solids were collected and analyzed by XRPD. Finally, experiments that did not produce solids (experiments FAS01, 02, 03, 04) were left under stirring (500 rpm) at 5°C for 1 week and checked periodically. After the time had passed, no precipitation occurred. The solutions were vacuum evaporated at 30°C and low pressure (final pressure = 20-21 mbar) for about 18 hours (experiments FAS01 and 04) or 4.5 days (experiments FAS02 and 03) and analyzed by XRPD. Based on the results obtained, some experiments were also analyzed by HPLC or TG / DSC. The results of the forward antisolvent addition method (FAS) at 25°C are shown in Table 15. [Table 15-1] [Table 15-2] [Table 15-3] [Table 15-4]

[0295] Based on the XRPD data, all experiments using water (and different antisolvents) yielded amorphous phase material, while most of the experiments using MeOH or TFE as solvents identified two different forms (forms S4 and S5).

[0296] Characterization of Form S4 Form S4 was obtained from the majority of the experiments with TFE: experiment FAS13 with toluene as anti-solvent, experiment FAS15 with iPrOAc, experiment FAS17 with MTBE, and experiment FAS18 with DIPE. All materials tested showed good HPLC purity at 212 nm (88.8% or higher, with the exception of experiment FAS13, which was 69.3%). Since it was obtained from the experiment with TFE, form S4 was assigned as its solvate.

[0297] Characterization of Form S5 Form S5 was obtained (generally with low crystallinity) from all FAS experiments using MeOH (experiment FAS07 with toluene as anti-solvent, experiment FAS08 with EtOAc, experiment FAS09 with MTBE, experiment FAS10 with acetone, experiment FAS11 with MEK, and experiment FAS12 with MeCN). The HPLC purity of the material was good (>91.3% with the exception of experiment FAS09, which was 80.3%) at 212 nm. The XPRD spectrum of the material obtained from experiment FAS08 is shown in Figure 23A and the corresponding data are summarized in Table S5-B. [Table 41-1] [Table 41-2]

[0298] Reverse antisolvent addition method Three stock solutions (using water, methanol, and 2,2,2-trifluoroethanol) were prepared at 1.5x solubility (determined in the solubility test in Example 8) at room temperature under stirring at 700 rpm and heated at 40° C. for 1 hour. Not all mixtures dissolved at 40° C., some mixtures were heated at 50° C. for additional stirring time or volume. The exact concentrations of each stock solution are shown in Table 13. After the above times the solutions were completely dissolved and the hot solutions were filtered through a 0.45 μm PTFE filter (or a 0.2 μm nylon filter in the case of the water stock solutions) and kept at the working temperature.

[0299] The appropriate volume of anti-solvent was added to an HPLC vial or 8 mL flask, and the equilibrated, hot filtered solutions (the amount of each solution was determined to end up with approximately 23 mg NaCDC per run, or approximately 39 mg per run for aqueous solutions) were added dropwise under stirring (500 rpm) to the appropriate vial to achieve a volume ratio between stock solution and anti-solvent of 1:10 (or approximately 1:12 for aqueous runs). All runs were left stirring overnight at 5°C or 25°C, and the resulting solids were collected, air-dried on the filter paper, and analyzed by XRPD. The remaining runs were left stirring at 5°C or 25°C for an additional 6 days and checked periodically. If no precipitation occurred, the solutions were dried under vacuum at 30 °C and low pressure (final pressure = 20-21 mbar) for approximately 18 h (experiments RAS01, 04, 07, 10, 13, and 25) or 4.5 days (experiments RAS02, 03, 08, and 09) and analyzed by XRPD. Based on the results obtained, some experiments were also analyzed by HPLC or TG / DSC. The results of the reverse antisolvent addition method (RAS) at 5 °C or 25 °C are summarized in Table 16. [Table 16-1] [Table 16-2] [Table 16-3] [Table 16-4] [Table 16-5] [Table 16-6] [Table 16-7]

[0300] Based on the XRPD data, much of the recovered material was in an amorphous phase, or in some cases was obtained as the starting material (NaCDC Form B). Seven different forms were also identified: Form S1 (or similar and / or isomorphous to Form S1), Form S3 (or similar and / or isomorphous to Form S3), Form S4, Form S5, Form S6 (or similar and / or isomorphous to Form S6), Form S13, and Form S15.

[0301] Characterization of Form S1 Form S1 (or a similar and / or isomorphous form to Form S1) was obtained from experiments RAS05 and RAS11 (water stock solution and acetone as antisolvent) at 5° C. and 25° C., respectively. HPLC purity of the material was good (>94.0%) at 212 nm. The XRPD pattern of the material from experiment RAS11 is shown in FIG. 24A.

[0302] The precipitate formed in aqueous solution in the presence of acetone (antisolvent) was stored at room temperature for 2 weeks and then subjected to thermal analysis. In this case, most of the material from experiment RAS11 was dried on a filter paper for 1-2 hours at room temperature, after which the recovered material was analyzed by XRPD. The results showed that the stored material had a high tendency towards amorphization with several peaks, some of which were similar and / or isomorphous to form S1 (Figure 48).

[0303] Based on TG / DSC analysis (FIG. 49), the material from experiment RAS11 stored for 2 weeks was assigned as a mixed solvate with acetone and water. Therefore, the first endothermic event gave rise to the T オンセット = 41.9 °C and a mass loss of 5.356%, which can be attributed to 0.5 acetone molecules (corresponding to 6.14% of the theoretical mass). The second endothermic event indicates desolvation of T オンセット = 107.2 °C and a mass loss of 1.237%, which can be attributed to 0.25 molecules of water (corresponding to a theoretical mass of 1.04%). A recrystallization event was observed at approximately 198.4 °C and finally at approximately 327 °C (T オンセット A melting event was observed at T オンセット was different from the starting material (NaCDC form B), which means that this form may be a solvate of another potential anhydrous form.

[0304] Characterization of morphology S3 Form S3 (or a form similar and / or isomorphous to Form S3) was obtained from experiment RAS34 (TFE stock solution and iPrOAc as anti-solvent) at 25° C. The HPLC purity of the material was 82.3% at 212 nm. The XRPD spectrum of the material obtained from experiment RAS34 is shown in FIG. 50A.

[0305] The precipitate formed in TFE solution in the presence of iPrOAC (anti-solvent) was stored at room temperature for 2 weeks and then subjected to thermal analysis. In this case, the majority of the material from experiment RAS34 was dried on filter paper at room temperature for 1-2 hours, after which the recovered material was analyzed by XRPD. The results showed that the stored material from experiment RAS34 remained unchanged and was Form S3 (or a form similar and / or isomorphous to Form S3).

[0306] Based on TG / DSC analysis (FIG. 50B), the material from experiment RAS34 stored for 2 weeks was assigned as a solvate with TFE or iPrOAc. Therefore, the first endothermic event was observed at T オンセット= 52.3 °C and a mass loss of 1.323% (which can be attributed to 0.0625 molecules of TFE or iPrOAc, corresponding to 1.21% or 1.23% of theoretical mass, respectively), suggesting desolvation, possibly due to residual solvent. A second exothermic event suggests recrystallization, which is observed at approximately 195 °C. Finally, a temperature of approximately 336 °C (T オンセット ) a melting event was observed.

[0307] Characterization of Form S4 Form S4 was obtained from four experiments, all using TFE stock solutions: experiment RAS28 (low crystallinity; nBuOAc as anti-solvent, 5° C.), experiment RAS29 (low crystallinity and additional peaks; MTBE as anti-solvent, 5° C.), experiment RAS30 (additional peaks; DIPE as anti-solvent, 5° C.), and experiment RAS32 (toluene as anti-solvent, 25° C.). HPLC purity of the material was good (>89.4%) at 212 nm.

[0308] Characterization of Form S5 Form S5 was obtained from the majority of experiments using MeOH stock solutions and different anti-solvents: experiments RAS14 and RAS20 using EtOAc at 5° C. and 25° C., RAS15 and RAS21 at 5° C. and 25° C., experiments RAS16 and RAS22 using acetone at 5° C. and 25° C., experiments RAS17 and RAS23 using MEK at 5° C. and 25° C., experiments RAS18 and RAS24 using MeCN at 5° C. and 25° C., and experiment RAS19 using toluene at 25° C. In some cases, Form S5 was obtained with low crystallinity (i.e., experiments RAS14, 16, 18, 24). The HPLC purity of the material was good (greater than 87.3%) at 212 nm.

[0309] Characterization of Form S6 Form S6 (or a similar and / or isomorphous form to Form S6) had a preferred orientation and the HPLC purity of the material obtained from experiment RAS33 (TFE stock solution, EtOAc as anti-solvent) at 25° C. was 96.1% at 212 nm. The XRPD spectrum of the material from experiment RAS33 is shown in Figure 50A and the corresponding data are summarized in Table S6. [Table 42]

[0310] The precipitate formed in TFE solution in the presence of EtOAc (anti-solvent) was stored at room temperature for 2 weeks and then subjected to thermal analysis. In this case, the majority of the material from experiment RAS33 was dried on a filter paper at room temperature for 1-2 hours, after which the recovered material was analyzed by XRPD. The results showed that the material from experiment RAS33 stored for 2 weeks converted to Form S1 (or a form similar and / or isomorphous to Form S1) (Figure 51).

[0311] Based on TG / DSC analysis (Figure 52), the material from experiment RAS33 stored for 2 weeks was assigned as a solvate with EtOAc. Therefore, the first endothermic event gave the T オンセット = 88.6 °C and suggested desolvation of 2.436% mass loss, which can be attributed to 0.125 molecules of EtOAc (corresponding to 2.191% theoretical mass). オンセット ) a melting event was observed.

[0312] Characterization of Form S13 Form S13 (with additional peaks) was obtained from experiment RAS37 using TFE (and DIPE as anti-solvent) at 25° C. The HPLC purity of the sample was 81.7% at 212 nm. XRPD analysis of the material obtained from experiment RAS37 is shown in FIG. 53 and the corresponding data is summarized in Table S13. [Table 43]

[0313] Characterization of Form S15 Form S15 was obtained from experiment RAS36 using TFE (and MTBE as anti-solvent) at 25° C. The HPLC purity of the sample was 86% at 212 nm.

[0314] The precipitate formed in the TFE solution in the presence of MTBE (anti-solvent) was stored at room temperature for 2 weeks and then subjected to thermal analysis. In this case, the majority of the material from experiment RAS36 stored for 2 weeks was dried on a filter paper for 1-2 hours at room temperature, after which the recovered material was analyzed by XRPD. The results showed that the material from experiment RAS36 stored for 2 weeks converted to form S14 (or a form similar and / or isomorphous to form S14) or a mixture of form S15 and another form (Figure 54A).

[0315] Based on TG / DSC analysis (Figure 54B), the material from experiment RAS36 stored for 2 weeks was assigned as a mixed solvate with MTBE and TFE. Thus, the first broad endothermic event indicated the T オンセット = 87.8 °C. The second event suggests desolvation with T オンセット = 125.4 °C. Both processes combined are assigned to a mass loss of 4.09%. An inflection point at approximately 185 °C may suggest recrystallization. Finally, a T of approximately 334 °C is observed. オンセット A melting event accompanied by

[0316] Having described several embodiments of the invention, it will be apparent that the basic examples of the invention may be modified to provide other embodiments which utilize the compounds and methods of the invention. It will therefore be appreciated that the scope of the invention is to be defined by the appended claims rather than by the specific embodiments which have been represented by way of example.

Claims

1. A crystalline solid form of sodium chenodeoxycholate, wherein the solid form is anhydrous and characterized in its XRPD pattern by one or more peaks selected from approximately 6.75, approximately 8.14, approximately 9.79, approximately 14.02, approximately 16.10, and approximately 18.63 degrees 2-theta.

2. The solid morphology according to claim 1, wherein the solid morphology is characterized in its XRPD pattern by peaks selected from peaks at approximately 6.75, 8.14, 9.79, 14.02, 16.10, and 18.63 degrees 2-theta.

3. The solid-state according to claim 2, wherein the solid-state is characterized in substantially all of the following peaks in its XRPD pattern. Table 44

4. The solid form according to claim 1, wherein the solid form is characterized by one or more of the following: (i) An XRPD pattern substantially similar to that shown in Figure 5, (ii) DSC pattern showing no thermal events from room temperature up to approximately 288°C. (iii) A DSC pattern substantially similar to that shown in Figure 6, (iv) A TGA pattern showing less than 0.1% weight loss at a maximum of 150°C, or (v) A TGA pattern substantially similar to that shown in Figure 7.

5. A crystalline solid form of sodium chenodeoxycholate, the solid form being prepared by a method comprising the steps of: obtaining a mixture of chenodeoxycholic acid in n-butanol; adding an aqueous sodium hydroxide solution to the mixture; heating the mixture (and, for example, azeotropically refluxing); and removing the solvent to obtain the crystalline solid form of sodium chenodeoxycholate.

6. A crystalline solid form of sodium chenodeoxycholate, wherein the solid form is a hydrate, and its XRPD pattern is characterized by one or more peaks selected from peaks at approximately 6.07, 6.55, 10.72, 14.64, 15.06, 17.58, and 18.34 degrees 2-theta.

7. The solid form according to claim 6, wherein the solid form is characterized in its XRPD pattern by peaks selected from peaks at approximately 6.07, 6.55, 10.72, 14.64, 15.06, 17.58, and 18.34 degrees 2-theta.

8. The solid-state according to claim 7, wherein the solid-state is characterized in substantially all of the following peaks in its XRPD pattern. Table 45

9. The solid form according to claim 6, wherein the solid form is characterized by one or more of the following: (i) An XRPD pattern substantially similar to that shown in Figure 1, (ii) DSC pattern showing water loss from a temperature slightly above ambient temperature up to approximately 150°C. (iii) A DSC pattern substantially similar to that shown in Figure 2, (iv) A TGA pattern showing a weight loss of 4.3% at a maximum of 150°C, or (v) A TGA pattern substantially similar to that shown in Figure 3.

10. A crystalline solid form of sodium chenodeoxycholate, the solid form being prepared by a method comprising the steps of: obtaining a mixture of chenodeoxycholic acid in methyl isobutyl ketone; adding an aqueous sodium hydroxide solution to the mixture; heating the mixture (and, for example, azeotropically refluxing); and removing the solvent to obtain the crystalline solid form of sodium chenodeoxycholate.

11. A crystalline solid form of sodium chenodeoxycholate, wherein the solid form is (i) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 5.45, 5.80, 7.46, 9.76, 12.40, 14.88, and 20.02 degrees 2-theta; (ii) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 7.11, 7.78, 9.81, 12.58, 12.96, and 13.54 degrees 2-theta; (iii) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 5.00, 7.56, 10.56, 11.45, 11.93, and 12.46 degrees 2-theta; (iv) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 7.07, 7.65, 9.70, 13.43, 15.02, 16.52, and 16.96 degrees 2-theta; (v) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 7.11, 8.63, 12.08, 12.75, 13.46, 14.25, and 16.68 degrees 2-theta; (vi) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 8.47, 9.90, 14.36, 15.26, 17.00, and 17.72 degrees 2-theta; (vii) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 5.10, 7.00, 13.52, 14.23, 15.46, and 18.78 degrees 2-theta; (viiii) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 5.47, 7.48, 9.82, 12.66, and 15.07 degrees 2-theta; (ix) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 5.13, 7.01, 8.69, 9.11, 13.55, 14.91, and 15.53 degrees 2-theta; (x) The XRPD pattern is characterized by one or more peaks selected from the peaks at approximately 4.82, 5.22, 5.89, 10.81, 13.00, 15.00, and 18.94 degrees 2-theta; (xi) The XRPD pattern is characterized by one or more peaks selected from peaks at approximately 4.95, 7.53, 9.85, 11.55, 12.12, and 15.01 degrees 2-theta; or (xi) The solid form, wherein the XRPD pattern is characterized by one or more peaks selected from peaks at approximately 5.15, 5.50, 7.05, 12.04, 14.90, and 16.56 degrees 2-theta.

12. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 5.45, 5.80, 7.46, 9.76, 12.40, 14.88, and 20.02 degrees 2-theta.

13. The solid form according to claim 12, wherein the solid form is characterized in substantially all of the peaks listed in Table S1-A or Table S1-B in its XRPD pattern.

14. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 7.11, 7.78, 9.81, 12.58, 12.96, and 13.54 degrees 2-theta.

15. The solid form according to claim 14, wherein the solid form is characterized by substantially all of the peaks listed in Table S2 in its XRPD pattern.

16. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 5.00, approximately 7.56, approximately 10.56, approximately 11.45, approximately 11.93, and approximately 12.46 degrees 2-theta.

17. The solid form according to claim 16, wherein the solid form is characterized in substantially all of the peaks listed in Table S3, Table S6, or Table S11 in its XRPD pattern.

18. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 7.07, 7.65, 9.70, 13.43, 15.02, 16.52, and 16.96 degrees 2-theta.

19. The solid form according to claim 18, wherein the solid form is characterized by substantially all of the peaks listed in Table S4 in its XRPD pattern.

20. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 7.11, approximately 8.63, approximately 12.08, approximately 12.75, approximately 13.46, approximately 14.25, and approximately 16.68 degrees 2-theta.

21. The solid form according to claim 20, wherein the solid form is characterized by substantially all of the peaks listed in Table S5 in its XRPD pattern.

22. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 8.47, approximately 9.90, approximately 14.36, approximately 15.26, approximately 17.00, and approximately 17.72 degrees 2-theta.

23. The solid form according to claim 22, wherein the solid form is characterized by substantially all of the peaks listed in Table S7 in its XRPD pattern.

24. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 5.10, approximately 7.00, approximately 13.52, approximately 14.23, approximately 15.46, and approximately 18.78 degrees 2-theta.

25. The solid form according to claim 24, wherein the solid form is characterized by substantially all of the peaks listed in Table S9-a in its XRPD pattern.

26. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 5.47, approximately 7.48, approximately 9.82, approximately 12.66, and approximately 15.07 degrees 2-theta.

27. The solid form according to claim 26, wherein the solid form is characterized by substantially all of the peaks listed in Table S9-b in its XRPD pattern.

28. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 5.13, 7.01, 8.69, 9.11, 13.55, 14.91, and 15.53 degrees 2-theta.

29. The solid form according to claim 28, wherein the solid form is characterized by substantially all of the peaks listed in Table S10 in its XRPD pattern.

30. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 4.82, 5.22, 5.89, 10.81, 13.00, 15.00, and 18.94 degrees 2-theta.

31. The solid form according to claim 30, wherein the solid form is characterized in substantially all of the peaks listed in Table S12 or Table S15 in its XRPD pattern.

32. The solid morphology according to claim 11, wherein the solid morphology is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 4.95, approximately 7.53, approximately 9.85, approximately 11.55, approximately 12.12, and approximately 15.01 degrees 2-theta.

33. The solid form according to claim 32, wherein the solid form is characterized by substantially all of the peaks listed in Table S13 in its XRPD pattern.

34. The solid form according to claim 11, wherein the solid form is characterized in its XRPD pattern by one or more peaks selected from peaks at approximately 5.15, 5.50, 7.05, 12.04, 14.90, and 16.56 degrees 2-theta.

35. The solid form according to claim 34, wherein the solid form is characterized by substantially all of the peaks listed in Table S14 in its XRPD pattern.

36. A crystalline solid form of sodium chenodeoxycholate that can be obtained by the method described herein.

37. A pharmaceutical composition comprising the solid form described in claim 1 and a pharmaceutically acceptable carrier.

38. The pharmaceutical composition according to claim 37, wherein the pharmaceutical composition is a solid.

39. The pharmaceutical composition according to claim 38, wherein the pharmaceutical composition is formulated for oral administration.

40. A pharmaceutical composition, which is prepared by a method comprising the steps of obtaining a solid form described in claim 1, and formulating the solid form together with a suitable excipient to obtain the pharmaceutical composition.

41. A pharmaceutical composition, A first portion comprising bile acid or a salt thereof, configured to be immediately released within the colon of the subject, A second portion adjacent to the first portion, comprising bile acid or a salt thereof, and configured to be continuously released within the colon of the subject, The pharmaceutical composition comprises a degradable or corrosive coating, The pharmaceutical composition wherein at least one of the first or second portion comprises the solid form described in claim 1.

42. A pharmaceutical composition, A first portion comprising bile acid or a salt thereof, configured to be immediately released within the colon of the subject, A second portion adjacent to the first portion, comprising bile acid or a salt thereof, and configured to be continuously released within the colon of the subject, A degradable or corrosive coating relating to the pharmaceutical composition, comprising the coating wherein at least one of the first or second portion comprises the solid form described in claim 1, A step of obtaining the solid form described in claim 1, The pharmaceutical composition is prepared by a method comprising the step of formulating the solid form with a suitable excipient to obtain the pharmaceutical composition.

43. The pharmaceutical composition according to claim 41 or 42, wherein the pharmaceutical composition is a tablet.

44. The pharmaceutical composition according to claim 41 or 42, wherein the bile acid or a salt thereof in the first and second portions is chenodeoxycholic acid or a salt thereof.

45. The pharmaceutical composition according to claim 44, wherein the first portion and the second portion comprise a crystalline solid form of sodium chenodeoxycholate, the solid form being anhydrous and characterized in its XRPD pattern by one or more peaks selected from approximately 6.75, approximately 8.14, approximately 9.79, approximately 14.02, approximately 16.10, and approximately 18.63 degrees 2-theta.

46. The pharmaceutical composition according to claim 41, wherein the coating is Eudragit S100 or comprises the same.

47. A composition comprising a solid form according to any one of claims 1 to 36, or a pharmaceutical composition according to any one of claims 37 to 42 and 46, for administration to a subject requiring the same.

48. The composition according to claim 47, characterized in that the composition or the pharmaceutical composition is administered orally.

49. A composition comprising a solid form according to any one of claims 1 to 36, or a pharmaceutical composition according to any one of claims 37 to 42 and 46, for treating a disease, disorder, or condition in a subject requiring the use thereof.

50. The composition according to claim 49, wherein the subject is suffering from a gastrointestinal disease, disorder, or condition.

51. The composition according to claim 49, wherein the subject suffers from constipation.

52. The composition according to claim 49, wherein the subject suffers from irritable bowel syndrome (IBS-C) accompanied by constipation.

53. A method for preparing a solid form according to any one of claims 1 to 10, The steps to obtain chenodeoxycholic acid, The steps include: contacting chenodeoxycholic acid with a suitable base in a suitable solvent to obtain the solid form; The method, including the method described above.

54. The method according to claim 53, wherein the preferred base is sodium hydroxide.

55. The method according to claim 53, wherein the preferred solvent is selected from methyl isobutyl ketone, n-butanol, and water.

56. A method for preparing the pharmaceutical composition described in claim 37, A step of obtaining a solid form according to any one of claims 1 to 36, The steps include: formulating the solid form with a suitable excipient to obtain the pharmaceutical composition; The method, including the method described above.

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