MATERIALS AND METHODS FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS

Abstract

The bulk composition comprising a trihydrate form of the dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxypiperidin-1-yl]hexanoic acid 1-azabicyclo[2.2.2]oct-3'-yl ester is provided herein. Pharmaceutical compositions and dosage forms comprising the trihydrate form, and methods and uses for treating a gastrointestinal disorder in a subject with the trihydrate form, are also provided. In some modalities, the gastrointestinal disorder is gastroesophageal reflux disease (GERD), dyspepsia (such as functional dyspepsia or functional motility disorder), gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), or esophagitis.In some cases, the gastrointestinal disorder is postoperative ileus, chronic grass disease, constipation, megacolon, gastritis, gastrointestinal stasis, or abomasal emptying defect.

Description

MATERIAL AND METHODS FOR THE TREATMENT OF GASTROINTESTINAL DISORDERS FIELD OF THE INVENTION The present disclosure relates to bulk compositions and pharmaceutical compositions comprising a trihydrate form of (3S,4R,3'R)-6[4-(4-amino-5-chloro-2-methoxy- benzoylamino)-3-methoxypiperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, and methods of treating gastrointestinal disorders in this form. BACKGROUND OF THE INVENTION Benzamide derivatives and their pharmaceutically acceptable salts may act as stimulators of gastrointestinal motility. Many of these compounds are also antagonists of the dopamine D2 receptor, which also plays an important role in the gastrointestinal system. Dopaminergic effects on the gastrointestinal system may include nausea and vomiting. Thus, some of these benzamides are effective antiemetic agents and can be used to control vomiting during cancer chemotherapy or radiotherapy, especially when highly emetogenic compounds such as cisplatin are used. This antiemetic action is believed to be the result of the ability of benzamides to accacn / i ζηζ / α / γίΛΐ Ref. 317769 to block the actions of serotonin (5HT) at specific sites of action, called 5HT3 receptors. A second prominent action of some benzamide derivatives is to increase gastrointestinal smooth muscle activity from the esophagus through the proximal small intestine, thereby accelerating esophageal and small intestinal transit, as well as facilitating gastric emptying and increasing sphincter tone. lower esophageal. It is now believed that the primary smooth muscle effects of some benzamide derivatives are the result of an agonist action on a class of serotonin receptors called 5HT4 receptors, which are found on interneurons in the myenteric plexus of the intestinal wall. The benzamide cisapride, a potent 5-HT4 agonist, was introduced more than 20 years ago and has been used primarily to treat gastroesophageal reflux disease (GERD). Subsequently, patients were introduced to other 5-HT4 agonists of the benzamide class. Due to their activity as prokinetic agents, some 5-HT4 agonists also appear to be useful for treating dyspepsia, gastroparesis, constipation, postoperative ileus, and intestinal pseudo-obstruction. However, many of these compounds, including cisapride, are associated with serious cardiac arrhythmias, accacn / i ζηζ / α / γίΛΐ such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, and QT prolongation. The safety of 5HT4 receptor agonists may also be limited by adverse drug interactions due to hepatic metabolism of cytochrome P-450. Therefore, what is needed in the art are benzamide 5-HT4 agonists having a lower incidence of cardiac arrhythmias, which can be used to treat gastrointestinal disorders. Naronapride ((3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl]-hexanoic acid dihydrochloride salt l -azabicyclo[2.2.2]oct-3'-yl ester) is an orally bioavailable selective serotonin 5HT4 receptor agonist that has been shown to be safe in animals and humans for the treatment of gastrointestinal disorders, and has a low incidence of adverse cardiovascular effects. See US 7,176,218; US 7,282,509; US 7,326,787; US 7,629,466; US 8,138,204; and US 8,524,736, incorporated herein by reference in their entirety. What is needed in the art are improved forms of naronapride for clinical use and methods for producing bulk compositions thereof. BRIEF DESCRIPTION OF THE INVENTION In some aspects, provided herein is a bulk composition comprising a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5QCCRCn / l 7Π7 / 3) dihydrochloride salt. / ΥΙΛΙ chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, having the following formula: γΧ©2HCL3H2O I , and at least one container. In other aspects, provided herein is a pharmaceutical composition comprising a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino5-chloro-2-methoxy-benzoylamino )-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, having the following formula: 2HCI.3H2O and a pharmaceutically acceptable excipient. In certain aspects, a dosage form is provided herein that includes the pharmaceutical composition. Also provided herein is a method of treating a gastrointestinal disorder in a subject in need thereof, including administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition provided herein, or a dosage form provided herein. , comprising (3S,4R,3'R)-6[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl] dihydrochloride salt trihydrate form -hexanoic l-azabicyclo[2.2.2]oct-3'-yl ester. In some modalities, the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis. In some embodiments, the subject in need is a human being. In other embodiments, the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect. In some embodiments, the subject in need thereof is a non-human animal, such as a ruminant, equine, cat, dog, rabbit, or guinea pig. In other embodiments, provided herein is the use of a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino )-3 QCCECn / l ΖηΖ / 3 / ΥΙΛΙ methoxy-piperidin-l-yl]-hexanoic l-azabicyclo[2.2.2]oct-3'yl ester in the manufacture of a medicament for treating a gastrointestinal disorder in a subject in need thereof. In some modalities, the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel (IBS), constipation, enteral feeding intolerance (EFI) and esophagitis. In some embodiments, the subject in need is a human being. In other embodiments, the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect. In some embodiments, the subject in need thereof is a non-human animal, such as a ruminant, equine, cat, dog, rabbit, or guinea pig. In still other aspects, there is provided herein a compound, or a pharmaceutical composition comprising a compound, for use in the treatment of a gastrointestinal disorder in a subject in need thereof, wherein the compound is a dihydrochloride salt trihydrate form. (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1 QCCRCn / l 7Π7 / 3 / ΥΙΛΙ azabicyclo[2.2.2]oct-3'-yl ester. In some modalities, the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel (IBS), constipation, enteral feeding intolerance (EFI) and esophagitis. In some embodiments, the subject in need is a human being. In other embodiments, the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect. In some embodiments, the subject in need thereof is a non-human animal, such as a ruminant, equine, cat, dog, rabbit, or guinea pig. In other aspects, a method of improving a gastrointestinal motility in a subject in need thereof, including administering to the subject in need thereof a therapeutically effective amount of a pharmaceutical composition provided herein, or a dosage form provided herein, is provided herein. herein comprising (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzollamino)-3-methoxypiperidine- dihydrochloride salt trihydrate form l-yl ] -hexanoic l-azabicyclo^^^Joct-S'-yl accacn / i ζηζ / α / γίΛΐ ester. In some embodiments, the subject in need thereof has a gastrointestinal disorder. In some modalities, the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel (IBS), constipation, enteral feeding intolerance (EFI) and esophagitis. In some embodiments, the subject in need is a human being. In other embodiments, the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect. In some embodiments, the subject in need thereof is a non-human animal, such as a ruminant, equine, cat, dog, rabbit, or guinea pig. In other embodiments, provided herein is the use of a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino )-3-methoxy-piperidin-l-yl]-hexanoic l-azabicyclo[2.2.2]oct-3 / 'yl ester in the manufacture of a medicament to improve gastrointestinal motility in a subject in need thereof. In some embodiments, the subject in need thereof has a gastrointestinal disorder selected from the group accacn / i ζηζ / α / γίΛΐ consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, ileus postoperative emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis. In some embodiments, the subject in need is a human being. In other embodiments, the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect. In some embodiments, the subject in need thereof is a non-human animal, such as a ruminant, equine, cat, dog, rabbit, or guinea pig. In yet other aspects, there is provided herein a compound, or a pharmaceutical composition comprising a compound, for use in improving gastrointestinal motility in a subject in need thereof, wherein the compound is a dihydrochloride salt trihydrate form. (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct -3'-yl ester. In some embodiments, the subject in need thereof has a gastrointestinal disorder. In some modalities, the gastrointestinal disorder is selected from the group consisting of reflux disease QCCECn / l Gastroesophageal ΖηΖ / 3 / ΥΙΛΙ (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, Irritable Bowel Syndrome (IBS), constipation, intolerance to enteral feeding (EFI) and esophagitis. In some embodiments, the subject in need is a human being. In other embodiments, the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect. In some embodiments, the subject in need thereof is a non-human animal, such as a ruminant, equine, cat, dog, rabbit, or guinea pig. BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a water vapor absorption isotherm of the dihydrochloride salt at 25°C (two lines to the left) and 50°C (two lines to the right). Figure 2 depicts Fourier transform infrared (FTIR) spectra of the anhydrous and trihydrate forms of the acid dihydrochloride salt (3S, 4R, 3'R)-6[4-(4-amino-5-chloro- 2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester. Figure 3 depicts the X-ray powder diffraction (XRPD) patterns of the anhydrous forms (part QCCECn / l ΖηΖ / 3 / ΥΙΛΙ bottom) and trihydrate (top) of (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino) acid dihydrochloride salt )-3-methoxy-piperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester. Figure 4 is a water vapor absorption isotherm of the dihydrochloride salt at 25°C. Figure 5 provides thermographic analysis scans for the anhydrous (upper line) and trihydrate (lower line) forms. Figure 6 is a representative 1H-NMR spectrum of the trihydrate form. Figure 7 is a representative 13C-NMR spectrum of the trihydrate form. Figure 8 represents the XRPD patterns of the trihydrate form at the beginning of the experiment (zero time, bottom), at 25°C and 60% relative humidity (RH), open, for one week (middle), and at 25° C and 60% relative humidity (RH), open, for two weeks (top). Figure 9 represents the XRPD patterns of the trihydrate form at the beginning of the experiment (zero time, bottom), at 40°C and 75% relative humidity (RH), open, for one week (middle), and at 40° C and 75% relative humidity (RH), open, for two weeks (top). Figure 10 represents the XRPD patterns of the trihydrate form at the beginning of the experiment (time zero, part QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ bottom), at 60°C and closed for one week (middle), and at 60°C and closed for two weeks (top). DETAILED DESCRIPTION OF THE INVENTION Provided herein is a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-acid dihydrochloride salt. -yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester (Compound 1), having the following formula: QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ Also provided herein are bulk compositions comprising Compound 1 and a container. In other aspects, there is provided herein a pharmaceutical composition comprising Compound 1 and a pharmaceutically acceptable carrier. Also provided herein are methods of treating a disorder in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or a pharmaceutical composition comprising a therapeutically effective amount of Compound 1; the use of Compound 1, or a pharmaceutical composition comprising Compound 1, in the treatment of a disorder in a subject in need thereof; and the use of Compound 1 in the manufacture of a medicament for treating a disorder in a subject in need thereof. I. Compound 1 It has surprisingly been found that (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl] dihydrochloride salt -hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester can exist in the trihydrate form. The trihydrate form (Compound 1) has many advantages over the anhydrous form, including tolerance of a broader range of storage conditions and the ability to be formulated with hydrated and / or hygroscopic excipients. The difference in formula weights between the anhydrous form (FW = 610.01 g / mol) and the trihydrate (FW = 664.06 g / mol) would result in a deficit of approximately 8% to 9% in a final formulation if the formula is used. incorrectly (for example, by using the trihydrate when the anhydrous is intended, or the anhydrous when the trihydrate is intended). Therefore, X-ray powder diffraction peaks are also provided herein which, in some embodiments, can be used to identify which form is present in a composition. A. X-ray powder diffraction (XRPD) In some embodiments, Compound 1 (including Compound 1 in bulk compositions, compositions QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ pharmaceuticals, dosage forms, kits or medicaments comprising any of these as provided herein) is in a crystalline form, and the crystalline form has 2-zeta (2Θ) XRPD peaks at : 7.74°±0.5° (>50% relative intensity) and 20.95°±0.5° (100% relative intensity). In some modalities, Compound 1 has 2-zeta (2Θ) XRPD peaks at: 7.6°±0.2° (>50% relative intensity) and 20.7°±0.2° (100% relative intensity). In other embodiments, Compound 1 is in an amorphous form. In some embodiments, Compound 1 is in crystalline form, and the crystalline form has XRPD peaks at (degrees 2-zeta (2Θ)) 7.74°±0.5° and 20.95°±0.5°, and at least one, at least two , at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least least, at least fifteen, at least sixteen, at least seventeen, at least eighteen, at least nineteen, at least twenty, or each of the XRPD 2-zeta (2Θ) peaks selected from the group consisting of 10.3°±0.2 °, 13.6°±0.2°, 14.8°±0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 21.3°±0.2°, 22.0°±0.2°, 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2°, and 39.4°±0.2°. In some embodiments, Compound 1 is in the accacn / i ζηζ / α / γίΛΐ crystalline form and the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2°, 10.3°±0.2°, and 20.7°± 0.2°. In certain embodiments, Compound 1 is in crystalline form and the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2°, 10.3°±0.2°, 19.2°±0.2°, and 20.7°±0.2° . In other embodiments, Compound 1 is in crystalline form and the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2°, 10.3°±0.2°, 19.2°±0.2°, 20.7°±0.2°, and 33.4°±0.2°. In yet other embodiments, Compound 1 is in crystalline form and the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2°, 10.3°±0.2°, 19.2°±0.2°, 20.7°±0.2° , 33.4°±0.2°, and 38.2°±0.2°. In some embodiments, Compound 1 is in crystalline form and the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2°, 10.3°±0.2°, 13.6°±0.2°, 19.2°±0.2°, 20.7°±0.2°, 33.4°±0.2°, and 38.2°±0.2°. In other embodiments, Compound 1 is in crystalline form, and the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2°, 10.3°±0.2°, 13.6°±0.2°, 19.2°±0.2° , 20.7°±0.2°, 30.1°±0.2°, 33.4°±0.2°, and 38.2°±0.2°. In certain embodiments, Compound 1 is in crystalline form, and the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2°, 10.3°±0.2°, 13.6°±0.2°, 19.2°±0.2° , 20.7°±0.2°, 26.0°±0.2°, 30.1°±0.2°, 33.4°±0.2°, and 38.2°±0.2°. In still other embodiments, Compound 1 is in crystalline form, and the crystalline form has at least three, at least four, at least five, al accacn / i ζηζ / α / γίΛΐ minus six, at least seven, at least eight, at least nine, at least ten, at least eleven, at least twelve, at least thirteen, at least fourteen, at least fifteen, at least sixteen, at least seventeen, at least eighteen, at least nineteen, at least twenty, at least twenty-one, at least twenty-two, or each of the 2-zeta (2Θ) XRPD peaks selected from the group consisting of 7.6°±0.2°, 10.3°±0.2°, 13.6°±0.2°, 14.8°±0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 20.7°±0.2°, 21.3°±0.2°, 22.0°±0.2°, 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2°, and 39.4°±0.2°. In some embodiments, the crystalline form of Compound 1 has at least three of these peaks. In other embodiments, the crystalline form of Compound 1 has at least four of these peaks. In other embodiments, the crystalline form of Compound 1 has at least five of these peaks. In other embodiments, the crystalline form of Compound 1 has at least six of these peaks. In other embodiments, the crystalline form of Compound 1 has at least seven of these peaks. In other embodiments, the crystalline form of Compound 1 has at least eight of these peaks. In other embodiments, the crystalline form of Compound 1 has at least nine of these peaks. In other embodiments, the crystalline form of Compound 1 has at least ten of these peaks. In certain embodiments, for a crystalline form of the Compound 1 with 2-zeta (2Θ) XRPD peaks at 7.6°±0.2° and 20.7°±0.2° (including, for example, a crystalline form with three, four, five, six, seven, eight or more peaks of XRPD as described herein), the peak at 7.6°±0.2° has a relative intensity greater than 50%, and the peak at 20.7°±0.2° has a relative intensity of 100%. B. Bulk Compositions In some embodiments, bulk compositions comprising Compound 1 are provided herein. Bulk compositions can include, for example, compositions comprising at least 1 kg of Compound 1, at least 10 kg of Compound 1, at least 50 kg of Compound 1, at least 100 kg of Compound 1, at least 150 kg of Compound 1, at least 200 kg of Compound 1, at least 250 kg of Compound 1, at least 300 kg of Compound 1, at least 350 kg of Compound 1, at least 400 kg of Compound 1, at least 450 kg of Compound 1, or at least at least 500 kg of Compound 1. In some embodiments, the bulk composition comprises between about 50 kg and about 500 kg of Compound 1, between about 100 kg and about 400 kg of Compound 1, between about 100 kg and about 300 kg of Compound 1, between about 150 kg and about 250 kg of Compound 1, between about 200 kg and about 350 kg of Compound 1, or between about 200 kg and about 300 kg of Compound 1. In additional embodiments, bulk compositions comprising Compound 1 and at least one container are provided herein. Any suitable container can be used. For example, in some embodiments, the container is a box, bucket, barrel, bottle, jar, bag, box, bucket, tray, or tarp. In some embodiments, the bulk composition comprises Compound 1 and two or more containers, such as three containers, four containers, five containers, or more than five containers. In bulk compositions comprising two or more containers, in some embodiments each of the two or more containers is of the same type, eg each is a barrel, each is a pail, each is a box, etc. In other embodiments of bulk compositions comprising two or more containers, at least two containers are of different types. In certain embodiments, the bulk composition comprises Compound 1 and at least one container, wherein each container is independently selected from the group consisting of a box, a pail, a barrel, a bottle, a jar, a bag, a box , a bucket, a tray and a tarp. In certain embodiments, the container comprises a lid, for example a screw-on lid or a snap-on lid. In some embodiments, the lid is detachable, while in other embodiments it is attached, for example, by a strap. The container can comprise any material QCCECn / l ΖηΖ / 3 / ΥΙΛΙ suitable or combination of materials. For example, in some embodiments, the container comprises glass, metal, plastic, cardboard, wood, or any combination of these. In embodiments where the bulk composition comprises two or more containers, in some embodiments each container comprises the same material, while in other embodiments at least two of the containers comprise different materials. In some embodiments, the one or more containers of the bulk composition are free of contaminants. For example, in some embodiments, the one or more containers are suitable for use in storing an active pharmaceutical ingredient (API) intended for administration to a mammal, such as a human. In some embodiments, at least a portion of Compound 1 of the bulk composition is within one or more containers. In certain modalities, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80 %, at least 90%, at least 95%, at least 99% of the bulk composition is contained within one or more containers. In some embodiments, provided herein is a bulk composition comprising Compound 1 and two or more containers, each container containing at least a portion of Compound 1. In certain embodiments, accacn / i ζηζ / α / γίΛΐ to least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 99% of Composition 1, in total, is within one or more containers. At least a portion of Compound 1 in the bulk composition may, in some embodiments, be distributed evenly between the two or more containers, or in other embodiments may be distributed unevenly. In some embodiments, the bulk composition comprises at least 50% by weight, at least 55% by weight, at least 60% by weight, at least 65% by weight, at least 70% by weight, at least 75% by weight , at least 80% by weight, at least 85% by weight, at least 90% by weight, at least 95% by weight, at least 96% by weight, at least 97% by weight, at least 98% by weight, at least at least 99% by weight, or at least 99.9% by weight of Compound 1, where the % by weight excludes the weight of the container. In certain embodiments, the bulk composition comprises at least 75% by weight of Compound 1, which excludes the weight of the container. In some embodiments, the bulk composition comprises less than about 6,000 ppm organic solvent. In some embodiments, the bulk composition comprises less than about 5,500 ppm, less than about 5,000 ppm, less than about 4,500 ppm, less than about 4,000 ppm, less than about 3,500 ppm, less QCCECn / l ΖηΖ / 3 / ΥΙΛΙ of about 3000 ppm, less than about 2500 ppm, or less than about 2000 ppm organic solvent. In some embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Cs, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the organic solvent comprises isopropanol. C. Pharmaceutical Compositions, Dosage Forms, and Kits Also provided herein are pharmaceutical compositions comprising Compound 1 and a pharmaceutically acceptable carrier. Pharmaceutically acceptable excipients may include, for example, an adjuvant, carrier, glidant, sweetening agent, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer , isotonic agent, solvent, or emulsifier that has been approved by the United States Food and Drug Administration as acceptable for use in humans or domestic animals. In some embodiments, the pharmaceutical composition is a solid. For example, in some embodiments, the pharmaceutical composition is a powder or a tablet. In QCCECn / l ΖηΖ / 3 / ΥΙΛΙ certain modalities, a solid form of Compound 1, or a solid pharmaceutical composition comprising Compound 1, is administered orally to a subject in need thereof (for example, as a powder, one or more tablets or one or more capsules). In certain embodiments, the pharmaceutical composition is combined with a suitable medium to produce a liquid, and the liquid is administered to a subject in need thereof. In some embodiments, the fluid is administered parenterally (eg, intravenously). In other embodiments, the fluid is administered enterally, such as through a gastrointestinal tube (eg, orally or rectally through a gastrointestinal tube). In some embodiments, the liquid is administered orally, such as with a syringe, cup, or spoon. In some embodiments, the suitable medium is aqueous. Also provided herein are dosage forms comprising a pharmaceutical composition as described herein. In some embodiments, the dosage form comprises one or more tablets or one or more capsules. In some embodiments, the dosage form is a powder in a sealed vial, which is combined with a suitable medium before administration. In some embodiments, the suitable medium is aqueous. In still other embodiments, provided herein are kits comprising a dosage form as QCCRCn / l 7Π7 / 3 / ΥΙΛΙ described herein, and a container. Any suitable container may be used. In some embodiments, the package comprises a bottle, blister pack, or vial. In some further embodiments, the kit comprises a dosage form, wherein the dosage form comprises one or more tablets or one or more capsules, and a package, wherein the package is a blister pack. The blister pack, in some embodiments, is sealed with a plastic film, or a foil film, or a film comprising plastic and foil. In some embodiments, the kit comprises a suitable medium for mixing with the dosage form prior to administration to the subject in need thereof. For example, in some embodiments, the kit comprises a powdered dosage form in a sealed vial and an aqueous medium in a separate container (such as a vial, syringe, or bottle), and the dosage form is combined with the aqueous medium before being administered to the subject in need (for example, orally). In some embodiments, the pharmaceutical composition, dosage form, or kit comprises less than about 6000 ppm organic solvent. In some embodiments, the pharmaceutical composition, dosage form, or kit comprises less than about 5,500 ppm, less than about 5,000 ppm, less than about 4,500 ppm, less than about 4,000 ppm, less than about 3,500 ppm , less than about 3000 ppm, less than about 2500 ppm, or less than accacn / i ζηζ / α / γίΛΐ about 2000 ppm organic solvent. In some embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the solvent QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ organic comprises isopropanol. d. Water content and relationships In certain embodiments, the bulk composition, the kit or the pharmaceutical composition, the dosage form, the medicine includes least j about 5.0%, at least about 5.5%, at least about 6.0%, at least about 6.5%, at least about 7.0%, at least about 7.5%, at least about 8.0%, at least about least about 8.5%, at least about 9.0%, at least about 9.5%, at least about 10.0%, at least about 10.5%, at least about 11.0%, at least about 11.5%, 0 to minus about 12.0% by weight of dihydrochloride with respect to that of water with total weight of acid salt (3S 4R 3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form. In some embodiments, the bulk composition, pharmaceutical composition, dosage form, kit, or medicament comprises between about 6.5% by weight and about 10% by weight, or between about 7.5% by weight and about 9.0% in weight, or about 8.5% by weight of water, with respect to the total weight of acid dihydrochloride salt (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino )-3-methoxy-piperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester present in trihydrate form, and (if present) in anhydrous form. In some embodiments, only the trihydrate form is present. In certain embodiments, the anhydrous form is also present and the water content is evaluated relative to the total weight of (33,4R,3'R)-6-[4-(4-amino5-chloro) acid dihydrochloride salt. -2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester in both the trihydrate and anhydrous forms. In some embodiments, the bulk composition, pharmaceutical composition, dosage form, kit or medicament comprises about 7.5% by weight of water, with respect to the total weight of acid dihydrochloride salt (33, 4R, 3'R) - 6-[4-(4-amino-5-chloro-2methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester present in trihydrate form, and (if present) in anhydrous form. The water content of the bulk composition, pharmaceutical composition, dosage form, kit, or medicament includes water present in the trihydrate form of the compound. accacn / i ζηζ / α / γίΛΐ In some embodiments, the bulk composition, pharmaceutical composition, dosage form, kit or medicament provided herein further comprises an anhydrous form of (3S, 4R, 3'R)6-[4-( 4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl]-hexanoic l-azabicyclofl.i.lJoct-S'-yl ester. In certain embodiments, the ratio of Compound 1 to the anhydrous form is at least about 2 to, at least about 3 to 1, at least about 4 to 1, at least about 5 to 1, at least about 6 to 1, at least about at least about 7 to 1, at least about 8 to 1, at least about 9 to 1, at least about 10 to 1, at least about 11 to 1, or at least about 12 to 1. In some embodiments, the bulk composition, pharmaceutical composition, dosage form, kit or medicament comprises an anhydrous form of (3S, 4R, 3'R)-6 acid dihydrochloride salt. -[4-(4-amino-5-chloro-2methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester, and the ratio of Compound 1 with respect to the anhydrous form is at least 4 to 1, or at least 11 to 1. E. Stability In some embodiments, bulk compositions, pharmaceutical compositions, dosage forms, medicaments, or kits comprising Compound 1 QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ provided herein have increased stability over bulk compositions, pharmaceutical compositions, dosage forms, medicaments or kits comprising the anhydrous form of acid dihydrochloride salt ( 3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3' -yl ester. For example, in some embodiments, bulk compositions, pharmaceutical compositions, dosage forms, medicaments or kits comprising Compound 1 provided herein have a more stable weight over time compared to bulk compositions, pharmaceutical compositions , dosage forms, medications or kits comprising the anhydrous compound. In certain embodiments, bulk compositions, pharmaceutical compositions, dosage forms, medicaments or kits comprising Compound 1 provided herein have less than 10%, less than 9%, less than 8%, less than 7%, less than 6%, less than 5%, less than 4%, less than 3%, less than 2.5%, less than 2%, less than 1.5%, less than 1%, or less than 0.5% change in mass during at least 3 months, at least 6 months, at least 9 months, at least 12 months, at least 15 months, at least 18 months, at least 24 months, at least 30 months, at least 36 months, at least 42 months, or at least 48 months. In some embodiments, the change in mass is an increase in mass. In some QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ modalities, the change in mass is a decrease in mass. In some embodiments, bulk compositions, pharmaceutical compositions, dosage forms, medicaments or kits comprising Compound 1 are more stable under certain conditions than bulk compositions, pharmaceutical compositions, dosage forms, medicaments or kits comprising the anhydrous compound. For example, in some modes, the environment has a relative humidity greater than 10%, greater than 20%, greater than 30%, greater than 40%, greater than 50%, greater than 60%, greater than 70%, greater than 80%, greater than 90%, 10% or greater, 20% or greater, 30% or greater, 40% or greater, 50% or greater, 60% or greater, 70% or greater, 80% or greater, 90% or greater, or about 60%. In some modalities, the temperature is between 15°C and 35°C or between 20°C and 30°C. In certain modalities, the temperature is around 25°C. In other modes, the temperature is less than 35°C, less than 30°C, greater than 10°C, greater than 15°C, or greater than 20°C. In certain embodiments, bulk compositions, pharmaceutical compositions, dosage forms, medicaments, or kits comprising Compound 1 provided herein have less than 8%, less than 4%, or less than 2% change in mass (such as an increase in mass) for at least 3 months, at least 6 months, at least 9 months, at least 12 months, at least 18 months, at least 24 months, or at least 36 months when stored in an accacn / i ζηζ / α / γίΛΐ environment between 15°C and 35°C (such as between 20°C and 30°C, or around 25°C) and a relative humidity greater than 30% (such as greater than 50%, or about 60%) . II. Methods of use of Compound 1 Also provided herein are methods of treating a disorder in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1. In some embodiments, the subject is administered a pharmaceutical composition comprising Compound 1 and a pharmaceutically acceptable excipient. Also provided herein are methods of improving gastrointestinal motility in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1 or administering a pharmaceutical composition comprising Compound 1 and a carrier acceptable from the pharmaceutical point of view. Furthermore, provided herein is the use of Compound 1, or a pharmaceutical composition comprising Compound 1, for treating a disorder in a subject in need thereof or for improving gastrointestinal motility in a subject in need thereof, and the use of Compound 1 in the manufacture of a medicament for treating a disorder in a subject in need thereof or for improving gastrointestinal motility in a subject in need thereof. In some modalities of treating a disorder in a subject in need thereof (such as methods, use of Compound 1, use of a pharmaceutical composition comprising Compound 1, or use of Compound 1 in the manufacture of a medicament), the disorder is a gastrointestinal disorder. In some modalities for improving gastrointestinal motility in a subject in need thereof (such as methods, use of Compound 1, use of a pharmaceutical composition comprising Compound 1, or use of Compound 1 in the manufacture of a medicament), the subject who you need it you have a gastrointestinal disorder. In certain modalities, the gastrointestinal disorder is gastroesophageal reflux disease (GERD), dyspepsia (such as functional dyspepsia or functional motility disorder), gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, bowel syndrome irritable (IBS), constipation, enteral feeding intolerance (EFI), esophagitis, chronic grass disease, megacolon, gastritis, gastrointestinal stasis or abomasal emptying defect. In some embodiments, the subject in need is a human being. In certain embodiments, where the subject in need thereof is a human, the gastrointestinal disorder is gastroesophageal reflux disease (GERD), dyspepsia (such as QCCECn / l ΖηΖ / 3 / ΥΙΛΙ as functional dyspepsia or functional motility disorder), gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, Irritable Bowel Syndrome (IBS), constipation, feeding intolerance enteral infection (EFI), or esophagitis. In other embodiments, the subject in need thereof is a non-human mammal, such as a ruminant (for example, sheep, cow, yak, bison, or buffalo), an equine (for example, a horse (including a pony), or a donkey). ), a cat, dog, rabbit, or guinea pig. In some embodiments, where the subject in need thereof is a non-human mammal, the gastrointestinal disorder is postoperative ileus, chronic turf disease, constipation, megacolon, gastritis, gastrointestinal stasis, or abomasum emptying defect. In some embodiments, there is provided herein a method of treating gastroesophageal reflux disease (GERD) in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof need a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition accacn / i ζηζ / α / γίΛΐ comprising Compound 1, for use in the treatment of GERD, or use of Compound 1 in the manufacture of a medicine for the treatment of GERD. In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or the use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is GERD. GERD is a disease characterized by the reflux of stomach contents into the esophagus. An important factor in the pathogenesis of gastroesophageal reflux disease is a reduction in the pressure barrier due to failure of the lower esophageal sphincter. Lower esophageal sphincter failure may arise due to low basal pressure, sphincter relaxation, or an uncompensated increase in intragastric pressure. Other factors in the pathogenesis of the disease may include delayed gastric emptying, insufficient esophageal clearance due to impaired peristalsis, or the corrosive nature of the refluxed material, which can damage the esophageal mucosa. In some modalities, the GERD is proton pump inhibitor (DPI) resistant GERD. PPI-resistant GERD may include, for example, GERD in subjects that does not improve with administration QCCECn / l ΖηΖ / 3 / ΥΙΛΙ of a PPI, or in which the subject's main complaint has improved less than 50% with the administration of a PPI. Thus, in some embodiments, a method of treatment is provided herein; Compound 1 for use in treatment; a pharmaceutical composition comprising Compound 1 for use in treatment; or the use of Compound 1 in the manufacture of a medicament for treating GERD, wherein the GERD is PPI-resistant GERD. In some embodiments, the subject in need is a human being. In some embodiments, provided herein is a method of treating dyspepsia in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of dyspepsia, or use of Compound 1 in the manufacture of a medicament for the treatment of dyspepsia. . In some embodiments of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof, the subject in need thereof having a gastrointestinal disorder, wherein the gastrointestinal disorder is dyspepsia. Dyspepsia is a condition characterized by impaired digestive power or function and may arise as a symptom of primary gastrointestinal dysfunction or as a complication of other disorders, such as appendicitis, gallbladder disorders, or malnutrition. Thus, in some modalities, treatment of dyspepsia comprises treatment of dyspepsia associated with appendicitis, treatment of dyspepsia associated with a gallbladder disorder, or treatment of dyspepsia associated with malnutrition, or treatment of functional dyspepsia (FD), or treatment of all of these. In some modalities, the treatment of dyspepsia is the treatment of functional dyspepsia (FD). Functional dyspepsia may also be called functional motility disorder (FMD). In some embodiments, the subject in need is a human being. In other embodiments, the subject in need is a non-human animal, such as a ruminant (such as a sheep, cow, yak, bison, or buffalo), or an equine (such as a horse (which may include a pony) or a donkey), a cat, a dog, a rabbit or a guinea pig. QCCRCn / l 7Π7 / 3 / ΥΙΛΙ In some embodiments, provided herein is a method of treating gastroparesis in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of gastroparesis, or use of Compound 1 in the manufacture of a medicament for the treatment of gastroparesis. . In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is gastroparesis. Gastroparesis is paralysis of the stomach caused by a motor abnormality in the stomach and may be a complication of a disease such as diabetes, progressive systemic sclerosis, anorexia nervosa, or myotonic dystrophy. In some modalities, treatment of gastroparesis comprises treatment of QCCECn / l ΖηΖ / 3 / ΥΙΛΙ diabetic gastroparesis, treatment of gastroparesis associated with progressive systemic sclerosis, treatment of gastroparesis associated with anorexia nervosa or treatment of gastroparesis associated with myotonic dystrophy, or treatment of any combination of these. In some modalities, the gastroparesis is idiopathic gastroparesis or functional gastroparesis. In some embodiments, the subject in need is a human being. In some embodiments, provided herein is a method of treating paralytic ileus in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition that it comprises a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of paralytic ileus, or use of Compound 1 in the manufacture of a medicament for the treatment of paralytic ileus. . In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving the accacn / i ζηζ / α / γίΛΐ gastrointestinal motility in a subject in need thereof, the subject in need thereof having a gastrointestinal disorder, wherein the gastrointestinal disorder is paralytic ileus. In some embodiments, the subject in need is a human being. In some embodiments, provided herein is a method of treating postoperative ileus in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition that it comprises a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of postoperative ileus, or use of Compound 1 in the manufacture of a medicament for the treatment of postoperative ileus. . In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is postoperative ileus. Postoperative ileus is an obstruction QCCRCn / l 7Π7 / 3 / ΥΙΛΙ in the intestine due to impaired muscle tone after surgery. In some modalities of postoperative ileus treatment, the subject in need thereof is a human. In other embodiments, the subject in need thereof is a non-human animal, such as an equine animal, for example a horse (which may include a pony). In some embodiments, there is provided herein a method of treating nausea or emesis in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, there is provided herein Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of nausea, or use in the treatment of emesis, or use of Compound 1 in the manufacture of a medicament. for the treatment of nausea, or for the treatment of emesis. In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, accacn / i ζηζ / α / γίΛΐ wherein the gastrointestinal disorder is nausea. In other modalities, the gastrointestinal disorder is emesis. In some embodiments, the subject in need is a human being. In some embodiments, provided herein is a method of treating heartburn in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of heartburn, or use of Compound 1 in the manufacture of a medicament for the treatment of heartburn. . In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is heartburn. In some embodiments, the subject in need is a human being. In some embodiments, a QCCECn / l ΖηΖ / 3 / ΥΙΛΙ method of treating intestinal pseudo-obstruction in a subject in need thereof, which comprises administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of intestinal pseudo-obstruction, or use of Compound 1 in the manufacture of a medicament for the treatment of intestinal pseudo-obstruction. intestinal pseudo-obstruction. In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is intestinal pseudo-obstruction. Intestinal pseudo-obstruction is a condition characterized by constipation, colicky pain, and vomiting, but without evidence of physical obstruction. In some modalities, treating intestinal pseudo-obstruction comprises treatment of constipation associated with intestinal pseudo-obstruction, treatment of colic pain accacn / i ζηζ / α / γίΛΐ associated with intestinal pseudo-obstruction or treatment of vomiting associated with intestinal pseudo-obstruction, or treatment of all these. In some embodiments, the subject in need is a human being. In some embodiments, there is provided herein a method of treating irritable bowel syndrome (IBS) in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof need a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of IBS, or use of Compound 1 in the manufacture of a medicament for the treatment of IBS. In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is IBS. IBS is a condition characterized by abdominal pain due to abnormal contractions of the colon and is often associated with QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ constipation and diarrhea. Thus, in some embodiments, treatment of IBS comprises treatment of abdominal pain associated with IBS or treatment of constipation associated with IBS or treatment of diarrhea with IBS. In some forms, the IBS is of the constipation type of irritable bowel syndrome (IBSc). In some embodiments, the subject in need is a human being. In some embodiments, there is provided herein a method of treating constipation in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of constipation, or the use of Compound 1 in the manufacture of a medicament for the treatment of constipation. In some modalities of treatment methods, Compound 1, or a pharmaceutical composition comprising Compound 1, for use in, or the use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof, the QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is constipation. Constipation is a condition characterized by infrequent or difficult evacuation of stool, and can result from a condition such as lack of intestinal muscle tone or intestinal spasticity. Thus, in some modalities, treatment of constipation comprises treatment of constipation associated with low intestinal muscle tone, treatment of constipation associated with intestinal spasticity, treatment of constipation associated with IBS, treatment of constipation associated with intestinal pseudo-obstruction, treatment of opioid-induced constipation (QIC), treatment of chronic idiopathic constipation (CIC), or treatment of constipation associated with irritable bowel type constipation (IBSc) ) . In some modalities, the constipation is chronic constipation. In some embodiments, the subject in need is a human being. In other embodiments, the subject in need thereof is a non-human mammal, such as a cat or dog. In some embodiments, provided herein is a method of treating enteral feeding intolerance (EFI) in a subject in need thereof, comprising administering to the subject in need thereof a QCCECn / l ΖηΖ / 3 / ΥΙΛΙ therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of FID, or use of Compound 1 in the manufacture of a medicament for the treatment of FID. . In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is EFI . IFD in critically ill patients is common. Often characterized by one or more vomiting, bloating, complaints of malaise, high nasogastric tube outlet, elevated gastric residual volumes (GRV) measured at intervals, diarrhoea, reduced passage of flatus and stool, or abnormal abdominal radiographs. Critically ill patients with IFD are associated with a longer ICU stay and reduced survival. In some modalities, the accacn / i ζηζ / α / γίΛΐ treatment of EFI comprises one or more of treatment of vomiting associated with EFI, treatment of abdominal bloating associated with EFI, treatment of discomfort associated with EFI, treatment of high nasogastric tube outlet associated with EFI, treatment of high gastric residual volumes (RGVs) associated with EFI, treatment of diarrhea associated with EFI, or treatment of reduced passage of flatus and stool associated with EFI. In some embodiments, the subject in need is a human being. In yet other embodiments, there is provided herein a method of treating esophagitis in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or administering to the subject in need thereof a pharmaceutical composition that it comprises a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of esophagitis, or use of Compound 1 in the manufacture of a medicament for the treatment of esophagitis. . In some embodiments of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof, the subject in need thereof having a gastrointestinal disorder, wherein the gastrointestinal disorder is esophagitis. Esophagitis includes inflammation of the lining of the esophagus and can be caused, for example, by reflux of stomach acid into the esophagus (eg, in GERD), or allergic inflammation of the esophageal tissue. In some forms, the esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE). Thus, in some modalities, treatment of esophagitis includes treatment of erosive esophagitis or eosinophilic esophagitis. In some embodiments, the subject in need is a human being. In other embodiments, there is provided herein a method of treating chronic grazing disease in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or a pharmaceutical composition comprising a therapeutically effective amount effective compound of Compound 1 and a pharmaceutically acceptable excipient. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of chronic grass disease, or use of Compound 1 in the manufacture QCCRCn / l 7Π7 / 3 / ΥΙΛΙ of a drug for the treatment of chronic grass disease in a subject in need thereof. In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is chronic grass disease. In some embodiments of the treatment methods, Compound 1 for use in, a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for treating chronic grazing disease in a subject suffering from needs it, the subject that needs it is a non-human animal, such as an equine or a ruminant. In some modalities, the equine is a horse (which can be a pony) or a donkey. In some embodiments, the ruminant is a sheep. Chronic grass disease includes altered bowel activity due to damage to the autonomic (involuntary) nervous system and is a form of autonomic dystonia. Chronic pasture disease in an equine is also known as equine dysautonomia. In other embodiments, a method of treating megacolon in a subject in need thereof is provided herein, QCCECn / l ΖηΖ / 3 / ΥΙΛΙ comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or a pharmaceutical composition comprising a therapeutically effective amount of Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of megacolon, or use of Compound 1 in the manufacture of a medicament for the treatment of megacolon. In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is megacolon. In some modalities of treatment methods, Compound 1 for use in, a pharmaceutical composition comprising Compound 1 for use in, or the use of the Compound in the manufacture of a medicament for treating megacolon in a subject in need thereof, the subject in need is a non-human animal, such as a companion animal. In certain embodiments, the subject in need is a cat or a dog. Megacolon includes abnormal dilation of the colon (also called accacn / i ζηζ / α / γίΛΐ large intestine) and is often accompanied by paralysis of the peristaltic movements of the intestine. In yet other embodiments, there is provided herein a method of treating gastritis in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or a pharmaceutical composition comprising a therapeutically effective amount of Compound 1. Compound 1 and a pharmaceutically acceptable excipient. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of gastritis, or use of Compound 1 in the manufacture of a medicament for the treatment of gastritis. . In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving gastrointestinal motility in a subject in need thereof , the subject in need thereof has a gastrointestinal disorder, wherein the gastrointestinal disorder is gastritis. In some modalities of treatment methods, Compound 1 for use in, a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for treating gastritis in a subject having it. QCCRCn / l 7Π7 / 3 / ΥΙΛΙ needs it, the subject that needs it is a non-human animal, such as a companion animal. In certain embodiments, the subject in need is a cat. In certain embodiments, the gastritis is atrophic gastritis. Gastritis is an inflammation of the gastric lining and symptoms may include acute vomiting, decreased appetite, dehydration, lethargy or depression, increased thirst, blood in the vomit or stool, and abdominal pain. In certain embodiments, there is provided herein a method of treating gastrointestinal stasis in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or a pharmaceutical composition comprising a therapeutically effective amount of Compound 1. Compound 1 and a pharmaceutically acceptable excipient. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of gastrointestinal stasis, or use of Compound 1 in the manufacture of a medicament for the treatment of gastrointestinal stasis. gastrointestinal stasis in a subject in need thereof. In some modalities of treatment methods, Compound 1 for use in, a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for treating gastrointestinal stasis, the subject in need thereof QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ is a rabbit or guinea pig. Gastrointestinal stasis is the slowing down or complete cessation of gastrointestinal movement. In, for example, rabbits or guinea pigs, the gut can become static for a variety of reasons, which can include stress, dehydration, pain from another underlying disorder or disease (such as gas, dental problems, infections, or urinary tract disorders). ), an intestinal obstruction, or insufficient dietary crude fiber. If left untreated, the slowing or complete cessation of normal bowel movement (peristalsis) can lead to death. In other embodiments, there is provided herein a method of treating abomasal emptying defect in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of Compound 1, or a pharmaceutical composition comprising an amount therapeutically effective Compound 1 and a pharmaceutically acceptable carrier. In some embodiments, provided herein is Compound 1, or a pharmaceutical composition comprising Compound 1, for use in the treatment of abomasal emptying defect, or use of Compound 1 in the manufacture of a medicament for the treatment of the emptying defect of the abomasum. In some modalities of treatment methods, Compound 1 for use in, or a pharmaceutical accacn / i ζηζ / α / γίΛΐ composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for improving the gastrointestinal motility in a subject in need thereof, the subject in need thereof having a gastrointestinal disorder, wherein the gastrointestinal disorder is abomasal emptying defect. In some modalities of treatment methods, Compound 1 for use in, a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for treating emptying defect of the abomasum in a subject who needs it, the subject that needs it is a non-human animal, such as a ruminant, for example, a domesticated ruminant. In some embodiments, the ruminant is a sheep, cow (which may include a bull), yak, bison, or buffalo. Abomasal emptying defect is slowing or complete cessation of abomasal emptying, characterized by distension and impaction of the abomasum. In some embodiments, there is provided herein a method of enhancing the transfer of passive immunity to a colostrum-fed calf, comprising administering to the calf an effective amount of Compound 1, or a pharmaceutical composition comprising an effective amount of Compound 1 and a pharmaceutically acceptable excipient. In some embodiments, Compound 1, or a pharmaceutical composition is provided herein QCCRCn / l 7Π7 / 3 / ΥΙΛΙ comprising Compound 1, for use in increasing passive immunity transfer to a colostrum-fed calf, or use of Compound 1 in the manufacture of a medicament for increasing immunity transfer passive to a colostrum-fed calf. In some embodiments, the colostrum-fed calf is a colostrum-fed dairy calf. Newborn calves must ingest colostrum during the first 24 hours after birth to acquire passive immunity through active uptake of maternal IgG (maternal antibodies) through the epithelial cells of the small intestine. The mass of IgG absorbed from the small intestine of the colostrum-fed calf may depend, in part, on the rate of emptying of the abomasum (rate of emptying of the abomasum, the fourth chamber of the ruminant stomach). The rate of emptying of the abomasum can influence the rate at which colostral IgG is delivered to the IgG absorption site in the small intestine. An increased rate of emptying of the abomasum can, in some modalities, result in an increased apparent efficiency of absorption because colostrum IgG can reach the site of absorption in the small intestine sooner and with a higher luminal concentration. As described herein, treatment methods are provided, Compound 1 to be used or a composition QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ pharmaceutical comprising Compound 1 to be used, or use of the Compound in the manufacture of a medicament to improve gastrointestinal motility in a subject in need thereof. Impaired gastrointestinal motility may include impaired stomach motility, impaired small bowel motility, impaired large bowel motility, or impaired pelvic floor motility, or combinations of these. In some modalities, impaired gastrointestinal motility includes complete cessation of motility. Symptoms associated with poor gastrointestinal motility may include, for example, constipation, vomiting, bloating, diarrhea, or nausea. In some embodiments, impaired gastrointestinal motility is associated with a gastrointestinal disorder, such as one of the gastrointestinal disorders described herein. In certain embodiments, improving gastrointestinal motility as described herein comprises improving gastric motility or improving intestinal motility or a combination of these. In certain embodiments, improving intestinal motility comprises improving small intestinal motility or improving large intestinal motility or a combination of these. In some modalities, improving gastrointestinal motility includes increasing gastrointestinal smooth muscle activity from the esophagus through the proximal small intestine. In certain accacn / i ζηζ / α / γίΛΐ modalities, this accelerates esophageal and small bowel transit and may also facilitate gastric emptying and increase lower esophageal sphincter tone. In some embodiments, improving gastrointestinal motility comprises treating the functional motility disorder. Thus, in some embodiments, provided herein are methods of treatment, Compound 1 for use in, or a pharmaceutical composition comprising Compound 1 for use in, or use of the Compound in the manufacture of a medicament for treating eating disorder. functional motility (FMD). Functional motility disorder may also be called functional dyspepsia (FD). In some modalities for improving gastrointestinal motility, the subject in need thereof is a human. In other embodiments, the subject in need is a non-human animal, such as a ruminant (such as a sheep, cow, yak, bison, or buffalo), or an equine (such as a horse (which may include a pony) or donkey). , a cat, a dog, a rabbit or a guinea pig. In some embodiments of the methods and uses provided herein, the subject is a newborn. In some embodiments, the newborn is a newborn human. In other embodiments, the newborn is a bovine newborn, such as a colostrum-fed calf. In some embodiments, Compound 1 or a QCCECn / l ΖηΖ / 3 / ΥΙΛΙ pharmaceutical composition comprising Compound 1 and a pharmaceutically acceptable excipient is administered to the subject parenterally (such as intravenously). In some embodiments, it is administered subcutaneously. In other modalities, it is administered intramuscularly. In yet other additional modalities, it is administered intraperitoneally. In some embodiments, it is administered rectally. In certain embodiments, it is administered orally. In other modalities, it is administered through a gastric tube. For example, in some embodiments, a solid form of Compound 1 (such as a powder or tablets), or a solid pharmaceutical composition comprising Compound 1 (such as a powder or tablet composition comprising Compound 1) is dissolved in a suitable medium for forming a liquid and the liquid administered parenterally (such as intravenously), orally or by gastric tube. In certain embodiments, a solid form of Compound 1, or a solid pharmaceutical composition comprising Compound 1, is administered orally to a subject in need thereof (for example, as a powder, one or more tablets, or one or more capsules). ). In some embodiments, Compound 1 administered to a subject in need thereof as described herein (such as in a pharmaceutical composition), or QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ used in the manufacture of a medicament as described herein, has one or more of the properties described herein, for example, a crystalline form with one or more XRPD peaks as described at the moment. In certain embodiments of any of the methods and uses provided herein (including, for example, methods of treatment, Compound 1 for use, a pharmaceutical composition comprising Compound 1 for use, or uses of Compound 1 in the manufacture of a medicament) to treat the disorders described herein, or to improve gastrointestinal motility as described herein, in a subject in need thereof, where the subject in need thereof is an animal. In some embodiments, the animal is a mammal. In certain embodiments, the animal is a human. In other embodiments, the animal is a non-human animal. In certain embodiments, the animal is a ruminant, such as a domesticated ruminant. In some embodiments, the ruminant is a sheep, cow (which may include a bull), yak, bison, or buffalo. In other embodiments, the mammal is an equine, such as a domesticated equine. In certain embodiments, the equine is a horse (including a pony) or a donkey. In other embodiments, the animal is a cat, dog, rabbit, or guinea pig. In certain embodiments, the animal is a pet, for example, a horse, donkey, cat, dog, rabbit, or guinea pig as accacn / i ζηζ / α / γίΛΐ pet. In certain embodiments, the animal is an animal used for food production, such as a sheep, cow, bison, buffalo, or yak. Therefore, provided herein are methods of Compound 1 for use in, a pharmaceutical composition comprising Compound 1 for use, or uses of Compound 1 in the manufacture of a medicament for treating the disorders described herein or for ameliorating gastrointestinal motility as described herein, in a human. In another aspect, provided herein are methods of Compound 1 for use in, a pharmaceutical composition comprising Compound 1 for use, or uses of Compound 1 in the manufacture of a medicament for treating the disorders described herein or for ameliorating gastrointestinal motility as described herein, in a non-human mammal. As described herein, bulk compositions, pharmaceutical compositions, kits, and dosage forms are provided comprising Compound 1 that have a particular stability, or organic solvent content, or water content, or trihydrate to form ratios. to anhydrous form, or XRPD spectra, or various combinations of these. Any of these pharmaceutical compositions, dosage forms, or kits may, in some embodiments, be used in the methods and uses described in the QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ present to treat a disorder, or promote gastrointestinal motility, in a subject in need thereof as provided herein. In some embodiments, any of these bulk compositions may be used in the methods and uses described herein to treat a disorder, or promote gastrointestinal motility, in a subject in need thereof, as provided herein, or may be used in the manufacture of a pharmaceutical formulation or dosage form or kit for use in the methods and uses described herein for treating a disorder, or promoting gastrointestinal motility, in a subject in need thereof, as provided herein. III. Production Methods of Compound 1 In some aspects, methods for producing Compound 1 and bulk compositions comprising Compound 1 are provided herein. In developing methods for producing bulk compositions of Compound 1, it has surprisingly been found that simply drying a wet mixture of salt 1-azabicyclo[2.2. 2]oct-3'-yl ester does not always reliably produce a composition comprising Compound 1 with low residual solvent (no water). Rather, a stepwise procedure of different temperatures and pressure ranges is, in some QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ modalities, a key aspect of the process for producing compositions comprising Compound 1 on a large scale. Furthermore, at least three crystalline forms of the anhydrous dihydrochloride salt of (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino) acid have been found to exist. -3methoxy-piperidin-l-yl]-hexanoic l-azabicyclo[2.2.2]oct-3'yl ester, and at least one crystalline form of Compound 1 (the trihydrate), and under certain solvent and temperature conditions, some In these ways they can be interchanged. The methods for preparing Compound 1 described herein can reproducibly produce Compound 1 with low residual solvent (no water) and may be suitable for both laboratory scale and commercial scale manufacture. Methods for preparing Compound 1 can also produce a crystalline form that has good handling properties, eg, low clumping and / or flows well. In some embodiments, the method for preparing Compound 1 (such as methods for preparing a bulk composition comprising Compound 1) comprises: (a) Combine (3S,4R,3'R)-6-[4(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-lyl]-hexanoic acid free base 1 -azabicyclo[2.2.2]oct-3'-yl ester with organic solvent to form a mixture; (b) adjust the pH of the mixture between 3.5 and 4.5 by accacn / i ζηζ / α / γίΛΐ the addition of hydrochloric acid; (c) stir the mixture until a precipitate forms; (d) isolating the precipitate to form an isolated precipitate; and (e) drying the isolated precipitate under reduced pressure to yield the trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy- benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester (Compound 1). Any suitable organic solvent can be combined with the free base to form the mixture. In some embodiments, the organic solvent comprises one or more compounds, such as one or more organic compounds, or at least one organic compound and one or more non-organic compounds. In certain embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Ce, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises one or more of methanol, ethanol, n-propanol, or isopropanol. In some embodiments, the organic solvent comprises isopropanol. In some embodiments, the organic solvent comprises ethanol and n-propanol. In still other embodiments, the organic solvent comprises at least one organic compound and one or more non-organic compounds. In certain embodiments, the free base is combined with a QCCECn / l ΖηΖ / 3 / ΥΙΛΙ organic solvent and water to form the mixture. For example, in some embodiments, the free base is combined with water and an organic solvent to form the mixture, wherein the organic solvent comprises one or more alcohols, such as isopropanol. In some embodiments, the mixture may comprise, for example, various amounts of water. In certain embodiments, the mixture comprises organic solvent and at least 1% by weight of water, at least 5% by weight of water, at least 10% by weight of water, not more than 20% by weight of water, not more than 15% by weight of water, not more than 10% by weight of water, from about 1% by weight to about 20% by weight of water, from about 5% by weight to about 15% by weight of water , from about 8% by weight to about 12% by weight of water, or from about 10% by weight of water, where the % by weight of water is relative to the weight of organic solvent in the mixture. In certain embodiments, the mixture comprises organic solvent and from about 5% by weight to about 15% by weight of water, based on the amount of organic solvent. In other embodiments, the organic solvent comprises from 8% by weight to about 12% by weight of water. In some embodiments, the mixture comprises an organic solvent and about 10% by weight of water. In certain embodiments, the mixture comprises an organic solvent, wherein the organic solvent comprises one or more alcohols; and water, where water is present at about 5% by weight to about 15% accacn / i ζηζ / α / γίΛΐ by weight, about 8% by weight to about 12% by weight, or about 10% by weight, where the % by weight of water is relative to the amount of organic solvent. In still other embodiments, the mixture comprises an organic solvent, wherein the organic solvent comprises ethanol, n-propanol, or isopropanol, or any combination of these; and water, wherein the water is present at about 5% by weight to about 15% by weight, about 8% by weight to about 12% by weight, or about 10% by weight with respect to the amount of organic solvent. In still other embodiments, the mixture comprises an organic solvent, wherein the organic solvent comprises isopropanol; and water, wherein the water is present at about 5% by weight to about 15% by weight, about 8% by weight to about 12% by weight, or about 10% by weight with respect to the amount of organic solvent. In certain embodiments, the mixture comprises water and organic solvent in a volume ratio of less than 3:7. In certain embodiments, the mixture comprises water and organic solvent in a volume ratio of less than 1:4. In certain embodiments, the mixture comprises water and organic solvent in a volume ratio of less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1: 8 or less than 1:9 by volume. In certain embodiments, the ratio is around 1:9. In any of these modalities, the organic solvent can comprise one or more QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In some embodiments, the organic solvent comprises ethanol and n-propanol. In certain embodiments, the organic solvent comprises isopropanol. In certain embodiments, the organic solvent is isopropanol. In some embodiments, a mixture comprising water and organic solvent in a volume ratio of less than 3:7 by volume (such as less than 1:4, for example, about 1:9) results in a higher yield of a crystalline form of Compound 1 than a process using a mixture with a higher ratio of water to organic solvent. In certain embodiments, the pH of the mixture is adjusted with hydrochloric acid by adding an aqueous solution of hydrochloric acid to the mixture of the free base and organic solvent, and optionally water. For example, in some embodiments, the hydrochloric acid is concentrated hydrochloric acid. In certain embodiments, hydrochloric acid is added as an aqueous solution comprising about 30% to about 45% by weight hydrochloric acid, or about 30% to about 40% by weight hydrochloric acid, or about 35% to about 40% by weight of hydrochloric acid, or about 37% by weight of hydrochloric acid. In some embodiments, aqueous hydrochloric acid of different concentration is used, for example, 20% by weight, 15% by weight, 10% by weight or 5% by weight of aqueous hydrochloric acid. In other modalities, the pH of the mixture QCCRCn / l 7Π7 / 3 / ΥΙΛΙ is adjusted with hydrochloric acid by bubbling hydrogen chloride gas through the mixture to form hydrochloric acid. In some embodiments of the methods provided herein, the pH of the mixture is adjusted between 3.5 and 4.5, or between 3.6 and 4.4, or between 3.7 and 4.3, or between 3.8 and 4.2, or between 3.9 and 4.1, or to about of 4.0 by adding hydrochloric acid. In some embodiments, the mixture is stirred at a temperature below 50°C until a precipitate forms. In some embodiments, the mixture is stirred at a temperature of 45°C or below, 40°C or below, 35°C or below, 30°C or below, 25°C or below, or 20°C or below until form a precipitate. In certain modalities, the mixture is stirred at a temperature between 20°C and 45°C, between 20°C and 40°C, between 20°C and 35°C, between 25°C and 45°C, between 25° C to 40°C or between 25°C to 35°C until a precipitate forms. In some embodiments, the mixture is stirred at a temperature of 30°C or less until a precipitate forms. In certain forms, agitate the mixture at a temperature of less than 50°C (such as between 20°C and 40°C, or between 25°C and 35°C, or around 30°C) until a precipitate forms results in a higher yield of a crystalline form of Compound 1 from the process than stirring the mixture at a higher temperature. In certain embodiments, after the QCCECn / l ΖηΖ / 3 / ΥΙΛΙ precipitate, is isolated to produce the isolated precipitate. In certain embodiments, the precipitate is isolated directly from the mixture to form the isolated precipitate. In other embodiments, one or more steps occur after forming the precipitate before isolating the precipitate to form the isolated precipitate, such as one or more recrystallization steps. The precipitate can be isolated by any suitable means, such as centrifugation, filtration, or other means, to form an isolated precipitate. The isolated precipitate may undergo one or more additional steps (such as one or more washing steps) before being dried under reduced pressure. In certain embodiments, which may be combined with any other embodiment described herein, water is added in one or more stages before drying the isolated precipitate under reduced pressure. For example, in some embodiments, the free base is combined with an organic solvent and water to form a mixture; or water is added to the mixture formed by combining the free base and the organic solvent; or water with hydrochloric acid is added to adjust the pH of the mixture; or water is added to the mix after adjusting the pH; or water is added to the mixture after the precipitate forms but before the precipitate is isolated; or water is added during or before or after any of the additional steps described herein, such as QCCRCn / l 7Π7 / 3 / ΥΙΛΙ recrystallization or washing. In some embodiments, water is added two or more times during the method, eg, combining with the organic solvent and the free base to form a mixture, and while adjusting the pH of the mixture by adding hydrochloric acid. A. Organic solvent and water content In some embodiments, the isolated precipitate is dried under reduced pressure until a water content between 6.5% by weight and 10% by weight is reached to produce Compound 1. In certain embodiments, the isolated precipitate is dried under reduced pressure, as the reduced pressures described herein, until a water content of between 6.5% by weight, 6.6% by weight, 6.7% by weight, 6.8% by weight, 6.9% by weight, 7.0% by weight, 7.1% by weight is reached , 7.2% by weight, 7.3% by weight, 7.4% by weight, 7.5% by weight, 7.6% by weight, 7.7% by weight, 7.8% by weight, 7.9% by weight, or 8.0% by weight to 8.4% by weight. weight, 8.5% by weight, 8.6% by weight 8.7% by weight, 8.8% by weight, 8.9% by weight, 9.0% by weight, 9.1% by weight, 9.2% by weight, 9.3% by weight, 9.4% by weight , 9.5% by weight, 9.6% by weight, 9.7% by weight, 9.8% by weight, 9.9% by weight, or 10.0% by weight. In some embodiments, the isolated precipitate is dried under reduced pressure until a water content of between 7.5% by weight and 9.0% by weight is reached to produce Compound 1. In certain embodiments, the isolated precipitate is dried under reduced pressure until that a water content of between 7.6% by weight and 8.8% by weight is reached to produce Compound 1. In still other embodiments, the isolated precipitate is dried under reduced pressure until a water content of about 8.2% is reached. by weight to produce Compound 1. The water content of the isolated precipitate includes water present in the trihydrate form (Compound 1). In some embodiments, the isolated precipitate is dried under reduced pressure, such as the reduced pressures described herein, until the organic solvent content is less than about 6000 ppm. In some embodiments, it is dried under reduced pressure until the organic solvent content is less than about 5,500 ppm, less than about 5,000 ppm, less than about 4,500 ppm, less than about 4,000 ppm, less than about 3,500 ppm, less than about 3000 ppm, less than about 2500 ppm, or less than about 2000 ppm. In certain embodiments, it is dried under reduced pressure until the organic solvent content is less than about 5,000 ppm, or less than about 4,000 ppm. In some embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the solvent QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ organic comprises ethanol and n-propanol. In some embodiments, the organic solvent comprises isopropanol. B. Drying conditions In some embodiments, the reduced pressure used to dry the isolated precipitate is between about 20 mm Hg and about 60 mm Hg, or between about 20 mm Hg and about 55 mm Hg, or between about 20 mm Hg and about 50 mm Hg, or about 25 mm Hg to about 50 mm Hg, or about 25 mm Hg to about 45 mm Hg, or about 30 mm Hg to about 40 mm Hg, or about 35 mm Hg. In some modalities, the reduced pressure is between about 20 mm Hg and about 60 mm Hg. In other modalities, the reduced pressure is from about 25 mm Hg to about 50 mm Hg. In certain modalities, the reduced pressure is from about 30 mm Hg to about 50 mm Hg. In still other modalities, the reduced pressure is from about 30 mm Hg to about 40 mm Hg, or about 35 mm Hg. In some embodiments of the methods provided herein, the isolated precipitate is dried under reduced pressure at a temperature between about 10°C and about 70°C, or between about 20°C and about 60°C, or between about 25°C and about 55°C, or between about 30°C and about 50°C. In some embodiments, the isolated precipitate is dried under reduced accacn / i ζηζ / α / γίΛΐ pressure in one or more stages, for example, where the temperature of the isolated precipitate is changed with time during the drying process. In certain embodiments, drying the isolated precipitate in stages over a range of temperatures results in a composition (such as a bulk composition) comprising Compound 1 with a lower residual organic solvent level than is achieved by drying the precipitate. insulated at a single temperature or a narrower range of temperatures. For example, in some embodiments, drying the isolated precipitate in stages produces a composition (such as a bulk composition) comprising Compound 1 with a residual organic solvent content of less than 6000 ppm. In other embodiments, drying the isolated precipitate in stages produces a composition (such as a bulk composition) comprising Compound 1 with a residual organic solvent content of less than about 5000 ppm, or less than about 4000 ppm, or less than about 3000 ppm, or less than about 2000 ppm. In some embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the organic solvent comprises ethanol and n-propanol. in still others QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ modes, the organic solvent comprises isopropanol. In some embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 10°C and about 50°C, and then at a temperature between about 35°C and about 70°C to produce Compound 1. In certain embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 20°C and about 50°C, and then at a temperature between about 35°C and about 60°C; or between about 25°C and about 45°C, and then at a temperature between about 40°C and about 55°C. In certain embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 20°C and about 40°C, and then at a temperature between about 30°C and about 50°C; then at a temperature between about 35°C and about 55°C, and then at a temperature between about 40°C and about 60°C. In certain embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 25°C and about 35°C, and then at a temperature between about 35°C and about 45°C; then at a temperature between about 40°C and about 50°C, and then at a temperature between about 45°C and about 55°C. In some embodiments, the isolated precipitate is dried under reduced pressure for a period of time. QCCRCn / l 7Π7 / 3 / ΥΙΛΙ specified and a specified temperature or temperature range. For example, in certain embodiments, performing staged drying comprises drying the isolated precipitate at the specified temperature or temperature range for a particular period of time. In certain embodiments, drying the isolated precipitate in such a manner provides a composition comprising Compound 1 (such as a bulk composition) with a lower level of residual organic solvent than would otherwise be achieved. In some embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 10°C and about 50°C for about 0.5 hours to about 10 hours, and then at a temperature between about 35°C and about 70°C for about 0.5 hours to about 10 hours to produce Compound 1 or a bulk composition comprising Compound 1. In certain embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 20°C and about 50°C for about 0.5 hours to about 10 hours, and then at a temperature between about 35°C and about 60°C for about 0.5 hours to about 10 hours; or between about 25°C and about 45°C for about 0.5 hours to about 10 hours, and then at a temperature between about 40°C and about 55°C for about QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 0.5 hours to around 10 hours. In certain embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 20°C and about 40°C for from about 0.5 hours to about 4 hours, then at a temperature between about 30°C and about 50°C for about 0.5 hours to about 4 hours; then at a temperature between about 35°C and about 55°C for about 0.5 hours to about 4 hours, and then at a temperature between about 40°C and about 60°C. In certain embodiments, the step of drying the isolated precipitate at a temperature of from about 40°C to about 60°C is carried out for about 0.5 to 10 hours, or for about 2 to 10 hours, or for about from 3 to 7 hours. In certain embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 25°C and about 35°C for about 0.5 hours to about 3 hours, then at a temperature between about 35°C and about 45°C for about 0.5 hours to about 3 hours; then at a temperature between about 40°C and about 50°C for about 0.5 hours to about 3 hours, and then at a temperature between about 45°C and about 55°C. In still other embodiments, the isolated precipitate is dried under reduced pressure at a temperature between about 25°C and about 35°C for about 0.5 to about 2.5 hours; then at a temperature between about 35°C and about 45°C for about 0.5 to about 2.5 hours, then at a temperature between about 40°C and about 50°C for about 0.5 to about 2.5 hours, and then at a temperature between about 45°C and about 55°C. In certain embodiments, the step of drying the isolated precipitate at a temperature of from about 45°C to about 55°C is carried out for about 0.5 to 15 hours, or for about 2 to 12 hours, or for about from 3 to 10 hours, or for about 3 to 7 hours, or for about 4 to 8 hours. In still other embodiments, the isolated precipitate is dried under reduced pressure at a temperature of about 30°C for about 0.5 to about 2.5 hours; then at a temperature of about 40°C for about 0.5 to about 2.5 hours; then at a temperature of about 45°C for about 0.5 to about 2.5 hours; and then at a temperature of around 50°C. In certain embodiments, the step of drying the isolated precipitate at a temperature of about 50°C is carried out for about 0.5 to 15 hours, or for about 2 to 12 hours, or for about 3 to 10 hours, or for about 3 to 7 hours, or for about 4 to 8 hours. In other embodiments of the methods provided herein, the isolated precipitate is dried under reduced pressure for between about 2 hours and about 20 hours, between about 2 hours and about 18 hours, between about 2 hours and about 16 hours, between about 2 hours and about 14 hours, between about 2 hours and about 12 hours, between about 2 hours and about 10 hours, between about 2 hours and about 8 hours, between about 2 hours and about 6 hours, about 3 hours and about 20 hours, between about 3 hours and about 18 hours, between about 3 hours and about 16 hours, between about 3 hours and about 14 hours , between about 3 hours and about 12 hours, between about 3 hours and about 10 hours, between about 3 hours and about 8 hours, between and about 3 hours and about 6 hours, between and about 5 hours and around 20 hours, between and around 5 hours and around 18 hours, between around 5 hours and around 16 hours, between around 5 hours and around 14 hours, between around 5 hours to around 12 hours, between about 5 hours to about 10 hours, between about 5 hours and about 8 hours, between about 7 hours and about 20 hours, between about 7 hours and about 18 hours, between about 7 o'clock and around 16 o'clock, between around 7 o'clock and around 14 o'clock, between around accacn / i ζηζ / α / γίΛΐ of 7 o'clock and around around 12 o'clock, or between around 7 o'clock and around 10 o'clock hours. In other embodiments of the methods provided herein, the isolated precipitate is dried under reduced pressure for between about 3 hours and about 10 hours. In other embodiments, the isolated precipitate is dried under reduced pressure for between about 5 hours and about 10 hours. In still other embodiments, the isolated precipitate is dried under reduced pressure for between about 7 hours and about 10 hours. In some embodiments, between about 150 kg and about 400 kg or between about 200 kg and about 300 kg of isolated precipitate is dried under reduced pressure for between about 3 hours and about 10 hours, or between about 5 hours to about 10 hours, or between about 7 hours and about 10 hours to produce Compound 1. In certain embodiments, the isolated precipitate (such as between about 150 kg and about 400 kg) is dried under reduced pressure. (for example, between about 3 hours and about 12 hours, or between about 5 hours and about 12 hours, or between about 3 hours and about 10 hours, or between about 5 hours to about 10 hours , or between about 7 hours to about 10 hours) until there is less than about 6000 ppm organic solvent, or less than about 5000 ppm organic solvent, or less than about 4000 ppm organic solvent, or less than about 3000 ppm organic solvent, or less than about 2000 ppm organic solvent, to produce Compound 1. In some embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the organic solvent comprises ethanol and n-propanol. In still other embodiments, the organic solvent comprises isopropanol. In some embodiments, between about 150 kg and about 400 kg or between about 200 kg and about 300 kg of isolated precipitate is dried under reduced pressure of about 20 mm Hg to about 60 mm Hg, or about 25 mm Hg and about 45 mm, or about 35 mm Hg, for about 3 hours to about 15 hours, or about 5 hours to about 12 hours, or about 7 hours to about 10 hours to produce Compound 1. In certain embodiments, the isolated precipitate (eg, between about 150 kg and about 400 kg) is dried under reduced pressure (eg, from about 20 mm Hg to about 60 mm Hg , or from about 25 mm Hg to about 45 mm Hg, or about 35 mm Hg, for example between about 3 hours and about 15 hours, or between about 5 hours and about 12 hours, or between about 7 hours and about 10 hours) until there is less than about 6000 ppm organic solvent, or less than about 5000 ppm organic solvent, or less than about 4000 ppm organic solvent, or less than about 3000 ppm organic solvent, or less than about 2000 ppm organic solvent, to produce the Compound 1. In some embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the organic solvent comprises ethanol and n-propanol. In still other embodiments, the organic solvent comprises isopropanol. For any of the isolated precipitate drying methods provided herein, in some embodiments the indicated temperature is the temperature of the isolated precipitate during drying. In other embodiments, it is the temperature of one or more heating elements that is in contact with at least part of the isolated precipitate. For example, in some embodiments, the temperature of the isolated precipitate is controlled during drying through the use of a jacketed vessel. In some embodiments, the jacketed vessel is a jacketed batch reactor. In certain embodiments, the jacketed container is a jacketed vacuum dryer, such as a cone dryer, spiral dryer, or paddle dryer. Therefore, in some embodiments, the temperature indicated in the drying methods of the isolated precipitate is the jacket temperature of the jacketed vessel. In some embodiments, the isolated precipitate is dried using a jacketed cone drier, and the temperature indicated in the method is the jacket temperature. In some embodiments, the use of one of specified temperatures or pressures or times, or ranges of temperatures or pressures or times, or any combination of these, results in a bulk composition comprising Compound 1 having particular stability, o Organic solvent content, o Water content, o Ratio of trihydrate to anhydrous form, o XRPD spectra, or various combinations of these, as described herein. In some embodiments, the temperatures or pressures or times, or ranges thereof, or combinations of any of the foregoing, as described herein for drying the isolated precipitate, may be combined with, for example, any of the amounts of precipitate or isolated precipitate or free base accacn / i ζηζ / α / γίΛΐ o Compound 1 used in the described process; or one or more additional steps, such as recrystallization or washing; or any of the other conditions or steps described herein. C. Quantities In some embodiments, the amount of time required to dry the isolated precipitate to produce Compound 1 is related to the amount of Compound 1 that is prepared, or the amount of free base used, or the amount of precipitate that is isolated, or the amount of amount of isolated precipitate that dries. In some embodiments, at least about 100 kg of the free acid base (3S, 4R, 3'R)6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidine- l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester is combined with the organic solvent, at least about 150 kg of the free base is combined with the organic solvent, at least about 175 kg of the free base is combined with the organic solvent, at least about 200 kg of the free base is combined with the organic solvent, at least about 250 kg of the free base is combined with the organic solvent, at least about 300 kg of the free base is combined with the organic solvent, at least about 350 kg of the free base is combined with the organic solvent, at least about 400 kg of the free base is combined with the organic solvent, at least QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ about 450 kg of the free base is combined with the organic solvent, or at least about 500 kg of the free base is combined with the organic solvent. In some embodiments, for example, through the use of a large capacity reactor, at least about 1 metric ton of the free base is combined with the organic solvent. In some embodiments, between about 100 kg and about 2000 kg of the free base are combined with the organic solvent, between about 100 kg and about 1000 kg of the free base are combined with the organic solvent, between about 100 kg and about 800 kg of the free base are combined with the organic solvent, between about 100 kg and about 600 kg of the free base are combined with the organic solvent, between about 100 kg and about 400 kg of the free base are combined with the organic solvent, between about 150 kg and about 2000 kg of the free base are combined with the organic solvent, between about 150 kg and about 1000 kg of the free base are combined with the organic solvent , between about 150 kg and about 800 kg of the free base are combined with the organic solvent, between about 150 kg and about 600 kg of the free base are combined with the organic solvent, between about 150 kg and about About 400 kg of the free base are combined with the organic solvent, between about 150 kg and about 300 kg of the free base are combined with the QCCRCn / l 7Π7 / 3 / ΥΙΛΙ organic solvent, between about 150 kg and about 250 kg of the free base are combined with the organic solvent, between about 200 kg and about 350 kg of the free base are combined with the organic solvent, or between about 200 kg and about 300 kg of the free base are combined with the organic solvent. As described herein, in QCCRCn / l 7Π7 / 3 / ΥΙΛΙ some modalities the free base is combined with an organic solvent and water to prepare the mixture. Thus, for any amount of free base that is combined with organic solvent as described herein, in some embodiments that amount of free base is combined with organic solvent and water to form the mixture. In some embodiments, they are isolated at least about 100 kg of precipitate, at least about 150 kg of precipitate is isolated, at least about 175 kg of precipitate is isolated, at least about 200 kg of precipitate is isolated, at least about 250 kg of precipitate is isolated , at least about 300 kg of precipitate is isolated, at least about 350 kg of precipitate is isolated, at least about 400 kg of precipitate is isolated, at least about 450 kg of precipitate is isolated, or at least about 450 kg of precipitate is isolated about 500 kg of precipitate. In certain modalities, for example, through the use of a large capacity reactor, at least 1 metric ton of precipitate. In some embodiments, between about 100 kg and about 2000 kg of precipitate are isolated, between about 100 kg and about 1000 kg of precipitate are isolated, between about 100 kg and about 800 kg of precipitate are isolated, isolate between about 100 kg and about 600 kg of precipitate, isolate between about 100 kg and about 400 kg of precipitate, isolate between about 150 kg and about 2000 kg of precipitate, isolate between about 150 kg and about 1000 kg of precipitate, are isolated between about 150 kg and about 800 kg of precipitate, are isolated between about 150 kg and about 600 kg of precipitate, isolated, are isolated between about 150 kg and about of 400 kg of precipitate, between about 150 kg and about 300 kg of precipitate are isolated, between about 150 kg and about 250 kg of precipitate are isolated, between about 200 kg and about 350 kg of precipitate are isolated or between about 200 kg and about 300 kg of precipitate are isolated. In some embodiments, at least about 100 kg of isolated precipitate is dried, at least about 150 kg of isolated precipitate is dried, at least about 175 kg of isolated precipitate is dried, at least about 200 kg of precipitate is dried isolated, dry at least about 250 kg of isolated precipitate, dry at least about QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 300 kg of isolated precipitate, dry at least about 350 kg of isolated precipitate, at least about 400 kg of isolated precipitate is dried, at least about 450 kg of isolated precipitate is dried, or at least about 500 kg of isolated precipitate is dried. In the commercial sector, for example, by using a large capacity dryer, at least 1 metric ton of isolated precipitate is dried. In some modes, between about 100 kg and about 2000 kg of isolated precipitate are dried, between about 100 kg and about 1000 kg of isolated precipitate are dried, between about 100 kg and about 800 kg of precipitate are dried isolated, between about 100 kg and about 600 kg of isolated precipitate are dried, between about 100 kg and about 400 kg of isolated precipitate are dried, between about 150 kg and about 2000 kg of isolated precipitate are dried, between about 150 kg and about 1000 kg of isolated precipitate are dried between about 150 kg and about 800 kg of isolated precipitate are dried between about 150 kg and about 600 kg of isolated precipitate are dried between about 150 kg and about 400 kg of isolated precipitate, are dried between about 150 kg and about 300 kg of isolated precipitate, are dried between about 150 kg and about 250 kg of isolated precipitate, are dried between about of 200 kg and about 350 kg of isolated precipitate or dry between about 200 kg and about 300 kg of isolated precipitate. In still other embodiments, at least about 100 kg of Compound 1 are produced, at least about 150 kg of Compound 1 are produced, at least about 175 QCCECn / l ΖηΖ / 3 / ΥΙΛΙ kg of Compound 1, at least about 200 kg of Compound 1 are produced, at least about 250 kg of Compound 1 are produced, at least about 300 kg of Compound 1 are produced, at least about 350 kg of Compound 1 are produced Compound 1, at least about 400 kg of Compound 1 is produced, at least about 450 kg of Compound 1 is produced, or at least about 500 kg of Compound 1 is produced. Compound 1. In certain embodiments, for example, through the use of a commercial production facility, at least 1 metric ton of Compound 1 is produced. In some embodiments, between about 100 kg and about 2000 kg of Compound 1 are produced , between about 100 kg and about 1000 kg of Compound 1 are produced, between about 100 kg and about 800 kg of Compound 1 are produced, between about 100 kg and about 600 kg of Compound 1 are produced, produce between about 100 kg and about 400 kg of Compound 1, produce between about 150 kg and about 2000 kg of Compound 1, produce between about 150 kg and about 1000 kg of Compound 1, produce between about 150 kg and about 800 kg of Compound 1, are produced between about 150 kg and about 600 kg of Compound 1, are produced between about 150 kg and about 400 kg of Compound 1, are produced between about 150 kg and about 300 kg of Compound 1, are produced between about 150 kg and about 250 kg of Compound 1, are produced between about 200 kg and about 350 kg of Compound 1 or are produced between about 200 kg and about 300 kg of Compound 1. D. Additional steps The methods for producing a bulk composition comprising Compound 1 provided herein, in some embodiments, may comprise one or more additional steps. For example, in some embodiments, after or during agitation of the mixture until a precipitate forms in step (c), additional solvent is added to the mixture before isolating the precipitate. In some embodiments, the additional solvent comprises an organic solvent. In certain embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the organic solvent comprises ethanol and n-propanol. in still others QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ modes, the organic solvent comprises isopropanol. In some embodiments, the mixture of step (c) is adjusted so that it comprises water and organic solvent, wherein the water is present between 5% and 15% by weight, or about 8% to about 12% by weight. . In some embodiments, the mixture of step (c) is adjusted so that it comprises water and organic solvent in a volume ratio of less than 3:7. In some embodiments, the mixture of step (c) is adjusted so that it comprises water and organic solvent in a volume ratio of less than 1:4. In certain embodiments, the mixture of step (c) is adjusted so that it comprises water and organic solvent in a volume ratio of less than 1:3, less than 1:4, less than 1:5, less than 1:6 , less than 1:7, less than 1:8 or less than 1:9 by volume. In certain embodiments, the ratio is around 1:9. In some embodiments, the organic solvent comprises one or more alcohols. In any of these modalities, the organic solvent may comprise one or more Ci-Cs, or Ci-Cs, or C1-C4 alcohols. In embodiments, the organic solvent comprises ethanol and n-propanoi. In certain embodiments, the organic solvent comprises isopropanol. In certain embodiments, the organic solvent is isopropanol. to. recrystallization In some embodiments, which may be combined with any of the other embodiments described herein, accacn / i ζηζ / α / γίΛΐ the method of producing Compound 1 comprises one or more recrystallization steps. Thus, for example, in some embodiments, after the isolated precipitate in step (d) is formed, and before the isolated precipitate in step (e) is dried, at least a portion of the isolated precipitate is dissolved in a recrystallization solvent to form a recrystallization mixture, the recrystallization mixture is stirred until a recrystallized precipitate is formed, and the recrystallized precipitate is isolated to form an isolated precipitate. This isolated precipitate, for example, can be taken to step (e) and dried to form Compound 1 or, in some embodiments, can be subjected to one or more additional steps, such as another recrystallization or a washing step, or a combination of this. Any suitable recrystallization condition can be used. In certain embodiments, a recrystallization solvent comprising water and organic solvent is used. In some embodiments, the organic solvent comprises one or more alcohols, for example, isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the recrystallization solvent comprises water and organic solvent, wherein water is present at between 5% and 15% by weight, or about 8% to about 12% by weight. In some embodiments, the recrystallization solvent comprises water and organic solvent in a volume ratio QCCECn / l ΖηΖ / 3 / ΥΙΛΙ less than 3:7. In certain embodiments, the recrystallization solvent comprises water and organic solvent in a volume ratio of less than 1:4. In certain embodiments, the recrystallization solvent comprises water and organic solvent in a volume ratio of less than 1:3, less than 1:4, less than 1:5, less than 1:6, less than 1:7, less than 1:8 or less than 1:9 by volume. In certain embodiments, the ratio is around 1:9. In any of these modalities, the organic solvent may comprise one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In some embodiments, the organic solvent comprises ethanol and n-propanol. In certain embodiments, the organic solvent comprises isopropanol. In certain embodiments, the organic solvent is isopropanol. In some embodiments, by using a recrystallization solvent comprising water and an organic solvent in a volume ratio of less than 3:7 by volume (such as less than 1:4, for example around 1:9) produces a crystalline form of Compound 1 in a higher yield than by using a higher ratio of water to organic solvent (such as isopropanol). In certain embodiments, the recrystallization mixture is filtered before stirring until a recrystallized precipitate forms. In some embodiments, the recrystallized precipitate is isolated by centrifugation, filtration, or other means to form an isolated precipitate. QCCECn / l ΖηΖ / 3 / ΥΙΛΙ In some embodiments, when at least a portion of the isolated precipitate is recrystallized, the recrystallization mixture is stirred at a temperature of less than 50°C. In some embodiments, the recrystallization mixture is stirred at a temperature of 45°C or below, 40°C or below, 35°C or below, 30°C or below, 25°C or below, or 20°C or below. In certain embodiments, the recrystallization mixture is stirred at a temperature between 20°C and 45°C, between 20°C and 40°C, between 20°C and 35°C, between 25°C and 45°C, between 25°C to 40°C or between 25°C to 35°C. In some embodiments, the recrystallization mixture is stirred at a temperature of 30°C or less. In certain embodiments, recrystallizing at least a portion of the isolated precipitate at a temperature less than 50°C (such as, for example, between 20°C and 40°C, or between 25°C and 35°C, or about 30 °C) produces a crystalline form of Compound 1 in a higher yield than using a higher recrystallization temperature. In certain embodiments, by recrystallizing at least a portion of the isolated precipitate at a temperature less than 50°C (such as, for example, between 20°C and 40°C, or between 25°C and 35°C, or about 30°C), and by using a recrystallization solvent comprising water and organic solvent in a volume ratio of less than 3:7 by volume (such as less than 1:4, for example around 1:9) produces a crystalline form of Compound 1 with a higher accacn / i ζηζ / α / γίΛΐ yield than by using a higher recrystallization temperature or a higher ratio of water to organic solvent. In some embodiments, using isopropanol as the organic solvent in the recrystallization also contributes to a higher yield, compared to using a different organic solvent in the same process. Thus, in some embodiments, the method of preparing Compound 1 (such as methods of preparing a bulk composition comprising Compound 1) comprises combining the acid free base (3S, 4R, 3'R)-6- [4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-lyl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester with organic solvent to form a mixture ; adjust the pH of the mixture between 3.5 and 4.5 by adding hydrochloric acid; shake the mixture until a precipitate forms; isolate the precipitate; dissolving at least a part of the isolated precipitate in a recrystallization solvent to form a recrystallization mixture; stir the recrystallization mixture until a recrystallized precipitate forms; isolating the recrystallized precipitate to form an isolated precipitate; and drying the isolated precipitate under reduced pressure to yield the trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-dihydrochloride salt. 3-methoxyQCCRCn / l ΖηΖ / 3 / ΥΙΛΙ piperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester (Compound 1). b. washing stage In other embodiments, at least a portion of the isolated precipitate is washed one or more times before being dried under reduced pressure. In some embodiments, at least a portion of the isolated precipitate is washed one or more times with an aqueous wash before being dried under reduced pressure. In some embodiments, the isolated precipitate that is washed one or more times was isolated from a recrystallization mixture. In other embodiments, the isolated precipitate that is washed one or more times has not recrystallized. In certain embodiments, the aqueous wash comprises an organic solvent. In some embodiments, the organic solvent comprises one or more alcohols. In some embodiments, the organic solvent comprises one or more Ci-Cs, or Ci-Ce, or C1-C4 alcohols. In certain embodiments, the organic solvent comprises isopropanol, n-propanol, ethanol, or methanol, or any combination of these. In some embodiments, the organic solvent comprises ethanol and n-propanol. In still other embodiments, the organic solvent comprises isopropanol. In some embodiments, at least a portion of the isolated precipitate is washed one or more times with an aqueous wash before being dried under reduced pressure, wherein the aqueous wash comprises organic solvent and water. In some embodiments, accacn / i ζηζ / α / γίΛΐ the aqueous wash comprises water and one or more alcohols, for example, water and isopropanol, n-propanol, ethanol or methanol, or any combination of these. In some embodiments, the aqueous wash comprises water at about 5% to about 15% by weight, or about 8% to about 12% by weight. In some embodiments, the aqueous wash comprises water and organic solvent in a volume ratio of less than 3:7, or less than 1:4, such as about 1:9. In some embodiments, the isolated precipitate is washed one or more times with an aqueous washing solution comprising isopropanol and water before being dried under reduced pressure to produce Compound 1. Thus, in some embodiments, the method for preparing Compound 1 (such as methods for preparing a bulk composition comprising Compound 1) comprises combining the acid free base (3S,4R,3'R)-6[4-(4-amino-5-chloro-2-methoxy -benzoylamino)-3-methoxypiperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester with organic solvent to form a mixture; adjust the pH of the mixture between 3.5 and 4.5 by adding hydrochloric acid; shake the mixture until a precipitate forms; isolate the precipitate; wash the isolated precipitate; and, after washing, drying the isolated precipitate under reduced pressure to yield the trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy- benzoylamino)-3-methoxy-piperidin-l-yl]QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester (Compound 1). In some embodiments, the isolated precipitate is washed with an aqueous wash, wherein the aqueous wash comprises an organic solvent and about 5% to 15% by weight of water. In some embodiments, temperatures or solvents (including ratios or percentages of organic solvent and water), or ranges thereof, or combinations of any of the foregoing, as described herein for washing the isolated precipitate, or for recrystallization, or a combination thereof, can be combined, for example, with any of the amounts of precipitate or isolated precipitate or free base or Compound 1 used in the described process; or any of the temperatures or pressures or times, or ranges thereof, or combinations of any of these, in the drying step described herein; or any of the other conditions or steps described herein. In some embodiments, including one or more recrystallization or washing steps as described herein, or combinations thereof, in the process of preparing a bulk composition as described herein, results in a bulk composition comprising Compound 1 having a particular stability, or organic solvent content, or water content, or ratio of trihydrate to anhydrous form, or XRPD spectra, or various combinations thereof, as accacn / i ζηζ / α / γίΛΐ described herein. The description provided indicates numerous example configurations, methods, parameters, and the like. It should be recognized, however, that the description is not intended as a limitation on the scope of the present description, but is provided as a description of exemplary embodiments. LISTED MODALITIES Modality 1-1. A bulk composition comprising a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidine- dihydrochloride salt 1-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'yl ester, having the following formula: QCCRCn / l 7Π7 / 3 / ΥΙΛΙ Modality 1-2. The bulk composition according to embodiment 1-1, comprising at least 75% by weight of the acid dihydrochloride salt trihydrate form (3S,4R,3'R)-6-[4-(4- amino-5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, wherein the weight excludes the weight of the at least one bowl. Modality 1-3. The bulk composition according to embodiment 1-1 or 1-2, further comprising an anhydrous form of (3S,4R,3'R)-6-[4-(4-amino5-chloro -2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, wherein the ratio of the trihydrate to the anhydrous form is at least about 4 to 1. Modality 1-4. The bulk composition according to modality 1-1 or 1-2, comprising at least about 6.5% by weight of water with respect to the total weight of acid dihydrochloride salt (3S, 4R, 3' R) - 6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form . Mode 1-5. The bulk composition according to modality 1-3, wherein the ratio between the trihydrate form and the anhydrous form is at least about 11 to 1. Mode 1-6. The bulk composition according to any of the modalities 1-1 to 1-4, comprising at least about 7.5% by weight of water with respect to the total weight of acid dihydrochloride salt (3S, 4R, 3'R )-6-[4-(4amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-lyl ]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous form or trihydrate. Modality 1-7. The bulk composition according to any of the modalities 1-1 to 1-6, wherein the accacn / i ζηζ / α / γίΛΐ trihydrate form is in crystalline form, and wherein the crystalline form has XRPD peaks at 7.74± 0.5° and 20.9510.5°. Mode 1-8. A pharmaceutical composition comprising a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l acid dihydrochloride salt -yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester, having the following formula: accacn / i ζηζ / α / γίΛΐ and a pharmaceutically acceptable excipient. Mode 1-9. The pharmaceutical composition according to modality 1-8, further comprising an anhydrous form of (3S, 4R, 3'R)-6-[4-(4-amino5-chloro-2-methoxy- benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, wherein the ratio of the trihydrate to the anhydrous form is at least about 4 to 1. Modality 1-10. The pharmaceutical composition according to modality 1-8, comprising between about 6.5% and about 10% by weight of water with respect to the total weight of acid dihydrochloride salt (3S, 4R, 3'R)-6 -[4-(4-amino5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form . Modality 1-11. The pharmaceutical composition according to modality 1-9, wherein the ratio between the trihydrate form and the anhydrous form is at least about 11 to 1. Modality 1-12. The pharmaceutical composition according to any of the modalities 1-8 to 1-11, comprising between about 7.5% and about 9% by weight of water with respect to the total weight of acid dihydrochloride salt (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3methoxy-piperidin-1-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'yl ester present in anhydrous or trihydrate form. Modality 1-13. The pharmaceutical composition according to any of the modalities 1-8 to 1-12, comprising less than 1% by weight of the anhydrous form of dihydrochloride salt of (3S, 4R, 3'R)-6-[4 -(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form. Modality 1-14. The pharmaceutical composition according to any of modalities 1-8 to 1-13, wherein the trihydrate form is in crystalline form, and wherein the QCCRCn / l 7Π7 / 3 / ΥΙΛΙ crystal form has XRPD peaks at 7.74±0.5° and 20.9510.5o. Modality 1-15. A dosage form comprising the pharmaceutical composition according to any of modalities 1-8 to 1-14. Modality 1-16. The dosage form according to embodiment 1-15, wherein the dosage form comprises one or more tablets or one or more capsules. Modality 1-17. A kit comprising the dosage form according to the 1-15 or 1-16 modality and a container. Modality 1-18. The kit according to modality 1-17, where the container is a blister. Modality 1-19. A method of improving gastrointestinal motility in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to any of modalities 1-8 to 1-14, or dosage form according to the modality 1-15 or 1-16. Modality 1-20. The method according to the I19 modality, wherein the subject in need of it has a gastrointestinal disorder. Modality 1-21. A method of treating a gastrointestinal disorder in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of the pharmaceutical composition of QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 100 according to any of modalities 1-8 to 1-14, or the dosage form according to modality 1-15 or 1-16. Modality 1-22. The method according to modality I20 or 1-21, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis. Modality 1-23. Use according to modality 1-22, where the GERD is proton pump inhibitor (DPI) resistant GERD. Modality 1-24. Use according to modality 1-22, where the constipation is opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), or constipation associated with irritable bowel syndrome (IBSc) type of constipation. Modality 1-25. Use according to modality 1-22, where the esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE). Modality 1-26. Use according to mode 1-22, wherein the IBS is of the constipation type of irritable bowel syndrome (IBSc). QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 101 Modality 1-27. Use according to modality 1-22, wherein the gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis. Modality 1-28. Use according to modality 1-20 or 1-21, where the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, emesis, gastroparesis, opioid-induced constipation (QIC ), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (ED) or functional motility disorder (FMD), intestinal pseudo-obstruction, irritable bowel syndrome (IBSc) type of constipation , intolerance to enteral feeding (IFE) and postoperative i leo. Modality 1-29. Use according to modality 1-20 or 1-21, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasum emptying defect. Modality 1-30. Use according to mode 1-29, wherein the gastritis is atrophic gastritis. Modality 1-31. The use of a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl dihydrochloride salt ]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester in the manufacture of a QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 102 medicine to improve a gastrointestinal motility in a subject who needs it. Modality 1-32. Use according to modality 1-31, wherein the subject in need thereof has a gastrointestinal disorder. Modality 1-33. The use of a trihydrate form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl dihydrochloride salt ]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester in the manufacture of a medicament for treating a gastrointestinal disorder in a subject in need thereof. Modality 1-34. Use according to modality 1-32 or 1-33, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, ileus postoperative emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis. Modality 1-35. Use according to modality 1-34, where the GERD is proton pump inhibitor (PPI) resistant GERD. Modality 1-36. Use according to modality 1-34, where the constipation is constipation induced by QCCRCn / l 7Π7 / 3 / ΥΙΛΙ 103 opioid constipation (QIC), chronic idiopathic constipation (CIC), or constipation associated with the irritable bowel syndrome (IBSc) type of constipation. Modality 1-37. Use according to modality 1-34, where the esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE). Modality 1-38. Use according to modality 1-34, wherein the IBS is of the constipation type of irritable bowel syndrome (IBSc). Modality 1-39. Use according to modality 1-34, wherein the gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis. Modality 1-40. Use according to modality 1-32 or 1-33, where the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, emesis, gastroparesis, opioid-induced constipation (QIC ), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (FD) or functional motility disorder (FMD), intestinal pseudo-obstruction, irritable bowel syndrome type of constipation (IBSc) , intolerance to enteral feeding (IFE) and postoperative i leo. Modality 1-41. Use according to modality 1-32 or 1-33, where the gastrointestinal disorder is selected QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 104 from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasum emptying defect. Modality 1-42. Use according to mode 1-41, wherein the gastritis is atrophic gastritis. Modality 1-43. A compound, for use in improving gastrointestinal motility in a subject in need thereof, wherein the compound is a trihydrate form of (3S, 4R, 3'R)-6-[4-(4 -amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester. Modality 1-44. The compound to be used according to modality 1-43, wherein the subject in need thereof has a gastrointestinal disorder. Modality 1-45. A compound, for use in the treatment of a gastrointestinal disorder in a subject in need thereof, wherein the compound is a trihydrate form of (3S, 4R, 3'R)-6-[4-(4 -amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester. Modality 1-46. The compound to be used according to modality 1-44 or 1-45, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia, or functional motility disorder, QCCECn / l ΖηΖ / 3 / ΥΙΛΙ 105 gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis. Modality 1-47. The compound to be used according to embodiment 1-46, wherein the GERD is proton pump inhibitor (PPI) resistant GERD. Modality 1-48. The compound to be used according to modality 1-46, wherein the constipation is opioid-induced constipation (QIC), chronic idiopathic constipation (CIC) or constipation associated with irritable bowel syndrome (IBSc) type of constipation. Modality 1-49. The compound to be used according to modality 1-46, wherein the esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE). Modality 1-50. The compound to be used according to embodiment 1-46, wherein the IBS is of the constipation type of irritable bowel syndrome (IBSc). Modality 1-51. The compound to be used according to embodiment 1-46, wherein the gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis. Modality 1-52. The compound to be used according to modality 1-44 or 1-45, wherein the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, QCCECn / l ΖηΖ / 3 / ΥΙΛΙ 106 emesis, gastroparesis, opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (FD) or functional motility disorder (FMD), intestinal pseudo-obstruction, constipation type of irritable bowel syndrome (IBSc), enteral feeding intolerance (EFI), and postoperative ileus. Modality 1-53. The compound for use according to modality 1-44 or 1-45, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and defect emptying of the abomasum. Modality 1-54. The compound to be used according to embodiment 1-53, wherein the gastritis is atrophic gastritis. Modality 1-55. A pharmaceutical composition for use in improving gastrointestinal motility in a subject in need thereof, wherein the pharmaceutical composition comprises a trihydrate form of acid dihydrochloride salt (3S, 4R, 3'R)-6-[4-( 4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester. Modality 1-56. The pharmaceutical composition to be used according to modality 1-55, wherein the subject who QCCECn / l ΖηΖ / 3 / ΥΙΛΙ 107 need has a gastrointestinal disorder. Modality 1-57. A pharmaceutical composition, for use in the treatment of a gastrointestinal disorder in a subject in need thereof, wherein the pharmaceutical composition comprises a trihydrate form of (3S, 4R, 3'R)-6-[4- (4-amino-5-chloro-2methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester. Modality 1-58. The pharmaceutical composition for use according to modality 1-56 or 1-57, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, ileus paralytic, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis. Modality 1-59. The pharmaceutical composition for use according to modality 1-58, wherein the GERD is proton pump inhibitor (PPI) resistant GERD. Modality 1-60. The pharmaceutical composition to be used according to modality 1-58, wherein the constipation is opioid-induced constipation (QIC), chronic idiopathic constipation (CIC) or constipation associated with irritable bowel syndrome (IBSc) type of constipation. accacn / i ζηζ / α / γίΛΐ 108 Modality 1-61. The pharmaceutical composition to be used according to modality 1-58, wherein the esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE). Modality 1-62. The pharmaceutical composition to be used according to modality 1-58, wherein the IBS is of the constipation type of irritable bowel syndrome (IBSc). Modality 1-63. The pharmaceutical composition to be used according to modality 1-58, wherein the gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis. Modality 1-64. The pharmaceutical composition for use according to modality 1-56 or 1-57, wherein the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, emesis, gastroparesis, constipation induced by opioids (QIC), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (ED) or functional motility disorder (MDD), intestinal pseudo-obstruction, irritable bowel syndrome type of constipation (IBSc), enteral feeding intolerance (EFI) and postoperative i leo. Modality 1-65. The pharmaceutical composition to be used according to modality 1-56 or 1-57, wherein the gastrointestinal disorder is selected from the group that accacn / i ζηζ / α / γίΛΐ 109 consists of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect. Modality 1-66. The pharmaceutical composition to be used according to modality 1-65, wherein the gastritis is atrophic gastritis. Modality 1-67. The method according to any of the modalities 1-19 to 1-26, the use of any of the modalities 1-31 to 1-40, the compound to be used of any of the modalities 1-43 to 1-52, or the pharmaceutical composition to be used in any of the modalities I55 to 1-64, wherein the subject in need of it is a human being. Modality 1-68. The method according to any of the modalities 1-19 to 1-21 or 1-26 to 1-28, the use of any of the modalities 1-31 to 1-33 or 1-40 to 1-42, the compound to be used in any of the modalities 1-43 to 1-45 or 1-52 to 1-54, or the pharmaceutical composition to be used in any of the modalities 1-55 to 1-57 or 1-64 to 1-66, where the subject that needs it is a non-human animal. Modality 1-69. The method, use, compound to be used or the pharmaceutical composition to be used according to modality 1-68, wherein the non-human animal is a ruminant, equine, cat, dog, rabbit or guinea pig. i ζηζ / α / γίΛΐ Indian. 110 Modality 1-70. The method, use, compound to be used or the pharmaceutical composition to be used according to embodiment 1-69, wherein the ruminant is sheep, cow, yak, bison or buffalo. Modality 1-71. The method, use, compound to be used or the pharmaceutical composition to be used according to embodiment 1-69, wherein the equine is a horse or a donkey. Modality 1-72. The method according to any of the modalities 1-19 to 1-28 or 1-67 to 1-71, the use of any of the modalities 1-31 to 1-42 or 1-67 to 1-71, the compound to be used in any of the modalities 1-43 to 1-54 or 1-67 to 1-71, or the pharmaceutical composition to be used in any of the modalities 1-55 to 1-71, where the subject that needs it is a newborn. Modality 1-73. The method according to any of the modalities 1-19 to 1-28 or 1-67 to 1-72; use in accordance with any of the modalities 1-31 to 1-42 or 1-67 to 1-72; the compound to be used according to any of the modalities 1-43 to 1-54 or 1-67 to 1-72; or the pharmaceutical composition for use according to any of modalities 1-55 to 1-72, wherein the pharmaceutical composition is administered parenterally. Modality 1-74. The method according to any of the modalities 1-19 to 1-28 or 1-67 to 1-72; use in accordance with any of the modalities 1-31 to 1-42 or 1-67 to 1-72; accacn / i ζηζ / α / γίΛΐ 111 the compound to be used according to any of modalities 1-43 to 1-54 or 1-67 to 1-72; or the pharmaceutical composition for use according to any of the modalities 1-55 to 1-72, wherein the pharmaceutical composition is administered orally. Modality 1-75. The method according to any of the modalities 1-19 to 1-28 or 1-67 to 1-72; use in accordance with any of the modalities 1-31 to 1-42 or 1-67 to 1-72; the compound to be used according to any of the modalities 1-43 to 1-54 or 1-67 to 1-72; or the pharmaceutical composition for use according to any of the modalities 1-55 to 1-72, wherein the pharmaceutical composition is administered through a gastric tube. Modality 1-76. The method according to any of the modalities 1-19 to 1-30 or 1-67 to 1-75; the use according to any of the modalities 1-31 to 1-42 or 1-67 to 1-75; the compound to be used according to any of the modalities 1-43 to 1-54 or 1-67 to 1-75; or the pharmaceutical composition for use according to any of modalities 1-55 to 1-75, wherein the trihydrate form is in crystalline form and wherein the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.74±0.5 ° and 20.95+0.5°. Modality 1-77. The bulk composition according to any of the modalities 1-1 to 1-7; or the pharmaceutical composition according to any of the modalities 1-8 accacn / i ζηζ / α / γίΛΐ 112 to 1-14; or the dosage form according to modality 1-15 or 1-16; or the kit according to modality 1-17 or 1-18; or the method according to any of the modalities 1-19 to 1-30 or 1-67 to 1-76; or use in accordance with any of modalities 1-31 to 1-42 or 1-67 to 1-76; or the compound to be used according to any of modalities 1-43 to I54 or 1-67 to 1-76; or the pharmaceutical composition for use according to any of modalities 1-55 to 1-76, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has a 2-zeta (2Θ) XRPD peak intensity greater than 50% relative intensity at 7.74°±0.5°, and a 2-zeta (2Θ) XRPD peak of 100% relative intensity at 20.95°±0.5°. Modality 1-78. The composition in bulk according to any of the modalities 1-1 to 1-7 or 1-77; or the pharmaceutical composition according to any of modalities 1-8 to 1-14 or 1-77; or the dosage form according to any of modalities 1-15, 1-16 or 1-77; or the kit according to any of the modalities 1-17, 1-18 or I77; or the method according to any of the modalities 1-19 to 1-30 or 1-67 to 1-77; or use in accordance with any of the modalities 1-31 to 1-42 or 1-67 to 1-77; or the compound to be used according to any of modalities 1-43 to 1-54 or 1-67 to 1-77; or the pharmaceutical composition to be used according to any of the modalities 1-55 to IQCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 113 77, where the trihydrate form is in crystalline form, and where the crystalline form has two or more 2zeta (2Θ) XRPD peaks selected from the group consisting of 10.3°±0.2°, 13.6°±0.2°, 14.8°± 0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 21.3°±0.2°, 22.0°±0.2° , 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2 °±0.2°, and 39.4°±0.2°. Modality 1-79. The composition in bulk according to any of the modalities 1-1 to 1-7, 1-77 or 1-78; or the pharmaceutical composition according to any of modalities 1-8 to 1-14, 1-77 or 1-78; or the dosage form according to any of modalities 1-15, 1-16, 1-77 or 1-78; or the kit according to any of modalities 1-17, 1-18, 1-77 or 1-78; or the method according to any of the modalities 1-19 to 1-30 or 1-67 to 1-78; or use in accordance with any of modalities 1-31 to 1-42 or 1-67 to 1-78; or the compound to be used according to any of modalities 1-43 to 1-54 or 1-67 to 1-78; or the pharmaceutical composition for use according to any of modalities 1-55 to 1-78, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6° ±0.2° and 20.7°±0.2° . Modality 1-80. Bulk Composition, Pharmaceutical Composition, Dosage Form, Kit, Method, Usage, QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 114 the compound to be used or the pharmaceutical composition to be used of modality 1-79, wherein the XRPD 2-zeta (2Θ) peak of 7.6°±0.2° has a relative intensity greater than 50% and the XRPD 2 peak -zeta (2Θ) of 20.7°±0.2° has a relative intensity of 100%. Modality 1-81. The bulk composition, the pharmaceutical composition, the dosage form, the kit, the method, the use, the compound to be used or the pharmaceutical composition to be used of the modality 1-79 or 1-80, wherein the crystal form is also has two or more 2-zeta (2Θ) XRPD peaks selected from the group consisting of 10.3°±0.2°, 13.6°±0.2°, 14.8°±0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5 °±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 21.3°±0.2°, 22.0°±0.2° 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2°, and 39.4°±0.2°. Modality 1-82. The composition in bulk according to any of the modalities 1-1 to 1-7, or 1-77 to 1-81; or the pharmaceutical composition according to any of modalities 1-8 to 1-14, or 1-77 to 1-81; or the dosage form according to any of modalities 1-15, 1-16 or 1-77 to 1-81; or the kit according to any of modalities 1-17, 1-18 or 1-77 to 1-81; the method according to any of the modalities 1-19 to 1-30 or 1-67 to 1-81; or use in accordance with any of modalities 1-31 to 1-42 or 1-67 to 1-81; or the compound to be used according to any accacn / i ζηζ / α / γίΛΐ 115 of modalities 1-43 to 1-54 or 1-67 to 1-81; or the pharmaceutical composition for use according to any of modalities 1-55 to 1-81, wherein the bulk composition, pharmaceutical composition, dosage form, kit, or medicament comprises less than about 6000 ppm of organic solvent. Modality 1-83. The bulk composition, or the pharmaceutical composition, or the dosage form, or the kit, or the method, or the compound to be used or the pharmaceutical composition to be used of modality 1-82, wherein the bulk composition, the pharmaceutical composition, dosage form, kit, or medicament comprises less than about 5,000 ppm, less than about 4,000 ppm, less than about 3,000 ppm, or less than about 2,000 ppm organic solvent. Modality 1-84. The bulk composition, or the pharmaceutical composition, or the dosage form, or the kit, or the method, or the compound to be used or the pharmaceutical composition to be used of modality 1-82 or 1-83, wherein the solvent organic comprises one or more Ci-Cs alcohols. Modality 1-85. The bulk composition, or the pharmaceutical composition, or the dosage form, or the kit, or the method, or the compound to be used or the pharmaceutical composition to be used according to any of the QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 116 embodiments 1-82 to 1-84, wherein the organic solvent comprises ethanol, n-propanol or isopropanol or a combination thereof. Modality 1-86. The bulk composition, or the pharmaceutical composition, or the dosage form, or the kit, or the method, or the compound to be used or the pharmaceutical composition to be used according to any of modalities 1-82 to 1-85, wherein the organic solvent comprises isopropanol. Modality II-l. A method for preparing a trihydrate form of (3S,4R,3'R)-6[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl dihydrochloride salt ]-hexanoic l-azabicyclo[2.2.2]oct-3'-yl ester, having the following formula: QCCECn / l ΖηΖ / 3 / ΥΙΛΙ where the method comprises: (a) Combine (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid free base 1-azabicyclo[2.2.2]oct-3'-yl ester with organic solvent to form a mixture; (b) adjust the pH of the mixture between 3.5 and 4.5 by means of 117 addition of hydrochloric acid; (c) stir the mixture until a precipitate forms; (d) isolating the precipitate to form an isolated precipitate; and (e) drying the isolated precipitate under reduced pressure until a water content of between 6.5 wt% and 10 wt% is reached to produce the acid dihydrochloride salt trihydrate form (3S, 4R, 3'R) - 6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester. Mode II-2. The method according to modality II-1, wherein the isolated precipitate is dried under reduced pressure until the organic solvent content is less than about 6000 ppm. Mode II-3. The method according to modality II-1 or II-2, wherein the organic solvent comprises one or more alcohols. Mode II-4. The method according to any of modalities II-1 to II-3, wherein the organic solvent comprises ethanol, n-propanol or isopropanol, or a combination of these. Mode II-5. The method according to any of the modalities II-1 to II-4, wherein the organic solvent comprises isopropanol. Mode II-6. The method according to any of QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 118 modalities II-l to II-5, where the free base is combined with water and organic solvent to form the mixture. Modality II-7. The method according to any of the modalities II-1 to II-6, wherein the free base is combined with water and organic solvent to form the mixture, wherein water is present in the mixture in about 5% to about of 15% by weight in relation to organic solvent. Modality II-8. The method according to any of modalities II-1 to II-7, wherein the organic solvent combined with the free base comprises one or more alcohols. Modality II-9. The method according to any of modalities II-1 to II-8, wherein the organic solvent combined with the free base comprises one or more Ci-Cs alcohols. Modality 11-10. The method according to any of the modalities II-1 to II-9, wherein the organic solvent combined with the free base comprises isopropanol. Modality 11-11. The method according to any of the modalities II-1 to 11-10, wherein the isolated precipitate is dried under reduced pressure at a temperature between about 20°C and about 60°C. Modality 11-12. The method according to any of the modalities II-1 to 11-11, wherein the isolated precipitate is dried under reduced pressure for between about 3 QCCRCn / l 7Π7 / 3 / ΥΙΛΙ 119 hours and around 12 hours. Modality 11-13. The method according to any of the modalities II-1 to 11-12, wherein the isolated precipitate is dried under reduced pressure at a temperature between about 25°C and about 35°C, then at a temperature between about 30°C and around 45°C, then at a temperature between around 30°C and around 50°C, and then at a temperature between around 30°C and around 55°C. Modality 11-14. The method according to any of the modalities II-1 to 11-13, wherein the isolated precipitate is dried under reduced pressure at a temperature between about 25°C and about 35°C, then at a temperature between about 35°C and around 45°C, then at a temperature between around 40°C and around 50°C, and then at a temperature between around 45°C and around 55°C. Modality 11-15. The method according to any of the modalities II-1 to 11-14, wherein the isolated precipitate is dried under reduced pressure at a temperature between about 25°C and about 35°C for about 0.5 to about 2.5 hours; then at a temperature between about 35°C and about 45°C for about 0.5 to about 2.5 hours, then at a temperature between about 40°C and about 50°C for about QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 120 0.5 to about 2.5 hours, and then at a temperature between about 45°C and about 55°C. Modality 11-16. The method according to any of the modalities II-1 to 11-15, wherein the isolated precipitate is dried under reduced pressure until a water content of between 7.5% by weight and 9.0% by weight is reached to produce the form (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid 1-dihydrochloride salt trihydrate azabicyclo[2.2.2]oct-3'yl ester. Modality 11-17. The method according to any of the modalities II-1 to 11-16, wherein the reduced pressure is from about 20 mm Hg to about 60 mm Hg. Modality 11-18. The method according to any of the modalities II-1 to 11-17, wherein the reduced pressure is from about 30 mm Hg to about 55 mm Hg. Modality 11-19. The method according to any of the embodiments II-1 to 11-18, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD peaks at 7.7410.5° and 20.9510.5°. Modality 11-20. The method according to any of the modalities II-1 to 11-19, wherein at least 100 kg of the free base are combined with the organic solvent to form the mixture. Modality 11-21. The method according to any of QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ 121 modalities II-l to 11-20, where at least 100 kg of the precipitate are isolated. Modality 11-22. The method according to any of the modalities II-1 to II-2Í, where at least 100 kg of the isolated precipitate are dried. Modality 11-23. The method according to any of the modalities II-1 to 11-22, wherein at least 100 kq of the trihydrate form are produced. Modality 11-24. The method according to any of the modalities II-1 to 11-23, wherein at least 200 kg of the free base are combined with the organic solvent to form the mixture. Modality 11-25. The method according to any of the modalities II-1 to 11-24, where at least 200 kg of the precipitate are isolated. Modality 11-26. The method according to any of the modalities II-1 to 11-25, wherein at least 200 kg of the isolated precipitate are dried. Modality 11-27. The method according to any of the modalities II-1 to 11-26, wherein at least 200 kg of the trihydrate form are produced. Modality 11-28. The method according to any of the modalities II-1 to 11-27, wherein after step (b) and before step (c), the mixture is adjusted to comprise water and isopropanol in a volume ratio minor accacn / i ζηζ / α / γίΛΐ 122 of 3:7. Modality 11-29. The method according to any of the modalities II-1 to 11-28, wherein after step (b) and before step (c), the mixture is adjusted to comprise aqua and isopropanol in a volume ratio less than 1:4. Modality 11-30. The method according to any of the modalities II-1 to 11-28, wherein after step (b) and before step (c), the mixture is adjusted to comprise aqua and isopropanol, wherein the aqua is present between 5% and 15% by weight. Modality 11-31. The method according to any of the modalities II-1 to 11-30, wherein the mixture of step (c) is stirred at a temperature of 40°C or less to form the precipitate. Modality 11-32. The method according to any of the modalities II-1 to 11-31, wherein the mixture of step (c) is stirred at a temperature of 30°C or less to form the precipitate. Modality 11-33. The method according to any of the modalities II-1 to 11-32, wherein after step (d) and before step (e), at least a portion of the isolated precipitate is dissolved in a recrystallization solvent to to form a recrystallization mixture, the recrystallization mixture is stirred until an accacn / i ζηζ / α / γ is formed 123 recrystallized precipitate and the recrystallized precipitate is isolated to form an isolated precipitate. Modality 11-34. The method according to Embodiment 11-33, wherein the recrystallization mixture comprises water and isopropanol in a volume ratio of less than 3:7. Modality 11-35. The method according to Embodiment 11-33, wherein the recrystallization mixture comprises water and isopropanol in a volume ratio of less than 1:4. Modality 11-36. The method according to Embodiment 11-33, wherein the recrystallization mixture comprises water at 5% to 10% by weight. Modality 11-37. The method according to Embodiment 11-33, wherein the recrystallization mixture comprises isopropanol and water, wherein water is present at 5% to 10% by weight. Modality 11-38. The method according to either of 11-33 or 11-37, wherein the recrystallization mixture is stirred at a temperature of 40°C or less to form the recrystallization precipitate. Modality 11-39. The method according to either of 11-33 or 11-37, wherein the recrystallization mixture is stirred at a temperature of 30°C or less to form the recrystallization precipitate. Modality 11-40. The method according to any of the modalities II-l to 11-39, where the isolated precipitate accacn / i ζηζ / α / γίΛΐ 124 is washed before drying. Modality 11-41. The method of mode 11-40, wherein the isolated precipitate is washed with a washing solvent comprising water and isopropanol in a volume ratio of less than 3:7. Modality 11-42. The method of modality 11-40 or II41, wherein the isolated precipitate is washed with a washing solvent comprising water and isopropanol in a volume ratio of less than 1:4. Modality 11-43. The method according to any of the modalities II-1 to 11-39, wherein the isolated precipitate is washed with an aqueous wash before being dried under reduced pressure, wherein the aqueous wash comprises an organic solvent and about 5% a about 15% by weight of water. Modality 11-44. The method according to any of the modalities II-1 to 11-43, wherein the isolated precipitate is dried under reduced pressure until the organic solvent content is less than about 5000 ppm, less than about 4000 ppm, less of about 3000 ppm or less than about 2000 ppm. Modality 11-45. The method according to modality 11-44, wherein the organic solvent comprises one or more alcohols. Modality 11-46. The method according to any of accacn / i ζηζ / α / γίΛΐ 125 modalities II-2, 11-44 or 11-45, wherein the organic solvent comprises one or more Ct-Cs alcohols. Modality 11-47. The method according to any of Embodiments 11-44 to 11-46, wherein the organic solvent comprises isopropanol. Modality 11-48. The method according to any of the modalities II-1 to 11-47, wherein the isolated precipitate is dried under reduced pressure until the isopropanol content is less than about 6000 ppm. Modality 11-49. The method according to any of the modalities II-1 to 11-48, wherein the isolated precipitate is dried under reduced pressure until the isopropanol content is less than about 5000 ppm, less than about 4000 ppm, less than about 3000 ppm or less than about 2000 ppm. Modality 11-50. The method according to any of the modalities II-1 to 11-49, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has a 2-zeta (2Θ) XRPD peak of relative intensity greater than 50 % at 7.74°±0.5°, and a 2-zeta (2Θ) XRPD peak of 100% relative intensity at 20.95°±0.5o. Modality 11-51. The method according to any of the embodiments II-1 to 11-50, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has two or more XRPD 2-zeta (2Θ) peaks selected from the accacn / i ζηζ / α / γίΛΐ 126 group consisting of 10.3°±0.2°, 13.6°±0.2°, 14.8°±0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 21.3°±0.2°, 22.0°±0.2°, 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2°, and 39.4°±0.2°. Modality 11-52. The method according to any of the embodiments II-1 to 11-51, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2° and 20.7°±0.2°. Modality 11-53. The method according to modality 11-52, where the XRPD 2-zeta (2Θ) peak at 7.6°±0.2° has a relative intensity greater than 50% and the XRPD 2-zeta (2Θ) peak at 20.7 °±0.2° has a relative intensity of 100%. Modality 11-54. The method according to mode 11-52 or 11-53, wherein the crystalline form further has two or more XRPD 2-zeta (2Θ) peaks selected from the group consisting of 10.3°±0.2°, 13.6°±0.2 °, 14.8°±0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 21.3°±0.2°, 22.0°±0.2° 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2°, and 39.4°±0.2°. Modality 11-55. A method of treating a gastrointestinal disorder in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of a salt trihydrate form of QCCECn / l ΖηΖ / 3 / ΥΙΛΙ 127 (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid dihydrochloride 1azabicyclo[2.2.2 ]oct-3'-yl ester. QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ Modality 11-56. The method according to modality 11-55, wherein the gastrointestinal disorder is selected from the group consisting of PPI-resistant GERD, emesis, gastroparesis, opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (FD) or functional motility disorder (FMD), intestinal pseudo-obstruction, irritable bowel syndrome type of constipation ( IBSc), enteral feeding intolerance (EFI) and postoperative ileus. Modality 11-57. The method according to modality 11-55, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasum emptying defect. Modality III-l. A bulk composition comprising 128 a form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3methoxy-piperidin-l-yl]-dihydrochloride salt trihydrate hexanoic l-azabicyclo[2.2.2]oct-3 / 'yl ester, having the following formula: QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ and at least one container. Modality III-2. The bulk composition according to modality III-1, comprising at least 75% by weight of the acid dihydrochloride salt trihydrate form (3S, 4R, 3'R)-6-[4-(4- amino-5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, wherein the weight excludes the weight of the at least one bowl. Modality III-3. The bulk composition according to modality III-1, further comprising an anhydrous form of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy) acid dihydrochloride salt -benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, wherein the ratio of the trihydrate to anhydrous form is at least about 4 to 1. Modality III-4. The bulk composition according to modality III-l, comprising between about 6.5% to 129 about 10% by weight of water with respect to the total weight of acid dihydrochloride salt (3S, 4R, 3'R)-6-[4-(4-amino5-chloro-2-methoxy-benzoylamino)-3 -methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form. Modality III-5. The bulk composition according to Mode III-2, where the trihydrate form is in crystalline form, and where the crystalline form has XRPD peaks at 7.7410.5° and 20.9510.5o. Modality III-6. A pharmaceutical composition comprising a trihydrate form of (33,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-1 dihydrochloride salt -yl]-hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester, having the following formula: QCCRCn / l 7Π7 / 3 / ΥΙΛΙ and a pharmaceutically acceptable excipient. Modality III-7. The pharmaceutical composition according to modality III-6, further comprising an anhydrous form of (3S, 4R, 3'R)-6-[4(4-amino-5-chloro-2-methoxy) acid dihydrochloride salt -benzollamino)-3-methoxy-piperidin-l 130 yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester, wherein the ratio of the trihydrate to anhydrous form is at least about 4 to 1. Modality III-8. The pharmaceutical composition according to modality III-6, comprising between about 6.5% to about 9% by weight of water with respect to the total weight of acid dihydrochloride salt (3S, 4R, 3'R)-6 -[4-(4-amino5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form . Modality III-9. The pharmaceutical composition according to modality III-6, comprising less than 1% by weight of the anhydrous form of dihydrochloride salt of (3S, 4R, 3'R)-6-[4-(4-amino- 5-chloro-2-methoxy-benzoylamino)-3-methoxypiperidin-l-yl ]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form. Modality III-10. The pharmaceutical composition according to modality III-6, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD peaks at 7.74±0.5° and 20.9510.5o. Modality III-ll. A method of treating a gastrointestinal disorder in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of the accacn / i ζηζ / α / γίΛΐ pharmaceutical composition according to modality III-6. 131 Modality III-12. The method according to modality III-ll, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and oesophagitis. Modality III-13. The method according to mode III-12, wherein the GERD is proton pump inhibitor (PPI) resistant GERD. Modality III-14. The method according to modality III-12, wherein the constipation is opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), or constipation associated with irritable bowel syndrome (IBSc) type of constipation. Modality III-15. The method according to mode III-12, wherein the esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE). Modality III-16. The method according to mode III-12, wherein the IBS is of the constipation type of irritable bowel syndrome (IBSc). Modality III-17. The method according to modality III-12, wherein the gastroparesis is diabetic gastroparesis accacn / i ζηζ / α / γίΛΐ 132 or idiopathic or functional gastroparesis. Modality III-18. The method according to modality III-12, where the subject that needs it is a newborn. Modality III-19. The method according to modality III-ll, wherein the pharmaceutical composition is administered parenterally. Modality III-20. The method according to modality III-ll, wherein the pharmaceutical composition is administered orally. Modality III-21. The method according to modality III-ll, wherein the pharmaceutical composition is administered through a gastric tube. Modality III-22. The method according to mode III-ll, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grazing disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasum emptying defect. Modality III-23. The method according to modality III-22, wherein the subject that needs it is a non-human animal. Modality III-24. The method according to modality III-ll, wherein the pharmaceutical composition comprises less than 1% by weight of the anhydrous form of acid dihydrochloride salt (3S, 4R, 3'R)-6-[4-(4 -amino-5-chloro-2-methoxyaccn / i ζηζ / α / γίΛΐ 133-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-lio ester present in anhydrous or trihydrate form. Modality III-25. A method of improving a gastrointestinal motility in a subject in need thereof, comprising administering to the subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to modality III-6. Modality III-26. The method according to modality III-25, where the subject that needs it is a newborn. Modality III-27. The method according to modality III-25, wherein the pharmaceutical composition is administered parenterally. Modality III-28. The method according to modality III-25, wherein the pharmaceutical composition is administered orally. Modality III-29. The method according to mode III-25, wherein the pharmaceutical composition is administered through a gastric tube. Modality III-30. The method according to modality III-25, wherein the pharmaceutical composition comprises less than 1% by weight of the anhydrous form of the acid dihydrochloride salt (3S, 4R, 3'R)-6-[4-(4 -amino-5-chloro-2-methoxyQCCRCn / l ΖηΖ / 3 / ΥΙΛΙ benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1134 azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form. EXAMPLES The following examples are merely illustrative and are not intended to limit any aspect of the present description in any way. Example 1: Synthesis of (3S, 4R, 3'R)-6-[4-(4amino-5-chloro-2-methoxy-benzollamino)-3-methoxy-piperidin-lyl]-hexanoic acid 1-azabicyclo[2.2 .2]oct-3'-yl ester, dihydrochloride salt, trihydrate A 4000 L reactor was charged with approximately 250 kg of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-1- Crude yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester in isopropyl alcohol (300 kg) and water (80 L). Then, under a nitrogen atmosphere and stirring at 80 rpm, 80 kg of 32% HCl were slowly introduced, keeping the temperature of the mixture below 45°C and the pH around 4.0. When the addition was complete, the temperature of the solution was cooled to 25°C and stirring continued for at least 2 hours until the product precipitated. Then, 800 kg of isopropyl alcohol was charged to the reactor over a period of 2 to 4 hours and the mixture was stirred for another 90 minutes. The crude precipitate (283 kg) was isolated by centrifugation. The crude product was purified by accacn / i ζηζ / α / γίΛΐ 135 crystallization as follows: water (100 L) was added to the crude product. A partial vacuum was applied and then the reactor was purged with nitrogen. Stirring was set to 80 rpm and the temperature of the aqueous mixture was brought to 55°C. The mixture was stirred at 55°C until the solid had dissolved, then the solution was filtered to remove any extraneous solid matter. 330 kg of isopropyl alcohol was added to the solution (resulting in approximately 100 L:420 L water:isopropanol). The solution temperature was brought to 25°C and then stirred at 80 rpm for at least 2 hours until material precipitated. The precipitate was isolated by centrifugation. The wet dihydrochloride salt (252 kg) was then charged into a cone drier and the drier hood temperature set at 30°C and vacuum applied (pressure = 35 mm Hg) for 1 hour and 20 minutes. The jacket temperature was then brought to 40°C, still below 35 mm Hg pressure, for 1 hour and 10 minutes. Then the cover temperature was brought to 45°C for 1 hour. Finally, the jacket temperature was brought to 50°C until the % water in the product, as measured by Karl Fisher analysis, was 8.0 to 8.4% and the isopropanol content was below 5000 ppm. After 2 hours at 50°C, the water content was 8.46% and the isopropanol content was 50,238 ppm. after 5 136 hours at 50°C, the content was 8.40% and 1994 ppm, respectively, and the drying was stopped. Example 2: Dehydration profile by thermographic analysis Thermographic analysis (TGA) curves for the anhydrate and trihydrate were generated using a Perkin Elmer TGA-7. Three to five milligram samples were weighed into aluminum sample trays and run under dry nitrogen at 5°C / minute from 25°C to 250°C. Data was exported to Excel to allow representation. The sample of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2 ]oct-3'-yl ester, dihydrochloride salt, trihydrate, exhibited a % loss of 8.2% at 63°C, which corresponds to the loss of 3 water molecules per compound molecule. Representative TGA scans for the anhydrate and trihydrate are shown in Figure 5. The two differ in the appearance of the dehydration mass loss observed for the trihydrate and absent as expected from the anhydrate. Dehydration of the trihydrate started immediately after the start of heating and was completed at approximately 50°C. Complete dehydration below 100°C is consistent with the assignment of the trihydrate as a type of channel hydrate. QCCRCn / l 7Π7 / 3 / ΥΙΛΙ 137 Example 3: Water vapor absorption isotherm A water vapor isotherm was obtained by using a DVS-1 surface measurement system equilibrated at 25°C. Approximately 7 mg of the trihydrate compound was spread in a thin layer on a glass slide and pre-dried at 0% relative humidity (RH) before starting the run. The isotherm was then obtained by scanning the sample from 0% RH to 90% RH and back to 0% RH at a rate of 2% RH per hour. The results are shown in Figure 4. As shown in the figure, dehydration and rehydration occur rapidly through a thin layer of compound. Factors that influence the rate of reequilibration include the depth of the bed and / or the mass of the sample, and the magnitude of the moisture change from the critical moisture. For example, increasing the bed depth from 1 millimeter to 7 millimeters resulted in a change in the rate of dehydration or rehydration. Reequilibration was established in minutes for the 1mm layer, but required hours for the 7mm layer, when 0% RH and 55% RH were used as moisture drivers. Had relative humidities (RH) closer to the critical RH (15-20% RH) been chosen, reequilibration times would generally be expected to have been longer. accacn / i ζηζ / α / γίΛΐ The critical relative humidity increased with increasing temperature. 138 temperature. The minimum relative humidities required to maintain the trihydrate were: 20% RH (25°C), 25% RH (40°C), 30% RH (50°C) and 50% RH (60°C). . The use of very high humidities at elevated temperatures to maintain the hydrate may not be advisable as deliquescence was observed at 100% RH for temperatures of 40°C and above. Example 4: X-ray powder diffraction X-ray powder diffraction (XRPD) was performed on samples of the anhydrous and trihydrate form using a Bruker D5000 X-ray diffractometer. The D5000 was equipped with a 2.2 kW Cu-anode X-ray tube, an Anton Parr TTK-1 low-temperature stage, and a high-speed position-sensitive detector (PSD). Cu Κα radiation (λ=1.5418 Á) was used to obtain all dust patterns. A double sheet nickel filter was placed in the X-ray receiving path to remove Κβ radiation. The material was mounted and analyzed in a front-loading sample holder. Scans were performed in the range below 4o to 40° 2-zeta (2Θ), at a step size of 0.02° for 0.2 and 0.5 seconds per step. Representative XRPD patterns for the anhydrous and trihydrate forms are shown in Figure 3. Each form is a single crystalline phase as is evident from the 139 individual diffraction patterns. The anhydrous form presents main specific peaks at 4.55°±0.5° (>50% relative intensity) and at 13.50°±0.5°, where the latter is the most intense peak (100% relative intensity). The anhydrous form presents main specific peaks at 7.74°±0.5° (>50% relative intensity) and at 20.95°±0.5°, where the latter is the most intense peak (100% relative intensity). A more detailed list of peaks for the XRPD analysis trihydrate includes (in degrees 2-zeta (2Θ) ) approximately 7.6°±0.2°, 10.3°±0.2°, 13.6°±0.2°, 14.8°±0.2°, 15.0° ±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 20.7°±0.2°, 21.3°±0.2°, 22.0°±0.2 °, 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2°, 39.4°±0.2°. During dehydration and rehydration of the trihydrate, no transition state was observed, rather the material exists in one form or another depending on the amount of water retained in each individual crystal. During in situ dehydration and rehydration, both forms were observed in the same pattern, at different levels. Example 5: NMR characterization of the trihydrate ^-Nuclear magnetic resonance (ΡΜΝ-1]^,): Approximately 6 mg of the trihydrate were dissolved in 1 g of deuterated solvent (dimethylsulfoxide (DMSO)-C45 99.9% d, with 0.05% v / v tetramethylsilane (TMS)). A Varying Gemini spectrometer accacn / i ζηζ / α / γίΛΐ 140 300 MHz FT-NMR was used to obtain the 1H-NMR spectrum. A list of the peaks is provided in Table 1 below. A representative 1H-NMR spectrum is provided in Figure 6. QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ Table 1. List of ΡΜΝ^Η peaks for trihydrate Chemical Shift (ppm) Peak Type Integral 10.76 Broad Singlet 1.14 9.44 Broad Singlet 0.89 8.11,8.51 Broad Doublet 1.01 7.72 Broad Singlet 0.93 6.53 Broad Singlet 1.00 6.06 Broad Singlet 2.00 4.97, 4.96, 4.94 Broad Multiplet 0.91 -4.20-4.10 wide multiplet 0.96 3.86 singlet 21.53 3.79, 3.75 broad multiplet 3.69 broad peak 3.65, 3.62, 3.60, 3.57 doublet, doublet 3.46 singlet -3.38 broad peak 3.34 singlet -3.24-3.08 overlapping multiplets -3.08-2.96 broad peak 2.42, 2.39, 2. 37 triplet 2.15 -2.24-2.18 wide multiplet 1.21 -2.02-1.64 overlapping multiplets 10.44 1.63, 1.61, 1.58, 1.56, 1.53 triplet, triplet 1.35, 1.33, 1.30, 1.28, -1.25 triplet, triplet 2.11 1.05, 1.03 doublet 0.13 0.00 NA singlet (TMS) 13C-Nuclear Magnetic Resonance Spectroscopy (13C-NMR) : Approximately 46 mg of the trihydrate was dissolved in 1 mL of deuterated solvent (deuterium oxide, Aldrich, 99.9% D, TPAS 0.75%) . 13C-NMR spectrum was obtained using a Varian Gemini 300 MHz FT-NMR spectrometer. In the table 141 below provides a list of peaks. In the Figure 7 provides a representative 13C-NMR spectrum. Table 2. List of 13C-NMR peaks for accacn / i ζηζ / α / γίΛΐ trihydrate Chemical Shift (ppm) Relative Peak Height 188.305 NA (TPAS) 178.368 81 68.659 82 160.787 85 151.267 84 134.247 59 113.575 88 112.604 82 101.171 55 76.757 63 70,297 77 60,322 75 59,350 52 58,834 72 55,736 73 54,355 45 54,051 36 49,845 53 49,473 76 48,638 79 36,241 69 28,179 67 26,965 45 26,411 70 26,168 74 25,978 66 22,395 64 19,168 67 0,000 NA (TPAS) Example 6: Stability for 12 months of the anhydrous form of the dihydrochloride salt at controlled temperature and humidity The dihydrochloride salt, anhydrous form of (3S, 4R, 3' R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1 -azabicyclo[2.2.2]oct3'-yl ester, was placed in stability chambers with 142 controlled temperature and humidity, up to 12 months. The temperature was set at 25°C and the relative humidity was set at 60%. Samples were analyzed at time zero, then at 3, 6, 9, and 12 months using an HPLC method. HPLC conditions were as follows: Column: Inertsil C8-3, 250 mm length, 3 mm diameter, 5 um particle size Mobile phase A: 2000 mL of water + 3 mL of formic acid Mobile phase B: 1000 mL of methanol + 3 mL of formic acid Flow rate: 0.6 mL / min Detection Wavelength: 275 nm Injection volume: 20 pL Time: 50 minutes. The results are shown in Table 3 below. Although the purity of the compound remained within the specifications originally established for the active material (HPLC area % purity), the concentration of the active pharmaceutical ingredient (API) decreased over time due to an increase in water content ( from 0.45% at time zero to 8.47% at 6 months and then stable up to 12 months). This is a decrease of approximately 8% in the concentration of the active ingredient, which places the product outside the acceptable range of the accacn / i ζηζ / α / γίΛΐ specifications. 143 release of Good Manufacturing Practices (GMPs) originally established for this material. Table 3. Stability of the anhydrous form of the dihydrochloride salt at 25°C / 60% RH occRcn / i ζηζ / α / γίΛΐ Time (months) 0 3 6 9 12 HPLC purity (area %) 99.3 99.2 99.3 99.2 99.3 Water content 0.45% 6.47% 8.47% 8.20% 8.43% Example 7: 36-month stability of the trihydrate form of the dihydrochloride salt under strictly controlled conditions of temperature and humidity The trihydrate form of the acid dihydrochloride salt (3S, 4R, 3'R)- 6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]- hexanoic 1azabicyclo[2.2.2]oct-3'-yl ester was placed in stability chambers with temperature and humidity control for up to 36 months. The temperature was set at 25°C and the relative humidity was set at 60%. Samples were analyzed at time zero, then at 3, 6, 9, 12, 18, 24, and 36 months using an HPLC method as described in the previous example. The results are displayed on the Table 4 below. 144 Table 4. Stability of the trihydrate form of the accacn / i ζηζ / α / γίΛΐ dihydrochloride salt at 25°C / 60% RH Time (months) 0 3 6 9 12 18 24 36 HPLC purity (area %) 99.8 100.2 100 99.9 99.1 100 99.6 99.5 Water content 8.5% 8.6% 8.6% 8.4% 8.4% 8.6% 8 . 6% 8 . 6% The results show that the trihydrate form is stable for at least 36 months in terms of purity and concentration. The API water content did not change for up to 36 months. This batch of material would pass GMP certification for human use 36 months after API synthesis. Example 8: Stability of the trihydrate form of the dihydrochloride salt when stored in bulk in a GMP storage facility The stability of the trihydrate form was evaluated for purity and concentration for a period of time up to 11 years when stored in a GMP facility under controlled conditions of temperature and relative humidity (temperature = room temperature and relative humidity >30%). The results are presented in Table 5 below. 145 Table 5. Stability of the trihydrate form of the salt of QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ dihydrochloride when stored in bulk at room temperature and RH>30% Year Tested 2007 2018 (#1 Drum) 2018 (#2 Drum) HPLC Purity (Area%) 99.6 99.6 99.6 Water Content 8.8% 8.4% 8.7% These results demonstrate that the trihydrate form of API is stable in GMP storage when stored under the temperature and humidity conditions normally applied in GMP storage facilities. Example 9: Screening for polymorphs Polymorph screening was performed in the anhydrous dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzollamino)-3-methoxy-piperidine acid -1yl]-hexanoic 1-azabicyclo[2.2.2]oct-3'-yl ester by recrystallizing the material under approximately 90 different crystal growth conditions and by analyzing the recovered solids using X-ray diffraction powder (XRPD) . Secondary screening was performed using non-competitive suspension experiments followed by 146 X-ray diffraction of solids. From this screen, three different solid state crystalline forms of the anhydrous salt were identified (Form I, Form II and Form III), and one solid state crystalline form of the trihydrate (Form IV) was identified. An amorphous form was also identified. Furthermore, it was discovered that Form I could be converted to Form IV under certain conditions. The crystal growth or desaturation conditions for the recrystallization panels are summarized in Table 6 below. Each recrystallization panel contained 22-32 wells, and each well contained different solvent compositions. The solvent matrices used for the three panels of the polymorph screen and the conditions of the screens are provided in Tables 7, 8 and 9, which also list the crystal form resulting from each crystallization experiment based on ray diffraction data. X Table 6. Synthesis of occEcn / i ζηζ / α / γ solvent recrystallization panels Panel Number of experiments (number of cavities) Scale (mL) velocity Saturation temperature (mL) Growth temperature (°C) Nitrogen flow rate (psig) 1 22 5-10 40 40 5 II 32 10 30 30 7 III 32 10 50 50 10 147 Table 7. Matrix of Panel I (saturation / growth temperature = 40°C). The top half of the panel lists the solvent ratios as solvent:cosolvent. Panel results are in the lower half Cavity Solvent system Solvent volume (mL) Solute mass (mg) Solids recovered Form 1 methanol 5 250 white / brown Amorphous 2 ethanol 10 100 tan type Form I 3 1 propanol 10 50 tan type Form IV 4 ethylene glycol 10 100 amorphous 5 water 10 150 brown amorphous 6 MEK 10 50 tan type insol 7 methylene chloride 10 50 insol 8 chloroform 10 50 tan type insol 9 acetone 10 50 insol 10 2 propanol 10 50 Form I 11 1 butanol 10 50 Form I 12 DMF 10 50 type tan Form I 13 DMA 10 50 yellow type 14 butylamine 10 150 brown gel w / needles 15 MTBE 10 50 insol 16 isopropyl acetate 10 50 insol 17 nitromethane 10 50 insol 18 isopropyl ether 10 50 tan gel type w / needles 19 EtOAc 10 25 insol 20 acetonitrile 10 25 white Form I 21 toluene 10 25 insol 22 heptane 10 25 insol 148 Table 8. Panel II matrix (saturation / growth temperature = 30°C). The top half of the panel lists the solvent ratios as solvent:cosolvent. occRcn / i ζηζ / α / γίΛΐ Panel results are in the lower half Solvent 1 2 3 4 Cosolvent EtOH A 9:1 7:3 3:7 1:9 water MeOH B 9:1 7:3 3:7 1:9 1-propanol water C 9:1 7:3 3:7 1 :9 2-propanol butylamine D 9:1 7:3 3:7 1:9 1-butanol 1 -propanol E 9:1 7:3 3:7 1:9 AON EtOH F 9:1 7:3 3:7 1:9 1-propanol DMF G 9:1 7:3 3:7 1:9 toluene DMA H 9:1 7:3 3:7 1:9 nitromethane EtOH A Form II am am am water MeOH B Form II Form II Form II + IV Form IV 1-propanol water C am am am Form IV 2-propanol butylamine D gel gel gel gel 1-butanol 1 -propanol E Form IV Form II Form IV Form IV ACN EtOH F Form IV Form IV Form IV Form IV 1-propanol DMF G Form IV Form I insol gel toluene DMA H Form IV Form IV Form IV nitromethane Table 9. Panel III matrix (saturation / growth temperature = 50°C). The top half of the panel lists the solvent ratios as solvent:cosolvent. Panel results are in the lower half Solvent 1 2 3 4 Cosolvent EtOH A 9:1 7:3 3:7 1:9 water MeOH B 9:1 7:3 3:7 1:9 1-propanol water C 9:1 7:3 3:7 1 :9 2-propanol DMF D 9:1 7:3 3:7 1:9 methanol 1 -propanol E 9:1 7:3 3:7 1:9 ACN EtOH F 9:1 7:3 3:7 1: 9 1-propanol DMF G 9:1 7:3 3:7 1:9 toluene DMA H 9:1 7:3 3:7 1:9 nitromethane EtOH A III + am am am am water MeOH B am II II I 1 -propanol water C am am am II 2-propanol DMF D III + am II III III methanol 1 -propanol E I I I + am I ACN EtOH F am II + I I I 1-propanol DMF G IV II insol insol toluene DMA H low sol IV I I nitromethane 149 Non-competitive suspension experiments for polymorph screening: Non-competitive suspension experiments were performed as a complementary polymorph screening method. When preparing suspensions of a polymorphic material, any polymorphic form with a lower solubility (more thermodynamically stable form) can nucleate. The nucleated forms can convert all residual solids to the nucleated form via a solvent-mediated phase transition. Suspensions of the isolated Form I were prepared by adding an excess of solid to several different solvent systems. The suspensions were shaken vigorously at room temperature for 3 weeks. The remaining solids were collected by vacuum filtration and analyzed by X-ray powder diffraction to determine if any change in the crystalline form of the solids occurred. The results of the non-competitive suspension work are shown in Table 10 below. Table 10. Synthesis of non-competitive suspension experiments Solvent Antisolvent Temperature Resulting form 1 -propanol water Ambient Form 1 Ethanol water Ambient Form 1 Methanol water Ambient Form 1 water water Ambient Form 1 Acetonitrile water Ambient Form 1 150 Based on the results of the suspension experiments, Form I was determined to be the most thermodynamically stable anhydrous form. The recrystallization data in Table 8 (Panel II) show that Form IV trihydrate can be obtained by recrystallization from a water:2-propanol solvent mixture in a ratio of less than 3:7 by volume (less than 30% water and 70% isopropanol by volume) and at a temperature not exceeding 40°C. Certain solvents used in the experiments, such as DMA and DMF, can be difficult to remove from compositions (such as bulk compositions) due to their high boiling points. In some situations, trying to remove these high-boiling solvents from a composition requires conditions that can destabilize the desired compound, such as requiring heating in combination with very low pressure. Example 10: Bulk stability of the trihydrate form of the dihydrochloride salt Bulk stability under stress: About 20-30 mg of the trihydrate form of the dihydrochloride salt were weighed into HPLC vials and stressed at 25°C and 60% relative humidity (open), 40° C and 75% relative humidity (open) and 60°C (closed) for one week and for two weeks. As shown in Table 11 accacn / i ζηζ / α / γίΛΐ 151 and in Figures 8-10, the trihydrate form was physically and chemically stable at all temperatures and humidities for one to two weeks. Table 11: Physical and chemical stability for one or two QCCacn / l 7Π7 / 3 / ΥΙΛΙ weeks Polymorph Trihydrate form Initial purity (zero time) 99.75% Solid state, 252C / 60% open relative humidity Purity after 1 week 99.74% Purity after 2 weeks 99.79% XRPD after 1 week Trihydrate form (Figure 8) XRPD after 2 weeks Trihydrate form (Figure 8) Physical appearance after 1 week White powder Physical appearance after 2 weeks White powder Solid state, 40oC / 75% open relative humidity Purity after 1 week 99.75% Purity after 2 weeks 99.79% XRPD after 1 week Trihydrate form (Figure 9) XRPD after 2 weeks Trihydrate form (Figure 9) Physical appearance after 1 week White powder Physical appearance after 2 weeks Agglomerate Solid state, 60-C closed Purity after 1 week 99.75% Purity after 2 weeks 99.75% XRPD after 1 week Trihydrate form (Figure 10) XRPD after 2 weeks Trihydrate form (Figure 10) Physical appearance after 1 week White powder Physical appearance after 2 weeks White powder Bulk stability under very high humidity conditions: The trihydrate form of the dihydrochloride salt was stressed at 25°C and 97% relative humidity (open), 40°C and 96% relative humidity (open), and 60°C and 96% relative humidity (open). ) for a week. As shown in Table 12, the trihydrate form was physical and 152 chemically stable at 25°C and 97% relative humidity (open) for one week, but liquefied when the temperature was raised to 40°C or 60°C, making it less chemically stable. Table 12: Physical and chemical stability for one week at QCCRCn / l ΖηΖ / 3 / ΥΙΛΙ high humidity Polymorph Trihydrate form Initial purity (zero moment) 99.75% Solid state, 25-0 / 97% relative humidity Purity after 1 week 99.63% Agglomerate, white powder Solid state, 40gC / 96% relative humidity Purity after 1 week 99.25 % Deliquescent Solid State, 60-0 / 96% relative humidity Purity after 1 week 95.42% Deliquescent It is noted that as of this date, the best method known to the applicant for putting said invention into practice is the one that is clear from the present description of the invention.

Claims

1. A bulk composition characterized in that it comprises a trihydrate form of (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3'-yl ester salt, having the following formula: and at least one container.

2. The bulk composition according to claim 1, characterized in that it comprises at least 75% by weight of the trihydrate form of the dihydrochloride salt of (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3'-yl ester, wherein the weight excludes the weight of at least one container.

3. The bulk composition according to claim 1 or 2, characterized in that it further comprises an anhydrous form of the dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxypiperidin-l-yl]hexanoic acid 1-azabicyclo[2.2.2]oct-3'-yl ester, wherein the ratio of the trihydrate form to the anhydrous form is at least about 4 to 1.

4. The bulk composition according to claim 1 or 2, characterized in that it comprises at least about 6.5% by weight of water with respect to the total weight of (3S, 4R, 3'R)-6-[4-(4-amino5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic acid dihydrochloride 1-azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form.

5. The bulk composition according to claim 3, characterized in that the ratio of the trihydrate form to the anhydrous form is at least around 11 to 1.

6. The bulk composition according to any of claims 1 to 4, characterized in that it comprises at least about 7.5% by weight of water with respect to the total weight of (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid dihydrochloride l-azabicyclo[2.2.2]oct-3,yl ester present in anhydrous or trihydrate form.

7. The bulk composition according to any of claims 1 to 6, characterized in that the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD peaks at 7.7410.5° and 20.9510.5°.

8. A pharmaceutical composition characterized in that it comprises a trihydrate form of the dihydrochloride salt of (3S, 4R, 3'R)-6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3'-yl ester, having the following formula: accacn / i ζηζ / α / γίΛΐ and a pharmaceutically acceptable excipient.

9. The pharmaceutical composition according to claim 8, characterized in that it further comprises an anhydrous form of the dihydrochloride salt of (3S,4R,3'R)6-[4-(4-amino-5-chloro-2-methoxybenzoylamino)-3-methoxypiperidin-l-yl]-hexanoic acid l-azabicycloti.i.Ljoct-S'-yl ester, wherein the ratio of the trihydrate form to the anhydrous form is at least about 4 to 1.

10. The pharmaceutical composition according to claim 8, characterized in that it comprises from about 6.5% to about 10% by weight of water with respect to the total weight of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-1-yl]-hexanoic acid 1-azabicyclo[2.2.2]oct-3'lyo ester dihydrochloride salt present in anhydrous or trihydrate form.

11. The pharmaceutical composition according to claim 9, characterized in that the ratio of the trihydrate form to the anhydrous form is at least around 11 to 1.

12. The pharmaceutical composition according to any of claims 8 to 11, characterized in that it comprises from about 7.5% to about 9% by weight of water with respect to the total weight of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid dihydrochloride salt 1azabicyclo[2.2.2]oct-3'-yl ester present in anhydrous or trihydrate form.

13. The pharmaceutical composition according to any of claims 8 to 12, characterized in that it comprises less than 1% by weight of the anhydrous form of the (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]hexanoic acid 1-azabicyclo[2.2.2]oct-3'-yl ester dihydrochloride salt present in anhydrous or trihydrate form.

14. The pharmaceutical composition in accordance with QCCECn / l ZηZ� / 3 / YILI 157 any of claims 8 to 13, characterized in that the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD peaks at 7.7410.5° and 20.9510.5°.

15. A dosage form characterized in that it comprises the pharmaceutical composition in accordance with any of claims 8 to 14.

16. The dosage form according to claim 15, characterized in that it comprises one or more tablets or one or more capsules.

17. A kit characterized in that it comprises the dosage form according to claim 15 or 16 and a container.

18. The kit according to claim 17, characterized in that the packaging is a blister pack.

19. A method for improving gastrointestinal motility in a subject in need, characterized in that it comprises administering to the subject in need a therapeutically effective amount of the pharmaceutical composition according to any of claims 8 to 14, or the dosage form according to claim 15 or 16.

20. The method according to claim 19, characterized in that the subject requiring it has a gastrointestinal disorder. QCCRCn / l 7P7 / 3 / YILI 158 21. A method for treating a gastrointestinal disorder in a subject in need, characterized in that it comprises administering to the subject in need a therapeutically effective amount of the pharmaceutical composition according to any of claims 8 to 14, or the dosage form according to claim 15 or 16.

22. The method according to claim 20 or 21, characterized in that the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis.

23. Use in accordance with claim 22, wherein the GERD is proton pump inhibitor (PPI) resistant GERD.

24. Use according to claim 22, wherein constipation is opiate-induced constipation (OIC), chronic idiopathic constipation (CIC), or constipation associated with the irritable bowel syndrome (IBS) type of constipation.

25. Use in accordance with claim 22, in QCCRCn / l 7P7 / 3 / YILI 159 where esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE).

26. Use in accordance with claim 22, wherein IBS is of the irritable bowel syndrome (IBSc) type of constipation.

27. Use in accordance with claim 22, wherein gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis.

28. Use according to claim 20 or 21, wherein the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, emesis, gastroparesis, opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (ED) or functional motility disorder (FMD), intestinal pseudo-obstruction, irritable bowel syndrome (IBSc) type of constipation, enteral feeding intolerance (EFI), and postoperative ileus.

29. Use according to claim 20 or 21, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grass disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect.

30. Use in accordance with claim 29, in accacn / i ζηζ / α / γίΛΐ 160 where gastritis is atrophic gastritis.

31. The use of a trihydrate form of the dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3'-yl ester in the manufacture of a medicament to improve gastrointestinal motility in a subject in need.

32. Use in accordance with claim 31, wherein the subject who needs it has a gastrointestinal disorder.

33. The use of a trihydrate form of the dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3'-yl ester in the manufacture of a medicament to treat a gastrointestinal disorder in a subject in need.

34. Use according to claim 32 or 33, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis. accacn / i ζηζ / α / γίΛΐ 161 35. Use in accordance with claim 34, wherein the GERD is proton pump inhibitor (PPI) resistant GERD.

36. Use according to claim 34, wherein constipation is opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), or constipation associated with the irritable bowel syndrome (IBSc) type of constipation.

37. Use according to claim 34, wherein esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE).

38. Use according to claim 34, wherein IBS is of the irritable bowel syndrome (IBSc) type of constipation.

39. Use in accordance with claim 34, wherein gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis.

40. Use according to claim 32 or 33, wherein the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, emesis, gastroparesis, opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (FD) or functional motility disorder (FMD), intestinal pseudo-obstruction, irritable bowel syndrome (IBS) type 162 constipation, enteral feeding intolerance (EFI), and postoperative ileus.

41. Use according to claim 32 or 33, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grass disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect.

42. Use according to claim 41, wherein gastritis is atrophic gastritis.

43. A compound, for use in the enhancement of gastrointestinal motility in a subject in need thereof, wherein it is a trihydrate form of the dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3'-yl ester.

44. The compound to be used in accordance with claim 43, wherein the subject who needs it has a gastrointestinal disorder.

45. A compound, for use in the treatment of a gastrointestinal disorder in a subject in need thereof, which is a trihydrate form of the dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1-3Z30ίοίο1ο[2.2.2]οοί-3' QCCRCn / l ZηZΖ / 3 / YΙΛΙ yl ester. 163 46. ​​The compound for use according to claim 44 or 45, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis.

47. The compound for use in accordance with claim 46, wherein the GERD is proton pump inhibitor (PBI) resistant GERD.

48. The compound for use according to claim 46, wherein constipation is opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), or constipation associated with the irritable bowel syndrome (IBSc) type of constipation.

49. The compound for use according to claim 46, wherein esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE).

50. The compound for use according to claim 46, wherein the IBS is of the irritable bowel syndrome (IBSc) type of constipation.

51. The compound for use in accordance with claim 46, wherein gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis.

52. The compound for use according to claim 44 or 45, wherein the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, emesis, gastroparesis, opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (FD) or functional motility disorder (FMD), intestinal pseudo-obstruction, irritable bowel syndrome (IBSc) type of constipation, enteral feeding intolerance (EFI), and postoperative ileus.

53. The compound for use according to claim 44 or 45, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grass disease, constipation, megacolon, cystastritis, gastrointestinal stasis, and abomasal emptying defect.

54. The compound for use in accordance with claim 53, wherein gastritis is atrophic gastritis.

55. A pharmaceutical composition for use in the improvement of gastrointestinal motility in a subject in need thereof, comprising a trihydrate form of the dihydrochloride salt of (3S, 4R, 3' R)-6-[4-(4-amino-5-chloro-2- QCCacn / l 7P7 / 3 / YILI 165 methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid 1azabicyclo[2.2.2]oct-3'-yl ester.

56. The pharmaceutical composition for use according to claim 55, wherein the subject requiring it has a gastrointestinal disorder.

57. A pharmaceutical composition, for use in the treatment of a gastrointestinal disorder in a subject in need thereof, wherein the pharmaceutical composition comprises a trihydrate form of the dihydrochloride salt of (3S,4R,3'R)-6-[4-(4-amino-5-chloro-2-methoxy-benzoylamino)-3-methoxy-piperidin-l-yl]-hexanoic acid l-azabicyclo[2.2.2]oct-3,yl ester.

58. The pharmaceutical composition for use according to claim 56 or 57, wherein the gastrointestinal disorder is selected from the group consisting of gastroesophageal reflux disease (GERD), functional dyspepsia or functional motility disorder, gastroparesis, paralytic ileus, postoperative ileus, emesis, nausea, heartburn, intestinal pseudo-obstruction, irritable bowel syndrome (IBS), constipation, enteral feeding intolerance (EFI), and esophagitis.

59. The pharmaceutical composition for use according to claim 58, wherein the GERD is proton pump inhibitor (PPI) resistant GERD.

60. The pharmaceutical composition for use of QCCRCn / l 7P7 / 3 / YILI 166 in accordance with claim 58, wherein constipation is opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), or constipation associated with the irritable bowel syndrome (IBSc) type of constipation.

61. The pharmaceutical composition for use according to claim 58, wherein esophagitis is erosive esophagitis (EE) or eosinophilic esophagitis (EoE).

62. The pharmaceutical composition for use according to claim 58, wherein the IBS is of the irritable bowel syndrome (IBSc) type of constipation.

63. The pharmaceutical composition for use according to claim 58, wherein gastroparesis is diabetic gastroparesis or idiopathic or functional gastroparesis.

64. The pharmaceutical composition for use according to claim 56 or 57, wherein the gastrointestinal disorder is selected from the group consisting of proton pump inhibitor (PPI) resistant GERD, emesis, gastroparesis, opioid-induced constipation (QIC), chronic idiopathic constipation (CIC), erosive esophagitis (EE), eosinophilic esophagitis (EoE), functional dyspepsia (FD) or functional motility disorder (FMD), intestinal pseudo-obstruction, irritable bowel syndrome (IBS) type 167 constipation, enteral feeding intolerance (EFI), and postoperative ileus.

65. The pharmaceutical composition for use according to claim 56 or 57, wherein the gastrointestinal disorder is selected from the group consisting of postoperative ileus, chronic grass disease, constipation, megacolon, gastritis, gastrointestinal stasis, and abomasal emptying defect.

66. The pharmaceutical composition for use according to claim 65, wherein gastritis is atrophic gastritis.

67. The method according to any of claims 19 to 26, the use according to any of claims 31 to 40, the compound for use according to any of claims 43 to 52, or the pharmaceutical composition for use according to any of claims 55 to 64, wherein the subject in need is a human being.

68. The method according to any of claims 19 to 21 or 26 to 28, the use according to any of claims 31 to 33 or 40 to 42, the compound for use according to any of claims 43 to 45 or 52 to 54, or the pharmaceutical composition for use according to any of claims 55 to 57 or 64 to 66, wherein the subject in need is a non-human animal.

69. The method, use, compound for use or pharmaceutical composition for use according to claim 68, wherein the non-human animal is a ruminant, equine, cat, dog, rabbit or guinea pig.

70. The method, use, compound for use or pharmaceutical composition for use according to claim 69, wherein the ruminant is a sheep, a cow, a yak, a bison or a buffalo.

71. The method, use, compound for use or pharmaceutical composition for use in accordance with claim 69, wherein the equine is a horse or a donkey.

72. The method according to any of claims 19 to 28 or 67 to 71, the use according to any of claims 31 to 42 or 67 to 71, the compound for use according to any of claims 43 to 54 or 67 to 71, or the pharmaceutical composition for use according to any of claims 55 to 71, wherein the subject in need is a non-human animal.

73. The method according to any of claims 19 to 28 or 67 to 72, the use according to any of claims 31 to 42 or 67 to 72, the compound for use according to any of claims 43 to 54 or 67 to 72, or the pharmaceutical composition for use according to any of claims 55 to 72, wherein the pharmaceutical composition is administered parenterally.

74. The method according to any of claims 19 to 28 or 67 to 72, the use according to any of claims 31 to 42 or 67 to 72, the compound for use according to any of claims 43 to 54 or 67 to 72, or the pharmaceutical composition for use according to any of claims 55 to 72, wherein the pharmaceutical composition is administered orally.

75. The method according to any of claims 19 to 28 or 67 to 72, the use according to any of claims 31 to 42 or 67 to 72, the compound for use according to any of claims 43 to 54 or 67 to 72, or the pharmaceutical composition for use according to any of claims 55 to 72, wherein the pharmaceutical composition is administered through a gastric tube.

76. The method according to any of claims 19 to 30 or 67 to 75, the use according to any of claims 31 to 42 or 67 to 75, the compound for use according to any of claims 43 to 54 or 67 to 75, or the pharmaceutical composition for use according to claims 55 to 75, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.74±0.5° and 20.9510.5°.

77. The bulk composition according to any one of claims 1 to 7; or the pharmaceutical composition according to any one of claims 8 to 14; or the dosage form according to claim 15 or 16; or the kit according to claim 17 or 18; or the method according to any one of claims 19 to 30 or 67 to 76; or the use according to any one of claims 31 to 42 or 67 to 76; or the compound for use according to any one of claims 43 to 54 or 67 to 76; or the pharmaceutical composition for use according to any of claims 55 to 76, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has an XRPD 2-zeta (2Θ) peak of relative intensity greater than 50% at 7.74°±0.5°, and an XRPD 2-zeta (2Θ) peak of relative intensity of 100% at 20.95°±0.5°.

78. The bulk composition according to any one of claims 1 to 7 or 77; or the pharmaceutical composition according to any one of claims 8 to 14 or 77; or the dosage form according to any one of claims 15, 16 or 77; or the kit according to any one of claims 17, 18 or 77; or the method according to any one of claims 19 to 30 or 67 to 77; or the use according to any one of claims 31 to 42 or 67 to 77; or the compound for use according to any one of claims 43 to 54 or 67 to 77; or the pharmaceutical composition for use according to any of claims 55 to 77, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has two or more XRPD 2-zeta (2Θ) peaks selected from the group consisting of 10.3°±0.2°, 13.6°±0.2°, 14.8°±0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 21.3°±0.2°, 22.0°±0.2°, 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2°, y 39.4°±0.2°.

79. The bulk composition according to any one of claims 1 to 7, 77, or 78; or the pharmaceutical composition according to any one of claims 8 to 14, 77, or 78; or the dosage form according to any one of claims 15, 16, 77, or 78; or the kit according to any one of claims 17, 18, 77, or 78; or the method according to any one of claims 19 to 30 or 67 to 78; or the use according to any one of claims 31 to 42 or 67 to 78; or the compound for use according to any one of claims 43 to 54 or 67 to 78; or the pharmaceutical composition for use in accordance with any of claims 55 to 78, wherein the trihydrate form is in crystalline form, and wherein the crystalline form has XRPD 2-zeta (2Θ) peaks at 7.6°±0.2° and 20.7°±0.2°.

80. The composition, pharmaceutical composition, dosage form, kit, method, use, compound to be used, or pharmaceutical composition to be used according to claim 79, wherein the 7.6°±0.2° XRPD 2-zeta (2Θ) peak has a relative intensity greater than 50% and the 20.7°±0.2° XRPD 2-zeta (2Θ) peak has a relative intensity of 100%.

81. The bulk composition, pharmaceutical composition, dosage form, kit, method, use, compound for use, or pharmaceutical composition for use according to claim 79 or 80, wherein the crystalline form further has two or more 2Θ XRPD peaks selected from the group consisting of 10.3°±0.2°, 13.6°±0.2°, 14.8°±0.2°, 15.0°±0.2°, 15.4°±0.2°, 17.5°±0.2°, 18.3°±0.2°, 18.6°±0.2°, 19.2°±0.2°, 21.3°±0.2°, 22.0°±0.2°, 23.6°±0.2°, 24.3°±0.2°, 25.2°±0.2°, 26.0°±0.2°, 27.2°±0.2°, 30.1°±0.2°, 32.4°±0.2°, 33.4°±0.2°, 38.2°±0.2° and 39.4°±0.2° . 173 82. The bulk composition according to any one of claims 1 to 7, or 77 to 81; or the pharmaceutical composition according to any one of claims 8 to 14, or 77 to 81; or the dosage form according to any one of claims 15, 16 or 77 to 81; or the kit according to any one of claims 17, 18 or 77 to 81; the method according to any one of claims 19 to 30 or 67 to 81; or the use according to any one of claims 31 to 42 or 67 to 81; or the compound for use according to any one of claims 43 to 54 or 67 to 81; or the pharmaceutical composition for use in accordance with any of claims 55 to 81, wherein the bulk composition, pharmaceutical composition, dosage form, kit or drug comprises less than about 6000 ppm of organic solvent.

83. The bulk composition, or pharmaceutical composition, or dosage form, or kit, or method, or compound for use, or pharmaceutical composition for use according to claim 82, wherein the bulk composition, pharmaceutical composition, dosage form, kit, or drug comprises less than about 5000 ppm, less than about 4000 ppm, less than about 3000 ppm, or less than about 2000 ppm of organic solvent. QCCRCn / l ZηZ / 3 / YILI 174 84. The bulk composition, or pharmaceutical composition, or dosage form, or kit, or method, or compound to be used or pharmaceutical composition to be used in accordance with claim 82 or 83, wherein the organic solvent comprises one or more Ci-Cs alcohols.

85. The bulk composition, or pharmaceutical composition, or dosage form, or kit, or method, or compound to be used or pharmaceutical composition to be used in accordance with any of claims 82 to 84, wherein the organic solvent comprises ethanol, n-propanol or isopropanol or a combination thereof.

86. The bulk composition, or pharmaceutical composition, or dosage form, or kit, or method, or compound to be used or pharmaceutical composition to be used in accordance with any of claims 82 to 85, wherein the organic solvent comprises isopropanol.