Rifaximin liquid formulation

Abstract

Provided herein are pharmaceutical compositions that increase intestinal levels of soluble rifaximin, formulations containing the compositions, and uses thereof in the treatment of one or more bowel-related disorders.

Description

[Technical Field]

[0001] The present invention relates to a liquid formulation of rifaximin.

[0002] Related Applications This application claims priority to U.S. Provisional Application No. 62 / 904,790, filed September 24, 2019, and U.S. Provisional Application No. 63 / 044,447, filed June 26, 2020, the entire contents of each of which are incorporated herein by reference. [Background technology]

[0003] Rifaximin (e.g., Xifaxan®) is an orally available, broad-spectrum antibiotic with antibacterial activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. Rifaximin is currently indicated for the treatment of traveler's diarrhea (TD), maintenance of remission in hepatic encephalopathy (HE), and treatment of irritable bowel syndrome with diarrhea (IBS-D). Other uses of rifaximin include the treatment of C. difficile infection, infectious diarrhea, small intestinal bacterial overgrowth (SIBO), inflammatory diseases, inflammatory bowel disease (IBD), and diverticular disease. Rifaximin is largely water-insoluble and poorly absorbed, resulting in rare systemic effects. For example, when taken orally, less than 0.5% of rifaximin is absorbed into the bloodstream. This translates to a very favorable safety profile comparable to placebo. However, rifaximin is highly soluble in bile. This results in a higher intraluminal concentration and stronger antibacterial activity against intestinal bacteria. Rifaximin is also found to be more effective in the small intestine, with lower microbial resistance and less impact on the large intestinal microflora. Therefore, rifaximin is highly preferred for use in conditions related to the small intestine and for long-term use (e.g., for more than 6 months or when bacterial resistance is a concern). Summary of the Invention [Problem to be solved by the invention]

[0004] However, even with these beneficial characteristics, over 90% of rifaximin is excreted almost entirely in the feces as the unchanged drug. Furthermore, due to its low systemic availability, rifaximin has previously been overlooked for treating systemic infections caused by invasive organisms. Patient compliance is an additional concern, as poor adsorption leads to high and frequent dosing. Currently, rifaximin is manufactured as 200 mg and 550 mg tablets and is approved for administration at daily doses of 600 mg (TD) or 1650 mg (HE).

[0005] There is a need for rifaximin formulations that improve the availability of soluble rifaximin to the stomach, small intestine, and / or large intestine. [Means for solving the problem]

[0006] In one embodiment, the invention described herein includes a composition comprising rifaximin, hydrogenated castor oil, and at least one additional solubilizing excipient. In some embodiments, the compositions described herein include low-dose rifaximin. In some embodiments, the compositions described herein can be pharmaceutically acceptable compositions. In one embodiment, the invention described herein includes a pharmaceutically acceptable composition comprising low-dose rifaximin, hydrogenated castor oil, and at least one additional solubilizing excipient.

[0007] In some embodiments, the hydrogenated castor oil can be polyoxyl 40 hydrogenated castor oil (eg, Cremophor® RH-40).

[0008] In some embodiments, hydrogenated castor oil may be present in an amount ranging from about 25% to about 65% by weight of the composition.

[0009] In some embodiments, hydrogenated castor oil may be present in an amount ranging from about 25% to about 50% by weight of the composition.

[0010] In some embodiments, hydrogenated castor oil may be present in an amount ranging from about 30% to about 45% by weight of the composition.

[0011] In some embodiments, hydrogenated castor oil can be present in an amount ranging from about 35% to about 40% by weight of the composition. In some embodiments, hydrogenated castor oil can be present in an amount of about 35% or about 40% by weight of the composition.

[0012] In some embodiments, hydrogenated castor oil may be present in an amount ranging from about 45% to about 65% by weight of the composition.

[0013] In some embodiments, the at least one additional solubilizing excipient can be a plurality of additional solubilizing excipients. In some embodiments, the at least one additional solubilizing excipient can be selected from the group consisting of a water-soluble organic solvent, a nonionic surfactant, a water-insoluble lipid, a long-chain triglyceride, and combinations thereof. In some embodiments, the at least one additional solubilizing excipient can comprise one or more of a water-soluble organic solvent, a nonionic surfactant, a water-insoluble lipid, and a long-chain triglyceride. In some embodiments, the at least one additional solubilizing excipient can be selected from the group consisting of polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, and combinations thereof. In some embodiments, the at least one additional solubilizing excipient can include one or more of polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, and oleyl alcohol.

[0014] In some embodiments, the at least one additional solubilizing excipient can be one or more additional solubilizing excipients that allow for or otherwise provide a saturation solubility of rifaximin of greater than about 10% by weight of rifaximin in the composition, hi some embodiments, the at least one additional solubilizing excipient can be one or more additional solubilizing excipients that allow for or otherwise provide a saturation solubility of rifaximin of greater than about 14% by weight of rifaximin in the composition.

[0015] In some embodiments, the at least one additional solubilizing excipient can be selected from the group consisting of polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, polysorbate 20, oleic acid, caprylic / capric triglyceride, propylene glycol, sesame oil, soybean oil, corn oil, and combinations thereof. In some embodiments, the at least one additional solubilizing excipient can include at least one of polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, polysorbate 20, oleic acid, caprylic / capric triglyceride, propylene glycol, sesame oil, soybean oil, and corn oil.

[0016] In some embodiments, the at least one additional solubilizing excipient can be selected from the group consisting of castor oil, glyceryl caprylate, polysorbate 80, diethyl sebacate, diethylene glycol monoethyl ether, and combinations thereof. In some embodiments, the at least one additional solubilizing excipient can include one or more of castor oil, glyceryl caprylate, polysorbate 80, and diethyl sebacate.

[0017] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 25% to about 65% by weight of the composition.

[0018] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 30% to about 65% by weight of the composition.

[0019] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 35% to about 65% by weight of the composition.

[0020] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 40% to about 65% by weight of the composition.

[0021] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 45% to about 65% by weight of the composition.

[0022] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 50% to about 65% by weight of the composition.

[0023] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 50% to about 60% by weight of the composition.

[0024] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 55% to about 60% by weight of the composition.

[0025] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 55% to about 65% by weight of the composition.

[0026] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 60% to about 65% by weight of the composition.

[0027] In some embodiments, the at least one additional solubilizing excipient may be present in an amount ranging from about 62% to about 63% by weight of the composition.

[0028] In some embodiments, the at least one additional solubilizing excipient can be a combination of at least two additional solubilizing excipients. In some embodiments, the at least one additional solubilizing excipient can be a combination of at least three additional solubilizing excipients. In some embodiments, the at least one additional solubilizing excipient includes castor oil and glyceryl caprylate. In some embodiments, the at least one additional solubilizing excipient includes castor oil and polysorbate 80. In some embodiments, the at least one additional solubilizing excipient includes glyceryl caprylate and polysorbate 80. In some embodiments, the at least one additional solubilizing excipient includes castor oil, glyceryl caprylate, and polysorbate 80. In some embodiments, the at least one additional solubilizing excipient is a combination of castor oil, glyceryl caprylate, and polysorbate 80.

[0029] In some embodiments, the compositions described herein comprise castor oil in an amount ranging from about 5% to about 15% by weight of the composition; glyceryl caprylate in an amount ranging from about 5% to about 15% by weight of the composition; and polysorbate 80 in an amount ranging from about 20% to about 40% by weight of the composition.

[0030] In some embodiments, the compositions described herein comprise castor oil in an amount ranging from about 5% to about 15% by weight of the composition; glyceryl caprylate in an amount ranging from about 5% to about 15% by weight of the composition; and polysorbate 80 in an amount ranging from about 20% to about 40% by weight of the composition.

[0031] In some embodiments, the compositions described herein comprise castor oil in an amount ranging from about 8% to about 12% by weight of the composition; glyceryl caprylate in an amount ranging from about 10% to about 14% by weight of the composition; and polysorbate 80 in an amount ranging from about 30% to about 35% by weight of the composition.

[0032] In some embodiments, the compositions described herein comprise castor oil in an amount ranging from about 10% to about 20% by weight of the composition; glyceryl caprylate in an amount ranging from about 5% to about 15% by weight of the composition; and polysorbate 80 in an amount ranging from about 20% to about 40% by weight of the composition.

[0033] In some embodiments, the compositions described herein comprise castor oil in an amount ranging from about 13% to about 18% by weight of the composition; glyceryl caprylate in an amount ranging from about 10% to about 14% by weight of the composition; and polysorbate 80 in an amount ranging from about 30% to about 35% by weight of the composition.

[0034] In some embodiments, the compositions described herein comprise castor oil in an amount ranging from about 5% to about 15% by weight of the composition; glyceryl caprylate in an amount ranging from about 10% to about 15% by weight of the composition; and polysorbate 80 in an amount ranging from about 35% to about 45% by weight of the composition.

[0035] In some embodiments, the compositions described herein comprise castor oil in an amount ranging from about 8% to about 12% by weight of the composition; glyceryl caprylate in an amount ranging from about 10% to about 15% by weight of the composition; and polysorbate 80 in an amount ranging from about 38% to about 42% by weight of the composition.

[0036] In some embodiments, the at least one additional solubilizing excipient comprises diethyl sebacate and diethylene glycol monoethyl ether. In some embodiments, the at least one additional solubilizing excipient comprises diethyl sebacate and diethylene glycol monoethyl ether. In some embodiments, the at least one additional solubilizing excipient is a combination of diethyl sebacate and diethylene glycol monoethyl ether. In some embodiments, the at least one additional solubilizing excipient is a combination of diethyl sebacate and diethylene glycol monoethyl ether.

[0037] In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 20% to about 35% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 20% to about 35% by weight of the composition. In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 20% to about 35% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 20% to about 35% by weight of the composition.

[0038] In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 25% to about 30% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 25% to about 30% by weight of the composition. In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 25% to about 30% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 25% to about 30% by weight of the composition.

[0039] In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 10% to about 20% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 30% to about 45% by weight of the composition. In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 10% to about 20% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 30% to about 45% by weight of the composition.

[0040] In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 14% to about 18% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 36% to about 40% by weight of the composition. In some embodiments, the compositions described herein comprise diethyl sebacate in an amount ranging from about 14% to about 18% by weight of the composition; and diethylene glycol monoethyl ether in an amount ranging from about 36% to about 40% by weight of the composition.

[0041] In some embodiments, the compositions described herein may comprise an antioxidant and / or a chelating agent. In some embodiments, the compositions described herein may comprise an antioxidant and / or a chelating agent selected from the group consisting of ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene (BHT), citric acid, potassium metabisulfite, sodium metabisulfite, cysteine, propyl gallate, sodium thiosulfate, vitamin E, 3,4-dihydroxybenzoic acid, and combinations thereof. In some embodiments, the compositions described herein may comprise one or more of ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene (BHT), citric acid, potassium metabisulfite, sodium metabisulfite, propyl gallate, sodium thiosulfate, cysteine, vitamin E, and 3,4-dihydroxybenzoic acid.

[0042] In some embodiments, the compositions described herein may comprise an antioxidant in an amount ranging from about 0.01% to about 0.1% by weight of the composition.

[0043] In some embodiments, the compositions described herein can include BHT.

[0044] In some embodiments, the compositions described herein may include BHT in an amount ranging from about 0.01% to about 0.1% by weight of the composition.

[0045] In some embodiments, the compositions described herein may include citric acid.

[0046] In some embodiments, the compositions described herein may comprise citric acid in an amount ranging from about 0.01% to about 0.1% by weight of the composition.

[0047] In some embodiments, the compositions described herein can include ascorbyl palmitate.

[0048] In some embodiments, the compositions described herein may comprise ascorbyl palmitate in an amount ranging from about 0.05% to about 0.15% by weight of the composition.

[0049] In some embodiments, the compositions described herein can include BHT and citric acid.

[0050] In some embodiments, the compositions described herein may include BHT and citric acid in an amount ranging from about 0.01% to about 0.1% by weight of the composition, respectively.

[0051] In some embodiments, the compositions described herein can include BHT, citric acid, and ascorbyl palmitate.

[0052] In some embodiments, the compositions described herein can include BHT, citric acid, and ascorbyl palmitate, each in an amount ranging from about 0.05% to about 0.15% by weight of the composition.

[0053] In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 2.5% to about 15% by weight of the composition.

[0054] In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 2.5% to about 12% by weight of the composition.

[0055] In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 5% to about 10% by weight of the composition.

[0056] In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 1.0% to about 15% by weight of the composition.

[0057] In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 1.0% to about 5% by weight of the composition.

[0058] In some embodiments, the compositions described herein may comprise rifaximin in an amount less than about 125 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 10 mg to about 125 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 25 mg to about 125 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 25 mg to about 75 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 75 mg to about 125 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount of about 50 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount of about 100 mg.

[0059] In some embodiments, the compositions described herein may comprise rifaximin in an amount less than about 125 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 1 mg to about 50 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 1 mg to about 25 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 1 mg to about 10 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 1 mg to about 5 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 2 mg to about 5 mg. In some embodiments, the compositions described herein may comprise rifaximin in an amount ranging from about 3 mg to about 4 mg.

[0060] In one embodiment, the invention can include a composition comprising, by weight of the composition, about 10% rifaximin, about 10% castor oil, about 12% glyceryl caprylate, about 33% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil. In one embodiment, the invention can include a composition comprising, by weight of the composition, about 10% rifaximin, about 10% castor oil, about 12% glyceryl caprylate, about 33% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

[0061] In one embodiment, the present invention can include a composition comprising, by weight of the composition, about 10% rifaximin, about 35% polyoxyl 40 hydrogenated castor oil, about 27.5% diethyl sebacate, and about 27.5% diethylene glycol monoethyl ether.

[0062] In one embodiment, the present invention can include a composition comprising, by weight of the composition, about 5% rifaximin, about 15% castor oil, about 12% glyceryl caprylate, about 33% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

[0063] In one embodiment, the present invention can include a composition comprising, by weight of the composition, about 10% rifaximin, about 40% polyoxyl 40 hydrogenated castor oil, about 16.5% diethyl sebacate, and about 38.5% diethylene glycol monoethyl ether.

[0064] In one embodiment, the present invention can include a composition comprising, by weight of the composition, about 2.5% rifaximin, about 10% castor oil, about 12% glyceryl caprylate, about 40% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

[0065] In some embodiments, the compositions described herein are liquid compositions. In some embodiments, the compositions described herein can be formulated in the form of a soft capsule. In some embodiments, the compositions described herein can be liquid compositions formulated in a soft capsule dosage form. In some embodiments, the compositions described herein can be formulated in a hard capsule dosage form. In some embodiments, the compositions described herein can be liquid compositions formulated in a hard capsule dosage form. In some embodiments, the compositions described herein can be formulated in a gelatin capsule dosage form. In some embodiments, the compositions described herein can be liquid compositions formulated in a gelatin capsule dosage form.

[0066] In one embodiment, the invention includes a method of treating one or more diseases in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition described herein. In some embodiments, the one or more diseases include a bowel-related disease or liver dysfunction. In some embodiments, the invention includes a method of treating one or more bowel-related diseases or liver dysfunction in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition described herein. In some embodiments, the one or more gut-related or liver dysfunction disorders can be selected from the group consisting of irritable bowel syndrome (IBS), e.g., IBS-D, diarrhea, microbial-associated diarrhea, infectious diarrhea, Clostridium difficile infection and symptoms, traveler's diarrhea, small intestinal bacterial overgrowth (SIBO), Crohn's disease, diverticular disease, pancreatitis, pancreatic insufficiency, enteritis, ulcerative colitis, antibiotic-associated colitis, hepatic encephalopathy, gastric dyspepsia, cirrhosis, polycystic liver disease, pouchitis, peritonitis, inflammatory bowel disease, rosacea, sickle cell disease, H. pylori infection, and combinations thereof. [Brief explanation of the drawings]

[0067] [Figure 1]FIG. 1 shows dissolution results for composition of the present invention 5425-67A compared to placebo (i.e., no rifaximin) 5425-67B, xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO 2018 / 064472 (see also U.S. Application Publication No. 2019-0224175, which is incorporated herein by reference in its entirety). [Figure 2] FIG. 1 shows dissolution results for composition of the present invention 5425-66A compared to placebo (i.e., no rifaximin) 5425-66B, xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO2018 / 064472. [Figure 3] FIG. 1 shows dissolution results for inventive composition 5425-68A at pH 7.4 compared to placebo (i.e., no rifaximin) 5425-68B, xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO2018 / 064472. [Figure 4] FIG. 1 shows dissolution results for inventive composition 5425-68A at pH 4.5 compared to placebo (i.e., no rifaximin) 5425-68B, xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO2018 / 064472. [Figure 5] FIG. 1 shows dissolution results for inventive composition 5425-68A in 0.1 N HCl compared to placebo (i.e., no rifaximin) 5425-68B, xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO2018 / 064472. [Figure 6] FIG. 1 shows dissolution results for compositions 5425-70A, 5425-70B, and 5425-70C of the present invention at pH 7.4 compared to placebo (i.e., no rifaximin) 5425-66B, Xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO 2018 / 064472. [Figure 7]FIG. 1 shows dissolution results for inventive compositions 5425-70A, 5425-70B, and 5425-70C at pH 4.5 compared to placebo (i.e., no rifaximin) 5425-66B, Xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO 2018 / 064472. [Figure 8] FIG. 1 shows dissolution results for compositions of the invention 5425-70A, 5425-70B, and 5425-70C in 0.1 N HCl compared to placebo (i.e., no rifaximin) 5425-66B, Xifaxan 550 mg (Opadry II), and the 40 mg and 80 mg solid dispersion formulations described in WO 2018 / 064472. [Figure 9] FIG. 1 shows the percentage reduction in E. coli as a function of time (min) after treatment with formulation 5507-65A of the invention compared to placebo and Xifaxan 550 mg. [Figure 10] FIG. 1 shows the percentage reduction as a function of time (minutes) for Salmonella choleraesuis after treatment with formulation 5507-65A of the invention compared to placebo and Xifaxan 550 mg. [Figure 11] FIG. 1 shows the percentage reduction as a function of time (min) for Shigella flexneri after treatment with formulation 5507-65A of the invention compared to placebo and Xifaxan 550 mg. DETAILED DESCRIPTION OF THE INVENTION

[0068] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0069]

[0013] When ranges are used herein to describe, for example, amounts of particular compounds or components, all combinations and subcombinations of the ranges and specific embodiments are intended to be included. The use of the term "about" when referring to a numerical value or numerical range means that the referenced numerical value or numerical range is an approximation within experimental variability (or within statistical experimental error), and thus the numerical value or numerical range may vary. The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") includes embodiments thereof, such as, for example, embodiments of any composition of matter, method, or process that "consist" or "consist essentially of" the described features.

[0070] 1.Definition "Rifaximin" refers to the antibiotic 4-deoxy-4'-methylpyrido[1',2'-1,2]imidazo[5,4-c]rifamycin SV, which has the chemical structure depicted in Formula I below.

[0071] [ka]

[0072] Forms, formulations, and methods of use of rifaximin are described, for example, in U.S. Patent Nos. 7,045,620, 7,906,542, 7,915,275, 8,193,196, 8,309,569, 8,518,949, 8,741,904, and 9,737,610, which are incorporated herein by reference in their entireties.

[0073] The term "low dose rifaximin" means that rifaximin is present in an amount of 150 mg or less.

[0074] A "solubilizing excipient" refers to an inert substance included in the disclosed compositions that has the ability to solubilize an active pharmaceutical ingredient (API), such as rifaximin. Solubilizing excipients can be used, for example, in oral and injectable dosage forms. In one aspect, a "solubilizing excipient" refers to an excipient that provides a saturated solubility of rifaximin of greater than about 10% by weight. See, for example, the solubility preformulation procedure in the Examples section below. Solubilizing excipients include, but are not limited to, pH adjusters, organic solvents (e.g., water-soluble organic solvents), surfactants (e.g., nonionic surfactants), lipids (e.g., water-soluble lipids), long-chain triglycerides, organic liquids / semisolids, cyclodextrins, and phospholipids.

[0075] The term "solubilization" means to solubilize or increase the solubility of a particular compound, such as rifaximin.

[0076] As used herein, "antioxidant" refers to a substance that inhibits the oxidation of rifaximin, for example, in the disclosed compositions.

[0077] "Hepatic encephalopathy," or "HE" for short, is defined as an abnormal mental state diagnosed as HE and as an increase in the Conn score to Grade ≥ 2 (i.e., from 0 or 1 to ≥ 2). HE can be considered "subclinical" or "overt" HE (CHE or OHE, respectively), depending on the severity of its associated symptoms. HE can be described as a continuum indicated by the West Haven Criteria (WHC): Grade 0 - minimal hepatic encephalopathy with symptoms that may include complex and persistent impaired attention; Grade 1 (CHE) - symptoms include subtle lack of awareness, euphoria or anxiety, impaired concentration, difficulty with addition or subtraction, and altered sleep rhythms, and clinical findings include mild asterixis or tremor; Grade 2 (OHE) - symptoms include lethargy or Symptoms include apathy, disorientation, significant personality changes, and inappropriate behavior. Clinical findings include obvious asterixis (flapping tremor), dyspraxia, and slurred speech; Grade 3 (OHE): Symptoms include drowsiness or semicomatosis, unresponsiveness to stimuli, confusion, severe disorientation, and bizarre behavior. Clinical findings include muscle rigidity, clonus, and hyperreflexia; and Grade 4 (OHE): Symptoms include coma and clinical findings include decerebrate posturing. OHE can also be observed with the Hepatic Encephalopathy Grading Instrument (HEGI), which uses clinical findings (present for at least 1 hour) to measure the patient's disorientation and thereby the severity of the HE episode (on a scale of Grade 2 to Grade 4), with Grade 4 being the most severe and Grade 2 being the least severe.

[0078] "Esophageal variceal bleeding," or "EVB" for short, is defined as the occurrence of clinically significant gastrointestinal bleeding defined as 1) bleeding from esophageal or gastric varices during endoscopy, or 2) the presence of multiple varices with visible blood in the stomach and no other identifiable cause for the bleeding observed during endoscopy, in the presence of at least one of the following criteria: i) a decrease in hemoglobin of more than 2 g / dL throughout the first 48 hours after admission, ii) the need for transfusion of two or more units of blood within 24 hours of admission, iii) a systolic blood pressure of less than 100 mmHg, or iv) a pulse rate of more than 100 beats / min on admission.

[0079] Spontaneous bacterial peritonitis, or "SBP" for short, is defined as a polymorphonuclear leukocyte (PMN) count of 250 / mm3 in the ascites. 3 Defined as a positive culture of more than one and / or only one bacterium.

[0080] "Hepatorenal syndrome" (HRS) was defined as i) a gradual increase in serum creatinine (>1.5 mg / dL) without improvement at least 2 days after diuretic withdrawal and volume expansion with albumin, ii) absence of parenchymal kidney disease, iii) oliguria, iv) absence of shock, and v) no current or recent (within 3 months prior to randomization) treatment with nephrotoxic drugs.

[0081] The term "effective amount" or "therapeutically effective amount" refers to an amount of a composition described herein that elicits a physiological or medical response in a subject, e.g., a composition having a rifaximin dosage of about 0.001 to about 100 mg / kg / day.

[0082] As used herein, the terms "subject" and "patient" can be used interchangeably and refer to a mammal in need of treatment, such as companion animals (e.g., dogs, cats, etc.), livestock (e.g., cows, pigs, horses, sheep, goats, etc.), and laboratory animals (e.g., rats, mice, guinea pigs, etc.). Typically, a subject is a human in need of treatment.

[0083] "Pharmaceutically acceptable" means molecular entities and compositions that do not produce adverse, allergic or other untoward reactions when administered to an animal or human, as appropriate.

[0084] The terms "treatment," "treat," and "treating," as used herein, refer to the reversal, alleviation, reduction in likelihood of onset, or inhibition of progression of a disease or disorder, or one or more symptoms thereof. In some embodiments, treatment may be administered after one or more symptoms have developed, i.e., therapeutic treatment. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to susceptible individuals prior to the onset of symptoms (e.g., given a history of the condition and / or given genetic or other susceptibility factors), i.e., prophylactic treatment. Treatment may also be continued after symptoms have subsided, e.g., to prevent or delay recurrence.

[0085] 2. Composition Disclosed herein are pharmaceutical compositions that significantly improve intestinal levels of soluble rifaximin compared to Xifaxan® powder. See, e.g., Table 8, which demonstrates a greater than 150-fold increase in solubility compared to Xifaxan® powder. As demonstrated herein, the percent of available soluble rifaximin was observed in phosphate buffer at pH 7.4. Increased solubility using the disclosed compositions was also observed in intestinal fluids. See, e.g., Tables 6A and 6B. Additionally, the effect of antioxidant additives was investigated and is shown in Table 7.

[0086] The solubility results and additional data described herein suggest that the disclosed compositions provide a means for administering lower doses of rifaximin without compromising therapeutic efficacy. Such compositions include, for example, pharmaceutically acceptable compositions comprising rifaximin (e.g., low-dose rifaximin), hydrogenated castor oil, and at least one additional solubilizing excipient. Formulations comprising one or more of the disclosed compositions and their use in treating gut-related disorders or liver dysfunction are also provided.

[0087] Rifaximin, hydrogenated castor oil, and at least one additional solubilizing excipient In a first embodiment, provided herein is a pharmaceutically acceptable composition comprising rifaximin, hydrogenated castor oil, and at least one additional solubilizing excipient. Alternatively, as part of the first embodiment, the rifaximin can be low-dose rifaximin.

[0088] In a second embodiment, the hydrogenated castor oil in the disclosed composition is selected from polyoxyl 8 hydrogenated castor oil, polyoxyl 10 hydrogenated castor oil, polyoxyl 16 hydrogenated castor oil, polyoxyl 20 hydrogenated castor oil, polyoxyl 25 hydrogenated castor oil, polyoxyl 35 hydrogenated castor oil, polyoxyl 40 hydrogenated castor oil (e.g., Cremophor® RH-40), polyoxyl 45 hydrogenated castor oil, polyoxyl 50 hydrogenated castor oil, polyoxyl 54 hydrogenated castor oil, polyoxyl 55 hydrogenated castor oil, polyoxyl 60 hydrogenated castor oil, polyoxyl 65 hydrogenated castor oil, polyoxyl 80 hydrogenated castor oil, polyoxyl 100 hydrogenated castor oil, and polyoxyl 200 hydrogenated castor oil, and combinations thereof, such as in the first embodiment. Alternatively, as in the first embodiment, as part of a second embodiment, the hydrogenated castor oil in the disclosed composition is polyoxyl 60 hydrogenated castor oil or polyoxyl 40 hydrogenated castor oil. In another alternative, as in the first embodiment, as part of a second embodiment, the hydrogenated castor oil in the disclosed composition is polyoxyl 40 hydrogenated castor oil (e.g., Cremophor® RH-40).

[0089] In a third embodiment, the hydrogenated castor oil in the disclosed composition is, by weight of the composition, about 25% to about 65%, about 25% to about 60%, about 25% to about 55%, about 25% to about 50%, about 30% to about 45%, about 35% to about 40%, about 30% to about 40%, about 31% to about 39%, about 32% to about 38%, about 33% to about 37%, about 34% to about 36%, about 40% to about 50%, about 41% to about 49%, about 42% to about 48%, about 43% to about 47%, or is present in an amount ranging from about 44% to about 46%; or at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, or at least about 50%; or at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, at most about 37%, at most about 38%, at most about 39%, at most about 40%, at most about 41% , at most about 42%, at most about 43%, at most about 44%, at most about 45%, at most about 46%, at most about 47%, at most about 48%, at most about 49%, or at most about 50%; or at most about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50%;or about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50%;

[0090] In another third embodiment, the hydrogenated castor oil in the disclosed compositions is present in an amount of from about 25% to about 65%, from about 25% to about 60%, from about 25% to about 55%, from about 25% to about 50%, from about 30% to about 45%, from about 35% to about 40%, from about 30% to about 40%, from about 31% to about 39%, from about 32% to about 38%, from about 33% to about 37%, from about 34% to about 36%, from about 40% to about 50%, from about 41%, from about 42% to about 45%, from about 43% to about 46%, from about 48% to about 49%, from about 51% to about 52%, from about 53% to about 54%, from about 55% to about 55%, from about 55% to about 50%, from about 55% to about 55%, from about 55% to about 50%, from about 60% to about 65%, from about 65% to about 60%, from about 65% to about 70%, from about 65% to about 75%, from about 75% to about 75%, from about 75% to about 76%, from about 77% to about 78%, from about 78% to about 79%, from about 80% to about 82%, from about 83% to about 84%, from about 85% to about 86%, from about 87% to about 88%, from about 89% to about 90%, from about 91% to about 92%, from about 93% to about 94%, from about 95% to about 96%, from about 97% to about 98%, from about 99% to about 100%, from about 100% to about 101%, from % to about 49%, about 42% to about 48%, about 43% to about 47%, or about 44% to about 46%; or at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least or at most about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, or at least about 50%; or at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, at most about 37%, at most about 38%, at most about 39%, at most about 40%, at most about 41%, at most about 42%; %, up to about 41%, up to about 42%, up to about 43%, up to about 44%, up to about 45%, up to about 46%, up to about 47%, up to about 48%, up to about 49%, or up to about 50%; or present in an amount of about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50%;or about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, or about 50%;

[0091] In a fourth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first to third embodiments, is a water-soluble organic solvent (e.g., polyethylene glycol (e.g., PEG 300, PEG 400, and PEG 600), ethanol, propylene glycol, benzyl alcohol, oleyl alcohol, triethylene glycol, n-methyl-2-pyrrolidone, dimethylacetamide, dimethyl sulfoxide, diethylene glycol monoethyl ether (e.g., Transcutol® grade HP and P), diisopropyl adipate, and diethyl sebacate), nonionic surfactants (e.g., PEG-8 castor oil, PEG-9 castor oil, PEG-10 castor oil, PEG-11 castor oil, PEG-15 castor oil, PEG-16 castor oil, PEG-20 castor oil, PEG-25 castor oil, PEG-26 castor oil, PEG-29 castor oil, PEG-40 castor oil, PEG-44 castor oil, PEG-50 castor oil, PEG-54 castor oil, PEG-55 castor oil, PEG-60 castor oil, PEG-75 castor oil, PEG-80 castor oil, PEG-100 castor oil, Canola Oil, PEG-200 Castor Oil, Polyethylene Glycol 1000 Succinate, Polysorbate 20, Polysorbate 80, Poly-oxyethylene Ester of 12-Hydroxystearic Acid, Sorbitan Monooleate, Poloxamer 407, Oleoyl Macrogol-6 / Polyoxyl-6 Glycerides, Caprylcaproyl Macrogol-8 / Polyoxyl-8 Glycerides, PEG-6 Caprylic / Capric Glycerides, Lauroyl Polyoxyl-32 Glycerides, and PEG300, PEG400, or PEG1750 Mono- and Di-Fatty Acids esters), water-insoluble lipids (e.g., castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, hydrogenated vegetable oils, hydrogenated soybean oil, and medium-chain triglycerides of coconut oil and palm oil), organic liquids / semi-solids (e.g., beeswax, d-α-tocopherol, oleic acid, and medium-chain mono-, di-, and triglycerides (e.g., glyceryl caprylate, glyceryl monooleate, glyceryl monolinoleate, and caprylic / capric triglyceride)), cyclodextrins (e.g., α-cyclodextrin,β-cyclodextrin, and hydroxypropyl-β-cyclodextrin), and phospholipids (e.g., hydrogenated soy phosphatidylcholine).

[0092] In a fifth embodiment, such as in any one of the first through fourth embodiments, the at least one additional solubilizing excipient in the disclosed composition is selected from a water-soluble organic solvent, a nonionic surfactant, a water-insoluble lipid, and a long-chain triglyceride, and combinations thereof. Alternatively, as part of a fourth embodiment, such as in any one of the first through fourth embodiments, the at least one additional solubilizing excipient in the disclosed composition is selected from polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, polysorbate 20, oleic acid, caprylic / capric triglyceride, propylene glycol, sesame oil, soybean oil, and corn oil, and combinations thereof.

[0093] In a sixth embodiment, the at least one additional solubilizing excipient in the disclosed composition, e.g., in any one of the first through fifth embodiments, allows for a rifaximin saturation solubility of greater than about 10% by weight (e.g., greater than about 11%, greater than about 12%, greater than about 13%, greater than about 14%, greater than about 15%, greater than about 16%, greater than about 17%, greater than about 18%, greater than about 19%, or greater than about 20% by weight). Alternatively, as part of the sixth embodiment, the at least one additional solubilizing excipient in the disclosed composition, e.g., in any one of the first through fifth embodiments, allows for a rifaximin saturation solubility of about 10% to about 25% by weight, about 12% to about 25% by weight, about 12% to about 23% by weight, about 13% to about 23% by weight, or about 14% to about 22% by weight.

[0094] In a seventh embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first through sixth embodiments, is selected from polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, and combinations thereof. Alternatively, as part of the seventh embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first through sixth embodiments, is selected from castor oil, glyceryl caprylate, polysorbate 80, diethyl sebacate, and diethylene glycol monoethyl ether, and combinations thereof.

[0095] In an eighth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first to seventh embodiments, is present in an amount, by weight of the composition, of about 25% to about 70%, about 25% to about 65%, about 30% to about 65%, about 35% to about 65%, about 40% to about 65%, about 40% to about 70%, about 45% to about 65%, about 46% to about 65%, about 47% to about 65%, about 48% to about 65%, about 49% to about 65%, about 50% to about 65%, about 51% to about 65%, about 52% to about 65%, about 53% to about 65%, about 54% to about 65%, about 55% to about 65%, about 56% to about 65%, about 57% to about 65%, about 58% to about 65%, about 59% to about 65%, about 60% to about 60%, about 61% to about 61%, about 62% to about 62%, about 63% to about 63%, about 64% to about 64%, about 65% to about 65%, about 66% to about 66%, about 67% to about 67%, about 68% to about 68%, about 69% to about 69%, about 70% to about 70%, about 71% to about 71%, about 72% to about 72%, about 73% to about 73%, about 74% to about 74%, about 75% to about 75%, about 76% to about 75%, about 77% to about 75%, about 78% to about 75%, about 79% to about 75%, about 80% to about 80%, about 5% to about 60%, about 46% to about 60%, about 47% to about 60%, about 48% to about 60%, about 49% to about 60%, about 50% to about 60%, about 51% to about 60%, about 52% to about 60%, about 53% to about 60%, about 54% to about 60%, or about 55% to about 60%; or at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 5 ...55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 60%, at least about 60%, at least about 60%, at least about 60%, at least about 60%, at least about 60%, at least about 60%, at least about 60%, at least about or is present in an amount of at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, or at least about 70%;or up to about 25%, up to about 26%, up to about 27%, up to about 28%, up to about 29%, up to about 30%, up to about 31%, up to about 32%, up to about 33%, up to about 34%, up to about 35%, up to about 36%, up to about 37%, up to about 38%, up to about 39%, up to about 40%, up to about 41%, up to about 42%, up to about 43%, Up to about 44%, up to about 45%, up to about 46%, up to about 47%, up to about 48%, up to about 49%, up to about 50%, up to about 51%, up to about 52%, up to about 53%, up to about 54%, up to about 55%, up to about 56%, up to about 57%, up to about 58%, up to about 59%, up to about 60%, up to about 61%, up to about 62%, up to about 63%, up to about 64%, up to about 65%, up to about 66%, up to about 67%, up to about 68%, up to about 69%, or up to about 70%; or about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, or about 70%; or about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 54% %, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, or about 70% by weight of the composition. Alternatively, as part of an eighth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through seventh embodiments, is present in an amount ranging from about 51% to about 59%, from about 52% to about 58%, from about 53% to about 57%, or from about 54% to about 56% by weight of the composition. Alternatively, as part of an eighth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through seventh embodiments, is present in an amount ranging from about 59% to about 66%, about 60% to about 65%, about 61% to about 64%, or about 62% to about 63% by weight of the composition;

[0096] In another eighth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first through seventh embodiments, is present in an amount of from about 40% to about 70%, from about 45% to about 65%, from about 46% to about 65%, from about 47% to about 65%, from about 48% to about 65%, from about 49% to about 65%, from about 50% to about 65%, from about 45% to about 60%, from about 46% to about 60%, from about 47% to about 60%, from about 48% to about 60%, by weight of the total weight of rifaximin, hydrogenated castor oil, and the at least one additional solubilizing excipient in the composition. is present in an amount ranging from about 49% to about 60%, about 50% to about 60%, about 51% to about 60%, about 52% to about 60%, about 53% to about 60%, about 54% to about 60%, about 55% to about 65%, about 62% to about 63%, or about 55% to about 60%; or at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, or at least about 70%; or at most about 40%, at most about 41%, at most about 42%, at most about 43%, at most about 44%, at most about 45%, at most about 46%, at most about 47%, at most about 48%, at most about 49%, at most about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, or at least about 70%. present in an amount of up to about 3%, up to about 44%, up to about 45%, up to about 46%, up to about 47%, up to about 48%, up to about 49%, up to about 50%, up to about 51%, up to about 52%, up to about 53%, up to about 54%, up to about 55%, up to about 56%, up to about 57%, up to about 58%, up to about 59%, up to about 60%, up to about 61%, up to about 62%, up to about 63%, up to about 64%, up to about 65%, up to about 66%, up to about 67%, up to about 68%, up to about 69%, or up to about 70%;Or, it is present in an amount of about 40%, about 41%, about 42%, about 43%, about 44%, about 45%, about 46%, about 47%, about 48%, about 49%, about 50%, about 51%, about 52%, about 53%, about 54%, about 55%, about 56%, about 57%, about 58%, about 59%, about 60%, about 61%, about 62%, about 63%, about 64%, about 65%, about 66%, about 67%, about 68%, about 69%, or about 70%. Alternatively, as part of an eighth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through seventh embodiments, is present in an amount ranging from about 51% to about 59%, about 52% to about 58%, about 53% to about 57%, or about 54% to about 56% by weight of the total weight of rifaximin, hydrogenated castor oil, and the at least one additional solubilizing excipient in the composition;

[0097] In some embodiments of any one of the first through eighth embodiments, the hydrogenated castor oil and the at least one additional solubilizing excipient may be provided in a ratio of about 1:3 and about 1.5:1 by weight of hydrogenated castor oil to the at least one additional solubilizing excipient, respectively. In some embodiments of any one of the first through eighth embodiments, the hydrogenated castor oil and the at least one additional solubilizing excipient may be provided in a ratio of about 1:3 to about 1.5:1 by weight of hydrogenated castor oil to the at least one additional solubilizing excipient, respectively.

[0098] In some embodiments of any one of the first through eighth embodiments, the hydrogenated castor oil and the at least one additional solubilizing excipient may be provided in a ratio of about 1:1 and about 1:2.5 by weight of hydrogenated castor oil to the at least one additional solubilizing excipient, respectively. In some embodiments of any one of the first through eighth embodiments, the hydrogenated castor oil and the at least one additional solubilizing excipient may be provided in a ratio of about 1:1 to about 1:2.5 by weight of hydrogenated castor oil to the at least one additional solubilizing excipient, respectively.

[0099] Rifaximin, hydrogenated castor oil, castor oil, glyceryl caprylate and polysorbate 80 In a ninth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first through eighth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80.

[0100] In a tenth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80; The castor oil is present in an amount ranging from about 5% to about 15%, or from about 6% to about 14%, or from about 7% to about 13%, or from about 8% to about 12%, or from about 9% to about 11%, by weight of the composition; or at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, %, or at least about 15%; or present in an amount of at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, or at most about 15%; or present in an amount of about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%; Glyceryl caprylate is present in an amount ranging from about 5% to about 15%, or from about 10% to about 15%, or from about 38% to about 42%, or from about 6% to about 14%, or from about 7% to about 13%, or from about 8% to about 12%, or from about 9% to about 11%, by weight of the composition; or at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about or at least about 13%, at least about 14%, or at least about 15%; or at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, or at most about 15%; or at most about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%; Polysorbate 80 is present in an amount ranging from about 20% to about 40%, 35% to about 45%, or about 25% to about 40%, or about 27% to about 40%, or about 25% to about 37%, or about 27% to about 37%, or about 28% to about 36%, or about 30% to about 35%, or about 32% to about 35%, by weight of the composition; or at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, or is present in an amount of at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, at most about 37%, at most about 38%, at most about 39%, or at most about 40%; or is present in an amount of about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40%.

[0101] Alternatively, as part of a tenth embodiment, at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80, wherein the castor oil is present in an amount ranging from about 8% to about 12% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the composition; and the polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the composition. In another alternative, as part of a tenth embodiment, at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80, The castor oil is present in an amount ranging from about 10% to about 20% (e.g., from about 11% to about 19%, from about 12% to about 18%, from about 13% to about 17%, or from about 14% to about 16%) by weight of the composition, or at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, or at least about 20% by weight of the composition. %, or at least about 20%, or is present in an amount of at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, at most about 15%, at most about 16%, at most about 17%, at most about 18%, at most about 19%, or at most about 20%, or is present in an amount of about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%; Glyceryl caprylate is present in an amount ranging from about 5% to about 15% (e.g., from about 6% to about 14%, from about 7% to about 13%, from about 8% to about 12%, or from about 9% to about 11%) by weight of the composition, or at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, present in an amount of about 14%, or at least about 15%, or present in an amount of at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, or at most about 15%, or present in an amount of about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%; Polysorbate 80 is present in an amount ranging from about 20% to about 40% (e.g., about 25% to about 40%, about 27% to about 40%, about 25% to about 37%, about 27% to about 37%, about 28% to about 36%, about 30% to about 35%, or about 32% to about 35%) by weight of the composition, or at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, or at least about 40%, or at most about 20%, at most about 21%, at most about 22%, at most about 23%, at most about 24%, at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, %, up to about 37%, up to about 38%, up to about 39%, or up to about 40%, or is present in an amount of about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40%.

[0102] In another alternative, as part of the tenth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80, wherein the castor oil is present in an amount ranging from about 13% to about 18% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the composition; and the polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the composition.

[0103] In another tenth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80; The castor oil is present in an amount ranging from about 5% to about 15%, or from about 6% to about 14%, or from about 7% to about 13%, or from about 8% to about 12%, or from about 9% to about 11%, by weight of the total weight of rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80; or at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, present in an amount of at least about 13%, at least about 14%, or at least about 15%; or present in an amount of at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, or at most about 15%; or present in an amount of about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%; Glyceryl caprylate is present in an amount ranging from about 5% to about 15%, or from about 6% to about 14%, or from about 7% to about 13%, or from about 8% to about 12%, or from about 9% to about 11%, by weight of the total weight of rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80; or at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least 2%, at least about 13%, at least about 14%, or at least about 15%; or at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, or at most about 15%; or at most about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%; Polysorbate 80 is present in an amount ranging from about 20% to about 40%, or from about 25% to about 40%, or from about 27% to about 40%, or from about 25% to about 37%, or from about 27% to about 37%, or from about 28% to about 36%, or from about 30% to about 35%, or from about 32% to about 35%, by weight of the total weight of rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80; or at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, at least about 45%, at least about 46%, at least about 47%, at least about 48%, at least about 49%, at least about 50%, at least about 51%, at least about 52%, at least about 53%, at least about 54%, at least about 55%, at least about 56%, at least about 57%, at least about 58%, at least about 59%, at least about 60%, at least about 61%, at least about 62%, at least about 63%, at least about 64%, at least about 65%, at least about 66%, at least about 67%, at least about 68%, at least about 69%, at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 6%, at least about 37%, at least about 38%, at least about 39%, or at least about 40%; or at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, at most about 37%, at most about 38%, at most about 39%, or at most about 40%; or at most about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40%.

[0104] Alternatively, as part of a tenth embodiment, at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80, wherein the castor oil is present in an amount ranging from about 8% to about 12% by weight of the total weight of the rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80; the glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the total weight of the rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80; and the polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the total weight of the rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80. In another alternative, as part of the tenth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80; The castor oil is present in an amount ranging from about 10% to about 20% (e.g., about 11% to about 19%, about 12% to about 18%, about 13% to about 17%, or about 14% to about 16%) by weight of the total weight of rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80, or at least about 10%, 11%, 12%, 13%, 14%, , 15%, 16%, 17%, 18%, 19%, or 20%, or present in an amount of up to about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%, or present in an amount of up to about 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20%; Glyceryl caprylate is present in an amount ranging from about 5% to about 15% (e.g., about 6% to about 14%, about 7% to about 13%, about 8% to about 12%, or about 9% to about 11%), by weight of the total weight of rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80, or at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, or at least about 13%. 2%, at least about 13%, at least about 14%, or at least about 15%, or at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, or at most about 15%, or at most about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%; Polysorbate 80 is present in an amount ranging from about 20% to about 40% (e.g., about 25% to about 40%, about 27% to about 40%, about 25% to about 37%, about 27% to about 37%, about 28% to about 36%, about 30% to about 35%, or about 32% to about 35%), by weight of the total weight of rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80, or at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, or at least about 38%. %, at least about 38%, at least about 39%, or at least about 40%, or at most about 20%, at most about 21%, at most about 22%, at most about 23%, at most about 24%, at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, at most about 37%, at most ... most about 39%, at most about 40%, at most about 41%, at most about 42%, at most about 43%, at most about 44%, at most about 45%, at most about 46%, at most about 47%, at most about 48%, at most about 49%, at most about 50%, at most about 51%, at most about 52%, at most about 53%, at most about 54%, at most about 55%, at most about 56%, at most about 57%, at most about 58%, at most about 59%, at most about 60%, at most about 61%, at most about 62%, at most about 63%, at most about 64%, at most about 65%, at most about 66%, at most about 67%, at 5%, up to about 36%, up to about 37%, up to about 38%, up to about 39%, or up to about 40%, or about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, or about 40%.

[0105] In another alternative, as part of the tenth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80, wherein the castor oil is present in an amount ranging from about 13% to about 18% by weight of the total weight of the rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80; the glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the composition; and the polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the total weight of the rifaximin, hydrogenated castor oil, glyceryl caprylate, and polysorbate 80.

[0106] In another alternative, as part of the tenth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80, wherein the castor oil is present in an amount ranging from about 5% to about 15% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 10% to about 15% by weight of the composition; and the polysorbate 80 is present in an amount ranging from about 35% to about 45% by weight of the composition.

[0107] In another alternative, as part of the tenth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through ninth embodiments, is a combination of castor oil, glyceryl caprylate, and polysorbate 80, wherein the castor oil is present in an amount ranging from about 8% to about 12% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 10% to about 15% by weight of the composition; and the polysorbate 80 is present in an amount ranging from about 38% to about 42% by weight of the composition.

[0108] Rifaximin, hydrogenated castor oil, diethyl sebacate and diethylene glycol monoethyl ether In an eleventh embodiment, such as in any one of the first through eighth embodiments, the at least one additional solubilizing excipient in the disclosed composition is a combination of diethyl sebacate and diethylene glycol monoethyl ether. Alternatively, as part of the eleventh embodiment, the diethylene glycol monoethyl ether is diethylene glycol monoethyl ether.

[0109] In a twelfth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first to eighth and eleventh embodiments, is a combination of diethyl sebacate and diethylene glycol monoethyl ether; Diethyl sebacate is present in an amount ranging from about 20% to about 35%, or from about 21% to about 34%, or from about 22% to about 33%, or from about 23% to about 32%, or from about 24% to about 31%, or from about 25% to about 30%, or from about 26% to about 29%, or from about 26% to about 38%, or from about 27% to about 28%, or at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, or at least about 32% by weight of the composition. , at least about 33%, at least about 34%, or at least about 35%, or at most about 20%, at most about 21%, at most about 22%, at most about 23%, at most about 24%, at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, or at most about 35%, or at most about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, or about 35%; Diethylene glycol monoethyl ether is present in an amount ranging from about 20% to about 35%, or from about 21% to about 34%, or from about 22% to about 33%, or from about 23% to about 32%, or from about 24% to about 31%, or from about 25% to about 30%, or from about 26% to about 29%, or from about 26% to about 38%, or from about 27% to about 28%, or at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, at least about 30%, at least about 31%, or at least about 32%, by weight of the composition. or at least about 32%, at least about 33%, at least about 34%, or at least about 35%, or at most about 20%, at most about 21%, at most about 22%, at most about 23%, at most about 24%, at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, or at most about 35%, or at most about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, or about 35%.

[0110] Alternatively, as part of the twelfth embodiment, at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through eighth and eleventh embodiments, is a combination of diethyl sebacate and diethylene glycol monoethyl ether, wherein the diethyl sebacate is present in an amount ranging from about 25% to about 30% by weight of the composition; and the diethylene glycol monoethyl ether is present in an amount ranging from about 25% to about 30% by weight of the composition. In another alternative, as part of the twelfth embodiment, at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through eighth and eleventh embodiments, is a combination of diethyl sebacate and diethylene glycol monoethyl ether, Diethyl sebacate is present in an amount ranging from about 10% to about 20%, or from about 11% to about 19%, or from about 12% to about 18%, or from about 13% to about 18%, or from about 14% to about 18%, or from about 15% to about 18%, or from about 16% to about 18%, or from about 16% to about 17%, or at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, or at least about 18% by weight of the composition. 7%, at least about 18%, at least about 19%, or at least about 20%, or present in an amount of at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, at most about 15%, at most about 16%, at most about 17%, at most about 18%, at most about 19%, or at most about 20%, or present in an amount of about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%; Diethylene glycol monoethyl ether is present in an amount ranging from about 30% to about 45%, or from about 31% to about 44%, or from about 32% to about 43%, or from about 33% to about 42%, or from about 34% to about 41%, or from about 35% to about 40%, or from about 36% to about 49%, or from about 37% to about 49%, by weight of the composition, or at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, It is present in an amount of at least about 43%, at least about 44%, or at least about 45%, or at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, at most about 37%, at most about 38%, at most about 39%, at most about 40%, at most about 41%, at most about 42%, at most about 43%, at most about 44%, or at most about 45%, or at most about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, or about 45%.

[0111] In another alternative, as part of the twelfth embodiment, e.g., in any one of the first through eighth and eleventh embodiments, the at least one additional solubilizing excipient in the disclosed composition is a combination of diethyl sebacate and diethylene glycol monoethyl ether, wherein the diethyl sebacate is present in an amount ranging from about 14% to about 18% by weight of the composition; and the diethylene glycol monoethyl ether is present in an amount ranging from about 36% to about 40% by weight of the composition.

[0112] In another twelfth embodiment, the at least one additional solubilizing excipient in the disclosed composition, such as in any one of the first through eighth and eleventh embodiments, is a combination of diethyl sebacate and diethylene glycol monoethyl ether; Diethyl sebacate is present in an amount ranging from about 20% to about 35%, or from about 21% to about 34%, or from about 22% to about 33%, or from about 23% to about 32%, or from about 24% to about 31%, or from about 25% to about 30%, or from about 26% to about 29%, or from about 26% to about 38%, or from about 27% to about 28%, or at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, or at least about 30%, by weight of the combined weight of rifaximin, hydrogenated castor oil, diethyl sebacate, and diethylene glycol monoethyl ether. present in an amount of about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, or at least about 35%, or present in an amount of at most about 20%, at most about 21%, at most about 22%, at most about 23%, at most about 24%, at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, or at most about 35%, or present in an amount of about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, or about 35%; Diethylene glycol monoethyl ether is present in an amount ranging from about 20% to about 35%, or from about 21% to about 34%, or from about 22% to about 33%, or from about 23% to about 32%, or from about 24% to about 31%, or from about 25% to about 30%, or from about 26% to about 29%, or from about 26% to about 38%, or from about 27% to about 28%, or at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, or at least about 29%, by weight of the combined weight of rifaximin, hydrogenated castor oil, diethyl sebacate, and diethylene glycol monoethyl ether. It is present in an amount of at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, or at least about 35%, or it is present in an amount of at most about 20%, at most about 21%, at most about 22%, at most about 23%, at most about 24%, at most about 25%, at most about 26%, at most about 27%, at most about 28%, at most about 29%, at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, or at most about 35%, or it is present in an amount of about 20%, about 21%, about 22%, about 23%, about 24%, about 25%, about 26%, about 27%, about 28%, about 29%, about 30%, about 31%, about 32%, about 33%, about 34%, or about 35%.

[0113] Alternatively, as part of the twelfth embodiment, at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through eighth and eleventh embodiments, is a combination of diethyl sebacate and diethylene glycol monoethyl ether, wherein the diethyl sebacate is present in an amount ranging from about 25% to about 30% by weight of the combined weight of the rifaximin, hydrogenated castor oil, diethyl sebacate, and diethylene glycol monoethyl ether; and the diethylene glycol monoethyl ether is present in an amount ranging from about 25% to about 30% by weight of the combined weight of the rifaximin, hydrogenated castor oil, diethyl sebacate, and diethylene glycol monoethyl ether. In another alternative, as part of the twelfth embodiment, at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through eighth and eleventh embodiments, is a combination of diethyl sebacate and diethylene glycol monoethyl ether, Diethyl sebacate is present in an amount ranging from about 10% to about 20%, or from about 11% to about 19%, or from about 12% to about 18%, or from about 13% to about 18%, or from about 14% to about 18%, or from about 15% to about 18%, or from about 16% to about 18%, or from about 16% to about 17%, or at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, or at least about 15%. or at most about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, or at least about 20%, or at most about 10%, at most about 11%, at most about 12%, at most about 13%, at most about 14%, at most about 15%, at most about 16%, at most about 17%, at most about 18%, at most about 19%, or at most about 20%, or at most about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%; Diethylene glycol monoethyl ether is present in an amount ranging from about 30% to about 45%, or from about 31% to about 44%, or from about 32% to about 43%, or from about 33% to about 42%, or from about 34% to about 41%, or from about 35% to about 40%, or from about 36% to about 49%, or from about 37% to about 49%, by weight of the combined weight of rifaximin, hydrogenated castor oil, diethyl sebacate, and diethylene glycol monoethyl ether, or at least about 30%, at least about 31%, at least about 32%, at least about 33%, at least about 34%, at least about 35%, at least about 36%, at least about 37%, at least about 38%, at least about 39%, at least about 40%, at least about 41%, at least about 42%, at least about 43%, at least about 44%, or at least about 45%, or at most about 30%, at most about 31%, at most about 32%, at most about 33%, at most about 34%, at most about 35%, at most about 36%, at most about 37%, at most about 38%, at most about 39%, at most about 40%, at most about 41%, at most about 42%, at most about 43%, at most about 44%, or at most about 45%, or at most about 30%, about 31%, about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42%, about 43%, about 44%, or about 45%.

[0114] In another alternative, as part of the twelfth embodiment, the at least one additional solubilizing excipient in the disclosed compositions, such as in any one of the first through eighth and eleventh embodiments, is a combination of diethyl sebacate and diethylene glycol monoethyl ether, wherein the diethyl sebacate is present in an amount ranging from about 14% to about 18% by weight of the combined weight of rifaximin, hydrogenated castor oil, diethyl sebacate, and diethylene glycol monoethyl ether; and the diethylene glycol monoethyl ether is present in an amount ranging from about 36% to about 40% by weight of the combined weight of rifaximin, hydrogenated castor oil, diethyl sebacate, and diethylene glycol monoethyl ether.

[0115] Antioxidants / Chelating Agents In a thirteenth embodiment, the compositions described herein, eg, as described in any one of the first to twelfth embodiments, further comprise an antioxidant and / or a chelating agent.

[0116] In a fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise an antioxidant and / or chelating agent selected from ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene (BHT), citric acid, sodium metabisulfite, cysteine, potassium metabisulfite, propyl gallate, sodium thiosulfate, vitamin E, and 3,4-dihydroxybenzoic acid. Without being limited to any one theory of the invention, BHT and citric acid can be used as antioxidants and / or chelating agents, for example, to minimize potential degradation of rifaximin via oxidation.

[0117] Alternatively, as part of a fourteenth embodiment, the compositions described herein, e.g., in any one of the first through thirteenth embodiments, further comprise BHT. In another alternative, as part of a fourteenth embodiment, the compositions described herein, e.g., in any one of the first through thirteenth embodiments, further comprise BHT in an amount less than about 1% (e.g., less than about 0.5%, less than about 0.1%, less than about 0.08%, less than about 0.06%, less than about 0.04%) by weight of the composition.

[0118] In another alternative, as part of the fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise BHT in an amount ranging from about 0.01% to about 0.1%, about 0.02% to about 0.08%, about 0.025% to about 0.06%, about 0.03% to about 0.06%, about 0.03% to about 0.05%, about 0.05% to about 0.15%, or about 0.03% to about 0.04% by weight of the composition.

[0119] Alternatively, as part of a fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise citric acid. In another alternative, as part of a fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise citric acid in an amount less than about 1% (e.g., less than about 0.5%, less than about 0.1%, less than about 0.08%, less than about 0.06%, less than about 0.04%) by weight of the composition.

[0120] In another alternative, as part of the fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise citric acid in an amount ranging from about 0.01% to about 0.1%, from about 0.02% to about 0.08%, from about 0.025% to about 0.06%, from about 0.03% to about 0.06%, from about 0.03% to about 0.05%, or from about 0.03% to about 0.04% by weight of the composition.

[0121] Alternatively, as part of a fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise ascorbyl palmitate. Alternatively, as part of a fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise ascorbyl palmitate in an amount ranging from about 0.05% to about 0.15%, about 0.06% to about 0.14%, about 0.07% to about 0.13%, about 0.08% to about 0.12%, or about 0.08% to about 0.12% by weight of the composition.

[0122] Alternatively, as part of a fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise BHT and citric acid. In another alternative, as part of a fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise BHT and citric acid, each in an amount less than about 1% (e.g., less than about 0.5%, less than about 0.1%, less than about 0.08%, less than about 0.06%, less than about 0.04%) by weight of the composition.

[0123] In another alternative, as part of the fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise BHT and citric acid in an amount ranging from about 0.01% to about 0.1%, about 0.02% to about 0.08%, about 0.025% to about 0.06%, about 0.03% to about 0.06%, about 0.03% to about 0.05%, or about 0.03% to about 0.04% by weight of the composition, respectively.

[0124] In another alternative, as part of the fourteenth embodiment, the compositions described herein, such as in any one of the first through thirteenth embodiments, further comprise BHT, citric acid, and ascorbyl palmitate in amounts ranging from about 0.05% to about 0.15%, about 0.06% to about 0.14%, about 0.7% to about 0.13%, about 0.8% to about 0.12%, or about 0.09% to about 0.11%, respectively, by weight of the composition.

[0125] Rifaximin In a fifteenth embodiment, the rifaximin in the disclosed compositions, such as in any one of the first to fourteenth embodiments, is present in an amount, by weight of the composition, of about 1% to about 15%, about 1% to about 5%, or about 2.5% to about 15%, or about 2.5% to about 12%, or about 5% to about 10%, or about 7% to about 15%, or about 7% to about 14%, or about 8% to about 14%, or about 8% to about 13%, or about 8% to about 15%. It is present in an amount ranging from about 12%, or from about 8% to about 11%, or from about 9% to about 12%, or from about 9% to about 12%, or from about 1% to about 12%, or from 1% to about 10%, or from about 1% to about 8%, or from 2% to about 7%, or from 3% to about 7%, or from 3% to about 6%, or from 4% to about 5%, or at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least or at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, or at least about 15%, or at most about 1%, at most about 2%, at most about 3%, at most about 4%, at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, or at most about 11% , at most about 12%, at most about 13%, at most about 14%, or at most about 15%, or at most about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%.

[0126] In another fifteenth embodiment, the rifaximin in the disclosed compositions, such as in any one of the first through fourteenth embodiments, is present in an amount of from about 1% to about 15%, or from about 2.5% to about 15%, or from about 2.5% to about 12%, or from about 5% to about 10%, or from about 7% to about 15%, or from about 7% to about 14%, or from about 8% to about 14%, by weight of rifaximin, hydrogenated castor oil, and at least one additional solubilizing excipient. %, or about 8% to about 13%, or about 8% to about 12%, or about 8% to about 11%, or about 9% to about 12%, or about 9% to about 12%, or about 1% to about 12%, or 1% to about 10%, or about 1% to about 8%, or 2% to about 7%, 3% to about 7%, or 3% to about 6%, or 4% to about 5%, or at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, present in an amount of at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, or at least about 15%, or at most about 1%, at most about 2%, at most about 3%, at most about 4%, at most about 5%, at most about 6%, at most about 7%, at most about 8%, at most about 9%, at most about 10%, at most The soluble solids are present in an amount of at most about 11%, at most about 12%, at most about 13%, at most about 14%, or at most about 15%, or are present in an amount of about 1%, about 1.5%, about 2%, about 2.5%, about 3%, about 3.5%, about 4%, about 4.5%, about 5%, about 5.5%, about 6%, about 6.5%, about 7%, about 7.5%, about 8%, about 8.5%, about 9%, about 9.5%, about 10%, about 11%, about 12%, about 13%, about 14%, or about 15%.

[0127] In a sixteenth embodiment, the total amount of rifaximin in the composition, e.g., the disclosed composition, such as in any one of the first through fifteenth embodiments, is less than about 125 mg (e.g., less than about 120 mg, less than about 110 mg, less than about 100 mg, less than about 90 mg, less than about 80 mg, less than about 70 mg, less than about 60 mg, less than about 50 mg, less than about 40 mg, less than about 30 mg, less than about 20 mg, or less than about 15 mg, less than about 10 mg, or less than about 9 mg, or less than about 8 mg, or less than about 7 mg, or less than about 6 mg, or less than about 5 mg, or less than about 4 mg, or less than about 3 mg, or less than about 2 mg, or less than about 1 mg, or less than about 0.5 mg). Alternatively, as part of a sixteenth embodiment, the total amount of rifaximin in the disclosed compositions, such as in any one of the first through fifteenth embodiments, can be from about 1 mg to about 125 mg (e.g., from about 1 mg to about 5 mg, from about 2 mg to about 5 mg, from about 3 mg to about 5 mg, from about 3 mg to about 4 mg, from about 1 mg to about 125 mg, from about 5 mg to about 125 mg, from about 10 ... about 100 mg, about 25 mg to about 125 mg, about 25 mg to about 100 mg, about 25 mg to about 75 mg, about 30 mg to about 70 mg, about 35 mg to about 65 mg, about 40 mg to about 60 mg, about 45 mg to about 55 mg, about 75 mg to about 125 mg, about 80 mg to about 120 mg, 85 mg to about 115 mg, about 90 mg to about 110 mg, or about 95 mg to about 105 mg). Alternatively, as part of a sixteenth embodiment, the total amount of rifaximin (in milligrams) in the disclosed compositions, such as in any one of the first through fifteenth embodiments, can be about 1 mg, about 1.5 mg, about 2 mg, about 2.5 mg, about 3 mg, about 3.5 mg, about 4 mg, about 4.5 mg, about 5 mg, about 5.5 mg, about 6 mg, about 6.5 mg, about 7 mg, about 7.5 mg, about 8 mg, about 8.5 mg, about 9 mg, about 9.5 mg, about 10 mg, about 10 .5mg, about 11mg, about 11.5mg, about 12mg, about 12.5mg, about 13mg, about 13.5mg, about 14mg, about 14.5mg, about 15mg, about 16mg, about 17mg, about 18mg, about 19mg, about 20mg , about 21mg, about 22mg, about 23mg, about 24mg, about 25mg, about 26mg, about 27mg, about 28mg, about 29mg, about 30mg, about 31mg, about 32mg, about 33mg, about 34mg, about 35mg, about 36mg,About 37 mg, about 38 mg, about 39 mg, about 40 mg, about 41 mg, about 42 mg, about 43 mg, about 44 mg, about 45 mg, about 46 mg, about 47 mg, about 48 mg, about 49 mg, about 50 mg, about 51 mg, about 52 mg, about 53 mg, about 54 mg, about 55 mg, about 56 mg, about 57 mg, about 58 mg, about 59 mg, about 60 mg, about 61 mg, about 62 mg, about 63 mg, about 64 mg, about 65 mg, about 66 mg, about 67 mg, about 68 mg, about 69 mg, about 70 mg, about 71 mg, about 72 mg, about 73 mg, about 74 mg, about 75 mg, about 76 mg, about 77 mg, about 78 mg, about 79 mg, about 80 mg, about 81 mg, about 82 mg, about 83 mg, about 84 mg, about 85 mg, about 86 mg, about 87 mg, about 88 mg, about 89 mg, about 90 mg, about 91 mg, about 92 mg, about 93 mg, about 94 mg, about 95 mg, about 96 mg, about 97 mg, about 98 mg, about 99 mg, about 100 mg, about 101 mg, about 102 mg, about 103 mg, about 104 mg, about 105 mg, about 106 mg, about 107 mg, about 108 mg, about 109 mg, about 110 mg, about 111 mg, about 112 mg, about 113 mg, about 114 mg, about 115 mg, about 116 mg, about 117 mg, about 118 mg, 8 mg, about 79 mg, about 80 mg, about 81 mg, about 82 mg, about 83 mg, about 84 mg, about 85 mg, about 86 mg, about 87 mg, about 88 mg, about 89 mg, about 90 mg, about 91 mg, about 92 mg, about 93 mg, about 94 mg, about 95 mg, about 96 mg, about 97 mg, about 98 mg, about 99 mg, about 100 mg, about 101 mg, about 102 mg, about 103 mg, about 104 mg, about 105 mg, about 106 mg, about 107 mg, about 108 mg, about 109 mg, about 110 mg, about 111 mg, about 112 mg, about 113 mg, about 114 mg, about 115 mg, about 116 mg, about 117 mg, about 118 mg, about 119 mg, about 120 mg, about 121 mg, about 122 mg, about 123 mg, about 124 mg, or about 125 mg; or at least about 1 mg, at least about 1.5 mg, at least about 2 mg, at least about 2.5 mg, at least about 3 mg, at least about 3.5 mg, at least about 4 mg, at least about 4.5 mg, at least about 5 mg, at least about 5.5 mg, at least about 6 mg, at least about 6.5 mg, at least about 7 mg, at least about 7.5 mg, at least about 8 mg, at least about 8.5 mg, At least about 9 mg, at least about 9.5 mg, at least about 10 mg, at least about 10.5 mg, at least about 11 mg, at least about 11.5 mg, at least about 12 mg, at least about 12.5 mg, at least about 13 mg, at least about 13.5 mg, at least about 14 mg, at least about 14.5 mg, at least about 15 mg, at least about 16 mg, at least about 17 mg, at least about 18 mg, at least about 19 mg, at least about 20 mg, at least about 21 mg, at least about 22 mg, at least about 23 mg, at least about 24 mg,at least about 25 mg, at least about 26 mg, at least about 27 mg, at least about 28 mg, at least about 29 mg, at least about 30 mg, at least about 31 mg, at least about 32 mg, at least about 33 mg, at least about 34 mg, at least about 35 mg, at least about 36 mg, at least about 37 mg, at least about 38 mg, at least about 39 mg, at least about 40 mg, at least about 41 mg, at least about 42 mg, at least about 43 mg, at least about 44 mg, at least about 45 mg, at least about 46 mg, at least about 47 mg, at least about 48 mg, at least about 49 mg, at least about 50 mg, at least about 51 mg, at least about 52 mg, at least about 53 mg, at least about 54 mg, at least about 55 mg, at least about 56 mg, at least about 57 mg, at least about 58 mg, at least about 59 mg, at least about 60 mg, at least about 61 mg, at least about 62 mg, at least about 63 mg, at least about 64 mg, at least about 65 mg, at least about 66 mg, at least about 67 mg, at least about 68 mg, at least about 69 mg, At least about 70 mg, at least about 71 mg, at least about 72 mg, at least about 73 mg, at least about 74 mg, at least about 75 mg, at least about 76 mg, at least about 77 mg, at least about 78 mg, at least about 79 mg, at least about 80 mg, at least about 81 mg, at least about 82 mg, at least about 83 mg, at least about 84 mg, at least about 85 mg, at least about 86 mg, at least about 87 mg, at least about 88 mg, at least about 89 mg, at least about 90 mg, at least about 91 mg, at least about 9 2 mg, at least about 93 mg, at least about 94 mg, at least about 95 mg, at least about 96 mg, at least about 97 mg, at least about 98 mg, at least about 99 mg, at least about 100 mg, at least about 101 mg, at least about 102 mg, at least about 103 mg, at least about 104 mg, at least about 105 mg, at least about 106 mg, at least about 107 mg, at least about 108 mg, at least about 109 mg, at least about 110 mg, at least about 111 mg, at least about 112 mg, at least about 113 mg,at least about 114 mg, at least about 115 mg, at least about 116 mg, at least about 117 mg, at least about 118 mg, at least about 119 mg, at least about 120 mg, at least about 121 mg, at least about 122 mg, at least about 123 mg, at least about 124 mg, or at least about 125 mg; or at most about 1 mg, at most about 1.5 mg, at most about 2 mg, at most about 2.5 mg, at most about 3 mg, at most about 3.5 mg, at most about 4 mg, at most about 4.5 mg, at most about 5 mg, at most about 5.5 mg, at most about 6 mg, Maximum approximately 6.5 mg, maximum approximately 7 mg, maximum approximately 7.5 mg, maximum approximately 8 mg, maximum approximately 8.5 mg, maximum approximately 9 mg, maximum approximately 9.5 mg, maximum approximately 10 mg, maximum approximately 10.5 mg, maximum approximately 11 mg, maximum approximately 11.5 mg, maximum approximately 12 mg, maximum approximately 12.5 mg, maximum approximately 13 mg, maximum approximately 13.5 mg, maximum approximately 14 mg, maximum approximately 14.5 mg, maximum approximately 15 mg, maximum approximately 16 mg, maximum approximately 17 mg, maximum approximately 18 mg, maximum approximately 19 mg, maximum approximately 20 mg, maximum approximately 21 mg, maximum approximately 22 mg, maximum approximately 23 mg, maximum approximately 24 4mg, up to about 25mg, up to about 26mg, up to about 27mg, up to about 28mg, up to about 29mg, up to about 30mg, up to about 31mg, up to about 32mg, up to about 33mg, up to about 34mg, up to about 35mg, up to about 36mg, up to about 37mg, up to about 38mg, up to about 39mg, up to about 40mg, up to about 41mg, up to about 42mg, up to about 43mg, up to about 44mg, up to about 45mg, up to about 46mg, up to about 47mg, up to about 48mg, up to about 49mg, up to about 50mg, up to about 51mg, Approximately 52 mg, maximum approximately 53 mg, maximum approximately 54 mg, maximum approximately 55 mg, maximum approximately 56 mg, maximum approximately 57 mg, maximum approximately 58 mg, maximum approximately 59 mg, maximum approximately 60 mg, maximum approximately 61 mg, maximum approximately 62 mg, maximum approximately 63 mg, maximum approximately 64 mg, maximum approximately 65 mg, maximum approximately 66 mg, maximum approximately 67 mg, maximum approximately 68 mg, maximum approximately 69 mg, maximum approximately 70 mg, maximum approximately 71 mg, maximum approximately 72 mg, maximum approximately 73 mg, maximum approximately 74 mg, maximum approximately 75 mg, maximum approximately 76 mg, maximum approximately 77 mg, maximum approximately 78 mg, maximum approximately 79 mg,Maximum approximately 80 mg, maximum approximately 81 mg, maximum approximately 82 mg, maximum approximately 83 mg, maximum approximately 84 mg, maximum approximately 85 mg, maximum approximately 86 mg, maximum approximately 87 mg, maximum approximately 88 mg, maximum approximately 89 mg, maximum approximately 90 mg, maximum approximately 91 mg, maximum approximately 92 mg, maximum approximately 93 mg, maximum approximately 94 mg, maximum approximately 95 mg, maximum approximately 96 mg, maximum approximately 97 mg, maximum approximately 98 mg, maximum approximately 99 mg, maximum approximately 100 mg, maximum approximately 101 mg, maximum approximately 102 mg, maximum approximately 103 mg, maximum about 104 mg, at most about 105 mg, at most about 106 mg, at most about 107 mg, at most about 108 mg, at most about 109 mg, at most about 110 mg, at most about 111 mg, at most about 112 mg, at most about 113 mg, at most about 114 mg, at most about 115 mg, at most about 116 mg, at most about 117 mg, at most about 118 mg, at most about 119 mg, at most about 120 mg, at most about 121 mg, at most about 122 mg, at most about 123 mg, at most about 124 mg, or at most about 125 mg.

[0128] Alternatively, as part of another embodiment, the total amount of rifaximin (in milligrams) in the disclosed compositions, such as in any one of the first through sixteenth embodiments, can be at least about 0.5 mg, at least about 1.0 mg, at least about 1.5 mg, at least about 2.0 mg, at least about 2.5 mg, at least about 3.0 mg, at least about 3.5 mg, at least about 4.0 mg, at least about 4.5 mg, at least about 5.0 mg, at least about 5.5 mg, at least about 6.0 mg, at least about 6.5 mg, at least about 7.0 mg, at least about 7.5 mg, at least about 8.0 mg, at least about 8.5 mg, at least about 9.0 mg, at least about 9.5 mg, at least about 10.0 mg, at least about 10.5 mg, or at least about 11 mg, or at most about 0.5 mg, at most about 1.0 mg, at most ... most about 1.5 mg, at most about 1.5 mg, at most about 1.5 mg, at least about 1.5 mg, at least Approximately 1.5 mg at maximum, approximately 2.0 mg at maximum, approximately 2.5 mg at maximum, approximately 3.0 mg at maximum, approximately 3.5 mg at maximum, approximately 4.0 mg at maximum, approximately 4.5 mg at maximum, approximately 5.0 mg at maximum, approximately 5.5 mg at maximum, approximately 6.0 mg at maximum, approximately 6.5 mg at maximum, approximately 7.0 mg at maximum, approximately 7.5 mg at maximum, approximately 8.0 mg at maximum, approximately 8.5 mg at maximum, approximately 9.0 mg at maximum, approximately 9.5 mg at maximum, approximately 10.0 mg at maximum about 10.5 mg, or up to about 11 mg, or about 0.5 mg, about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, about 10.0 mg, about 10.5 mg, or about 11 mg.

[0129] liquid composition In a seventeenth embodiment, the composition described herein, such as in any one of the first to sixteenth embodiments, is a liquid composition.

[0130] 3. Dosage form Regarding administration, in certain embodiments, the compositions described herein can be administered directly or can be formulated into alternative dosage forms, for example, for oral delivery. Formulations for oral delivery can be in the form of lozenges, aqueous or oily suspensions, emulsions, capsules, syrups, or elixirs. Orally administered compositions can contain one or more optional agents, such as sweeteners such as fructose, aspartame, or saccharin; flavoring agents such as peppermint, wintergreen oil, or cherry; coloring agents; and preservatives, to provide a pharmaceutically palatable formulation. The compositions can be coated to delay disintegration and absorption in the digestive tract, thereby providing a sustained effect over a long period of time.

[0131] In certain embodiments, the disclosed compositions are formulated in capsule form. In certain embodiments, the disclosed compositions are formulated in soft or hard capsule form. In certain embodiments, the disclosed compositions are formulated in soft or hard gelatin capsule form.

[0132] It should be noted that the specific dosage and treatment regimen for a particular patient will depend on a variety of factors, including age, weight, general health, sex, diet, time of administration, rate of excretion, concomitant medications, the judgment of the treating physician, and the severity of the particular disease being treated.

[0133] 4.How to use The compositions described herein can be used in methods for treating or preventing a disease. For example, the invention described herein includes a method for treating or preventing a disease or disorder in a subject in need of such treatment. Such a method can include administering to the subject a therapeutically effective amount of any one or more of the aforementioned compositions, which can be in unit dosage form.

[0134] The compositions described herein are useful in treating one or more bowel-related disorders or liver dysfunction. Such disorders include, for example, irritable bowel syndrome (IBS) (e.g., IBS-D), diarrhea, microbial-associated diarrhea, infectious diarrhea, Clostridium difficile infection and symptoms (e.g., Clostridium difficile-associated diarrhea), traveler's diarrhea, small intestinal bacterial overgrowth (SIBO), Crohn's disease, diverticular disease, pancreatitis (including chronic pancreatitis), pancreatic insufficiency, enteritis, colitis (e.g., ulcerative colitis, antibiotic-associated colitis, and microscopic colitis), hepatic encephalopathy (or other diseases resulting in elevated ammonia levels) and symptoms thereof, gastric dyspepsia, cirrhosis (e.g., alcoholic cirrhosis), polycystic liver disease, pouchitis, peritonitis, short bowel syndrome, inflammatory bowel disease, rosacea, sickle cell disease, and H. pylori infection.

[0135] In some embodiments, the compositions described herein are useful for treating and / or preventing hepatic encephalopathy.For example, the compositions described herein can be useful for treating hepatic encephalopathy recurrence; and / or for treating overt hepatic encephalopathy; and / or for preventing overt hepatic encephalopathy.

[0136] The compositions described herein are useful in liver transplant preparation.

[0137] The compositions described herein are useful for treating cardiovascular conditions (eg, atherosclerosis).

[0138] The compositions described herein are useful in the treatment of disorders affecting the central nervous system and disorders associated with cognitive impairment, such as Parkinson's disease, Alzheimer's disease, and autism.

[0139] The compositions described herein are useful in the treatment of certain cancers, such as acute myeloid leukemia.

[0140] The compositions described herein are useful in the treatment of sickle cell disease and / or symptoms associated therewith.

[0141] Thus, provided are methods for treating one or more gut-related disorders or liver dysfunction in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a disclosed compound. Also provided are uses of the disclosed compositions for the manufacture of a medicament for treating one or more gut-related disorders or liver dysfunction described herein. Additionally, provided are uses of the disclosed compositions for treating one or more gut-related disorders or liver dysfunction described herein.

[0142] In some embodiments, the methods described herein comprise administering the composition to a subject QD (quaque die, once daily), BID (bis in die, twice daily), TID (ter in die, three times daily), or QID (quater in die, four times daily) to achieve a bolus of at least about 1.0 mg, at least about 1.5 mg, at least about 2.0 mg, at least about 2.5 mg, at least about 3.0 mg, at least about 3.5 mg, at least about 4.0 mg, at least about 4.5 mg, at least about 5.0 mg, at least about 5.5 mg, at least about 6.0 mg, at least about 6.5 mg, at least about 7.0 mg, at least about 7.5 mg, at least about 8.0 mg, at least about 8.5 mg, at least about 9.0 mg, at least about 10.0 mg, at least about 11.0 mg, at least about 12.0 mg, at least about 13.0 mg, at least about 14.0 mg, at least about 15.0 mg, at least about 16.0 mg, at least about 17.0 mg, at least about 18.0 mg, at least about 19.0 mg, at least about 20.0 mg, at least about 21.0 mg, at least about 22.0 mg, at least about 23.0 mg, at least about 24.0 mg, at least about 25.0 mg, at least about 26.0 mg, at least about 27.0 mg, at least about 28.0 mg, at least about 29.0 mg, at least about 30.0 mg, at least about 31.0 mg, at least about 32.0 mg, at least about 33.0 mg, at least about 34.0 mg, at least about 35.0 mg, at least about 36.0 mg, at least about 37.0 mg, at least about 38.0 mg, at at least about 9.5 mg, at least about 10.0 mg, at least about 10.5 mg, at least about 11.0 mg, at least about 11.5 mg, at least about 12.0 mg, at least about 12.5 mg, at least about 13.0 mg, at least about 13.5 mg, at least about 14.0 mg, at least about 14.5 mg, at least about 15.0 mg, at least about 15.5 mg, at least about 16.0 mg, at least about 16.5 mg, at least about 17.0 mg, at least about 17.5 mg, All of the above are about 18.0 mg, at least about 18.5 mg, at least about 19.0 mg, at least about 19.5 mg, at least about 20.0 mg, at least about 20.5 mg, at least about 21.0 mg, at least about 21.5 mg, at least about 22.0 mg, at least about 22.5 mg, at least about 23.0 mg, at least about 23.5 mg, at least about 24.0 mg, at least about 24.5 mg, at least about 25.0 mg, at least about 25.5 mg, at least about 26.0 mg, and 26. 5 mg, at least about 27.0 mg, at least about 27.5 mg, at least about 28.0 mg, at least about 28.5 mg, at least about 29.0 mg, at least about 29.5 mg, at least about 30.0 mg, at least about 30.5 mg, at least about 31.0 mg, at least about 31.5 mg, at least about 32.0 mg, at least about 32.5 mg, at least about 33.0 mg, at least about 33.5 mg, at least about 34.0 mg, at least about 34.5 mg, at least about 35.The method can include providing the subject with a daily dose of rifaximin in an amount (in milligrams) of at least about 0 mg, at least about 35.5 mg, at least about 36.0 mg, at least about 36.5 mg, at least about 37.0 mg, at least about 37.5 mg, at least about 38.0 mg, at least about 38.5 mg, at least about 39.0 mg, at least about 39.5 mg, or at least about 40.0 mg. In some embodiments, the methods described herein comprise administering the composition QD, BID, TID, or QID to a subject to achieve a total of up to about 1.0 mg, up to about 1.5 mg, up to about 2.0 mg, up to about 2.5 mg, up to about 3.0 mg, up to about 3.5 mg, up to about 4.0 mg, up to about 4.5 mg, up to about 5.0 mg, up to about 5.5 mg, up to about 6.0 mg, up to about 6.5 mg, up to about 7.0 mg, up to about 7.5 mg, up to about 8.0mg, maximum approximately 8.5mg, maximum approximately 9.0mg, maximum approximately 9.5mg, maximum approximately 10.0mg, maximum approximately 10.5mg, maximum approximately 11.0mg, maximum approximately 11.5mg, maximum approximately 12.0mg, maximum approximately 12.5mg, maximum approximately 13.0mg, maximum approximately 13.5mg, maximum approximately 14.0mg, maximum approximately 14.5mg, maximum approximately 15.0mg, maximum approximately 15.5mg, maximum approximately 16.0mg, maximum approximately 16.5mg, maximum approximately 17.0mg, maximum Approximately 17.5 mg, maximum approximately 18.0 mg, maximum approximately 18.5 mg, maximum approximately 19.0 mg, maximum approximately 19.5 mg, maximum approximately 20.0 mg, maximum approximately 20.5 mg, maximum approximately 21.0 mg, maximum approximately 21.5 mg, maximum approximately 22.0 mg, maximum approximately 22.5 mg, maximum approximately 23.0 mg, maximum approximately 23.5 mg, maximum approximately 24.0 mg, maximum approximately 24.5 mg, maximum approximately 25.0 mg, maximum approximately 25.5 mg, maximum approximately 26.0 mg, 26.5 mg, maximum Large: approximately 27.0 mg, maximum approximately 27.5 mg, maximum approximately 28.0 mg, maximum approximately 28.5 mg, maximum approximately 29.0 mg, maximum approximately 29.5 mg, maximum approximately 30.0 mg, maximum approximately 30.5 mg, maximum approximately 31.0 mg, maximum approximately 31.5 mg, maximum approximately 32.0 mg, maximum approximately 32.5 mg, maximum approximately 33.0 mg, maximum approximately 33.5 mg, maximum approximately 34.0 mg, maximum approximately 34.5 mg, maximum approximately 35.0 mg, maximum approximately 35.5 mg, maximum approximately 36.In some embodiments, the methods described herein can include administering the composition QD, BID, TID, or QID to a subject to provide a daily dose of rifaximin in an amount (in milligrams) of about 1.0 mg, about 1.5 mg, about 2.0 mg, about 2.5 mg, about 3.0 mg, about 3.5 mg, about 4.0 mg, about 4.5 mg, about 5.0 mg, about 5.5 mg, about 6.0 mg, about 6.5 mg, about 7.0 mg, about 7.5 mg, about 8.0 mg, about 8.5 mg, about 9.0 mg, about 9.5 mg, or about 10.0 mg. 0.5mg, about 10.0mg, about 10.5mg, about 11.0mg, about 11.5mg, about 12.0mg, about 12.5mg, about 13.0mg, about 13.5mg, about 14.0mg, about 14.5mg, about 15.0mg, about 15.5mg, about 16.0mg, about 16.5mg, about 17.0mg, about 17.5mg, about 18.0mg, about 18.5mg, about 19.0mg, about 19.5mg, about 20.0mg, about 20.5mg, About 21.0 mg, about 21.5 mg, about 22.0 mg, about 22.5 mg, about 23.0 mg, about 23.5 mg, about 24.0 mg, about 24.5 mg, about 25.0 mg, about 25.5 mg, about 26.0 mg, 26.5 mg, about 27.0 mg, about 27.5 mg, about 28.0 mg, about 28.5 mg, about 29.0 mg, about 29.5 mg, about 30.0 mg, about 30.5 mg, about 31.0 mg, about 31.5 mg, about 32.0 mg The method can include providing the subject with a daily dose of rifaximin in an amount (in milligrams) of about 32.5 mg, about 33.0 mg, about 33.5 mg, about 34.0 mg, about 34.5 mg, about 35.0 mg, about 35.5 mg, about 36.0 mg, about 36.5 mg, about 37.0 mg, about 37.5 mg, about 38.0 mg, about 38.5 mg, about 39.0 mg, about 39.5 mg, or about 40.0 mg.

[0143] In some embodiments, the methods described herein can include administering the composition BID at a dose of about 3.5 mg, or 7.0 mg, or 10.5 mg to provide a subject with a daily dose of rifaximin in an amount of about 7.0 mg, or 14.0 mg, or 21.0 mg, respectively.

[0144] In some embodiments, the aforementioned doses or daily doses can optionally be provided to a subject by administering to the subject at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 unit dosage forms (e.g., capsules) of the composition per dose or per day. In some embodiments, the aforementioned doses or daily doses can optionally be provided to a subject by administering to the subject up to 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 unit dosage forms (e.g., capsules) of the composition per dose or per day. In some embodiments, the aforementioned doses or daily doses can optionally be provided to a subject by administering to the subject about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 unit dosage forms (e.g., capsules) of the composition per dose or per day.

[0145] While specific embodiments of the present invention have been described and / or illustrated above, numerous other embodiments will be apparent to those skilled in the art from this disclosure. Accordingly, the present invention is not limited to the specific embodiments described and / or illustrated, but is capable of considerable variation and modification without departing from the scope and spirit of the appended claims.

[0146] (Example) The following representative examples are intended to help illustrate the present disclosure and are not intended, nor should they be construed, to limit the scope of the invention.

[0147] 1. Preformulation testing A. Solubility The solubility of rifaximin in various solubilizing excipients was investigated by adding an excess amount of rifaximin to each solubilizing excipient to measure the saturation solubility. The amount of dissolved rifaximin was analyzed by HPLC. The results from the solubility screening are shown in Table 1 below.

[0148] [Table 1]

[0149] B. Excipient Compatibility To determine excipient compatibility, a predetermined amount of rifaximin was added to each solvent, and the resulting solutions were exposed to various temperature conditions for up to 4 weeks, after which chemical purity was analyzed by HPLC, the results of which are shown in Table 2.

[0150] [Table 2]

[0151] C. Compatibility with Gelatin Shells The physical compatibility of each excipient with the gelatin shell substrate was examined. For hard gelatin capsules, the solvent was filled into hard capsules and placed in scintillation vials. For soft gelatin capsules, each capsule was immersed in the excipient and then placed in a scintillation vial. The vials were then exposed to various temperature conditions for up to four weeks. The capsules were then evaluated for physical changes (softening or hardening of the capsule shell).

[0152] The hard gel capsules were purchased from VWR (catalog number 70102) and were 0.68 mL in volume, 6.63 mm in diameter, 19.0 mm in length, size 1. The soft gel capsules were Advil liquid gel, 200 mg strength, 80 count. The results are shown in Tables 3 and 4. Table 3 - Hard gel capsules

[0153] [Table 3]

[0154] [Table 4]

[0155] 2. Formulation testing A. Evaluation of Available Soluble Drugs The percent of drug (rifaximin) soluble in phosphate buffer (pH 6.8) or simulated intestinal fluid (SIF, pH 6.8) was determined according to the following criteria: Controls were Xifaxan® tablets (200 mg) or Xifaxan® powder (representing a 200 mg API + glyceryl distearate-enteric coated tablet). Excipients, where listed, included bile acids (cholic acid), butylated hydroxytoluene (BHT), and isooctyl acrylate / acrylamide / vinyl acetate copolymer (Kollidon® VA64).

[0156] The composition was prepared by weighing out hydrogenated castor oil and at least one additional solubilizing excipient, followed by mixing. Next, BHT, if applicable, was added to the mixture and allowed to dissolve. Rifaximin was added last.

[0157] Dissolution studies were performed to assess the percent of drug solubilized over time from rifaximin SEDDS formulations compared to Xifaxan in pH 7.4 buffer at 37°C. Samples were analyzed by HPLC. The results are shown in Table 5 below and in Figures 1 and 2. As shown in the figures, dissolution of the formulations of the present invention (5425-66A; 70 mg rifaximin and 5425-67A; 35 mg rifaximin) was significantly faster than the previously disclosed 40 mg rifaximin IR and 80 mg rifaximin SER solid dispersion compositions (see WO 2018 / 064472) and Xifaxan 550 mg.

[0158] [Table 5]

[0159] For SIF, prototype compositions (1 g total, each containing 100 mg of API) or Xifaxan® powder were mixed in SIF (100 mL) for 1 hour at 37° C. The mixtures were then centrifuged for 20 minutes and analyzed via HPLC. The results are shown in Tables 6A and 6B below.

[0160] [Table 6A]

[0161] [Table 6B]

[0162] The effect of including certain additives such as butylated hydroxytoluene (BHT), crystallization inhibitors (CI), and bile acids is shown in Table 7. As above, the compositions of the present invention in Table 7 each contained a total of 1 g, including 100 mg of rifaximin.

[0163] [Table 7]

[0164] B. Compatibility of prototype with gelatin shell The compatibility of certain compositions of the present invention with a gelatin shell substrate was examined. The capsules were size 1, VWR catalog number 70102. The vials were then subjected to various temperature conditions for up to five weeks. The capsules were then evaluated for physical changes (softening or hardening of the capsule shell). The results from this study are shown in Table 8 below. The compositions of the present invention in Table 7 contained a total of 1 gram containing 50 mg or 100 mg of rifaximin, respectively.

[0165] [Table 8]

[0166] As shown above, the compositions of the present invention significantly improve the solubility of rifaximin under conditions similar to those present in vivo. In some cases, this effect represents a greater than 150-fold increase in the percent soluble rifaximin compared to commercially available Xifaxan®.

[0167] 3. Alternative Formulations Another formulation is shown in Table 9 below.

[0168] [Table 9]

[0169] The compositions can be placed in non-enteric coated capsules such as Quali-G, size 4, 140 mg fill. Dissolution results for 5425-68A, 5425-70A, 5425-70B, and 5425-70C under various pH conditions are shown in Figures 3-8 in comparison with previously disclosed 40 mg rifaximin IR and 80 mg rifaximin SER solid dispersion compositions (see WO 2018 / 064472) and Xifaxan 550 mg.

[0170] 4. Antibacterial activity The antimicrobial properties of representative compositions were examined according to the methods described herein.

[0171] Organisms were prepared by inoculating the surface of soybean casein digest agar (TSA) plates and incubating at 30-35°C for 18-24 hours. After the incubation period, plates were washed with sterile serum-grade saline to recover the used organisms. Dilutions were made in saline and plated onto TSA plates, incubated at 30-35°C for 18-24 hours, and concentrations were determined. The inoculum level was then adjusted to 10 cfW mL and used as a stock suspension. The stock suspension was thoroughly mixed and homogenized at each inoculation interval.

[0172] The following microorganisms were used in this sterilization time test: Escherichia coli ATCC 8739, Shigella flexneri ATCC 12022, and Salmonella choleraesuis ATCC 10708. Positive controls were performed at the beginning and end of the test by pour plate culture to enumerate inoculum levels and confirm culture purity at the time of the test, and negative controls were performed to establish the media, reagents, and materials used at the beginning. Neutralizer suitability tests using modified Leagin Broth (MLB) were performed simultaneously with the sterilization time test to confirm recovery of <100 CFU of the test organisms in the subculture medium in the presence of the product.

[0173] 1.0 g of formulation (5507-65A) was weighed out. In a separate container, a mixture of 70 mL of 0.1 N hydrochloric acid (pH 1.1) and 30 mL of 0.20 M sodium phosphate was prepared and the pH adjusted to approximately 6.8. This mixture was added to the formulation and stirred at room temperature for 1 hour. The mixture was then filtered through a 0.45 micron filter to remove precipitate, and the filtrate was collected. Duplicate 10 mL containers were prepared for each treatment specimen or material concentration and equilibrated to 25 ± 2°C. 0.1 mL of inoculum was added to each container to achieve a final concentration of 10 CFU / mL in the product.

[0174] Serial dilutions from each replicate were made, ranging from 1:10 to 1:1,000,000, at intervals of 10 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, and 4 hours, by adding 1 mL of the inoculated test product to 9 mL of MLB. Next, 1 mL of each dilution was pour plated in duplicate with TSA and incubated at 30–35°C for 48 hours. After the incubation period, all plates were counted to determine the microbial count, and the results were averaged and reported as log reductions. A placebo control (5507-66A) for formulation 5507-65A was prepared in the same manner. The placebo control did not contain rifaximin and contained 44.90% polyoxyl 40 hydrogenated castor oil by weight instead of 34.90% by weight. Xifaxan 550 mg tablets were also tested and compared. The results are shown in Figures 9–11.

[0175] 5. Stability Test Stability studies were conducted to determine whether rifaximin degrades in the representative liquid compositions described herein during storage. The formulations in Table 10 were stored at 5°C and 25°C (60% RH) and examined for changes in visual appearance and rifaximin concentration by LC-MS at 0.5 and 1.0 months. The results, shown in Table 11, indicate that little degradation of rifaximin was observed in the representative liquid compositions.

[0176] [Table 10]

[0177] [Table 11]

[0178] The contents of all documents (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are expressly incorporated herein by reference in their entirety. The present disclosure includes the following embodiments. [1] A pharmaceutically acceptable composition comprising rifaximin, hydrogenated castor oil, and at least one additional solubilizing excipient. [2] The composition of embodiment 1, wherein the hydrogenated castor oil is polyoxyl 60 hydrogenated castor oil or polyoxyl 40 hydrogenated castor oil. [3] The composition of embodiment 1 or 2, wherein the hydrogenated castor oil is polyoxyl 40 hydrogenated castor oil. [4] The composition of any one of embodiments 1 to 3, wherein the hydrogenated castor oil is present in an amount ranging from about 25% to about 65% by weight of the composition. [5] The composition of any one of embodiments 1 to 4, wherein the hydrogenated castor oil is present in an amount ranging from about 25% to about 50% by weight of the composition. [6] The composition of any one of embodiments 1 to 5, wherein the hydrogenated castor oil is present in an amount ranging from about 30% to about 45% by weight of the composition. [7] The composition of any one of embodiments 1 to 6, wherein the hydrogenated castor oil is present in an amount ranging from about 35% to about 40% by weight of the composition. [8] The composition of any one of embodiments 1 to 7, wherein the at least one additional solubilizing excipient is selected from a water-soluble organic solvent, a nonionic surfactant, a water-insoluble lipid, and a long-chain triglyceride, and combinations thereof. [9] The composition of any one of embodiments 1-8, wherein the at least one additional solubilizing excipient is selected from polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, and combinations thereof.

[10] The composition of any one of embodiments 1 to 9, wherein the at least one additional solubilizing excipient allows for a saturated solubility of rifaximin of greater than about 10% by weight.

[11] The composition of any one of the preceding claims, wherein the at least one additional solubilizing excipient is selected from polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, polysorbate 20, oleic acid, caprylic / capric triglyceride, propylene glycol, sesame oil, soybean oil, and corn oil, and combinations thereof.

[12] The composition of any one of embodiments 1 to 11, wherein the at least one additional solubilizing excipient enables a saturated solubility of rifaximin of greater than about 14% by weight.

[13] The composition of any one of embodiments 1-12, wherein the at least one additional solubilizing excipient is selected from castor oil, glyceryl caprylate, polysorbate 80, diethyl sebacate, and diethylene glycol monoethyl ether, and combinations thereof.

[14] The composition of any one of embodiments 1 to 13, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 45% to about 65% by weight of the composition.

[15] The composition of any one of embodiments 1 to 14, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 50% to about 65% by weight of the composition.

[16] The composition of any one of embodiments 1 to 15, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 55% to about 65% by weight of the composition.

[17] The composition of any one of embodiments 1 to 15, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 60% to about 65% by weight of the composition.

[18] The composition of any one of embodiments 1 to 16, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 55% to about 60% by weight of the composition.

[19] The composition of any of embodiments 1-16 and 18, wherein the at least one additional solubilizing excipient is present in an amount of about 55% by weight of the composition.

[20] The composition of any one of embodiments 1 to 17, wherein the at least one additional solubilizing excipient is present in an amount of about 62% or about 63% by weight of the composition.

[21] The composition of any one of embodiments 1-20, wherein the at least one additional solubilizing excipient is a combination of castor oil, glyceryl caprylate, and polysorbate 80.

[22] the castor oil is present in an amount ranging from about 5% to about 15% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 5% to about 15% by weight of the composition; 22. The composition of embodiment 21, wherein the polysorbate 80 is present in an amount ranging from about 20% to about 40% by weight of the composition.

[23] the castor oil is present in an amount ranging from about 8% to about 12% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the composition; 23. The composition of embodiment 21 or 22, wherein the Polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the composition.

[24] the castor oil is present in an amount ranging from about 10% to about 20% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 5% to about 15% by weight of the composition; 22. The composition of embodiment 21, wherein the polysorbate 80 is present in an amount ranging from about 20% to about 40% by weight of the composition.

[25] the castor oil is present in an amount ranging from about 13% to about 18% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the composition; 25. The composition of embodiment 21 or 24, wherein the Polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the composition.

[26] the castor oil is present in an amount ranging from about 5% to about 15% by weight of the composition; the glyceryl caprylate is present in an amount ranging from about 10% to about 15% by weight of the composition; 22. The composition of embodiment 21, wherein the polysorbate 80 is present in an amount ranging from about 35% to about 45% by weight of the composition.

[27] the castor oil is present in an amount ranging from about 8% to about 12% by weight of the composition; 27. The composition of embodiment 21 or 26, wherein the Polysorbate 80 is present in an amount ranging from about 38% to about 42% by weight of the composition.

[28] The composition of any one of embodiments 1-20, wherein the at least one additional solubilizing excipient is a combination of diethyl sebacate and diethylene glycol monoethyl ether.

[29] the diethyl sebacate is present in an amount ranging from about 20% to about 35% by weight of the composition; 29. The composition of embodiment 28, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 20% to about 35% by weight of the composition.

[30] the diethyl sebacate is present in an amount ranging from about 25% to about 30% by weight of the composition; 30. The composition of embodiment 28 or 29, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 25% to about 30% by weight of the composition.

[31] the diethyl sebacate is present in an amount ranging from about 10% to about 20% by weight of the composition; 29. The composition of embodiment 28, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 30% to about 45% by weight of the composition.

[32] the diethyl sebacate is present in an amount ranging from about 14% to about 18% by weight of the composition; 32. The composition of embodiment 28 or 31, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 36% to about 40% by weight of the composition.

[33] The composition of any one of embodiments 1 to 32, wherein the composition further comprises an antioxidant and / or a chelating agent.

[34] The composition of any of embodiments 1-33, wherein the composition further comprises an antioxidant and / or chelating agent selected from the group consisting of ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene (BHT), potassium metabisulfite, sodium metabisulfite, cysteine, propyl gallate, sodium thiosulfate, vitamin E, 3,4-dihydroxybenzoic acid, and combinations thereof.

[35] The composition of any one of embodiments 1-34, wherein the composition further comprises one or more of BHT and citric acid.

[36] The composition of any of embodiments 1-35, wherein the composition further comprises one or more of BHT and citric acid, each in an amount ranging from about 0.01% to about 0.1% by weight of the composition.

[37] The composition of any of embodiments 1-34, wherein the composition further comprises one or more of BHT, citric acid, and ascorbyl palmitate.

[38] The composition of any of embodiments 1-34 and 37, wherein the composition further comprises one or more of BHT, citric acid, and ascorbyl palmitate, each in an amount ranging from about 0.05% to about 0.15% by weight of the composition.

[39] The composition of any one of embodiments 1-38, wherein the rifaximin is present in an amount ranging from about 1.0% to about 15% by weight of the composition.

[40] The composition of any of embodiments 1-39, wherein the rifaximin is present in an amount ranging from about 2.5% to about 15% by weight of the composition.

[41] The composition of any of embodiments 1-40, wherein the rifaximin is present in an amount ranging from about 2.5% to about 12% by weight of the composition.

[42] The composition of any of embodiments 1-41, wherein the rifaximin is present in an amount ranging from about 5% to about 10% by weight of the composition.

[43] The composition of any of embodiments 1-42, wherein the rifaximin is present in an amount of about 5% or about 10% by weight of the composition.

[44] The composition of any of embodiments 1-39, wherein the rifaximin is present in an amount ranging from about 1% to about 5% by weight of the composition.

[45] The composition of any of embodiments 1-41 and 44, wherein the rifaximin is present in an amount of about 2.5% by weight of the composition.

[46] The composition of any of embodiments 1-45, wherein the total amount of rifaximin in the composition is less than about 125 mg.

[47] The composition of any of embodiments 1-46, wherein the total amount of rifaximin in the composition ranges from about 1 mg to about 125 mg.

[48] ​​The composition of any one of embodiments 1 to 47, wherein the total amount of rifaximin in the composition ranges from about 1 mg to about 50 mg.

[49] The composition of any one of embodiments 1 to 48, wherein the total amount of rifaximin in the composition ranges from about 1 mg to about 25 mg or from about 1 mg to about 10 mg.

[50] The composition of any one of embodiments 1-49, wherein the total amount of rifaximin in the composition is about 1 mg or about 5 mg.

[51] The composition of embodiment 1, wherein the composition comprises, by weight of the composition, about 10% rifaximin, about 10% castor oil, about 12% glyceryl caprylate, about 33% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

[52] The composition of embodiment 1, wherein the composition comprises, by weight of the composition, about 10% rifaximin, about 35% polyoxyl 40 hydrogenated castor oil, about 27.5% diethyl sebacate, and about 27.5% diethylene glycol monoethyl ether.

[53] The composition of embodiment 1, wherein the composition comprises, by weight of the composition, about 5% rifaximin, about 15% castor oil, about 12% glyceryl caprylate, about 33% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

[54] The composition of embodiment 1, wherein the composition comprises, by weight of the composition, about 10% rifaximin, about 40% polyoxyl 40 hydrogenated castor oil, about 16.5% diethyl sebacate, and about 38.5% diethylene glycol monoethyl ether.

[55] The composition of embodiment 1, wherein the composition comprises, by weight of the composition, about 2.5% rifaximin, about 10% castor oil, about 12% glyceryl caprylate, about 40% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

[56] The composition of any of embodiments 51-55, wherein the composition further comprises less than about 0.03% BHT to about 0.06% BHT, by weight of the composition.

[57] The composition of any of embodiments 51-56, wherein the composition further comprises less than about 0.03% BHT to about 0.04% BHT, by weight of the composition.

[58] The composition of any of embodiments 51-55, wherein the composition further comprises about 0.05% BHT to about 0.15% BHT, by weight of the composition.

[59] The composition of any of embodiments 51-55 and 58, wherein the composition further comprises about 0.1% BHT by weight of the composition.

[60] The composition of any of embodiments 51-59, wherein the composition further comprises about 0.05% to about 0.15% ascorbyl palmitate, by weight of the composition.

[61] The composition of any of embodiments 51-60, wherein the composition further comprises about 0.1% ascorbyl palmitate by weight of the composition.

[62] The composition of any one of embodiments 1 to 61, wherein the composition is a liquid composition.

[63] The composition of any one of embodiments 1 to 62, wherein the composition is present in a soft or hard capsule.

[64] The composition of any one of embodiments 1 to 63, wherein the composition is present in a gelatin capsule.

[65] A method for treating one or more bowel-related disorders or liver dysfunction in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition described in any one of embodiments 1 to 64.

[0066] The method of embodiment 65, wherein the one or more bowel-related disorders or liver dysfunction are selected from the group consisting of irritable bowel syndrome (IBS), diarrhea, microbial-associated diarrhea, infectious diarrhea, Clostridium difficile infection and symptoms, traveler's diarrhea, small intestinal bacterial overgrowth (SIBO), Crohn's disease, diverticular disease, pancreatitis, pancreatic insufficiency, enteritis, ulcerative colitis, antibiotic-associated colitis, hepatic encephalopathy, gastric dyspepsia, cirrhosis, polycystic liver disease, pouchitis, peritonitis, inflammatory bowel disease, rosacea, sickle cell disease, and H. pylori infection.

[67] The method of embodiment 65 or 66, wherein the pharmaceutical composition is administered to the subject QD, BID, TID, or QID.

[68] The method of any one of embodiments 65 to 67, wherein the pharmaceutical composition is administered to the subject BID.

Claims

1. A pharmaceutically acceptable oral composition comprising rifaximin, hydrogenated castor oil, and at least one additional solubilizing excipient selected from a water-soluble organic solvent, a nonionic surfactant, a water-insoluble lipid, and a long-chain triglyceride, and combinations thereof, wherein the hydrogenated castor oil is selected from polyoxyl 20 hydrogenated castor oil, polyoxyl 25 hydrogenated castor oil, polyoxyl 35 hydrogenated castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 45 hydrogenated castor oil, polyoxyl 50 hydrogenated castor oil, polyoxyl 54 hydrogenated castor oil, polyoxyl 55 hydrogenated castor oil, polyoxyl 60 hydrogenated castor oil, polyoxyl 65 hydrogenated castor oil, polyoxyl 80 hydrogenated castor oil, polyoxyl 100 hydrogenated castor oil, polyoxyl 200 hydrogenated castor oil, and combinations thereof.

2. 2. The oral composition according to claim 1, wherein the hydrogenated castor oil is polyoxyl 60 hydrogenated castor oil or polyoxyl 40 hydrogenated castor oil.

3. 3. The oral composition according to claim 1, wherein the hydrogenated castor oil is polyoxyl 40 hydrogenated castor oil.

4. 4. The oral composition of claim 1, wherein the hydrogenated castor oil is present in an amount ranging from about 25% to about 65% by weight of the composition.

5. 5. The oral composition of claim 1, wherein the hydrogenated castor oil is present in an amount ranging from about 25% to about 50% by weight of the composition.

6. 6. The oral composition of claim 1, wherein the hydrogenated castor oil is present in an amount ranging from about 30% to about 45% by weight of the composition.

7. 7. The oral composition of claim 1, wherein the hydrogenated castor oil is present in an amount ranging from about 35% to about 40% by weight of the composition.

8. 8. The oral composition of claim 1, wherein the at least one additional solubilizing excipient is selected from polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, and combinations thereof.

9. 9. The oral composition of claim 1, wherein the at least one additional solubilizing excipient allows for a saturated solubility of rifaximin of more than about 10% by weight.

10. 10. The oral composition of any one of claims 1 to 9, wherein the at least one additional solubilizing excipient is selected from polyethylene glycol 600, glyceryl caprylate, polysorbate 80, castor oil, benzyl alcohol, polyethylene glycol 400, diethylene glycol monoethyl ether, glyceryl monooleate, triethylene glycol, diisopropyl adipate, diethyl sebacate, oleyl alcohol, polysorbate 20, oleic acid, caprylic / capric triglyceride, propylene glycol, sesame oil, soybean oil, and corn oil, and combinations thereof.

11. 11. The oral composition of any one of claims 1 to 10, wherein the at least one additional solubilizing excipient allows for a saturated solubility of rifaximin of more than about 14% by weight.

12. 12. The oral composition of claim 1, wherein the at least one additional solubilizing excipient is selected from castor oil, glyceryl caprylate, polysorbate 80, diethyl sebacate, and diethylene glycol monoethyl ether, and combinations thereof.

13. 13. The oral composition of any one of claims 1 to 12, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 45% to about 65% by weight of the composition.

14. 14. The oral composition of any one of claims 1 to 13, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 50% to about 65% by weight of the composition.

15. 15. The oral composition of any one of claims 1 to 14, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 55% to about 65% by weight of the composition.

16. 15. The oral composition of any one of claims 1 to 14, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 60% to about 65% by weight of the composition.

17. 16. The oral composition of any one of claims 1 to 15, wherein the at least one additional solubilizing excipient is present in an amount ranging from about 55% to about 60% by weight of the composition.

18. 18. The oral composition of any one of claims 1 to 15 and 17, wherein the at least one additional solubilizing excipient is present in an amount of about 55% by weight of the composition.

19. 17. The oral composition of any one of claims 1 to 16, wherein the at least one additional solubilizing excipient is present in an amount of about 62% or about 63% by weight of the composition.

20. 20. The oral composition of any one of claims 1 to 19, wherein the at least one additional solubilizing excipient is a combination of castor oil, glyceryl caprylate, and polysorbate 80.

21. the castor oil is present in an amount ranging from about 5% to about 15% by weight of the composition; said glyceryl caprylate is present in an amount ranging from about 5% to about 15% by weight of the composition; 21. The oral composition of claim 20, wherein the polysorbate 80 is present in an amount ranging from about 20% to about 40% by weight of the composition.

22. the castor oil is present in an amount ranging from about 8% to about 12% by weight of the composition; said glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the composition; 22. The oral composition of claim 20 or 21, wherein the polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the composition.

23. the castor oil is present in an amount ranging from about 10% to about 20% by weight of the composition; said glyceryl caprylate is present in an amount ranging from about 5% to about 15% by weight of the composition; 21. The oral composition of claim 20, wherein the polysorbate 80 is present in an amount ranging from about 20% to about 40% by weight of the composition.

24. the castor oil is present in an amount ranging from about 13% to about 18% by weight of the composition; said glyceryl caprylate is present in an amount ranging from about 10% to about 14% by weight of the composition; 24. The oral composition of claim 20 or 23, wherein the polysorbate 80 is present in an amount ranging from about 30% to about 35% by weight of the composition.

25. the castor oil is present in an amount ranging from about 5% to about 15% by weight of the composition; said glyceryl caprylate is present in an amount ranging from about 10% to about 15% by weight of the composition; 21. The oral composition of claim 20, wherein the polysorbate 80 is present in an amount ranging from about 35% to about 45% by weight of the composition.

26. the castor oil is present in an amount ranging from about 8% to about 12% by weight of the composition; 26. The oral composition of claim 20 or 25, wherein the polysorbate 80 is present in an amount ranging from about 38% to about 42% by weight of the composition.

27. 20. The oral composition of any one of claims 1 to 19, wherein the at least one additional solubilizing excipient is a combination of diethyl sebacate and diethylene glycol monoethyl ether.

28. the diethyl sebacate is present in an amount ranging from about 20% to about 35% by weight of the composition; 28. The oral composition of claim 27, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 20% to about 35% by weight of the composition.

29. the diethyl sebacate is present in an amount ranging from about 25% to about 30% by weight of the composition; 29. The oral composition of claim 27 or 28, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 25% to about 30% by weight of the composition.

30. the diethyl sebacate is present in an amount ranging from about 10% to about 20% by weight of the composition; 28. The oral composition of claim 27, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 30% to about 45% by weight of the composition.

31. the diethyl sebacate is present in an amount ranging from about 14% to about 18% by weight of the composition; 31. The oral composition of claim 27 or 30, wherein the diethylene glycol monoethyl ether is present in an amount ranging from about 36% to about 40% by weight of the composition.

32. The oral composition according to any one of claims 1 to 31, wherein the composition further comprises an antioxidant and / or a chelating agent.

33. 33. The oral composition of any one of claims 1 to 32, wherein the composition further comprises an antioxidant and / or a chelating agent selected from the group consisting of ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene (BHT), citric acid, potassium metabisulfite, sodium metabisulfite, cysteine, propyl gallate, sodium thiosulfate, vitamin E, 3,4-dihydroxybenzoic acid, and combinations thereof.

34. 34. The oral composition of any one of claims 1 to 33, wherein the composition further comprises one or more of butylated hydroxytoluene (BHT) and citric acid.

35. 35. The oral composition of any one of claims 1 to 34, wherein the composition further comprises one or more of butylated hydroxytoluene (BHT) and citric acid, each in an amount ranging from about 0.01% to about 0.1% by weight of the composition.

36. 34. The oral composition of any one of claims 1 to 33, wherein the composition further comprises one or more of butylated hydroxytoluene (BHT), citric acid, and ascorbyl palmitate.

37. 37. The oral composition of any one of claims 1 to 33 and 36, wherein the composition further comprises one or more of butylated hydroxytoluene (BHT), citric acid, and ascorbyl palmitate, each in an amount ranging from about 0.05% to about 0.15% by weight of the composition.

38. 38. The oral composition of any one of claims 1 to 37, wherein the rifaximin is present in an amount ranging from about 1.0% to about 15% by weight of the composition.

39. 39. The oral composition of any one of claims 1 to 38, wherein the rifaximin is present in an amount ranging from about 2.5% to about 15% by weight of the composition.

40. 40. The oral composition of any one of claims 1 to 39, wherein the rifaximin is present in an amount ranging from about 2.5% to about 12% by weight of the composition.

41. 41. The oral composition of any one of claims 1 to 40, wherein the rifaximin is present in an amount ranging from about 5% to about 10% by weight of the composition.

42. 42. The oral composition of any one of claims 1 to 41, wherein the rifaximin is present in an amount of about 5% or about 10% by weight of the composition.

43. 39. The oral composition of any one of claims 1 to 38, wherein the rifaximin is present in an amount ranging from about 1% to about 5% by weight of the composition.

44. 44. The oral composition of any one of claims 1 to 40 and 43, wherein the rifaximin is present in an amount of about 2.5% by weight of the composition.

45. 45. The oral composition of any one of claims 1 to 44, wherein the total amount of rifaximin in the composition is less than about 125 mg.

46. 46. ​​The oral composition of any one of claims 1 to 45, wherein the total amount of rifaximin in the composition ranges from about 1 mg to about 125 mg.

47. 47. The oral composition of any one of claims 1 to 46, wherein the total amount of rifaximin in the composition ranges from about 1 mg to about 50 mg.

48. 48. The oral composition of any one of claims 1 to 47, wherein the total amount of rifaximin in the composition ranges from about 1 mg to about 25 mg or from about 1 mg to about 10 mg.

49. 49. The oral composition of any one of claims 1 to 48, wherein the total amount of rifaximin in the composition is about 1 mg or about 5 mg.

50. 10. The oral composition of claim 1, wherein the composition comprises, by weight of the composition, about 10% rifaximin, about 10% castor oil, about 12% glyceryl caprylate, about 33% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

51. 10. The oral composition of claim 1, wherein the composition comprises, by weight of the composition, about 10% rifaximin, about 35% polyoxyl 40 hydrogenated castor oil, about 27.5% diethyl sebacate, and about 27.5% diethylene glycol monoethyl ether.

52. 10. The oral composition of claim 1, wherein the composition comprises, by weight of the composition, about 5% rifaximin, about 15% castor oil, about 12% glyceryl caprylate, about 33% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

53. 10. The oral composition of claim 1, wherein the composition comprises, by weight of the composition, about 10% rifaximin, about 40% polyoxyl 40 hydrogenated castor oil, about 16.5% diethyl sebacate, and about 38.5% diethylene glycol monoethyl ether.

54. 10. The oral composition of claim 1, wherein the composition comprises, by weight of the composition, about 2.5% rifaximin, about 10% castor oil, about 12% glyceryl caprylate, about 40% polysorbate 80, and about 35% polyoxyl 40 hydrogenated castor oil.

55. 55. The oral composition of any one of claims 50-54, wherein the composition further comprises less than about 0.03% butylated hydroxytoluene (BHT) to about 0.06% BHT by weight of the composition.

56. 56. The oral composition of any one of claims 50-55, wherein the composition further comprises less than about 0.03% butylated hydroxytoluene (BHT) to about 0.04% BHT by weight of the composition.

57. 55. The oral composition of any one of claims 50 to 54, wherein the composition further comprises about 0.05% butylated hydroxytoluene (BHT) to about 0.15% BHT by weight of the composition.

58. 58. The oral composition of any one of claims 50 to 54 and 57, wherein the composition further comprises about 0.1% butylated hydroxytoluene (BHT) by weight of the composition.

59. 59. The oral composition of any one of claims 50 to 58, wherein the composition further comprises from about 0.05% to about 0.15% ascorbyl palmitate by weight of the composition.

60. 60. The oral composition of any one of claims 50 to 59, wherein the composition further comprises about 0.1% ascorbyl palmitate by weight of the composition.

61. The oral composition according to any one of claims 1 to 60, wherein the composition is a liquid composition.

62. 62. The oral composition of any one of claims 1 to 61, wherein the composition is present in a soft or hard capsule.

63. 63. The oral composition of any one of claims 1 to 62, wherein the composition is present in a gelatin capsule.

64. 64. The oral composition of any one of claims 1 to 63 for treating one or more bowel-related disorders or liver dysfunction in a subject in need thereof.

65. 65. The oral composition of claim 64, wherein the one or more bowel-related disorders or liver dysfunction are selected from the group consisting of irritable bowel syndrome (IBS), diarrhea, microbial-associated diarrhea, infectious diarrhea, Clostridium difficile infection and symptoms, traveler's diarrhea, small intestinal bacterial overgrowth (SIBO), Crohn's disease, diverticular disease, pancreatitis, pancreatic insufficiency, enteritis, ulcerative colitis, antibiotic-associated colitis, hepatic encephalopathy, gastric dyspepsia, cirrhosis, polycystic liver disease, pouchitis, peritonitis, inflammatory bowel disease, rosacea, sickle cell disease, and H. pylori infection.

66. 66. The oral composition of claim 64 or 65, wherein the oral composition is for administration to the subject once daily (QD), twice daily (BID), three times daily (TID), or four times daily (QID).

67. 67. The oral composition of any one of claims 64 to 66, wherein the oral composition is for administration to the subject twice daily (BID).

Images