Tranexamic acid formulations

Abstract

The present disclosure is generally directed to solutions comprising tranexamic acid (TXA). The invention is also directed to the use of the solutions comprising tranexamic acid provided herein for the treatment of hemorrhage in a subject.

Description

Tranexamic Acid FormulationsCROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority to U.S. Provisional Application No. 63 / 574,562, filed April 4, 2024, the entire contents of which is incorporated herein by reference.FIELD

[0002] The present disclosure generally relates to formulations of tranexamic acid (TXA).BACKGROUND

[0003] Tranexamic acid (TXA) is a synthetic lysine analog that inhibits fibrinolysis, the breakdown of fibrin clots, and therefore reduces bleeding. In emergency situations involving massive hemorrhage and hemorrhagic shock, TXA is considered a first-line medication.

[0004] Delay in managing bleeding reduces survival in, for example, trauma and postpartum hemorrhage, where deaths may occur soon after bleeding onset. Indeed, postpartum hemorrhage is the leading cause of maternal death worldwide. Therefore, early reduction in bleeding is key to lowering mortality. It follows that one of the challenges in TXA therapy is to obtain rapid inhibition of fibrinolysis, through achieving a therapeutic concentration of TXA in the blood of a subject administered with TXA.

[0005] Commercially available TXA formations are limited to 100 mg / mL of TXA in water or saline. This represents a challenge, for example, for intramuscular administration, whereby the dose is limited by the volume that can be given in a single injection. To give 1 g of TXA already requires two 5 mL injections. Much larger volumes would be impractical.

[0006] As such, there is a need for TXA formulations of higher concentrations in order to reduce bleeding rapidly and durably.SUMMARY

[0007] According to one embodiment, the present disclosure provides a solution comprising at least 110 mg / mL tranexamic acid (TXA), wherein the pH of the solution is 5 or less.

[0008] According to another embodiment, the present disclosure provides a use of any of the solutions as described herein for reducing or preventing hemorrhage in a subject in need thereof.

[0009] According to another embodiment, the present disclosure provides a method for reducing or preventing hemorrhage, comprising administering any of the solutions as described herein to a subject in need thereof.

[0010] According to another embodiment, the present disclosure provides a method of preparing a TXA solution comprising adding TXA to a liquid carrier and reducing the pH of liquid carrier to 5 or less.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG. 1 A is a photograph of 166 mg / mL TXA solutions at t=0, where sample 1 = pH 4, sample 2 = pH 5, sample 3 = pH 6, sample 4 = pH 7, sample 5 = pH 8, sample 6 = pH 9, sample 7 = pH 10;

[0012] FIG. 1 B is a photograph of 200 mg / mL TXA solutions at t=0, where sample 1 = pH 4, sample 2 = pH 5, sample 3 = pH 6, sample 4 = pH 7, sample 5 = pH 8, sample 6 = pH 9, sample 7 = pH 10;

[0013] FIG. 2A is a photograph of 166 mg / mL TXA solutions at t= 1 week at 40 °C, where sample 1 = pH 4, sample 2 = pH 5, sample 3 = pH 6, sample 4 = pH 7, sample 5 = pH 8, sample 6 = pH 9, sample 7 = pH 10;

[0014] FIG. 2B is a photograph of 166 mg / mL TXA solutions at t= 1 week at 60 °C, where sample 1 = pH 4, sample 2 = pH 5, sample 3 = pH 6, sample 4 = pH 7, sample 5 = pH 8, sample 6 = pH 9, sample 7 = pH 10;

[0015] FIG. 20 is a photograph of 200 mg / mL TXA solutions at t= 1 week at 40 °C, where sample 1 = pH 4, sample 2 = pH 5, sample 3 = pH 6, sample 4 = pH 7, sample 5 = pH 8, sample 6 = pH 9, sample 7 = pH 10;

[0016] FIG. 2D is a photograph of 200 mg / mL TXA solutions at t= 1 week at 60 °C, where sample 1 = pH 4, sample 2 = pH 5, sample 3 = pH 6, sample 4 = pH 7, sample 5 = pH 8, sample 6 = pH 9, sample 7 = pH 10;

[0017] FIG. 3A is a photograph of samples from the 11thtrial after 34 days at 40°C;

[0018] FIG. 3B is a photograph of samples from the 11thtrial after 34 days at 5°C and room temperature;

[0019] FIG. 4A is a photograph from the 15thtrial after 2 weeks at 5°C; and

[0020] FIG. 4B is a photograph from the 15thtrial after 2 weeks at 40°C.DETAILED DESCRIPTION

[0021] The present disclosure relates to concentrated Tranexamic acid (TXA) solutions

[0022] In one aspect there is provided a solution of TXA, wherein the solution has a pH of 5 or less.

[0023] In some embodiments, the pH of the solution is between about 1.5 and about 5, between about 1 .7 and about 4.8, between about 1 .9 and about 4.6, between about 2.1 and about 4.4, between about 2.3 and about 4.2, between about 2.5 and about 4, between about 2.7 and about 3.8, between about 2.9 and about 3.6 or between about 3.1 and about 3.4.

[0024] In some embodiments, the pH of the solution is about 5 or less, about 4.8 or less, about 4.6 or less, about 4.4 or less, about 4 2 or less, about 4 or less, about 3.8 or less, about 3.6 or less, about 3.4 or less, about 3 2 or less, about 3 or less, about 2.8 or less, about 2.6 or less, about 2.4 or less, about 2 2 or less, about 2 or less, about 1.8 or less, about 1 .6 or less or about 1 .5 or less.

[0025] In some embodiments, the pH of the solution is about 5, about 4.8, about 4.6, about 4.4, about 4.2, about 4, about 3.8, about 3.6, about 3.4, about 3.2, about 3, about 2.8, about 2.6, about 2.4, about 2.2, about 2, about 1 .8, about 1 .6 or about 1 .5.

[0026] In some embodiments, the solution has a TXA concentration of between about 110 mg / mL and about 600 mg / mL, between about 120 mg / mL and about 580 mg / mL, between about 140 mg / mL and about 560 mg / mL, between about 160 mg / mL and about 540 mg / mL, between about 180 mg / mL and about 520 mg / mL, between about 200 mg / mL and about 500 mg / mL, between about 220 mg / mL and about 480 mg / mL, between about 240 mg / mL and about 460 mg / mL, between about 260 mg / mL and about 440 mg / mL, between about 280 mg / mL and about 420 mg / mL, between about 300 mg / mL and about 400 mg / mL, between about 320 mg / mL and about 380 mg / mL or between about 340 mg / mL and about 360 mg / mL.

[0027] In some embodiments, the solution has a TXA concentration of at least about 110 mg / mL, at least about 120 mg / mL, at least about 140 mg / mL, at least about 160 mg / mL, at least about 180 mg / mL, at least about 200 mg / mL, at least about 220 mg / mL, at least about 240 mg / mL, at least about 260 mg / mL, at least about 280 mg / mL, at least about 300 mg / mL, at least about 320 mg / mL, at least about 340 mg / mL, at least about 360 mg / mL, at least about 380 mg / mL, at least about 400 mg / mL, at least about 420 mg / mL, at least about 440 mg / mL, at least about 460 mg / mL, at least about 480 mg / mL, at least about 500 mg / mL, at least about 520 mg / mL, at least about 540 mg / mL at least about 560 mg / mL at least about 580 mg / mL or at least about 600 mg / mL.

[0028] In some embodiments, the solution has a TXA concentration of about 110 mg / mL, about 120 mg / mL, about 140 mg / mL, about 160 mg / mL, about 180 mg / mL, about 200 mg / mL, about 220 mg / mL, about 240 mg / mL, about 260 mg / mL, about 280 mg / mL, about 300 mg / mL, about 320 mg / mL, about 340 mg / mL, about 360 mg / mL, about 380 mg / mL about 400 mg / mL, at least about 420 mg / mL, about 440 mg / mL, about 460 mg / mL about 480 mg / mL, about 500 mg / mL, about 520 mg / mL, about 540 mg / mL, about 560 mg / mL about 580 mg / mL or about 600 mg / mL.

[0029] As used herein, when referring to TXA in the solution, such as in relation to the term “TXA concentration”, this may refer to all forms of TXA that are present in the solution. This includes all neutrally charged (i.e. not in salt form), zwitterionic and charged species such as salts. For example, as the skilled person will understand, at acidic pH the amino group of the TXA may become protonated, such that a proportion of the TXA may be present in the conjugate base form. For example, when hydrochloric acid is present, at least a portion of the TXA may be present as the amine hydrochloride salt in solution, but the TXA concentration refers to the concentration of both TXA and TXA hydrochloride. Depending on the pH of the solution, the proportion of TXA present in the conjugate base form may vary. Generally speaking, the proportion of TXA in the conjugate base form will increase as the pH decreases.

[0030] In some embodiments, the ratio of neutrally charged TXA :TXA hydrochloride in the solution is between about 80:20 and about 1 :99, between about 75:25 and about 5:95, between about 70:30 and about 10:90, between about 65:35 and about 15:85, between about 60:40 and about 20:80, between about 55:45 and about 25:75, between about 50:50 and about 30:70 or between about 45:55 and about 35:65.

[0031] In some embodiments, the ratio of neutrally charged TXA :TXA hydrochloride in the solution is at least about 80:20, at least about 75:25, at least about 70:30, at least about 65:35, at least about 60:40, at least about 55:45, at least about 50:50, at least about 45:35, at least about 40:60, at least about 35:65, at least about 30:60, at least about 25:75, at least about 20:80, at least about 15:85, at least about 10:90, at least about 5:95 or at least about 1 :99.

[0032] In some embodiments, the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 80:20, about 75:25, about 70:30, about 65:35, about 60:40, about 55:45, about 50:50, about 45:35, about 40:60, about 35:65, about 30:60, about 25:75, about 20:80, about 15:85, about 10:90, about 5:95 or about 1 :99.

[0033] In some embodiments, the solution comprises a liquid carrier, such as water. In some embodiments, the liquid carrier comprises water and the solution is an aqueoussolution. In some embodiments, the aqueous solution is a saline solution. In other embodiments, the liquid carrier is an organic solvent such as dimethylformamide (DMF), acetonitrile, tetrahydrofuran, dimethylsulfoxide (DMSO) or any combination thereof. In other embodiments, the liquid carrier may include an alcohol, such as a straight or branched chain C1-C10 alcohol or mixture thereof. In some embodiments, the C1-C10 alcohol is ethanol, n- propanol, isopropanol (IPA), n-butanol, propanol, or t-butanol.

[0034] In some embodiments, the solution comprises an acid. In some embodiments, the acid comprises a mineral acid, such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, boric acid, hydrofluoric acid, hydrobromic acid, perchloric acid, hydroiodic acid, formic acid, acetic acid, trifluoroacetic acid or any combination thereof. In some embodiments, the acid is an organic acid such as lactic acid, acetic acid, formic acid, citric acid, oxalic acid, uric acid, malic acid, tartaric acid, butyric acid, folic acid or any combination thereof.

[0035] In some embodiments, the acid comprises a mixture of one or more acids, for example a mixture of one or more mineral acids and one or more organic acids.

[0036] In some embodiments, the solution does not comprise an added base, that is, no basic components (for example sodium hydroxide or potassium hydroxide) have been added to the solution.

[0037] The solution may include one or more additives, such as a pH buffer, surfactant or stabilizer. In some embodiments, the pH buffer is an acetate, phosphate, citrate, tris(hydroxymethyl)aminomethane (TRIS) or glutamate buffer. In some embodiments, the stabilizer is cyclodextrin. In some embodiments, the surfactant is a polysorbate, docecylsulfate, saponin, sorbitan monooleate, or any combination thereof.

[0038] In some embodiments, the solution may comprise, in addition to TXA, one or more additional drugs or medicaments.

[0039] In some embodiments, the solution may be substantially clear, colourless and free of any precipitates.

[0040] In some embodiments, the solution is a sterile solution.

[0041] In some embodiments, the solution may be stable for a prolonged period of time. The stability of the solution may refer to the solution remaining substantially clear, colourless and free of any precipitates over time. The stability of the solution may also refer to a high % of the structure of the TXA remaining structurally unaltered, for example without undergoing any degradation reactions, such as hydrolysis. In some embodiments, at least 90% w / w of TXA that is originally present in the solution may remain unaltered, at least 95% w / w or at least 98% w / w based on the amount of TXA that is originally present in the solution. In some embodiments, the stability may be assessed by a suitable assay, such as high performance liquid chromatography (HPLC), which may be used to determine the concentration of TXA in the solution.

[0042] In some embodiments, a stable solution may refer to a solution where at least about 95% w / w of TXA that is originally present in the solution may remain unaltered, based on the amount of TXA that is originally present in the solution.

[0043] In some embodiments, a stable solution may refer to a solution containing less than 0.5% of impurities. In some embodiments the impurities are products derived from degradation of TXA.

[0044] In some embodiments, the solution may remain stable at depressed or elevated temperatures. For example, the solution may remain stable after undergoing one or more freeze-thaw cycles, where the temperature of the sample is lowered to a temperature of about -20 °C or lower, before warming back to room temperature (or close to room temperature). Once the temperature of the same is at or close to room temperature, the solution may be clear, colourless and free of any precipitates. The sample may also be stable after being exposed to elevated temperatures (e.g. up to 40 °C) for a period of time.

[0045] The stability of the solutions described herein at room temperature and / or at depressed / elevated temperatures are such that the solutions may not require any special handling conditions (i.e., refrigeration) and may be stored and used in a wide range of environments / locations.

[0046] In some embodiments, the solution may remain stable at room temperature for between about 3 months and about 36 months, between about 6 months and about 33 months, between about 9 months and about 30 months, between about 12 months and about 27 months, between about 15 months and about 24 months or between about 18 months and about 21 months.

[0047] In some embodiments, the solution may remain stable at room temperature for at least about 3 months, at least about 6 months, at least about 9 months, at least about 12 months, at least about 15 months, at least about 18 months, at least about 21 months, at least about 24 months, at least about 27 months, at least about 30 months, at least about 33 months or at least about 36 months.

[0048] In some embodiments, the solution may remain stable at room temperature for about 3 months, about 6 months, about 9 months, about 12 months, about 15 months, about 18 months, about 21 months, about 24 months, about 27 months, about 30 months, about 33 months or about 36 months.

[0049] In some embodiments, the solution may remain stable at 40 °C for between about 1 week and about 6 months, between about 2 weeks and about 5 months, between about 3 weeks and about 4 months or between about 1 month and about 3 months.

[0050] In some embodiments, the solution may remain stable at 40 °C for at least about 1 week, at least about 2 weeks, at least about 3 weeks, at least about 4 weeks, at least about 5 weeks, at least about 6 weeks, at least about 7 weeks, at least about 8 weeks, at least about 9 weeks, at least about 10 weeks, at least about 11 weeks, at least about 12 weeks, at least about 4 months, at least about 5 months or at least about 6 months.

[0051] In some embodiments, the solution may remain stable at 40 °C for about 1 week, about 2 weeks, about 3 weeks, about 4 weeks, about 5 weeks, about 6 weeks, about 7 weeks, about 8 weeks, about 9 weeks, about 10 weeks, about 11 weeks, about 12 weeks, about 4 months, about 5 months or about 6 months.

[0052] In another aspect there is provided a method of producing the solution as described above comprising adding TXA to a liquid carrier, followed by reducing the pH to 5 or less.

[0053] In some embodiments, the liquid carrier comprises water and the solution is an aqueous solution. In some embodiments, the aqueous solution comprises a saline solution.

[0054] In some embodiments, the pH of the liquid carrier may be reduced to pH 5 or less prior to addition of TXA.

[0055] In some embodiments, the pH is reduced by addition of an acid to the liquid carrier. The acid may be any of the acids described above.

[0056] In some embodiments, the TXA is added to a liquid carrier that has a pH of 5 or less (for example a hydrochloric acid solution). In some embodiments, the pH of the liquid carrier may be reduced (or further reduced) after addition of the TXA, such by addition of any of the acids described herein. In some embodiments, the pH of the liquid carrier may be increased after addition of the TXA, such as by addition of any of the bases described herein. In some embodiments, the liquid carrier having a pH of 5 or less is a hydrochloric acid solution. In some embodiments, the hydrochloric acid solution has a pH of about 5 or less, about 4 or less, about 3 or less, about 2 or less or about 1 or less. In some embodiments, the hydrochloric acid solution is a between a 1 M (molar) and a 5 M hydrochloric acid solution, for example a 5 M hydrochloric acid solution, a 4 M hydrochloric acid solution, a 3 M hydrochloric acid solution, a 2 M hydrochloric acid solution or a 1 M hydrochloric solution.

[0057] In some embodiments, the TXA solution may be incubated, prior to addition of TXA to the carrier, after TXA is added to the liquid carrier, or after the pH is reduced to at least 5.

[0058] In some embodiments, incubation is performed at a temperature of between about 15 °C and about 60 °C. In some embodiments the incubation is performed for about 15 to about 120 minutes or longer.

[0059] In some embodiments, the solution may be agitated prior to or during incubation to assist with dissolution of the TXA added to the liquid carrier.

[0060] In some embodiments, the method further comprises the addition of a base, such as for example, potassium hydroxide, magnesium hydroxide, calcium hydroxide, ammonia, ammonium hydroxide or sodium hydroxide to adjust the pH of the solution to within a desired range / value, such as the pH ranges / values described above. In some embodiments, the base is added in solid form. In other embodiments, the base is added as a liquid (e.g., aqueous) solution.

[0061] According to another aspect, there is provided the use of the solution of any one of the embodiments described herein for reducing or preventing hemorrhage in a subject in need thereof.

[0062] In another aspect, there is provided a method for reducing or preventing hemorrhage, comprising administering the solution of any one of the embodiments of the described herein to a subject in need thereof. In some embodiments, the subject is a human.

[0063] In some embodiments, the solution is administered by an autoinjector.

[0064] In some embodiments, the solution is administered by a syringe. In some embodiments, the syringe is a pre-filled syringe

[0065] In some embodiments, the solution is administered intramuscularly, such as to an intramuscular site or an IM site. In some embodiments, the solution is delivered intramuscularly by an autoinjector. The term “intramuscular site” or “IM site” refers to a position where an injection of a fluid can be administered into any muscle of a subject, such as the deltoid, vastus lateralis, rectus femoris or the ventrogluteal and dorsogluteal areas.

[0066] In other embodiments, the solution is administered intravenously.

[0067] In other embodiments, the solution is administered intraosseously, such as to an intraosseous (IO) space. The term “intraosseous space” or “IO space” refers to thespongy, cancellous bone of the epiphysis and the medullary cavity of the diaphysis, which are connected.

[0068] In some embodiments, the solution is administered topically, for example directly onto a wound and optionally a periwound area around the wound. In some embodiments, the solution is applied to a substrate (for example a gauze or wound dressing) prior to topical administration. In some embodiments, the solution is applied to a packing product, such as a Rhino Rocket™ for treatment of a nosebleed.

[0069] In some embodiments, the hemorrhage is posttraumatic hemorrhage, postpartum hemorrhage, perioperative or postoperative hemorrhage. In some embodiments, the hemorrhage is posttraumatic hemorrhage, e.g., hemorrhage caused by a traumatic injury and / or a traumatic brain injury. In some embodiments, the hemorrhage is postpartum hemorrhage. In some embodiments, the hemorrhage is postoperative hemorrhage. In some embodiments, the hemorrhage is external. In some embodiments, the hemorrhage is internal. In some embodiments, the hemorrhage is associated with hemorrhagic shock and / or coagulopathy.

[0070] In some embodiments, the solution is administered within 48 hours, within 24 hours, within 12 hours, within 6 hours, within 5 hours, within 4 hours, within 3 hours, within 2 hours, within 1 hour, within 45 min, within 30 min, or within 15 min of the onset of the hemorrhage.

[0071] In some embodiments, the solution is administered for prophylactic use (i.e., for prevention) before the onset of the hemorrhage. In some embodiments, the solution is administered within 48 hours, within 24 hours, within 12 hours, within 6 hours, within 5 hours, within 4 hours, within 3 hours, within 2 hours, within 1 hour, within 45 min, within 30 min, or within 15 min before the onset of the hemorrhage.

[0072] In some embodiments, the solution administered to the subject (for example before or after the onset of the hemorrhage) comprises between about 0.1 g and about 2 g of TXA, between about 0.2 g and about 1 .9 g of TXA, between about 0.3 g and about 1.8 g of TXA, between about 0.4 g and about 1 .7 g of TXA, between about 0.5 g and about 1 .6 gof TXA, between about 0.6 g and about 1 .5 g of TXA, between about 0.7 g and about 1 .4 g of TXA, between about 0.8 g and about 1 .3 g of TXA, between about 0.9 g and about 1 .2 g of TXA or between about 1 g and about 1.1 g of TXA.

[0073] In some embodiments, the solution administered to the subject (for example before or after the onset of the hemorrhage) comprises at least about 0.1 g of TXA, at least about 0.2 g of TXA, at least about 0.3 g of TXA, at least about 0.4 g of TXA, at least about 0.5 g of TXA, at least about 0.6 g of TXA, at least about 0.7 g of TXA, at least about 0.8 g of TXA, at least about 0.9 g of TXA, at least about 1 g of TXA, at least about 1.1 g of TXA, at least about 1 .2 g of TXA, at least about 1 .3 g of TXA, at least about 1 .4 g of TXA, at least about 1 .5 g of TXA, at least about 1 .6 g of TXA, at least about 1 .7 g of TXA, at least about 1 .8 g of TXA at least about 1 .9 g of TXA or at least about 2.0 g of TXA,.

[0074] In some embodiments, the solution administered to the subject (for example before or after the onset of the hemorrhage) comprises about 0.1 g of TXA, about 0.2 g of TXA, about 0.3 g of TXA, about 0.4 g of TXA, about 0.5 g of TXA, about 0.6 g of TXA, about 0.7 g of TXA, about 0.8 g of TXA, about 0.9 g of TXA, about 1 g of TXA, about 1.1 g of TXA, about 1 .2 g of TXA, about 1 .3 g of TXA, about 1 .3 g of TXA, about 1 .4 g of TXA, about 1 .5 g of TXA, about 1 .6 g of TXA, about 1 .7 g of TXA, about 1 .8 g of TXA, about 1 .9 g of TXA or about 2.0 g of TXA.

[0075] In some embodiments, a first dose is administered to the subject, followed by the administration of a second dose of the solution to the subject, where the second dose is administered to the subject within a first time period. In some embodiments, the first time period is the time between the end of the administration of the first dose and the beginning of the administration of the second dose. In some embodiments, the second dose is administered by infusion to the subject over a second time period.

[0076] In some embodiments, the first time period is between about 10 minutes and about 24 hours, between about 15 minutes and about 23 hours, between about 30 minutes and about 22 hours, between about 1 hours and about 21 hours, between about 2 hours and about 20 hours, between about 3 hours and about 19 hours, between about 4 hoursand about 18 hours, between about 5 hours and about 17 hours, between about 6 hours and about 16 hours, between about 7 hours and about 15 hours, between about 8 hours and about 14 hours, between about 9 hours and about 13 hours or between about 10 hours and about 11 hours.

[0077] In some embodiments, the first time period is at least about 10 minutes, at least about 15 minutes, at least about 30 minutes, at least about 1 hour, at least about 2 hours, at least about 3 hours, at least about 4 hours, at least about 5 hours, at least about 6 hours, at least about 7 hours, at least about 8 hours, at least about 9 hours, at least about10 hours, at least about 11 hours, at least about 12 hours, at least about 13 hours, at least about 14 hours, at least about 15 hours, at least about 16 hours, at least about 17 hours, at least about 18 hours, at least about 19 hours, at least about 20 hours, at least about 21 hours, at least about 22 hours, at least about 23 hours or at least about 24 hours.

[0078] In some embodiments, the first time period is about 10 minutes, about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about11 hours, about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, about 22 hours, about 23 hours or about 24 hours.

[0079] In some embodiments, the second time period is between about 10 minutes and about 12 hours, between about 30 minutes and about 11 hours, between about 1 hour and about 10 hours, between about 2 hours and about 9 hours, between about 3 hours and about 8 hours, between about 4 hours and about 7 hours, or between about 5 hours and about 6 hours.

[0080] In some embodiments, the second time period is at least about 10 minutes, at least about 30 minutes, at least about 1 hour, at least about 2 hours, at least about 3 hours, at least about 4 hours, at least about 5 hours, at least about 6 hours, at least about 7 hours, at least about 8 hours, at least about 9 hours, at least about 10 hours, at least about 11 hours or at least about 12 hours.

[0081] In some embodiments, the second time period is about 10 minutes, about 30 minutes about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours or about 12 hours.

[0082] In some embodiments, the first dose comprises the same volume, concentration of TXA and / or amount of TXA as the second dose. In other embodiments, the first dose comprises a greater or smaller volume, concentration of TXA and / or amount of TXA as the second dose.

[0083] In some embodiments, the first and second dose are administered in the same way, for example both the first and second doses are administered intramuscularly, intraosseously or intravenously. In some embodiments, the first and second doses are administered in different ways. For example, in some embodiments, the first dose is administered intramuscularly, for example using an autoinjector and the second dose is administered intravenously. In some embodiments, the first dose is administered intramuscularly, for example using an autoinjector and the second dose is administered intraosseously. In some embodiments, the second dose is administered as an IV push / bolus.Examples

[0084] In the following examples solutions comprising TXA are prepared and analyzed according to the following methods.1 . Reagents and Instrumentation

[0085] The HPLC chromatograms observed were obtained using a HPLC system equipped with a VWD detector. The Agilent technologies 1100 HPLC with OpenLAB software was used for chromatographic integration. The instrument components used during the formulation development are presented in Table 1. Table 2 presents the raw materials used for this study.Table 1. HPLC System UsedTable 2. Raw Materials Used2. Method for Impurities Analysis

[0086] Chromatographic parameters are presented in Table 3.Table 3. Chromatographic Parameters used for Impurities Analysis3. Testing of 166 mq / mL and 200 mq / mL TXA SolutionsFormulations at t = 0

[0087] Tranexamic Acid was formulated in WFI (water for injection) at concentrations of 166 mg / mL and 200 mg / mL, then adjusted at pH 4.0, 5.0, 6.0, 7.0, 8.0, 9.0 and 10.0 with sodium hydroxide and hydrochloric acid. The liquid Formulations were filtered (0.22 pm, PVDF, Polyvinylidene difluoride) then incubated at 40°C / 75%RH (relative humidity) and 60°C and tested for appearance and assay / impurities after 1 , 2, 3 and 4 weeks. Tables 4A and 4B present the appearance and assay / impurity results observed at t=0 for each formulation. Assay values lower than 90.0% are presented in bold text. Tables 5A and 5B present the impurity profiles for each formulation. FIGS 1A and 1 B are photographs of the respective 166 mg / mL and 200 mg / mL formulations at each pH.Table 4A. Assay and Total Impurities in 166 mg / mL FormulationsTable 4B. Assay and Total Impurities in 200 mg / mL FormulationsTable 5A Impurity Profiles at t = 0 in 166 mg / mL FormulationsFormulations at t = 1 Week

[0088] All formulations were incubated at 40°C / 75%RH and 60°C and tested for appearance and assay / impurities after 1 week. All formulations were filtered (0.22 pm, PVDF) and analyzed for assay and impurities. Tables 6A-B, 7A-B, 8A-B, 9A-B present the appearance, assay / im purity results and impurity profiles observed at t = 1 week for each formulation stored at both conditions. Assay values lower than 90.0%, and any unspecified impurity > 0.1 % or total impurities > 0.5% are presented in bold text. Figures 2A to 2D are the photographs of the formulations stored at both conditions.Table 6A. Assay and Total Impurities at 1 week at 40 °C in 166 mg / mL FormulationsTable 6B Impurity Profiles at t = 1 week at 40 °C in 166 mg / mL FormulationsTable 7A. Assay and Total Impurities at 1 week at 60 °C in 166 mg / mL FormulationsTable 7B. Impurity Profiles at t = 1 week°C in 166 mg / mL FormulationsTable 8A. Assay and Total Impurities at 1 week at 40 °C in 200 mg / mL FormulationsTable 8B Impurity Profiles at t = 1 week at 40 °C in 200 mg / mL FormulationsTable 9A. Assay and Total Impurities at 1 week at 60 °C in 200 mg / mL FormulationsTable 9B Impurity Profiles at t = 1 week at 60 °C in 200 mg / mL FormulationsFormulations at t = 2 Weeks

[0089] The formulations were filtered and returned to incubation at 40°C / 75%RH and 60°C. Formulations at pH 6.0, 7.0, 8.0, and 9.0 were not analyzed for assay and impurities because 1 week stability stations showed low assay values (less than 90.0%). Tables 10A- B, 11A-B, 12A-B, 13A-B present the appearance, assay / im purity results and impurity profiles observed at t = 2 weeks for each formulation stored at both conditions. Assay values lower than 90.0%, and any unspecified impurity > 0.1 % or total impurities > 0.5% are presented in bold text.Table 10A. Assay and Total Impurities at 2 weeks at 40 °C in 166 mg / mL FormulationsTable 11A. Assay and Total Impurities at 2 weeks at 60 °C in 166 mg / mL Formulations2.260.038Table 12A. Assay and Total Impurities at 2 weeks at 40 °C in 200 mg / mL FormulationsTable 12B. Impurity Profiles at t = 2 weeks at 40 °C in 200 mg / mL FormulationsTable 13A. Assay and Total Impurities at 2 weeks at 60 °C in 200 mg / mL FormulationsTable 13B. Impurity Profiles at t = 2 weeks at 60 °C in 200 mg / mL FormulationsFormulations at t = 3 Weeks

[0090] The formulations of pH 4.0, 5.0, 10.0 were filtered and, along with other formulations at pH 6.0, 7.0, 8.0, and 9.0, were returned to incubation at 40°C / 75%RH and 60°C. Tables 14A-B, 15A-B, 16A-B, 17A-B present the appearance, assay / im purity results and impurity profiles observed at t = 3 weeks for each formulation stored at both conditions. Formulations at pH 6.0, 7.0, 8.0, and 9.0 were not analyzed for assay and impurities because 1 week stability stations showed low assay values (less than 90.0%). Assay values lower than 90.0%, and any unspecified impurity > 0.1 % or total impurities > 0.5% are presented in bold text.Table 14A. Assay and Total Impurities at 3 weeks at 40 °C in 166 mg / mL FormulationsTable 14B. Impurity Profiles at t = 3 weeks at 40 °C in 166 mg / mL FormulationsTable 15A. Assay and Total Impurities at 3 weeks at 60 °C in 166 mg / mL FormulationsTable 16A. Assay and Total Impurities at 3 weeks at 40 °C in 200 mg / mL FormulationsTable 16B. Impurity Profiles at t = 3 weeks at 40 °C in 200 mg / mL FormulationsTable 17A. Assay and Total Impurities at 3 weeks at 60 °C in 200 mg / mL FormulationsTable 17B. Impurity Profiles at t = 3 weeks at 60 °C in 200 mg / mL FormulationsFormulations at t = 4 Weeks

[0091] The formulations of pH 4.0, 5.0, 10.0 were filtered and, along with other formulations at pH 6.0, 7.0, 8.0, and 9.0, were returned to incubation at 40°C / 75%RH and 60°C. Formulations at pH 6.0, 7.0, 8.0, and 9.0 were not analyzed for assay and impurities because 1 week stability stations showed low assay values (less than 90.0%). Formulations at pH 10.0 incubated at 60°C were not analyzed because large amount of impurities were observed in 3 weeks stability station. Tables 18A-B, 19A-B, 20A-B, 21A-B present the appearance, assay / im purity results and impurity profiles observed at t = 4 weeks for each formulation stored at both conditions. Assay values lower than 90.0%, and any unspecified impurity > 0.1% or total impurities > 0.5% are presented in bold text.Table 18A. Assay and Total Impurities at 4 weeks at 40 °C in 166 mg / mL FormulationsTable 19A. Assay and Total Impurities at 4 weeks at 60 °C in 166 mg / mL FormulationsTable 19B. Impurity Profiles at t = 4 weeks at 60 °C in 166 mg / mL FormulationsTable 20A. Assay and Total Impurities at 4 weeks at 40 °C in 200 mg / mL FormulationsTable 21A. Assay and Total Impurities at 4 weeks at 60 °C in 200 mg / mL FormulationsTable 21 B. Impurity Profiles at t = 4 weeks at 60 °C in 200 mg / mL FormulationsSummary for Formulations at pH 4.0 and pH 5.0

[0092] The formulations at pH 6.0, 7.0, 8.0, 9.0 and 10.0 either formed cloudy white suspension or crystalline particles during storage. The formulations at pH 4.0 and 5.0 stored at both conditions showed assay values higher than 90.0%, with individual unspecified impurities < 0.1 % and total impurities < 0.5%. Thus, the assay and impurity profiles for formulations at pH 4.0 and pH 5.0 incubated at 40°C / 75%RH and 60°C are summarized below. Tables 22A-C, 23A-C present the assay / im purity results and impurity profiles (Impurities > 0.03% w / w) observed at both conditions.Table 22A. Assay and Total Impurities in 166 mg / mL FormulationsTable 22B. Impurity Profiles at 40 °C in 166 mg / mL FormulationsTable 22C. mpurity Profiles at 60 °C in 166 mg / mL FormulationsTable 23B Impurity Profiles at 40 °C in 200 mg / mL FormulationsTable 23C Impurity Profiles at 60 °C in 200 mg / mL FormulationsSummary

[0093] In order to establish a sterile liquid solution TXA was formulated at 166 mg / mL and 200 mg / mL in water for injection adjusted at pH 4.0, 5.0, 6.0, 7.0, 8.0, 9.0 and 10.0 with sodium hydroxide and hydrochloric acid. The liquid formulations were incubated at 40°C / 75%RH and 60°C and tested for appearance and assay / impurities after 1 , 2, 3 and 4 weeks.

[0094] The formulations at pH 6.0, 7.0, 8.0, 9.0 and 10.0 either formed cloudy white suspension or crystallized during the storage. The formulations at pH 4.0 and pH 5.0 stored at each condition showed the assay values were higher than 90.0%, any unspecified impurity was lower than 0.1 % and total impurities were lower than 0.5%.3. TXA Solutions in 4M and 6M HCIProcedure

[0095] A total of twelve (12) trials were made during the formulation procedure.

[0096] The calibration of the pH probe with pH buffers is performed at the beginning of each day of use. A 3-buffer calibration of the pH probe was performed, using NIST traceable buffers of pH 4, 7 and 10. The accuracy of the pH meter is checked prior to each use, using a one-buffer or two-buffer accuracy check.Attempt 1

[0097] In the first trial, 27.9 g of tranexamic acid was dissolved in 42.5 mL of HCI 4M and stirred for about 5 min. A clear solution was achieved within 3min. About 6.7 mL of NaOH 10M was added to it and the solution remained clear. A further addition of 0.8 mL of HCI 4M was done, and at this point, a solid precipitation was observed.Attempt 2

[0098] In the second trial, 13.9 g of tranexamic acid was dissolved in 21 .5 mL of HCI 4M while stirring, and this resulted into a clear solution within 90s. Upon addition of about 3 mL of NaOH 10M, the solution remained clear. The pH of the solution was measured using a calibrated pH meter, and a value of 4.33 was observed and recorded. The solution was left for 24 h on the bench, after which, a fine layer of crystals was observed at the bottom of the beaker.Attempt 3

[0099] About 15.0 g of Tranexamic acid was dissolved in 21.5 mL of HCI 4M while stirring. A clear solution was observed in less than 3 min. Upon addition of 3.35 mL of NaOH 10M, the solution initially remained clear for about 40s, but afterwards, turned cloudy. A pH value of 4.36 was observed.Attempt 4

[0100] About 15.0 g of tranexamic acid was dissolved in 22.4 mL of HCI 4M while stirring, resulting in a clear solution within 3 min. About 2.4 mL of NaOH 10M was added dropwise, over 2 min, while the solution still remained clear. The pH of the solution was measured and a value of 4.20 was observed and recorded. This solution was left overnight, and was observed to still remain clear. A hundred and twenty (120) hours after formulation, the solution was still perfectly clear and free from visible particles. The pH after 120h was 4.15, with a total final volume of 34.4 mL. The final concentration attained was 436 mg / mL.Attempt 5

[0101] About 15.0 g of Tranexamic acid was dissolved in 19.5 mL of HCI 4M while stirring. A clear solution was observed after 6 min. Stirring was continued for an additional 5 min, and then 1 .5 mL of NaOH 10M was added dropwise, over 1 min. The solution remained clear even after stirring for an additional 5 min. The pH of the solution was measured and a value of 4.40 was observed. Seventy-two (72) hours after formulation, the solution remained perfectly clear and free from visible particles. The pH value afterwards was 4.24, with a total volume of 31 .5 mL. The final concentration attained was 476 mg / mL.Attempt 6

[0102] About 15.0 g of Tranexamic acid was dissolved in 20.5 mL of HCI 4M while stirring, and a clear solution was observed after 4 min. Stirring was continued for an additional 5 min, and then 0.5 mL of NaOH 10 M was added dropwise over 30s. The solution remained clear even after stirring for an additional 5 min. The pH of the solution was measured and a value of 3.92 was observed. Seventy-two (72) hours after formulation, the solution remained clear and free from visible particles, with a pH of 3.71 and a total final volume of 31.5 mL. The final concentration attained was 476 mg / mL.Attempts 7 and 8

[0103] In the 7thand 8thtrial, about 15 g of tranexamic acid was dissolved in 14.5 mL and 14.7 mL of HCI 4M, respectively, while stirring. Clear solutions were not achieved even after elongated periods of stirring. Therefore, 2 drops of concentrated HCI were added and clearsolutions were observed. Upon the addition of 0.5 mL and 0.3 mL of NaOH 10M to solutions 7 and 8 respectively, the solutions remained clear. The pH measured for the 7thand 8thsolutions were 4.01 and 3.98 respectively. However, after 15 min, the solution of the 7thattempt started to crystalize. The solution in the 8thattempt however, remained clear.Attempt 9

[0104] In order to achieve a high final concentration in the 9thtrial, HCI 6M was used. About 15.0 g of Tranexamic acid was dissolved in 14.5 mL HCI 6M while stirring, and the experiment proceeded as with the other attempts. However, the sample remained insoluble.Attempt 10

[0105] During the tenth trial, 15g of tranexamic acid was initially dissolved with 16 mL of HCI 4M, which was gradually increased by 1 mL, to make 17 mL in total. A clear solution was observed after 30 minutes of stirring. The pH of the solution was 3.85, with a final volume of 30 mL and a concentration of about 500 mg / mL.Attempt 11

[0106] The 11thtrial was divided into 3 sub-trials, labelled as 11 A, 11 B and 11 C. The same sample weight of 15.00g of TXA was weighed for the three sub-trials. The volume of HCL 4M used was varied as follows:-11A: initially 16 mL, then additional 1 mL of HCL 4M, totalling 17 mL.-11 B: 17 mL-11 C: initially 15 mL, then additional 1 mL of HCL 4M, totalling 16 mL.

[0107] With the above variation and while stirring, solution 11 B was observed to have completely dissolved in about 7 min. Solution 11A was less cloudy than 11 C, however, indicating that the TXA not completely dissolved. Upon addition of an additional 1 mL of HCI 4M to solution 11A while stirring, the solution dissolved within 6 min. Since solution 11 C remained insoluble even after 20 min, the stirring speed was slightly increased at 56 min,however, there was no improvement in the solubility. Finally, 0.5 mL of HCL 4M was added to 11 C after 58 min of observation and 5 min afterwards, the solution became totally clear and free from visible crystals.

[0108] The experimental study implies that, under these conditions, the real limit of HCI 4M required to dissolve 15 g of the product is 16.5 mL, below which, complete solubility was not achieved. The pH observed for solutions 11A and 11 C was 3.94, with both having the same final volume of 29 mL. Solution 11 B had a pH of 3.91 , with a final volume of 28 mL (some fluid was lost to splashing / evaporation during the experiment).

[0109] The solutions 11 A, B and C were split into 3 equal portions and kept in the stability chambers at 40°C, 5°C, and room temperature, from 2023 / Dec / 17 to 2024 / Jan / 11. During this period, they were observed daily for clarity. Solutions at 40°C turned yellowish, while those at 5°C and room temperature remained colorless (see FIGS. 3A and 3B). The pH of the solutions taken upon removal from the stability chambers after equilibration to room temperature were 3.93, 3.98 and 4.02 for solutions 11 A, 11 B and 11 C respectively.Attempt 12

[0110] The experiment proceeded with dissolving 15 g of tranexamic acid in 16.5 mL HCI 4M, and was stirred until totally dissolved. However, the pH was lowered by using 1 mL HCI 36 % and stirring for additional 10 min, after which a pH of 3.52 was observed. Dropwise, an additional 1 mL of HCI 36 % was added, while stirring and the solution remained clear. However, further dropwise addition of HCI 36 % (about 10 drops) turned the solution turbid, with a pH of 2.85. After about 10 min, the solution turned into a jelly-like suspension. A stepwise addition of more tranexamic acid (about 9 g) did not revert the solution to its initial clear state.Attempt 13

[0111] Attempt 13 was performed in triplicate. About 15g of tranexamic acid was weighed into three separate beakers labelled, 13A, 13B and 13C and each dissolved in 15 mL of HCI 4M. No clear solution was observed after more than 9 min. Therefore, the solutions weresubjected to the addition of concentrated HCI, HCI 4M and a combination of both HCI 4M and concentrated HCI. 660 pL of concentrated HCI was added to 13A, and a clear solution was achieved withing 1 hour. 1 .5 mL of 4M HCI was added to 13B and a clear solution was achieved in about 70 minutes. 700 pL of 4M HCI was added to 13C, followed by 300 pL of concentrated HCI, and a clear solution was achieved within 1 hour.Attempt 14

[0112] Ten (10) grams of tranexamic acid was dissolved in 20 mL of HCI 4M while stirring. After 22 seconds of stirring, a clear solution was achieved. The pH of the solution was measured using a pH meter. A pH reading of -0.05 was observed (see Table 24).Attempt 15

[0113] Attempt 15 was performed in triplicate. About 30 g of tranexamic acid was weighed into three separate beakers labelled, 15A, 15B and 15C and the contents of each dissolved in 31 .4 mL of HCI 4M. This was followed by the addition of 0.6 mL of concentrated HCI, and stirring of the solutions. After 1 h 15 min, the solutions still contained undissolved particles. A plastic syringe was then used to dispense 300 pL of concentrated HCI into the solutions, while stirring continued. At about 1 h 35 min, a clear solution was achieved for all three preparations. pH Measurements of Attempts 13-15

[0114] The pH of the solutions prepared in the attempts 13-15 were measured using a calibrated pH meter. The calibration of the pH probe with pH buffers was performed before use. A 3-buffer calibration was done, using NIST traceable buffers of pH 4, 7 and 10. The accuracy of the pH meter was checked prior to each use, using a one-buffer or two-buffer accuracy check.

[0115] About 3 mL of each solution was transferred into a centrifuge tube and equilibrated at 25 °C (Water Bath L-016). The pH measurements of the solutions were taken after the accuracy check was performed and verified. The pH results measured are presented in Table 24.Table 24. Final concentrations of test solutions determined by HPLC method

[0116] About 7 mL of the solutions in attempts 15A, B and C were transferred into lyophilization vials. For each solution, one vial was stored away at 5°C (refrigerator), -20°C (freezer) and 40°C (in stability room). The solutions were observed every 2 days, over a period of three weeks and a brief description of the observations were made. Table 24 presents a brief description of the sample solutions as observed under storage at room temperature and at 40°C for a period of 2 weeks. As observed during the first week, the three solutions were clear and colorless at 5 and 40°C. However, at the beginning of week 2, solution 15C appeared largely clear and colorless, but did have some tiny crystals at the bottom of the bottle at 5°C (FIG. 4A). It was also observed that solutions 15A, 15B and 15C, all appeared slightly yellow at 40°C (FIG. 4B). The solutions are still under observation for the third week.Table 25. Description of test solutions 15A, 15B and 15C under different storage conditions

[0117] The pH was measured for solutions 15A, B and C which were stored in the freezer; about 3 mL of each solution was transferred into a centrifuge tube after equilibration at 25°C. At equilibration, the samples appeared clear and colorless. An accuracy check of the pH meter was done, after which the pH readings of the samples was measured. Table 26 presents the pH values of the test solutions observed.Table 26. pH of the test solutions 15A, 15B and 15C stored in the freezerAssay of Tranexamic acid in Attempt 11 by HPLC

[0118] For accurate evaluation of the concentration of tranexamic acid in solutions 11A, 11 B and 11 C, an in-house non-validated HPLC method was applied. The results observed are presented in Table 27Table 27. Final concentrations of test solutions determined by HPLC methodAssay of Tranexamic acid from Attempts 13-15 by HPLC

[0119] Formulations according to the methods of attempts 13-15 were prepared and analysed for their Tranexamic content. The results observed are presented in Table 28.Table 28 Final concentrations of test solutions determined by in-house HPLC methodConclusions

[0120] 1 . Solubility of tranexamic acid using HCI 4M was achieved when the final pH is between 3.5 to 4.1. At a low pH, a jelly-like suspension was observed, while higher pH led to undissolved suspensions.

[0121] 2. As observed in the 11thtrial, solubility was achieved with 15 g of TXA in 16.5 mL of HCI 4M.

[0122] 3. The average final concentration of tranexamic acid in solutions 11 A, 11 B and 11 C as evaluated using an in-house non-validated HPLC method was 523.6 mg / mL.

[0123] 4. After week 1 , solutions 15A, 15B and 15C kept at 5 and 40°C were clear and colorless. However, at the second week of storage, all three solutions stored at 40 °C became slightly yellow in color.Embodiments

[0124] Particular embodiments include, without limitation, the following:1 . A solution comprising: at least 110 mg / mL tranexamic acid (TXA);wherein the pH of the solution is 5 or less.2. The solution of embodiment 1 , where the solution is an aqueous solution.3. The solution of embodiment 2, where the aqueous solution is a saline solution.4. The solution of any one of embodiments 1 to 3, wherein the solution is substantially free of precipitates.5. The solution of any one of embodiments 1 to 4, wherein the solution is free of added base.6. The solution of any one of embodiments 1 to 5, wherein the solution comprises an acid.7. The solution of embodiment 6, wherein the acid is hydrochloric acid.8. The solution of any one of embodiments 1 to 7, wherein the pH of the solution is between about 1 .5 and about 5.9. The solution of embodiment 8, wherein the pH of the solution is about 1 .5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5 or about 5.10. The solution of any one of embodiments 1 to 9, wherein the solution comprises between about 110 mg / mL and about 600 mg / mL TXA.11 . The solution of embodiment 10, wherein the solution comprises about 110 mg / mL TXA.12. The solution of embodiment 10, wherein the solution comprises about 150 mg / mL TXA.13. The solution of embodiment 10, wherein the solution comprises about 200 mg / mL TXA.14. The solution of embodiment 10, wherein the solution comprises about 250 mg / mL TXA.15. The solution of embodiment 10, wherein the solution comprises about 300 mg / mL TXA.16. The solution of embodiment 10, wherein the solution comprises about 350 mg / mL TXA.17. The solution of embodiment 10, wherein the solution comprises about 400 mg / mL TXA.18. The solution of embodiment 10, wherein the solution comprises about 450 mg / mL TXA.19. The solution of embodiment 10, wherein the solution comprises about 500 mg / mL TXA.20. The solution of embodiment 10, wherein the solution comprises about 550 mg / mL TXA.21 . The solution of embodiment 10, wherein the solution comprises about 600 mg / mL TXA.22. The solution of any one of embodiments 1 to 21 , wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is between about 80:20 and about 1 :99.23. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 80:20.24. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 70:30.25. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 60:40.26. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 50:50.27. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 40:60.28. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 30:70.29. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 20:80.30. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 10:90.31 . The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 5:95.32. The solution of embodiment 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 1 :99.33. The solution of any one of embodiments 1 to 32, wherein the solution is stable for between about 3 months and about 36 months at room temperature.34. The solution of embodiment 33, wherein the solution is stable for at least about 3 months at room temperature.35. The solution of embodiment 33, wherein the solution is stable for at least about 12 months at room temperature.36. The solution of embodiment 33, wherein the solution is stable for at least about 24 months at room temperature.37. The solution of embodiment 33, wherein the solution is stable for at least about 36 months at room temperature.38. The solution of any one of embodiments 1 to 32, wherein the solution is stable for at between about 1 week and about 24 weeks at 40 °C.39. The solution of embodiment 38, wherein the solution is stable for at least about 1 week at 40 °C.40. The solution of embodiment 38, wherein the solution is stable for at least about 6 weeks at 40 °C.41 . The solution of embodiment 38, wherein the solution is stable for at least about 12 weeks at 40 °C.42. The solution of embodiment 38, wherein the solution is stable for at least about 24 weeks at 40 °C.43. Use of the solution of any one of embodiments 1 to 42 for reducing or preventing hemorrhage in a subject in need thereof.44. The use of embodiment 43, wherein the subject is a human.45. The use of embodiment 43 or embodiment 44, wherein the solution is administered intramuscularly.46. The use of embodiment 43 or embodiment 44, wherein the solution is for administration intraosseously.47. The use of embodiment 43 or embodiment 44, wherein the solution is for administration intravenously.48. The use of any one of embodiments 43 to 47, wherein the solution is for administration by a syringe.49. The use of any one of embodiments 43 to 47, wherein the solution is for administration by an autoinjector.50. The use of embodiment 43 or embodiment 44, wherein the solution is for administration topically.51. The use of any one of embodiments 43 to 50, wherein the hemorrhage is posttraumatic hemorrhage, postpartum hemorrhage, perioperative hemorrhage, or postoperative hemorrhage.52. The use of embodiment 51 , wherein the hemorrhage is posttraumatic hemorrhage.53. The use of embodiment 52, wherein the posttraumatic hemorrhage is a hemorrhage caused by a traumatic brain injury.54. The use of embodiment 51 , wherein the hemorrhage is postpartum hemorrhage.55. The use of embodiment 51 , wherein the hemorrhage is perioperative hemorrhage.56. The use of embodiment 51 , wherein the hemorrhage is postoperative hemorrhage.57. The use of any one of embodiments 43-56, wherein the hemorrhage is external.58. The use of any one of embodiments 43-56, wherein the hemorrhage is internal.59. The use of any one of embodiments 43-58, wherein the hemorrhage is associated with hemorrhagic shock and / or coagulopathy.60. The use of any one of embodiments 43-59, wherein the solution is for administration within 24 hours of the onset of the hemorrhage.61 . The use of embodiment 60, wherein the solution is for administration within 16 hours of the onset of the hemorrhage.62. The use of embodiment 60, wherein the solution is for administration within 12 hours of the onset of the hemorrhage.63. The use of embodiment 60, wherein the solution is for administration within 6 hours of the onset of the hemorrhage.64. The use of embodiment 60, wherein the solution is for administration within 5 hours of the onset of the hemorrhage.65. The use of embodiment 60, wherein the solution is for administration within 4 hours of the onset of the hemorrhage.66. The use of embodiment 60, wherein the solution is for administration within 3 hours of the onset of the hemorrhage.67. The use of embodiment 60, wherein the solution is for administration within 2 hours of the onset of the hemorrhage.68. The use of embodiment 60, wherein the solution is for administration within 1 hour of the onset of the hemorrhage.69. The use of embodiment 60, wherein the solution is for administration within 45 min of the onset of the hemorrhage.70. The use of embodiment 60, wherein the solution is for administration within 30 min of the onset of the hemorrhage.71 . The use of embodiment 60, wherein the solution is for administration within 15 min of the onset of the hemorrhage.72. The use of any one of embodiments 43-59, wherein the solution is for administration within 48 hours before the onset of the hemorrhage.73. The use of embodiment 72, wherein the solution is for administration within 24 hours before the onset of the hemorrhage.74. The use of embodiment 72, wherein the solution is for administration within 12 hours before the onset of the hemorrhage.75. The use of embodiment 72, wherein the solution is for administration within 6 hours before the onset of the hemorrhage.76. The use of embodiment 72, wherein the solution is for administration within 5 hours before the onset of the hemorrhage.77. The use of embodiment 72, wherein the solution is for administration within 4 hours before the onset of the hemorrhage.78. The use of embodiment 72, wherein the solution is for administration within 3 hours before the onset of the hemorrhage.79. The use of embodiment 72, wherein the solution is for administration within 2 hours before the onset of the hemorrhage.80. The use of embodiment 72, wherein the solution is for administration within 1 hour before the onset of the hemorrhage.81. The use of embodiment 72, wherein the solution is for administration within 45 min before the onset of the hemorrhage.82. The use of embodiment 72, wherein the solution is for administration within 30 min before the onset of the hemorrhage.83. The use of embodiment 72, wherein the solution is for administration within 15 min before the onset of the hemorrhage.84. The use of any one of embodiments 43-83, wherein the use comprises a first dose and a second dose of the solution, wherein the second dose is for administration to the subject within a first time period after the first dose, wherein the first time period is between about 10 minutes and about 24 hours.85. The use of embodiment 84, wherein the first time period is about 10 minutes.86. The use of embodiment 84, wherein the first time period is about 15 minutes.87. The use of embodiment 84, wherein the first time period is about 30 minutes.88. The use of embodiment 84, wherein the first time period is about 1 hour or about 2 hours.89. The use of embodiment 84, wherein the first time period is about 4 hours.90. The use of embodiment 84, wherein the first time period is about 6 hours.91 . The use of embodiment 84, wherein the first time period is about 8 hours.92. The use of embodiment 84, wherein the first time period is about 10 hours.93. The use of embodiment 84, wherein the first time period is about 12 hours.94. The use of embodiment 84, wherein the first time period is about 14 hours.95. The use of embodiment 84, wherein the first time period is about 16 hours.96. The use of embodiment 84, wherein the first time period is about 18 hours.97. The use of embodiment 84, wherein the first time period is about 20 hours.98. The use of embodiment 84, wherein the first time period is about 22 hours.99. The use of embodiment 84, wherein the first time period is about 24 hours.100. The use of any one of embodiments 84 to 100, wherein the second dose is for administration by infusion over a second time period of between about 10 minutes and about 12 hours.101. The use of embodiment 100, wherein the second time period is about 10 minutes, about 30 minutes or about 1 hour.102. The use of embodiment 100, wherein the second time period is about 2 hours.103. The use of embodiment 100, wherein the second time period is about 3 hours.104. The use of embodiment 100, wherein the second time period is about 4 hours.105. The use of embodiment 100, wherein the second time period is about 5 hours.106. The use of embodiment 100, wherein the second time period is about 6 hours.107. The use of embodiment 100, wherein the second time period is about 7 hours.108. The use of embodiment 100, wherein the second time period is about 8 hours.109. The use of embodiment 100, wherein the second time period is about 9 hours.110. The use of embodiment 100, wherein the second time period is about 10 hours.111. The use of embodiment 100, wherein the second time period is about 11 hours.112. The use of embodiment 100, wherein the second time period is about 12 hours.113. The use of any one of embodiments 84 to 112, wherein the second dose is for administration intravenously.114. A method for reducing or preventing hemorrhage, comprising administering the solution of any one of embodiments 1-42 to a subject in need thereof.115. The method of embodiment 114, wherein the subject is a human.116. The method of embodiment 114 or embodiment 115, wherein the solution is administered intramuscularly.117. The method of embodiment 114 or embodiment 115, wherein the solution is administered intraosseously.118. The method of embodiment 114 or embodiment 115, wherein the solution is administered intravenously.119. The method of any one of embodiments 114 to 118, wherein the solution is administered by a syringe.120. The method of any one of embodiments 114 to 118, wherein the solution is administered by an autoinjector.121. The method of embodiment 114 or embodiment 115, wherein the solution is administered topically.122. The method of any one of embodiments 114 to 121 , wherein the hemorrhage is posttraumatic hemorrhage, postpartum hemorrhage, perioperative hemorrhage, or postoperative hemorrhage.123. The method of embodiment 122, wherein the hemorrhage is posttraumatic hemorrhage.124. The method of embodiment 123, wherein the posttraumatic hemorrhage is a hemorrhage caused by a traumatic brain injury.125. The method of embodiment 122, wherein the hemorrhage is postpartum hemorrhage.126. The method of embodiment 122, wherein the hemorrhage is perioperative hemorrhage.127. The method of embodiment 122, wherein the hemorrhage is postoperative hemorrhage.128. The method of any one of embodiments 114-127, wherein the hemorrhage is external.129. The method of any one of embodiments 114-127, wherein the hemorrhage is internal.130. The method of any one of embodiments 114-129, wherein the hemorrhage is associated with hemorrhagic shock and / or coagulopathy.131. The method of any one of embodiments 114-130, wherein the solution is administered within 24 hours of the onset of the hemorrhage.132. The method of embodiment 131 , wherein the solution is administered within 16 hours of the onset of the hemorrhage.133. The method of embodiment 131 , wherein the solution is administered within 12 hours of the onset of the hemorrhage.134. The method of embodiment 131 , wherein the solution is administered within 6 hours of the onset of the hemorrhage.135. The method of embodiment 131 , wherein the solution is administered within 5 hours of the onset of the hemorrhage.136. The method of embodiment 131 , wherein the solution is administered within 4 hours of the onset of the hemorrhage.137. The method of embodiment 131 , wherein the solution is administered within 3 hours of the onset of the hemorrhage.138. The method of embodiment 131 , wherein the solution is administered within 2 hours of the onset of the hemorrhage.139. The method of embodiment 131 , wherein the solution is administered within 1 hour of the onset of the hemorrhage.140. The method of embodiment 131 , wherein the solution is administered within 45 min of the onset of the hemorrhage.141. The method of embodiment 131 , wherein the solution is administered within 30 min of the onset of the hemorrhage.142. The method of embodiment 131 , wherein the solution is administered within 15 min of the onset of the hemorrhage.143. The method of any one of embodiments 114-130, wherein the solution is administered within 48 hours before the onset of the hemorrhage.144. The method of embodiment 143, wherein the solution is administered within 24 hours before the onset of the hemorrhage.145. The method of embodiment 143, wherein the solution is administered within 12 hours before the onset of the hemorrhage.146. The method of embodiment 143, wherein the solution is administered within 6 hours before the onset of the hemorrhage.147. The method of embodiment 143, wherein the solution is administered within 5 hours before the onset of the hemorrhage.148. The method of embodiment 143, wherein the solution is administered within 4 hours before the onset of the hemorrhage.149. The method of embodiment 143, wherein the solution is administered within 3 hours before the onset of the hemorrhage.150. The method of embodiment 143, wherein the solution is administered within 2 hours before the onset of the hemorrhage.151. The method of embodiment 143, wherein the solution is administered within 1 hour before the onset of the hemorrhage.152. The method of embodiment 143, wherein the solution is administered within 45 min before the onset of the hemorrhage.153. The method of embodiment 143, wherein the solution is administered within 30 min before the onset of the hemorrhage.154. The method of embodiment 143, wherein the solution is administered within 15 min before the onset of the hemorrhage.155. The method of any one of embodiments 114-154, wherein a first dose of the solution is administered to the subject, followed by the administration of a second dose of the solution to the subject within a first time period, wherein the first time period is between about 10 minutes and about 24 hours.156. The method of embodiment 155, wherein the first time period is about 10 minutes.157. The method of embodiment 155, wherein the first time period is about 15 minutes.158. The method of embodiment 150, wherein the first time period is about 30 minutes.159. The method of embodiment 155, wherein the first time period is about 1 hour or about 2 hours.160. The method of embodiment 155, wherein the first time period is about 4 hours.161 . The method of embodiment 155, wherein the first time period is about 6 hours.162. The method of embodiment 155, wherein the first time period is about 8 hours.163. The method of embodiment 155, wherein the first time period is about 10 hours.164. The method of embodiment 155, wherein the first time period is about 12 hours.165. The method of embodiment 155, wherein the first time period is about 14 hours.166. The method of embodiment 155, wherein the first time period is about 16 hours.167. The method of embodiment 155, wherein the first time period is about 18 hours.168. The method of embodiment 155, wherein the first time period is about 20 hours.169. The method of embodiment 155, wherein the first time period is about 22 hours.170. The method of embodiment 155, wherein the first time period is about 24 hours.171. The method of any one of embodiments 155 to 170, wherein the second dose is administered by infusion over a second time period of between about 10 minutes and about 12 hours.172. The method of embodiment 171 , wherein the second time period is about 10 minutes, about 30 minutes or about 1 hour.173. The method of embodiment 171 , wherein the second time period is about 2 hours.174. The method of embodiment 171 , wherein the second time period is about 3 hours.175. The method of embodiment 171 , wherein the second time period is about 4 hours.176. The method of embodiment 171 , wherein the second time period is about 5 hours.177. The method of embodiment 171 , wherein the second time period is about 6 hours.178. The method of embodiment 171 , wherein the second time period is about 7 hours.179. The method of embodiment 171 , wherein the second time period is about 8 hours.180. The method of embodiment 171 , wherein the second time period is about 9 hours.181. The method of embodiment 171 , wherein the second time period is about 10 hours.182. The method of embodiment 171 , wherein the second time period is about 11 hours.183. The method of embodiment 171 , wherein the second time period is about 12 hours.184. The method of any one of embodiments 155 to 183, wherein the second dose is administered intravenously.185. A method of preparing a TXA solution comprising:(a) adding TXA to a liquid carrier;(b) reducing the pH of liquid carrier to 5 or less.186. The method of embodiment 185, wherein the TXA solution comprises at least 110 mg / mL TXA.187. The method of embodiment 185 or 186, wherein step (b) is performed before step (a).188. The method of any one of embodiments 185 to 187, wherein the TXA solution comprises at least 90% w / w of the TXA added in step (a).189. The method of embodiment 188, wherein the TXA solution comprises at least 95% w / w of the TXA added in step (a).190. The method of any one of embodiments 185 to 189, further comprising incubating the solution.191. The method of embodiment 190, wherein the solution is incubated after step (a).192. The method of embodiment 190, wherein the solution is incubated after step (b).193. The method of any one of embodiments 185 to 192, wherein the solution is free of added base.194. The method of any one of embodiments 185 to 193, further comprising adding base to the solution to adjust the pH.195. The method of embodiment 194, wherein the base is sodium hydroxide or potassium hydroxide.196. The method of any one of embodiments 185 to 195, where the liquid carrier comprises water.197. The method of any one of embodiments 185 to 195, where the liquid carrier comprises a saline solution.198. The method of any one of embodiments 185 to 197, wherein the solution is substantially free of precipitates.199. The method of any one of embodiments 185 to 198, wherein step (b) involves addition of acid.200. The method of embodiment 199, wherein the acid is hydrochloric acid.201. The method of any one of embodiments 185 to 200, wherein the pH of the solution is between about 1 .5 and about 5.202. The method of embodiment 201 , wherein the pH of the solution is about 1.5, about2, about 2.5, about 3, about 3.5, about 4, about 4.5 or about 5.203. The method of any one of embodiments 185 to 202, wherein the solution comprises between about 110 mg / mL and about 600 mg / mL TXA.204. The method of embodiment 203, wherein the solution comprises about 110 mg / mL TXA.205. The method of embodiment 203, wherein the solution comprises about 150 mg / mL TXA.206. The method of embodiment 203, wherein the solution comprises about 200 mg / mL TXA.207. The method of embodiment 203, wherein the solution comprises about 250 mg / mL TXA.208. The method of embodiment 203, wherein the solution comprises about 300 mg / mL TXA.209. The method of embodiment 203, wherein the solution comprises about 350 mg / mL TXA.210. The method of embodiment 203, wherein the solution comprises about 400 mg / mL TXA.211. The method of embodiment 203, wherein the solution comprises about 450 mg / mL TXA.212. The method of embodiment 203, wherein the solution comprises about 500 mg / mL TXA.213. The method of embodiment 203, wherein the solution comprises about 550 mg / mL TXA.214. The method of embodiment 203, wherein the solution comprises about 600 mg / mL TXA.215. The method of any one of embodiments 185 to 214, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is between about 80:20 and about 1 :99.216. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 80:20.217. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 70:30.218. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 60:40.219. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 50:50.220. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 40:60.221. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 30:70.222. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 20:80.223. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 10:90.224. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 5:95.225. The method of embodiment 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 1 :99.226. The method of any one of embodiments 185 to 225, wherein the solution is stable for between about 3 months and about 36 months at room temperature.227. The method of embodiment 226, wherein the solution is stable for at least about 3 months at room temperature.228. The method of embodiment 226, wherein the solution is stable for at least about 12 months at room temperature.229. The method of embodiment 226, wherein the solution is stable for at least about 24 months at room temperature.230. The method of embodiment 226, wherein the solution is stable for at least about 36 months at room temperature.231. The method of any one of embodiments 185 to 225, wherein the solution is stable for at between about 1 week and about 24 weeks at 40 °C.232. The solution of embodiment 231 , wherein the solution is stable for at least about 1 weeks at 40 °C.233. The solution of embodiment 231 , wherein the solution is stable for at least about 6 weeks at 40 °C.234. The solution of embodiment 231 , wherein the solution is stable for at least about 12 weeks at 40 °C.235. The solution of embodiment 231 , wherein the solution is stable for at least about 24 weeks at 40 °C.236. The use of any one of embodiments 43 to 113, wherein the solution comprises 0.1 g, 0.2 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1 g, 1 .1 g, 1 .2 g, 1 .3 g, 1 .4 g, 1 .5 g, 1 .6 g, 1 .7 g, 1.8 g, 1 .9 g or 2 g of TXA.237. The method of any one of embodiments 114 to 184, wherein 0.1 g, 0.2 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1 g, 1 .1 g, 1 .2 g, 1 .3 g, 1 .4 g, 1.5 g, 1 .6 g, 1 .7 g, 1 .8 g,1 .9 g or 2 g of TXA is administered to the subject.

[0125] The term “wt%” means weight percent.

[0126] The term w / w% means weight per weigh percent.

[0127] The term “about” as used herein can allow for a degree of variability in a value or range, for example, within 5% of a stated value or of a stated limit of a range.

[0128] When introducing elements of the present invention or the embodiments thereof, the articles “a,” “an,” “the,” and “said” are intended to mean that there are one or more of the elements. The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0129] Of course, the above described embodiments are intended to be illustrative only and in no way limiting. The described embodiments of carrying out the invention are susceptible to many modifications of form, arrangement of parts, details, and order of operation. The invention, therefore, is intended to encompass all such modifications within its scope.

Claims

WHAT IS CLAIMED IS:1 . A solution comprising: at least 110 mg / mL tranexamic acid (TXA); wherein the pH of the solution is 5 or less.

2. The solution of claim 1 , where the solution is an aqueous solution.

3. The solution of claim 2, where the aqueous solution is a saline solution.

4. The solution of any one of claims 1 to 3, wherein the solution is substantially free of precipitates.

5. The solution of any one of claims 1 to 4, wherein the solution is free of added base.

6. The solution of any one of claims 1 to 5, wherein the solution comprises an acid.

7. The solution of claim 6, wherein the acid is hydrochloric acid.

8. The solution of any one of claims 1 to 7, wherein the pH of the solution is between about 1 .5 and about 5.

9. The solution of claim 8, wherein the pH of the solution is about 1 .5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5 or about 5.

10. The solution of any one of claims 1 to 9, wherein the solution comprises between about 110 mg / mL and about 600 mg / mL TXA.11 . The solution of claim 10, wherein the solution comprises about 110 mg / mL TXA.

12. The solution of claim 10, wherein the solution comprises about 150 mg / mL TXA.

13. The solution of claim 10, wherein the solution comprises about 200 mg / mL TXA.

14. The solution of claim 10, wherein the solution comprises about 250 mg / mL TXA.

15. The solution of claim 10, wherein the solution comprises about 300 mg / mL TXA.

16. The solution of claim 10, wherein the solution comprises about 350 mg / mL TXA.

17. The solution of claim 10, wherein the solution comprises about 400 mg / mL TXA.

18. The solution of claim 10, wherein the solution comprises about 450 mg / mL TXA.

19. The solution of claim 10, wherein the solution comprises about 500 mg / mL TXA.

20. The solution of claim 10, wherein the solution comprises about 550 mg / mL TXA.21 . The solution of claim 10, wherein the solution comprises about 600 mg / mL TXA.

22. The solution of any one of claims 1 to 21 , wherein the ratio of neutrally charged TXA:TXA hydrochloride in the solution is between about 80:20 and about 1 :99.

23. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 80:20.

24. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 70:30.

25. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 60:40.

26. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 50:50.

27. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 40:60.

28. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 30:70.

29. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 20:80.

30. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 10:90.31 . The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 5:95.

32. The solution of claim 22, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 1 :99.

33. The solution of any one of claims 1 to 32, wherein the solution is stable for between about 3 months and about 36 months at room temperature.

34. The solution of claim 33, wherein the solution is stable for at least about 3 months at room temperature.

35. The solution of claim 33, wherein the solution is stable for at least about 12 months at room temperature.

36. The solution of claim 33, wherein the solution is stable for at least about 24 months at room temperature.

37. The solution of claim 33, wherein the solution is stable for at least about 36 months at room temperature.

38. The solution of any one of claims 1 to 32, wherein the solution is stable for at between about 1 week and about 24 weeks at 40 °C.

39. The solution of claim 38, wherein the solution is stable for at least about 1 week at 40 °C.

40. The solution of claim 38, wherein the solution is stable for at least about 6 weeks at 40 °C.41 . The solution of claim 38, wherein the solution is stable for at least about 12 weeks at 40 °C.

42. The solution of claim 38, wherein the solution is stable for at least about 24 weeks at 40 °C.

43. Use of the solution of any one of claims 1 to 42 for reducing or preventing hemorrhage in a subject in need thereof.

44. The use of claim 43, wherein the subject is a human.

45. The use of claim 43 or claim 44, wherein the solution is administered intramuscularly.

46. The use of claim 43 or claim 44, wherein the solution is for administration intraosseously.

47. The use of claim 43 or claim 44, wherein the solution is for administration intravenously.

48. The use of any one of claims 43 to 47, wherein the solution is for administration by a syringe.

49. The use of any one of claims 43 to 47, wherein the solution is for administration by an autoinjector.

50. The use of claim 43 or claim 44, wherein the solution is for administration topically.51 . The use of any one of claims 43 to 50, wherein the hemorrhage is posttraumatic hemorrhage, postpartum hemorrhage, perioperative hemorrhage, or postoperative hemorrhage.

52. The use of claim 51 , wherein the hemorrhage is posttraumatic hemorrhage.

53. The use of claim 52, wherein the posttraumatic hemorrhage is a hemorrhage caused by a traumatic brain injury.

54. The use of claim 51 , wherein the hemorrhage is postpartum hemorrhage.

55. The use of claim 51 , wherein the hemorrhage is perioperative hemorrhage.

56. The use of claim 51 , wherein the hemorrhage is postoperative hemorrhage.

57. The use of any one of claims 43-56, wherein the hemorrhage is external.

58. The use of any one of claims 43-56, wherein the hemorrhage is internal.

59. The use of any one of claims 43-58, wherein the hemorrhage is associated with hemorrhagic shock and / or coagulopathy.

60. The use of any one of claims 43-59, wherein the solution is for administration within 24 hours of the onset of the hemorrhage.61 . The use of claim 60, wherein the solution is for administration within 16 hours of the onset of the hemorrhage.

62. The use of claim 60, wherein the solution is for administration within 12 hours of the onset of the hemorrhage.

63. The use of claim 60, wherein the solution is for administration within 6 hours of the onset of the hemorrhage.

64. The use of claim 60, wherein the solution is for administration within 5 hours of the onset of the hemorrhage.

65. The use of claim 60, wherein the solution is for administration within 4 hours of the onset of the hemorrhage.

66. The use of claim 60, wherein the solution is for administration within 3 hours of the onset of the hemorrhage.

67. The use of claim 60, wherein the solution is for administration within 2 hours of the onset of the hemorrhage.

68. The use of claim 60, wherein the solution is for administration within 1 hour of the onset of the hemorrhage.

69. The use of claim 60, wherein the solution is for administration within 45 min of the onset of the hemorrhage.

70. The use of claim 60, wherein the solution is for administration within 30 min of the onset of the hemorrhage.

71. The use of claim 60, wherein the solution is for administration within 15 min of the onset of the hemorrhage.

72. The use of any one of claims 43-59, wherein the solution is for administration within 48 hours before the onset of the hemorrhage.

73. The use of claim 72, wherein the solution is for administration within 24 hours before the onset of the hemorrhage.

74. The use of claim 72, wherein the solution is for administration within 12 hours before the onset of the hemorrhage.

75. The use of claim 72, wherein the solution is for administration within 6 hours before the onset of the hemorrhage.

76. The use of claim 72, wherein the solution is for administration within 5 hours before the onset of the hemorrhage.

77. The use of claim 72, wherein the solution is for administration within 4 hours before the onset of the hemorrhage.

78. The use of claim 72, wherein the solution is for administration within 3 hours before the onset of the hemorrhage.

79. The use of claim 72, wherein the solution is for administration within 2 hours before the onset of the hemorrhage.

80. The use of claim 72, wherein the solution is for administration within 1 hour before the onset of the hemorrhage.

81. The use of claim 72, wherein the solution is for administration within 45 min before the onset of the hemorrhage.

82. The use of claim 72, wherein the solution is for administration within 30 min before the onset of the hemorrhage.

83. The use of claim 72, wherein the solution is for administration within 15 min before the onset of the hemorrhage.

84. The use of any one of claims 43-83, wherein the use comprises a first dose and a second dose of the solution, wherein the second dose is for administration to the subject within a first time period after the first dose, wherein the first time period is between about 10 minutes and about 24 hours.

85. The use of claim 84, wherein the first time period is about 10 minutes.

86. The use of claim 84, wherein the first time period is about 15 minutes.

87. The use of claim 84, wherein the first time period is about 30 minutes.

88. The use of claim 84, wherein the first time period is about 1 hour or about 2 hours.

89. The use of claim 84, wherein the first time period is about 4 hours.

90. The use of claim 84, wherein the first time period is about 6 hours.91 . The use of claim 84, wherein the first time period is about 8 hours.

92. The use of claim 84, wherein the first time period is about 10 hours.

93. The use of claim 84, wherein the first time period is about 12 hours.

94. The use of claim 84, wherein the first time period is about 14 hours.

95. The use of claim 84, wherein the first time period is about 16 hours.

96. The use of claim 84, wherein the first time period is about 18 hours.

97. The use of claim 84, wherein the first time period is about 20 hours.

98. The use of claim 84, wherein the first time period is about 22 hours.

99. The use of claim 84, wherein the first time period is about 24 hours.

100. The use of any one of claims 84 to 100, wherein the second dose is for administration by infusion over a second time period of between about 10 minutes and about 12 hours.

101. The use of claim 100, wherein the second time period is about 10 minutes, about 30 minutes or about 1 hour.

102. The use of claim 100, wherein the second time period is about 2 hours.

103. The use of claim 100, wherein the second time period is about 3 hours.

104. The use of claim 100, wherein the second time period is about 4 hours.

105. The use of claim 100, wherein the second time period is about 5 hours.

106. The use of claim 100, wherein the second time period is about 6 hours.

107. The use of claim 100, wherein the second time period is about 7 hours.

108. The use of claim 100, wherein the second time period is about 8 hours.

109. The use of claim 100, wherein the second time period is about 9 hours.

110. The use of claim 100, wherein the second time period is about 10 hours.

111. The use of claim 100, wherein the second time period is about 11 hours.

112. The use of claim 100, wherein the second time period is about 12 hours.

113. The use of any one of claims 84 to 112, wherein the second dose is for administration intravenously.

114. A method for reducing or preventing hemorrhage, comprising administering the solution of any one of claims 1-42 to a subject in need thereof.

115. The method of claim 114, wherein the subject is a human.

116. The method of claim 114 or claim 115, wherein the solution is administered intramuscularly.

117. The method of claim 114 or claim 115, wherein the solution is administered intraosseously.

118. The method of claim 114 or claim 115, wherein the solution is administered intravenously.

119. The method of any one of claims 114 to 118, wherein the solution is administered by a syringe.

120. The method of any one of claims 114 to 118, wherein the solution is administered by an autoinjector.

121. The method of claim 114 or claim 115, wherein the solution is administered topically.

122. The method of any one of claims 114 to 121 , wherein the hemorrhage is posttraumatic hemorrhage, postpartum hemorrhage, perioperative hemorrhage, or postoperative hemorrhage.

123. The method of claim 122, wherein the hemorrhage is posttraumatic hemorrhage.

124. The method of claim 123, wherein the posttraumatic hemorrhage is a hemorrhage caused by a traumatic brain injury.

125. The method of claim 122, wherein the hemorrhage is postpartum hemorrhage.

126. The method of claim 122, wherein the hemorrhage is perioperative hemorrhage.

127. The method of claim 122, wherein the hemorrhage is postoperative hemorrhage.

128. The method of any one of claims 114-127, wherein the hemorrhage is external.

129. The method of any one of claims 114-127, wherein the hemorrhage is internal.

130. The method of any one of claims 114-129, wherein the hemorrhage is associated with hemorrhagic shock and / or coagulopathy.131 . The method of any one of claims 114-130, wherein the solution is administered within 24 hours of the onset of the hemorrhage.

132. The method of claim 131 , wherein the solution is administered within 16 hours of the onset of the hemorrhage.

133. The method of claim 131 , wherein the solution is administered within 12 hours of the onset of the hemorrhage.

134. The method of claim 131 , wherein the solution is administered within 6 hours of the onset of the hemorrhage.

135. The method of claim 131 , wherein the solution is administered within 5 hours of the onset of the hemorrhage.

136. The method of claim 131 , wherein the solution is administered within 4 hours of the onset of the hemorrhage.

137. The method of claim 131 , wherein the solution is administered within 3 hours of the onset of the hemorrhage.

138. The method of claim 131 , wherein the solution is administered within 2 hours of the onset of the hemorrhage.

139. The method of claim 131 , wherein the solution is administered within 1 hour of the onset of the hemorrhage.

140. The method of claim 131 , wherein the solution is administered within 45 min of the onset of the hemorrhage.

141. The method of claim 131 , wherein the solution is administered within 30 min of the onset of the hemorrhage.

142. The method of claim 131 , wherein the solution is administered within 15 min of the onset of the hemorrhage.

143. The method of any one of claims 114-130, wherein the solution is administered within 48 hours before the onset of the hemorrhage.

144. The method of claim 143, wherein the solution is administered within 24 hours before the onset of the hemorrhage.

145. The method of claim 143, wherein the solution is administered within 12 hours before the onset of the hemorrhage.

146. The method of claim 143, wherein the solution is administered within 6 hours before the onset of the hemorrhage.

147. The method of claim 143, wherein the solution is administered within 5 hours before the onset of the hemorrhage.

148. The method of claim 143, wherein the solution is administered within 4 hours before the onset of the hemorrhage.

149. The method of claim 143, wherein the solution is administered within 3 hours before the onset of the hemorrhage.

150. The method of claim 143, wherein the solution is administered within 2 hours before the onset of the hemorrhage.

151. The method of claim 143, wherein the solution is administered within 1 hour before the onset of the hemorrhage.

152. The method of claim 143, wherein the solution is administered within 45 min before the onset of the hemorrhage.

153. The method of claim 143, wherein the solution is administered within 30 min before the onset of the hemorrhage.

154. The method of claim 143, wherein the solution is administered within 15 min before the onset of the hemorrhage.

155. The method of any one of claims 114-154, wherein a first dose of the solution is administered to the subject, followed by the administration of a second dose of the solution to the subject within a first time period, wherein the first time period is between about 10 minutes and about 24 hours.

156. The method of claim 155, wherein the first time period is about 10 minutes.

157. The method of claim 155, wherein the first time period is about 15 minutes.

158. The method of claim 150, wherein the first time period is about 30 minutes.

159. The method of claim 155, wherein the first time period is about 1 hour or about 2 hours.

160. The method of claim 155, wherein the first time period is about 4 hours,161 . The method of claim 155, wherein the first time period is about 6 hours,162. The method of claim 155, wherein the first time period is about 8 hours,163. The method of claim 155, wherein the first time period is about 10 hours,164. The method of claim 155, wherein the first time period is about 12 hours,165. The method of claim 155, wherein the first time period is about 14 hours,166. The method of claim 155, wherein the first time period is about 16 hours,167. The method of claim 155, wherein the first time period is about 18 hours,168. The method of claim 155, wherein the first time period is about 20 hours,169. The method of claim 155, wherein the first time period is about 22 hours.

170. The method of claim 155, wherein the first time period is about 24 hours.

171. The method of any one of claims 155 to 170, wherein the second dose is administered by infusion over a second time period of between about 10 minutes and about 12 hours.

172. The method of claim 171 , wherein the second time period is aboutI O minutes, about30 minutes or about 1 hour.

173. The method of claim 171 , wherein the second time period is about 2 hours.

174. The method of claim 171 , wherein the second time period is about 3 hours,175. The method of claim 171 , wherein the second time period is about 4 hours,176. The method of claim 171 , wherein the second time period is about 5 hours,177. The method of claim 171 , wherein the second time period is about 6 hours.

178. The method of claim 171 , wherein the second time period is about 7 hours.

179. The method of claim 171 , wherein the second time period is about 8 hours.

180. The method of claim 171 , wherein the second time period is about 9 hours.

181. The method of claim 171 , wherein the second time period is about 10 hours.

182. The method of claim 171 , wherein the second time period is about 11 hours.

183. The method of claim 171 , wherein the second time period is about 12 hours.

184. The method of any one of claims 155 to 183, wherein the second dose is administered intravenously.

185. A method of preparing a TXA solution comprising:(c) adding TXA to a liquid carrier;(d) reducing the pH of liquid carrier to 5 or less.

186. The method of claim 185, wherein the TXA solution comprises at least 110 mg / mL TXA.

187. The method of claim 185 or 186, wherein step (b) is performed before step (a).

188. The method of any one of claims 185 to 187, wherein the TXA solution comprises at least 90% w / w of the TXA added in step (a).

189. The method of claim 188, wherein the TXA solution comprises at least 95% w / w of the TXA added in step (a).

190. The method of any one of claims 185 to 189, further comprising incubating the solution.191 . The method of claim 190, wherein the solution is incubated after step (a).

192. The method of claim 190, wherein the solution is incubated after step (b).

193. The method of any one of claims 185 to 192, wherein the solution is free of added base.

194. The method of any one of claims 185 to 193, further comprising adding base to the solution to adjust the pH.

195. The method of claim 194, wherein the base is sodium hydroxide or potassium hydroxide.

196. The method of any one of claims 185 to 195, where the liquid carrier comprises water.

197. The method of any one of claims 185 to 195, where the liquid carrier comprises a saline solution.

198. The method of any one of claims 185 to 197, wherein the solution is substantially free of precipitates.

199. The method of any one of claims 185 to 198, wherein step (b) involves addition of acid.

200. The method of claim 199, wherein the acid is hydrochloric acid.

201. The method of any one of claims 185 to 200, wherein the pH of the solution is between about 1 .5 and about 5.

202. The method of claim 201 , wherein the pH of the solution is about 1 .5, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5 or about 5.

203. The method of any one of claims 185 to 202, wherein the solution comprises between about 110 mg / mL and about 600 mg / mL TXA.

204. The method of claim 203, wherein the solution comprises about 110 mg / mL TXA.

205. The method of claim 203, wherein the solution comprises about 150 mg / mL TXA.

206. The method of claim 203, wherein the solution comprises about 200 mg / mL TXA.

207. The method of claim 203, wherein the solution comprises about 250 mg / mL TXA.

208. The method of claim 203, wherein the solution comprises about 300 mg / mL TXA.

209. The method of claim 203, wherein the solution comprises about 350 mg / mL TXA.

210. The method of claim 203, wherein the solution comprises about 400 mg / mL TXA.

211. The method of claim 203, wherein the solution comprises about 450 mg / mL TXA.

212. The method of claim 203, wherein the solution comprises about 500 mg / mL TXA.

213. The method of claim 203, wherein the solution comprises about 550 mg / mL TXA.

214. The method of claim 203, wherein the solution comprises about 600 mg / mL TXA.

215. The method of any one of claims 185 to 214, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is between about 80:20 and about 1 :99.

216. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 80:20.

217. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 70:30.

218. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 60:40.

219. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 50:50.

220. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 40:60.

221. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 30:70.

222. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 20:80.

223. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 10:90.

224. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 5:95.

225. The method of claim 215, wherein the ratio of neutrally charged TXA :TXA hydrochloride in the solution is about 1 :99.

226. The method of any one of claims 185 to 225, wherein the solution is stable for between about 3 months and about 36 months at room temperature.

227. The method of claim 226, wherein the solution is stable for at least about 3 months at room temperature.

228. The method of claim 226, wherein the solution is stable for at least about 12 months at room temperature.

229. The method of claim 226, wherein the solution is stable for at least about 24 months at room temperature.

230. The method of claim 226, wherein the solution is stable for at least about 36 months at room temperature.

231. The method of any one of claims 185 to 225, wherein the solution is stable for at between about 1 week and about 24 weeks at 40 °C.

232. The solution of claim 231 , wherein the solution is stable for at least about 1 weeks at 40 °C.

233. The solution of claim 231 , wherein the solution is stable for at least about 6 weeks at 40 °C.

234. The solution of claim 231 , wherein the solution is stable for at least about 12 weeks at 40 °C.

235. The solution of claim 231 , wherein the solution is stable for at least about 24 weeks at 40 °C.

236. The use of any one of claims 43 to 113, wherein the solution comprises 0.1 g, 0.2 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1 g, 1.1 g, 1.2 g, 1.3 g, 1.4 g, 1.5 g, 1.6 g, 1.7 g, 1.8 g, 1 .9 g or 2 g of TXA.

237. The method of any one of claims 114 to 184, wherein 0.1 g, 0.2 g, 0.3 g, 0.4 g, 0.5 g, 0.6 g, 0.7 g, 0.8 g, 0.9 g, 1 g, 1 .1 g, 1 .2 g, 1 .3 g, 1 .4 g, 1.5 g, 1 .6 g, 1 .7 g, 1 .8 g, 1.9 g or 2 g of TXA is administered to the subject.

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