Compositions comprising an APX3330 hemicalcium salt monohydrate and therapeutic uses thereof

Abstract

This invention relates to compositions comprising APX3330 or an APX3330 hemicalcium salt monohydrate. The invention also provides methods for treating or preventing an ocular disease, an inflammatory disease, Barrett's esophagus (BE), cancer, a hepatic disease, a cardiovascular disease, idiopathic pulmonary fibrosis, a keloid, systemic sclerosis, chemotherapy-induced peripheral neuropathy, stroke, gastro-intestinal dysfunction, chronic gastroesophageal reflux disease, von Hippel-Lindau syndrome or a skin disorder; methods for inhibiting angiogenesis; methods for inhibiting vascular endothelial growth factor (VEGF) or VEGF protein expression; methods for inhibiting capillary tube formation; methods for suppressing neuronal sensitivity; methods for treating pain, methods for enhancing DNA base excision repair; and methods for enhancing neuronal DNA repair function; wherein each method comprises administering to a subject in need thereof an effective amount of a composition comprising APX3330 or an APX3330 hemicalcium salt monohydrate.

Description

COMPOSITIONS COMPRISING AN APX3330 HEMICALCIUM SALTMONOHYDRATE AND THERAPEUTIC USES THEREOFCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of and priority to United States Provisional Patent Application serial number 63 / 688,036, filed August 28, 2024; and United States Provisional Patent Application serial number 63 / 565,345, filed March 14. 2024; the contents of each of which are hereby incorporated by reference in their entirety.FIELD OF THE INVENTION

[0002] This invention relates to compositions comprising APX3330 or an APX3330 hemicalcium salt monohydrate. The invention also provides methods for treating or preventing an ocular disease, an inflammatory disease, Barret's esophagus (BE), cancer, a hepatic disease, a cardiovascular disease, idiopathic pulmonary fibrosis, a keloid, systemic sclerosis, chemotherapy -induced peripheral neuropathy, stroke, gastro-intestinal dysfunction, chronic gastroesophageal reflux disease, von Hippel-Lindau syndrome or a skin disorder; methods for inhibiting angiogenesis; methods for inhibiting vascular endothelial grow th factor (VEGF) or VEGF protein expression; methods for inhibiting capillary tube formation; methods for suppressing neuronal sensitivity; methods for treating pain; methods for enhancing DNA base excision repair; and methods for enhancing neuronal DNA repair function, wherein each method comprises administering to a subject in need thereof an effective amount of a composition comprising APX3330 or an APX3330 hemicalcium salt monohydrate.BACKGROUND OF THE INVENTION

[0003] APX3330, also known as (2E)-2-[(4,5-dimethoxy-2-methyl-3,6-dioxo-l,4- cyclohexadien- 1 -yl)methylene]-undecanoic acid, (2E)-2-[(4,5-dimethoxy-2-methyl-3,6- dioxocyclohexa-l,4-dien-l-yl)methylidene]undecanoic acid, (2E)-3-[2-(5,6-dimethoxy-3- methyl-l,4-benzoquinoyl)]-2-nonylpropenoic acid, “APX-3330” or “E3330”, has undergone clinical trials to evaluate its safety and efficacy to treat diabetic retinopathy, diabetic macular edema, or patients with advanced solid tumors.SUMMARY OF THE INVENTION

[0004] The present invention provides compositions comprising (i) APX3330 or an APX3330 hemi calcium salt monohydrate, (ii) talc, and (iii) crospovidone or low-substituted hydroxypropyl cellulose (each composition being a '‘composition of the invention”).

[0005] The present invention further provides methods for treating or preventing an ocular disease, an inflammatory disease, Barrett's esophagus (BE), cancer, a hepatic disease, a cardiovascular disease, idiopathic pulmonary fibrosis, a keloid, systemic sclerosis, chemotherapy-induced peripheral neuropathy, stroke, gastro-intestinal dysfunction, chronic gastroesophageal reflux disease, von Hippel-Lindau syndrome or a skin disorder; methods for inhibiting angiogenesis; methods for inhibiting vascular endothelial growth factor (VEGF) or VEGF protein expression; methods for inhibiting capillary tube formation; methods for suppressing neuronal sensitivity; methods for treating pain; methods for enhancing DNA base excision repair; and methods for enhancing neuronal DNA repair function, wherein each method comprises administering to a subject in need thereof an effective amount of a composition of the invention (each method being a “method of the invention”).BRIEF DESCRIPTION OF THE DRAWINGS

[0006] Fig. 1 shows an XRPD pattern of the APX3330 hemicalcium salt monohydrate obtained according to Reference Example A.

[0007] Fig. 2 shows an XRPD pattern of the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B.

[0008] Fig. 3 shows a dissolution profile of each of three batches of APX3330 tablets of Reference Example C.

[0009] Fig. 4 shows a dissolution profile of each of six APX3330 hemicalcium salt monohydrate tablets of Example 1.

[0010] Fig. 5 shows a dissolution profile of each of six APX3330 hemicalcium salt monohydrate tablets of Example 2.DETAILED DESCRIPTION OF THE INVENTIONDefinitions

[0011] The term “about” when immediately preceding a numerical value means ± 10% of the numerical value.

[0012] Throughout the present specification, numerical ranges are provided for certain quantities. These ranges comprise all subranges therein. Thus, the range “from 50 to 80”includes all possible ranges therein (e.g., 51-79, 52-78, 53-77, 54-76, 55-75, 60-70. etc ). Furthermore, all values within a given range may be an endpoint for the range encompassed thereby (e.g., the range 50-80 includes the ranges with endpoints such as 55-80, 50-75, etc.).

[0013] As used herein, “effective amount” refers to an amount of a composition of the invention that is effective to treat or prevent an ocular disease, an inflammatory disease, Barrett's esophagus (BE), cancer, a hepatic disease, a cardiovascular disease, idiopathic pulmonary fibrosis, a keloid, systemic sclerosis, chemotherapy -induced peripheral neuropathy, stroke, gastro-intestinal dysfunction, chronic gastroesophageal reflux disease, von Hippel-Lindau syndrome or a skin disorder; inhibit angiogenesis; inhibit vascular endothelial growth factor (VEGF) or VEGF protein expression; inhibit capillary tube formation; suppress neuronal sensitivity; treat pain; enhance DNA base excision repair; or enhance neuronal DNA repair function.

[0014] All weight percentages (e.g., “% by weight” and “wt. %” and “w / w”) referenced herein, unless otherwise indicated, are relative to the total weight of the compound or composition of the invention, as the case may be.

[0015] The term “pharmaceutically acceptable salt” includes a base addition salt. Pharmaceutically acceptable salts can be obtained by reacting a compound of the invention functioning as an acid, with an inorganic or organic base to form a salt, for example, a sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, ammonium, isopropylammonium, trimethylammonium, phenylalanine, arginine, or histidine salt. In some embodiments, the pharmaceutically acceptable salt is a mono- salt. In some embodiments, the pharmaceutically acceptable salt is a di- salt. In some embodiments, the pharmaceutically acceptable salt is a tri- salt. Those skilled in the art will further recognize that pharmaceutically acceptable salts can be prepared by reaction of a compound with an appropriate inorganic or organic acid or base via any of a number of known methods.

[0016] As used herein in connection w ith a compound of the invention, an “impurity ” is a compound or substance other than the compound of the invention.

[0017] As used herein, “predominantly amorphous” when used in connection with a compound means an admixture of the compound in amorphous form and the compound in crystalline form, wherein the admixture comprises at least 50% of the compound in amorphous form by weight of the admixture.

[0018] As used herein, “substantially the same as” when used in connection with an XRPD pattern means that each peak (having an at least 2% relative intensity) of the XRPD patterndiffers from a respective peak of a reference or comparative XRPD pattern by no more than ± 0.2 degrees 2-theta. The most intense peak in an XRPD pattern is assigned 100% relative peak intensity and the intensities of all other peaks in the XRPD pattern are measured relative to the most intense peak (relative peak intensity).

[0019] As used herein, “stable” when used in connection with APX3330, an APX3330 hemicalcium salt monohydrate or a composition of the invention means that the APX3330, APX3330 hemi calcium salt monohydrate or composition of the invention comprises no more than 10% of a degradation product of the APX3330 or the APX3330 hemi calcium salt monohydrate by weight of APX3330 or the APX3330 hemicalcium salt monohydrate.

[0020] As used herein, “low-substituted hydroxypropyl cellulose” when used in connection with a composition of the invention means a low-substituted O-(2-hydroxypropylated) cellulose having not less than 5.0% w / w and not more than 16.0% w / w 2-hydroxypropoxy group (-OCH2CHOHCH3), calculated on the dried basis of the low-substituted hydroxypropyl cellulose.

[0021] As used herein, “anhydrous lactose” means lactose comprising <1% water by weight as determined by Karl Fischer titration.

[0022] APX3330 has the structure:reference to a salt or a hydrate, e.g., a hemicalcium salt monohydrate, means a compound having the structure depicted above.APX3330 and APX3330 Hemicalcium Salt Monohydrate

[0023] In some embodiments, the compositions of the invention comprise APX3330.

[0024] In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate having the formula:

[0025] In some embodiments, the APX3330 hemicalcium salt monohydrate comprises about 4% w / w to about 10% w / w water. In some embodiments, the APX3330 hemicalcium salt monohydrate comprises about 4% w / w to about 8% w / w water. In some embodiments, the APX3330 hemi calcium salt monohydrate comprises about 4% w / w to about 6% w / w water.

[0026] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 5.1 ± 0.2 degrees 2-theta, a peak at5.3 ± 0.2 degrees 2-theta, and a peak at 10. 1 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at a peak at 8.0 ± 0.2 degrees 2-theta or a peak at 12.8 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at13.3 ± 0.2 degrees 2-theta, a peak at 17.9 ± 0.2 degrees 2-theta, or a peak at 19.6 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 14.6 ± 0.2 degrees 2-theta or a peak at 18.5 ± 0.2 degrees 2-theta.

[0027] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5. 1 ± 0.2 degrees 2-theta, a peak at 5.3 ± 0.2 degrees 2- theta, and a peak at 10.1 ± 0.2 degrees 2-theta, wherein the peak at 5. 1 ± 0.2 degrees 2-theta, the peak at 5.3 ± 0.2 degrees 2-theta, and the peak at 10. 1 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 25%. In some embodiments, the XRPD pattern further comprises a peak at 8.0 ± 0.2 degrees 2-theta or a peak at 12.8 ± 0.2 degrees 2-theta, wherein the peak at 8.0 ± 0.2 degrees 2-theta and the peak at 12.8 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 10%. In some embodiments, the XRPD pattern further comprises a peak at 13.3 ± 0.2 degrees 2-theta, a peak at 17.9 ± 0.2 degrees 2-theta, or a peak at 19.6 ± 0.2 degrees 2-theta, wherein the peak at 13.3 ± 0.2 degrees 2-theta, the peak at 17.9 ± 0.2 degrees 2-theta, and the peak at 19.6 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 10%. In some embodiments, the XRPD pattern further comprises a peak at 14.6 ± 0.2 degrees 2-theta or a peak at 18.5 ± 0.2 degrees 2-theta, wherein the peak at 14.6 ± 0.2 degrees 2-theta or the peak at 18.5 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 8%.

[0028] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 10. 1 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 13.3 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 14.6 ± 0.2 degrees 2-theta.

[0029] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta and a peak at 10. 1 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 10. 1 ± 0.2 degrees 2-theta and a peak at 14.6 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta, a peak at 10.1 ± 0.2 degrees 2-theta, and a peak at 13.3 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta, a peak at 10. 1 ± 0.2 degrees 2-theta, and a peak at 14.6 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta, a peak at 10.1 ± 0.2 degrees 2-theta, a peak at 13.3 ± 0.2 degrees 2-theta, or a peak at 14.6 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta, a peak at 10.1 ± 0.2 degrees 2-theta, a peak at 13.3 ± 0.2 degrees 2-theta, and a peak at 14.6 ± 0.2 degrees 2-theta.

[0030] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5. 1 ± 0.2 degrees 2-theta, a peak at 8.0 ± 0.2 degrees 2- theta, a peak at 10.1 ± 0.2 degrees 2-theta, a peak at 13.3 ± 0.2 degrees 2-theta, a peak at 14.6 ± 0.2 degrees 2-theta, and a peak at 18.5 ± 0.2 degrees 2-theta.

[0031] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 10.1 ± 0.2 degrees 2-theta and 1 peak, 2 peaks. 3 peaks, 4 peaks, 5 peaks. 6 peaks, 7 peaks. 8 peaks, or 9 peaks of Table 2. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 10. 1 ± 0.2 degrees 2-theta and 1 peak, 2 peaks, 3 peaks, 4 peaks, 5 peaks, 6 peaks, 7 peaks, 8 peaks, or 9 peaks of the following peaks: a peak at 5. 1 ± 0.2 degrees 2-theta, a peak at 5.3 ± 0.2 degrees 2-theta, a peak at 7.9 ± 0.2 degrees 2-theta, a peak at 12.8 ± 0.2 degrees 2-theta, apeak at 13.3 ± 0.2 degrees 2-theta, a peak at 14.6 ± 0.2 degrees 2-theta, a peak at 17.9 ± 0.2 degrees 2-theta, a peak at 18.5 ± 0.2 degrees 2-theta, and a peak at 19.6 ± 0.2 degrees 2-theta.

[0032] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.0 ± 0.2 degrees 2-theta, a peak at 7.9 ± 0.2 degrees 2- theta, a peak at 8.3 ± 0.2 degrees 2-theta, a peak at 10. 1 ± 0.2 degrees 2-theta, a peak at 10.4 ± 0.2 degrees 2-theta, a peak at 12.8 ± 0.2 degrees 2-theta, a peak at 13.3 ± 0.2 degrees 2- theta. a peak at 14.6 ± 0.2 degrees 2-theta. a peak at 17.9 ± 0.2 degrees 2-theta. a peak at 18.5 ± 0.2 degrees 2-theta, a peak at 20.5 ± 0.2 degrees 2-theta, a peak at 22.6 ± 0.2 degrees 2- theta, and a peak at 27.2 ± 0.2 degrees 2-theta.

[0033] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 10. 1 ± 0.2 degrees 2-theta and 1 peak, 2 peaks. 3 peaks, 4 peaks, 5 peaks, 6 peaks, 7 peaks, 8 peaks, 9 peaks, 10 peaks, 11 peaks, or 12 peaks of the following peaks: a peak at 5.0 ± 0.2 degrees 2-theta, a peak at 7.9 ± 0.2 degrees 2-theta, a peak at 8.3 ± 0.2 degrees 2-theta, a peak at 10.4 ± 0.2 degrees 2-theta, a peak at 12.8 ± 0.2 degrees 2-theta, a peak at 13.3 ± 0.2 degrees 2-theta, a peak at 14.6 ± 0.2 degrees 2-theta, a peak at 17.9 ± 0.2 degrees 2-theta. a peak at 18.5 ± 0.2 degrees 2-theta. a peak at 20.5 ± 0.2 degrees 2-theta, a peak at 22.6 ± 0.2 degrees 2-theta, and a peak at 27.2 ± 0.2 degrees 2-theta.

[0034] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak from Table 2 having a relative peak intensity (%) of greater than 25%. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak from Table 2 having a relative peak intensity (%) of greater than 15%. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak from Table 2 having a relative peak intensity (%) of greater than 12%.

[0035] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern that is substantially the same as that depicted in Fig. 1.

[0036] In some embodiments, the XRPD data are obtained using a reflection mode (scan type: Coupled TwoTheta / Theta) scanning the samples at between 3° and 40° 2-theta angles, and using the following measurements characteristics: increment per step of 0.02°, time per step of 0.3 s, and generator voltage / generator amperage of 10 mA / 30 kV to reach 0.3 kW power.

[0037] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a differential scanning calorimetry (DSC) thermogram comprising an endothermic peak having a peak maximum of from about 80 °C to about 105 °C. In some embodiments, the APX3330hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak having a peak maximum of from about 90 °C to about 105 °C. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak having a peak maximum of from about 95 °C to about 105 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak having a peak maximum of from about 98 °C to about 103 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak having a peak maximum of about 101 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak that onsets at about 77 °C.

[0038] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak having a peak maximum of from about 210 °C to about 216 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak having a peak maximum of from about 212 °C to about 215 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram compnsing an exothermic peak having a peak maximum of from about 213 °C to about 215 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak having a peak maximum at about 214 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak that onsets at about 211 °C.

[0039] In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example A is at least about 98% pure by weight. In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example A is at least about 99% pure by weight.

[0040] In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example A is at least about 98% pure by weight after being exposed to 40 °C / 75% relative humidity (RH) for 1 week. In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example A is at least about 99% pure by weight after being exposed to 40 °C / 75% RH for 1 week.

[0041] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 4. 1 ± 0.2 degrees 2-theta, a peak at 5.3 ± 0.2 degrees 2- theta. and a peak at 6.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further compnses a peak at 5.8 ± 0.2 degrees 2-theta or a peak at 14. 1 ± 0.2 degrees 2-theta.In some embodiments, the XRPD pattern further comprises a peak at 12.8 ± 0.2 degrees 2- theta or a peak at 13.7 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 10.8 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 6. 1 ± 0.2 degrees 2-theta or a peak at 11.4 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 17.6 ± 0.2 degrees 2- theta or a peak at 20.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 3.0 ± 0.2 degrees 2-theta or a peak at 12.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 1 1 .4 ± 0.2 degrees 2-theta, a peak at 17.6 ± 0.2 degrees 2-theta, and a peak at 21.9 ± 0.2 degrees 2-theta.

[0042] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 4. 1 ± 0.2 degrees 2-theta. a peak at 5.3 ± 0.2 degrees 2- theta, and a peak at 6.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 5.8 ± 0.2 degrees 2-theta or a peak at 13.7 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 12.8 ± 0.2 degrees 2- theta or a peak at 14. 1 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 12.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 11 .4 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 10.8 ± 0.2 degrees 2-theta

[0043] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 4. 1 ± 0.2 degrees 2-theta. a peak at 5.4 ± 0.2 degrees 2- theta, and a peak at 6.4 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 5.8 ± 0.2 degrees 2-theta or a peak at 13.8 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 12.8 ± 0.2 degrees 2- theta or a peak at 14.2 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 12.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 12.0 ± 0.2 degrees 2-theta or a peak at 11.4 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 10.8 ± 0.2 degrees 2- theta or a peak at 20.9 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 13. 1 ± 0.2 degrees 2-theta, a peak at 17.6 ± 0.2 degrees 2-theta, and a peak at 23.7 ± 0.2 degrees 2-theta.

[0044] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 4. 1 ± 0.2 degrees 2-theta, a peak at 5.3 ± 0.2 degrees 2- theta. and a peak at 6.3 ± 0.2 degrees 2-theta, wherein the peak at 4. 1 ± 0.2 degrees 2-theta, the peak at 5.3 ± 0.2 degrees 2-theta, and the peak at 6.3 ± 0.2 degrees 2-theta, have a relativepeak intensity (%) of greater than 30%. In some embodiments, the XRPD pattern further comprises a peak at 5.8 ± 0.2 degrees 2-theta or a peak at 14. 1 ± 0.2 degrees 2-theta, wherein the peak at 5.8 ± 0.2 degrees 2-theta and the peak at 14. 1 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 15%. In some embodiments, the XRPD pattern further comprises a peak at 12.8 ± 0.2 degrees 2-theta or a peak at 13.7 ± 0.2 degrees 2-theta, wherein the peak at 12.8 ± 0.2 degrees 2-theta and the peak at 13.7 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 10%. In some embodiments, the XRPD pattern further comprises a peak at 10.8 ± 0.2 degrees 2-theta, wherein the peak has a relative peak intensity (%) of greater than 10%. In some embodiments, the XRPD pattern further comprises a peak at 6. 1 ± 0.2 degrees 2-theta or a peak at 11.4 ± 0.2 degrees 2-theta, wherein the peak at 6. 1 ± 0.2 degrees 2-theta and the peak at 11.4 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 10%. In some embodiments, the XRPD pattern further comprises a peak at 17.6 ± 0.2 degrees 2-theta or a peak at 20.3 ± 0.2 degrees 2-theta, wherein the peak at 17.6 ± 0.2 degrees 2-theta and the peak at 20.3 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 8%. In some embodiments, the XRPD pattern further compnses a peak at 3.0 ± 0.2 degrees 2-theta or a peak at 12.3 ± 0.2 degrees 2-theta, wherein the peak at 3.0 ± 0.2 degrees 2-theta and the peak at 12.3 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 5%. In some embodiments, the XRPD pattern further comprises a peak at 11.4 ± 0.2 degrees 2-theta, a peak at 17.6 ± 0.2 degrees 2-theta, or a peak at 21.9 ± 0.2 degrees 2-theta, wherein the peak at 11.4 ± 0.2 degrees 2-theta, the peak at 17.6 ± 0.2 degrees 2-theta, and the peak at 21.9 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 5%.

[0045] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 4. 1 ± 0.2 degrees 2-theta, a peak at 5.4 ± 0.2 degrees 2- theta, and a peak at 6.4 ± 0.2 degrees 2-theta, wherein the peak at 4. 1 ± 0.2 degrees 2-theta, the peak at 5.4 ± 0.2 degrees 2-theta, and the peak at 6.4 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 30%. In some embodiments, the XRPD pattern further comprises a peak at 5.8 ± 0.2 degrees 2-theta or a peak at 13.8 ± 0.2 degrees 2-theta, wherein the peak at 5.8 ± 0.2 degrees 2-theta and the peak at 13.8 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 15%. In some embodiments, the XRPD pattern further comprises a peak at 12.8 ± 0.2 degrees 2-theta or a peak at 14.2 ± 0.2 degrees 2-theta, wherein the peak at 12.8 ± 0.2 degrees 2-theta and the peak at 14.2 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 10%. In some embodiments, the XRPD pattern further compnses a peak at 12.3 ± 0.2 degrees 2-theta, wherein the peak has a relative peakintensity (%) of greater than 10%. In some embodiments, the XRPD pattern further comprises a peak at 12.0 ± 0.2 degrees 2-theta or a peak at 11.4 ± 0.2 degrees 2-theta, wherein the peak at 12.0 ± 0.2 degrees 2-theta and the peak at 11.4 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 10%. In some embodiments, the XRPD pattern further comprises a peak at 10.8 ± 0.2 degrees 2-theta or a peak at 20.9 ± 0.2 degrees 2-theta, wherein the peak at 10.8 ± 0.2 degrees 2-theta and the peak at 20.9 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 6%. In some embodiments, the XRPD pattern further comprises a peak at 13.1 ± 0.2 degrees 2-theta, a peak at 17.6 ± 0.2 degrees 2-theta, or a peak at 23.7 ± 0.2 degrees 2-theta, wherein the peak at 13.1 ± 0.2 degrees 2-theta, the peak at 17.6 ± 0.2 degrees 2-theta, and the peak at 23.7 ± 0.2 degrees 2-theta have a relative peak intensity (%) of greater than 5%.

[0046] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.3 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 13.7 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 14.1 ± 0.2 degrees 2-theta.

[0047] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.3 ± 0.2 degrees 2-theta and a peak at 5.8 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.3 ± 0.2 degrees 2-theta and a peak at 14. 1 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.3 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2- theta, and a peak at 14. 1 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 6.3 ± 0.2 degrees 2-theta, and a peak at 13.7 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 6.3 ± 0.2 degrees 2-theta, a peak at 13.7 ± 0.2 degrees 2-theta, or a peak at 14.1 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 6.3 ± 0.2 degrees 2-theta, a peak at 13.7 ± 0.2 degrees 2-theta, and a peak at 14.1 ± 0.2 degrees 2-theta.

[0048] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta and a peak at 6.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 13.7 ± 0.2 degrees 2-theta or a peak at 14. 1 ± 0.2 degrees 2-theta.

[0049] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta and a peak at 6.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 13.7 ± 0.2 degrees 2-theta or a peak at 14.1 ± 0.2 degrees 2-theta.

[0050] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 13.8 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 14.2 ± 0.2 degrees 2-theta.

[0051] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta and a peak at 5.8 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta and a peak at 14.2 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2- theta, and a peak at 14.2 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 6.4 ± 0.2 degrees 2-theta, and a peak at 13.8 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 13.8 ± 0.2 degrees 2-theta, or a peak at 14.2 ± 0.2 degrees 2-theta. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 13.8 ± 0.2 degrees 2-theta, and a peak at 14.2 ± 0.2 degrees 2-theta.

[0052] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta and a peak at 6.4 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 13.8 ± 0.2 degrees 2-theta or a peak at 14.2 ± 0.2 degrees 2-theta.

[0053] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta and a peak at 6.4 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern further comprises a peak at 13.8 ± 0.2 degrees 2-theta or a peak at 14.2 ± 0.2 degrees 2-theta.

[0054] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.3 ± 0.2 degrees 2-theta and 1 peak, 2 peaks, 3 peaks, 4 peaks, 5 peaks. 6 peaks, 7 peaks. 8 peaks, or 9 peaks of Table 3. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.3 ± 0.2 degrees 2-theta and 1 peak, 2 peaks, 3 peaks, 4 peaks, 5 peaks, 6 peaks, 7 peaks, 8 peaks, or 9 peaks of the following peaks: a peak at 4. 1 ± 0.2 degrees 2-theta, a peak at 5.3 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 6. 1 ± 0.2 degrees 2-theta, a peak at 10.8 ± 0.2 degrees 2-theta, a peak at 11.4 ± 0.2 degrees 2-theta, a peak at 12.8 ± 0.2 degrees 2-theta, a peak at 13.7 ± 0.2 degrees 2-theta, and 14.1 ± 0.2 degrees 2-theta.

[0055] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta and 1 peak, 2 peaks, 3 peaks, 4 peaks, 5 peaks. 6 peaks, 7 peaks. 8 peaks, or 9 peaks of Table 3. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits an XRPD pattern comprising a peak at 6.4 ± 0.2 degrees 2-theta and 1 peak, 2 peaks, 3 peaks, 4 peaks, 5 peaks, 6 peaks, 7 peaks, 8 peaks, or 9 peaks of the following peaks: a peak at 4. 1 ± 0.2 degrees 2-theta, a peak at 5.4 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 11.4 ± 0.2 degrees 2-theta, a peak at 12.0 ± 0.2 degrees 2-theta, a peak at 12.3 ± 0.2 degrees 2-theta, a peak at 12.8 ± 0.2 degrees 2-theta, a peak at 13.8 ± 0.2 degrees 2-theta, and 14.2 ± 0.2 degrees 2-theta.

[0056] In some embodiments, the APX3330 hemicalcium salt monohy drate exhibits an XRPD pattern comprising a Table 3 peak having a relative peak intensity (%) of greater than 30%. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a Table 3 peak having a relative peak intensity (%) of greater than 20%. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a Table 3 peak having a relative peak intensity' (%) of greater than 15%. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern comprising a Table 3 peak having a relative peak intensity (%) of greater than 5%.

[0057] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern that is substantially the same as that depicted in Fig. 2.

[0058] In some embodiments, the XRPD data are obtained in transmission mode (scan ty pe: TwoTheta or Offset Coupled TwoTheta / Theta) scanning the samples at between 1.5° and 45°2-theta angles, and using the following measurements characteristics: acquisition time of 7.58 minutes, increment per step of 0.01°, time per step of 0. 1 s, and generator voltage / generator amperage of 40 mA / 40 kV to reach 1.6 kW power.

[0059] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak having a peak maximum of from about 80 °C to about 84 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak having a peak maximum of from about 81 °C to about 83 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak having a peak maximum of about 83 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak that onsets at about 58 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an endothermic peak that onsets at about 54 °C.

[0060] In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak having a peak maximum of from about 213 °C to about 216 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak having a peak maximum of from about 215 °C to about 216 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak having a peak maximum of from about 208 °C to about 216 °C. In some embodiments, the APX3330 hemicalcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak having a peak maximum of from about 210 °C to about 214 °C. In some embodiments, the APX3330 hemi calcium salt monohydrate exhibits a DSC thermogram comprising an exothermic peak that onsets at about 212 °C.

[0061] In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B is at least about 98% pure by weight. In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B is at least about 99% pure by weight.

[0062] In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B is at least about 98% pure by weight. In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B is at least about 99% pure by weight.

[0063] In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B is at least about 98% pure by weight after being exposedto 40 °C / 75% RH for 1 week. In some embodiments, the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B is at least about 99% pure by weight after being exposed to 40 °C / 75% RH for 1 week.

[0064] In some embodiments, the APX3330 hemicalcium salt monohydrate is at least about 98% pure by weight, and the hemicalcium salt monohydrate comprises no more than about 2% of an impurity by weight of the hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 95.0% to 100% pure by weight, and the hemicalcium salt monohydrate comprises 0% to about 5% of an impurity by weight of the hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 98% to 100% pure by weight, and the hemicalcium salt monohydrate comprises 0% to about 2% of an impurity by weight of the hemi calcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 98%, about 98.5%, about 99%, about 99.5%, or 100% pure by weight, and the hemicalcium salt monohydrate comprises about 2%, about 1.5%, about 1%, about 0.5%, or 0%, respectively, of an impurity by weight of the hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 99.5%, about 99.9%, or about 99.95% pure by weight, and the hemicalcium salt monohydrate comprises about 0.5%, about 0.1%, or about 0.05%, respectively, of an impurity by weight of the hemicalcium salt monohydrate. In some embodiments, the purity or the impurity are determined by high-performance liquid chromatography (HPLC). In some embodiments, the purity or impurity is determined by HPLC at 236 nm. In some embodiments, the purity or impurity is determined by HPLC at 262 nm. In some embodiments, the purity or impurity is determined by HPLC at 266 nm. In some embodiments, the purity or impurity is determined by HPLC at 270 nm. In some embodiments, the purity or impurity is determined by titration.

[0065] In some embodiments, the APX3330 hemicalcium salt monohydrate is at least about 98% pure by weight after being exposed to 40 °C / 75% RH for 1 week. In some embodiments, the APX3330 hemicalcium salt monohydrate is at least about 99% pure by weight after being exposed to 40 °C / 75% RH for 1 week.

[0066] In some embodiments, the APX3330 hemicalcium salt monohydrate is amorphous.

[0067] In some embodiments, the APX3330 hemicalcium salt monohydrate is predominantly amorphous. In some embodiments, the APX3330 hemicalcium salt monohydrate is predominantly amorphous, wherein the predominantly amorphous hemicalcium salt monohydrate exhibits an XRPD pattern comprising a peak at 4.5 ± 0.2 degrees 2-theta and a peak at 6.0 ± 0.2 degrees 2-theta.

[0068] In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than 5% of APX3330 by weight of the salt. In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than 4% of APX3330 by weight of the APX3330 hemi calcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than 3% APX3330 by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than 2% of APX3330 by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than 1% of APX3330 by weight of the APX3330 hemicalcium salt monohydrate.

[0069] In some embodiments, the APX3330 hemicalcium salt monohydrate is greater than 90% pure according to its HPLC chromatogram, based on the HPLC chromatogram’s relative peak area. In some embodiments, the APX3330 hemicalcium salt monohydrate is greater than 95% pure according to its HPLC chromatogram, based on the HPLC chromatogram’s relative peak area. In some embodiments, the APX3330 hemicalcium salt monohydrate is greater than 98% pure according to its HPLC chromatogram, based on the HPLC chromatogram’s relative peak area. In some embodiments, the APX3330 hemicalcium salt monohydrate is greater than 90%, greater than 91 %, greater than 92%, greater than 93%, greater than 94%, greater than 95%, greater than 96%, greater than 97%, greater than 98%, or greater than 99% pure according to its HPLC chromatogram, based on the HPLC chromatogram’s relative peak area. In some embodiments, purity is determined according to HPLC at 236 nm. In some embodiments, purity is determined according to HPLC at 266 nm.

[0070] In some embodiments, the APX3330 hemicalcium salt monohydrate is stable at 25 °C / 60%RH for at least one week. In some embodiments, the APX3330 hemicalcium salt monohydrate is stable at 25 °C / 60%RH for at least one week, at least two weeks, at least three weeks, at least four weeks, at least 1 month, at least 2 months, at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 18 months, at least 24 months, at least 30 months, or at least 36 months. In some embodiments, 1 month is 28 days. 29 days, 30 days, or 31 days.

[0071] In some embodiments, the APX3330 hemicalcium salt monohydrate is stable at 40 °C / 75%RH for at least one week. In some embodiments, the APX3330 hemicalcium salt monohydrate is stable at 40 °C / 75%RH for at least one week, at least two weeks, at least three weeks, at least four weeks, at least 1 month, at least 2 months, at least 3 months, at least4 months, at least 5 months, or at least 6 months. In some embodiments, 1 month is 28 days, 29 days, 30 days, or 31 days.

[0072] In some embodiments, the APX3330 hemicalcium salt monohydrate is crystalline.

[0073] In some embodiments, the APX3330 hemicalcium salt monohydrate is at least about 98% pure by weight, and the APX3330 hemicalcium salt monohydrate comprises no more than about 2% of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 95.0% to 100% pure by weight, and the APX3330 hemi calcium salt monohydrate comprises 0% to about 5% of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 98% to 100% pure by weight, and the APX3330 hemicalcium salt monohydrate comprises 0% to about 2% of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 98%, about 98.5%, about 99%, about 99.5%, or 100% pure by weight, and the APX3330 hemicalcium salt monohydrate comprises about 2%, about 1.5%, about 1%, about 0.5%. or 0%, respectively, of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 99.5%, about 99.9%, or about 99.95% pure by weight, and the APX3330 hemicalcium salt monohydrate comprises about 0.5%, about 0.1%, or about 0.05%, respectively, of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 98%, about 98.5%, about 99%, about 99.5%, or 100% pure by weight, and the APX3330 hemicalcium salt monohydrate comprises about 2%, about 1.5%, about 1%, about 0.5%, or 0%, respectively, of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 99.5%, about 99.9%, or about 99.95% pure by weight, and the APX3330 hemicalcium salt monohydrate comprises about 0.5%, about 0.1%, or about 0.05%, respectively, of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate is about 98%, about 98.5%, about 99%, about 99.5%, or 100% pure by weight, and the APX3330 hemicalcium salt monohydrate comprises about 2%, about 1.5%, about 1%, about 0.5%, or 0%, respectively, of an impurity by weight of the APX3330 hemi calcium salt monohydrate. In some embodiments, an impurity' is determined by high-performance liquid chromatography (HPLC). In some embodiments, an impurity is determined according to APX3330 hemicalcium salt monohydrate's HPLC chromatogramobtained at about 236 nm to about 266 nm. In some embodiments, an impurity is determined by titration.

[0074] In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than about 1% of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than about 0.5% of an impurity by weight of the APX3330 hemicalcium salt monohydrate. In some embodiments, the APX3330 hemicalcium salt monohydrate comprises less than about 1%. less than about 0.9%, less than about 0.8%, less than about 0.7%, less than about 0.6%, less than about 0.5%, less than about 0.4%, less than about 0.3%, or less than about 0.2% of an impurity by weight of the APX3330 hemicalcium salt monohydrate.Compositions

[0075] The compositions of the invention comprise (i) APX3330 or an APX3330 hemicalcium salt monohydrate, (ii) talc, and (iii) crospovidone or low-substituted hydroxypropyl cellulose.

[0076] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc, and (iii) crospovidone or low-substituted hydroxypropyl cellulose. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc, and (iii) crospovidone and low- substituted hydroxypropyl cellulose.

[0077] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxy methyl cellulose by weight of the mixture and about 81% to about 89%microcrystalline cellulose by weight of the mixture, and wherein not more than 0.1% byweight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieve as determined by7air jet sieving. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81 : 19 to about 89:11 by weight. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone or low- substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the ratio of mi crocry stall ine cellulose to sodium carboxymethyl cellulose in the mixture is about 81:19 to about 89:11 by w eight, and wherein not more than 0.1 % by weight of the mixture’ s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieve as determined by air jet sieving.

[0078] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemi calcium salt monohydrate, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% mi crocry stalline cellulose by weight of the mixture. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemi calcium salt monohydrate, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxy methyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture, and wherein not more than 0.1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieveas determined by air jet sieving. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the ratio of mi crocry stall ine cellulose to sodium carboxymethyl cellulose in the mixture is about 81: 19 to about 89: 11 by weight. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone and low- substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising mi crocry stall ine cellulose and sodium carboxymethyl cellulose, wherein the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81: 19 to about 89: 11 by weight, and wherein not more than 0.1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieve as determined by air jet sieving.

[0079] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc, and (iii) crospovidone or low-substituted hydroxypropyl cellulose. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc, and (iii) crospovidone and low-substituted hydroxypropyl cellulose.

[0080] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture, and wherein not more than 0.1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieve as determined by air jet sieving. In someembodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81:19 to about 89: 11 by weight. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight, and wherein not more than 0.1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture's particles are retained on a 325 mesh (45 microns) sieve as determined by air jet sieving.

[0081] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture, and wherein not more than 0.1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieve as determined by air jet sieving. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substitutedhydroxypropyl cellulose, and further comprise (iv) a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight, and wherein not more than 0.1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieve as determined by air jet sieving.

[0082] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose.

[0083] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemi calcium salt monohydrate, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) anhydrous lactose.

[0084] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose monohydrate.

[0085] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemi calcium salt monohydrate, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose.

[0086] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemi calcium salt monohydrate, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) anhydrous lactose.

[0087] In some embodiments, the compositions of the invention comprise (i) an APX3330 hemi calcium salt monohydrate, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose monohydrate.

[0088] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose.

[0089] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) anhydrous lactose.

[0090] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone or low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose monohydrate.

[0091] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose.

[0092] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) anhydrous lactose.

[0093] In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc and (iii) crospovidone and low-substituted hydroxypropyl cellulose, and further comprise (iv) lactose monohydrate.

[0094] In some embodiments, the compositions of the invention comprise crospovidone and low-substituted hydroxypropyl cellulose.

[0095] In some embodiments, the compositions of the invention further comprise lactose, mi crocry stall ine cellulose, dicalcium phosphate dihydrate, or calcium carbonate.

[0096] In some embodiments, the compositions of the invention further comprise anhydrous lactose, microcrystalline cellulose, dicalcium phosphate dihydrate, or calcium carbonate.

[0097] In some embodiments, the compositions of the invention further comprise lactose monohydrate, microcrystalline cellulose, dicalcium phosphate dihydrate, or calcium carbonate.

[0098] In some embodiments, the compositions of the invention further comprise partially pregelatinized maize starch. In some embodiments, the partially pregelatinized maize starch has the trademark STARCH 1500 (Colorcon, Inc.).

[0099] In some embodiments, the compositions of the invention further comprise D-a- tocopheryl polyethylene glycol succinate (vitamin E TPGS).

[0100] In some embodiments, the compositions of the invention further comprise sodium stearyl fumarate or magnesium stearate.

[0101] In some embodiments, the compositions of the invention further comprise lactose, mi crocry stall ine cellulose, dicalcium phosphate dihydrate, calcium carbonate, partially pregelatinized maize starch, sodium stearyl fumarate, polyethylene glycol, vitamin E TPGS, or magnesium stearate.

[0102] In some embodiments, the compositions of the invention further comprise anhydrous lactose, microcrystalline cellulose, dicalcium phosphate dihydrate, calcium carbonate, partially pregelatinized maize starch, sodium stearyl fumarate, polyethylene glycol, vitamin E TPGS, or magnesium stearate.

[0103] In some embodiments, the compositions of the invention further comprise lactose monohydrate, microcrystalline cellulose, dicalcium phosphate dihydrate, calcium carbonate, partially pregelatinized maize starch, sodium stearyl fumarate, polyethylene glycol, vitamin E TPGS, or magnesium stearate.

[0104] In some embodiments, the compositions of the invention comprise low-substituted hydroxypropyl cellulose. In some embodiments, the compositions of the invention further comprise lactose, microcrystalline cellulose, or magnesium stearate. In some embodiments, the compositions of the invention further comprise lactose, microcrystalline cellulose, and magnesium stearate. In some embodiments, the compositions of the invention further comprise dicalcium phosphate dihydrate, microcrystalline cellulose, or magnesium stearate. In some embodiments, the compositions of the invention further comprise dicalcium phosphate dihydrate, microcrystalline cellulose, and magnesium stearate. In some embodiments, the compositions of the invention further comprise lactose, microcrystalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, or crospovidone. In some embodiments, the compositions of the invention further comprise lactose, microcrystalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, and crospovidone. In some embodiments, the compositions of the invention further comprise lactose, magnesium stearate, crospovidone or a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise lactose, magnesium stearate, crospovidone and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise lactose, magnesium stearate, crospovidone, microcrystalline cellulose or a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise lactose, magnesium stearate, crospovidone, microcrystalline cellulose and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol, microcrystalline cellulose, crospovidone, or sodium stearyl fumarate. In some embodiments, the compositions of the invention further comprise lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol, microcrystalline cellulose, crospovidone, and sodium stearyl fumarate. In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity’) in the range of about 85 to about 95. In some embodiments, the microcrystalline cellulose has an average particle size of less than 50 pm. In some embodiments, themicrocrystalline cellulose has an average particle size of about 20 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 100 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 10 pm to about 30 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 20 pm to about 60 pm, D50 of about 10 pm to about 30 pm and D10 of about 2 pm to about 10 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 80 pm to about 140 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 170 pm to about 283 pm, D50 of about 80 pm to about 140 pm and D10 of about 15 pm to about 55 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-102. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-105.

[0105] In some embodiments, the compositions of the invention comprise low-substituted hydroxypropyl cellulose. In some embodiments, the compositions of the invention further comprise anhydrous lactose, microcrystalline cellulose, or magnesium stearate. In some embodiments, the compositions of the invention further comprise anhydrous lactose, microcrystalline cellulose, and magnesium stearate. In some embodiments, the compositions of the invention further comprise di calcium phosphate dihydrate, microcrystalline cellulose, or magnesium stearate. In some embodiments, the compositions of the invention further comprise dicalcium phosphate dihydrate, microcrystalline cellulose, and magnesium stearate. In some embodiments, the compositions of the invention further comprise anhydrous lactose, microcrystalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, or crospovidone. In some embodiments, the compositions of the invention further comprise anhydrous lactose, microcrystalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, and crospovidone. In some embodiments, the compositions of the invention further comprise anhydrous lactose, magnesium stearate, crospovidone or a mixture comprising mi crociy stall ine cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise anhydrous lactose, magnesium stearate, crospovidone and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise anhydrous lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol, microcrystalline cellulose, crospovidone, or sodium stearyl fumarate. In some embodiments, the compositions of the invention further comprise anhydrous lactose, partially pregelatimzed maize starch, polyvinylpyrrolidone, polyethylene glycol, microcrystallinecellulose, crospovidone, and sodium stearyl fumarate. In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity) in the range of about 85 to about 95. In some embodiments, the microcrystalline cellulose has an average particle size of less than 50 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 20 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 100 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 10 pm to about 30 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 20 pm to about 60 pm, D50 of about 10 pm to about 30 pm and D10 of about 2 pm to about 10 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 80 pm to about 140 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 170 pm to about 283 pm, D50 of about 80 pm to about 140 pm and D10 of about 15 pm to about 55 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-102. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-105.

[0106] In some embodiments, the compositions of the invention comprise low-substituted hydroxypropyl cellulose. In some embodiments, the compositions of the invention further comprise lactose monohydrate, microcrystalline cellulose, or magnesium stearate. In some embodiments, the compositions of the invention further comprise lactose monohydrate, microcrystalline cellulose, and magnesium stearate. In some embodiments, the compositions of the invention further comprise di calcium phosphate dihydrate, microcrystalline cellulose, or magnesium stearate. In some embodiments, the compositions of the invention further comprise dicalcium phosphate dihydrate, microcrystalline cellulose, and magnesium stearate. In some embodiments, the compositions of the invention further comprise lactose monohydrate, microcrystalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, or crospovidone. In some embodiments, the compositions of the invention further comprise lactose monohydrate, microcry stalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, and crospovidone. In some embodiments, the compositions of the invention further comprise lactose monohydrate, magnesium stearate, crospovidone or a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise lactose monohydrate, magnesium stearate, crospovidone and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the compositions of the invention further comprise lactose monohydrate, partially pregelatinized maize starch,polyvinylpyrrolidone, polyethylene glycol, microcrystalline cellulose, crospovidone, or sodium stearyl fumarate. In some embodiments, the compositions of the invention further comprise lactose monohydrate, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol, microcrystalline cellulose, crospovidone, and sodium stearyl fumarate. In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity ) in the range of about 85 to about 95. In some embodiments, the microcrystalline cellulose has an average particle size of less than 50 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 20 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 100 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 10 pm to about 30 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 20 pm to about 60 pm, D50 of about 10 pm to about 30 pm and D10 of about 2 pm to about 10 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 80 pm to about 140 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 170 pm to about 283 pm, D50 of about 80 pm to about 140 pm and D10 of about 15 pm to about 55 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-102. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-105.

[0107] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention is amorphous. In some embodiments, the APX3330 hemi calcium salt monohydrate of the compositions of the invention is crystalline.

[0108] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta and a peak at 10. 1 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern of the APX3330 hemicalcium salt monohydrate further comprises a peak at 13.3 ± 0.2 degrees 2-theta or a peak at 14.6 degrees 2-theta.

[0109] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 5. 1 ± 0.2 degrees 2-theta, a peak at 8.0 ± 0.2 degrees 2-theta, a peak at 10. 1 ± 0.2 degrees 2-theta, a peak at 13.3 ± 0.2 degrees 2-theta, a peak at 14.6 ± 0.2 degrees 2-theta, and a peak at 18.5 ± 0.2 degrees 2-theta.

[0110] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention exhibits an XRPD pattern that is substantially the same as that depicted in Fig. 1.[OHl] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention is the APX3330 hemicalcium salt monohydrate obtained according to Reference Example A.

[0112] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta and a peak at 6.3 ± 0.2 degrees 2-theta. In some embodiments, the XRPD pattern of the APX3330 hemicalcium salt monohydrate further comprises a peak at 13.7 ± 0.2 degrees 2-theta or a peak at 14.1 ± 0.2 degrees 2-theta.

[0113] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 4. 1 ± 0.2 degrees 2-theta, a peak at 5.3 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 6.3 ± 0.2 degrees 2-theta, a peak 13.7 ± 0.2 degrees 2- theta, and a peak at 14.1 ± 0.2 degrees 2-theta.

[0114] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention exhibits an XRPD pattern that is substantially the same as that depicted in Fig. 2.

[0115] In some embodiments, the APX3330 hemicalcium salt monohydrate of the compositions of the invention is the APX3330 hemicalcium salt monohydrate obtained according to Reference Example B.

[0116] In some embodiments, the compositions of the invention comprise the APX3330 hemicalcium salt monohydrate in an amount of about 30% w / w to about 80% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 30% w / w to about 75% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 30% w / w to about 70% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 35% w / w to about 65% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 35% w / w to about 60% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 35% w / w to about 55% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 35% w / w to about 50% w / w of the composition. In some embodiments, the compositions of the invention comprise theAPX3330 hemi calcium salt monohydrate in an amount of about 40% w / w to about 65% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 40% w / w to about 60% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 45% w / w to about 60% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 45% w / w to about 55% w / w of the composition. In some embodiments, the compositions of the invention comprise the APX3330 hemi calcium salt monohydrate in an amount of about 40% w / w to about 50% w / w of the composition.

[0117] In some embodiments, the compositions of the invention comprise the APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w, about 41% w / w, about 42% w / w, about 43% w / w, about 44% w / w, about 45% w / w, about 46% w / w, about 47% w / w, about 48% w / w, about 49% w / w, about 50% w / w. about 51% w / w. about 52% w / w, about 53% w / w, about 54% w / w, about 55% w / w, about 56% w / w, about 57% w / w, about 58% w / w, about 59% w / w, about 60% w / w, about 61% w / w, about 62% w / w, about 63% w / w, about 64% w / w, or about 65% w / w of the composition.

[0118] In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.1% w / w to about 35% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.1% w / w to about 30% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.1% w / w to about 25% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.1% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.2% w / w to about 15% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.3% w / w to about 10% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.5% w / w to about 8% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 1% w / w to about 8% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 2% w / w to about 8% w / w of the composition. In someembodiments, the compositions of the invention comprise the talc in an amount of about 3% w / w to about 8% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 3% w / w to about 7% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 3% w / w to about 6% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 4.5% w / w to about 5.5% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 3% w / w to about 5% w / w of the composition.

[0119] In some embodiments, the compositions of the invention comprise the talc in an amount of about 0.3% w / w, about 0.4% w / w, about 0.5% w / w, about 0.6% w / w, about 0.7% w / w, about 0.8% w / w, about 0.9% w / w, or about 1% w / w of the composition. In some embodiments, the compositions of the invention comprise the talc in an amount of about 1% w / w, about 2% w / w, about 3% w / w, about 4% w / w, about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, or about 10% w / w of the composition.

[0120] In some embodiments, the compositions of the invention comprise the low-substituted hydroxypropyl cellulose in an amount of about 1% w / w to about 30% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 25% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 15% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 10% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 9% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 8% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 10% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 9% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of thecomposition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 7% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition. In some embodiments, the compositions of the invention comprise the low- substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 5% w / w of the composition.

[0121] In some embodiments, the compositions of the invention comprise the low-substituted hydroxypropyl cellulose in an amount of about 1% w / w, about 2% w / w, about 3% w / w, about 4% w / w, about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, or about 10% w / w of the composition.

[0122] In some embodiments, the compositions of the invention comprise the lactose in an amount of about 2% w / w to about 50% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 3% w / w to about 45% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 4% w / w to about 40% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 4% w / w to about 35% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 5% w / w to about 30% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 5% w / w to about 25% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 8% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 9% w / w to about 18% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 10% w / w to about 16% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose in an amount of about 12% w / w to about 16% w / w of the composition.

[0123] In some embodiments, the compositions of the invention comprise the lactose in an amount about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11% w / w, about 12% w / w, about 13% w / w, about 14% w / w, about 15% w / w, about 16% w / w, about 17% w / w, about 18% w / w, about 19% w / w, or about 20% w / w of the composition.

[0124] In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 2% w / w to about 50% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 3% w / w to about 45% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 4% w / w to about 40% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 4% w / w to about 35% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 5% w / w to about 30% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 5% w / w to about 25% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 8% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 9% w / w to about 18% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 10% w / w to about 16% w / w of the composition. In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount of about 12% w / w to about 16% w / w of the composition.

[0125] In some embodiments, the compositions of the invention comprise the anhydrous lactose in an amount about 5% w / w. about 6% w / w. about 7% w / w. about 8% w / w, about 9% w / w, about 10% w / w, about 11% w / w, about 12% w / w, about 13% w / w, about 14% w / w, about 15% w / w, about 16% w / w, about 17% w / w, about 18% w / w, about 19% w / w, or about 20% w / w of the composition.

[0126] In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 2% w / w to about 50% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 3% w / w to about 45% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 4% w / w to about 40% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 4% w / w to about 35% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 5% w / w to about 30% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 5% w / w to about 25% w / w of the composition. In someembodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 8% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 9% w / w to about 18% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 10% w / w to about 16% w / w of the composition. In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount of about 12% w / w to about 16% w / w of the composition.

[0127] In some embodiments, the compositions of the invention comprise the lactose monohydrate in an amount about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w. about 10% w / w, about 11% w / w, about 12% w / w, about 13% w / w. about 14% w / w, about 15% w / w, about 16% w / w, about 17% w / w, about 18% w / w, about 19% w / w, or about 20% w / w of the composition.

[0128] In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 2% w / w to about 55% w / w of the composition. In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 2% w / w to about 50% w / w of the composition. In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 3% w / w to about 45% w / w of the composition. In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 4% w / w to about 40% w / w of the composition. In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 4% w / w to about 35% w / w of the composition. In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 5% w / w to about 30% w / w of the composition. In some embodiments, the compositions of the invention comprise the mi crocry stall ine cellulose in an amount of about 5% w / w to about 25% w / w of the composition. In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 8% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the mi crocry stall ine cellulose in an amount of about 10% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the microcrystalline cellulose in an amount of about 12% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise themicrocrystalline cellulose in an amount of about 15% w / w to about 20% w / w of the composition.

[0129] In some embodiments, the compositions of the invention comprise the microcry stall ine cellulose in an amount about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11% w / w, about 12% w / w, about 13% w / w, about 14% w / w, about 15% w / w, about 16% w / w, about 17% w / w, about 18% w / w, about 19% w / w, about 20% w / w, about 21% w / w. about 22% w / w, about 23% w / w, about 24% w / w, or about 25% w / w, of the composition.

[0130] In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.1% w / w to about 10% w / w of the composition. In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.2% w / w to about 8% w / w of the composition. In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.3% w / w to about 7% w / w of the composition. In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.4% w / w to about 6% w / w of the composition. In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.5% w / w to about 5% w / w of the composition. In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.5% w / w to about 4% w / w of the composition. In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.5% w / w to about 3% w / w of the composition. In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.5% w / w to about 2% w / w of the composition.

[0131] In some embodiments, the compositions of the invention comprise the magnesium stearate in an amount of about 0.3% w / w, about 0.4% w / w, about 0.5% w / w, about 0.6% w / w, about 0.7% w / w, about 0.8% w / w, about 0.9% w / w, about 1% w / w, about 1.2% w / w, about 1.4% w / w, about 1.6% w / w, about 1.8% w / w, or about 2% w / w of the composition.

[0132] In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount of about 2% w / w to about 50% w / w of the composition. In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount of about 3% w / w to about 45% w / w of the composition. In some embodiments, the compositions of the invention comprise dicalcium phosphate dihydrate in an amount of about 4% w / w to about 40% w / w of the composition. In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amountof about 4% w / w to about 35% w / w of the composition. In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount of about 5% w / w to about 30% w / w of the composition. In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount of about 5% w / w to about 25% w / w of the composition. In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount of about 8% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount of about 9% w / w to about 18% w / w of the composition. In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount of about 10% w / w to about 16% w / w of the composition.

[0133] In some embodiments, the compositions of the invention comprise the dicalcium phosphate dihydrate in an amount about 5% w / w, about 6% w / w, about 7% w / w, about 8% w / w, about 9% w / w, about 10% w / w, about 11% w / w, about 12% w / w, about 13% w / w, about 14% w / w, about 15% w / w, about 16% w / w. about 17% w / w, about 18% w / w, about 19% w / w, or about 20% w / w of the composition.

[0134] In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.1% w / w to about 10% w / w of the composition. In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.2% w / w to about 8% w / w of the composition. In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.3% w / w to about 7% w / w of the composition. In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.4% w / w to about 6% w / w of the composition. In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.5% w / w to about 5% w / w of the composition. In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.5% w / w to about 4% w / w of the composition. In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.5% w / w to about 3% w / w of the composition. In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.5% w / w to about 2% w / w of the composition.

[0135] In some embodiments, the compositions of the invention comprise the crospovidone in an amount of about 0.3% w / w, about 0.4% w / w, about 0.5% w / w, about 0.6% w / w, about0.7% w / w, about 0.8% w / w, about 0.9% w / w, about 1% w / w, about 1.2% w / w, about 1.4% w / w, about 1.6% w / w, about 1.8% w / w, or about 2% w / w of the composition.

[0136] In some embodiments, the compositions of the invention comprise a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 0.1% w / w to about 20% w / w of the composition. In some embodiments, the compositions of the invention comprise a mixture comprising microcry stall ine cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 0.5% w / w to about 15% w / w of the composition. In some embodiments, the compositions of the invention comprise a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 0.5% w / w to about 10% w / w of the composition. In some embodiments, the compositions of the invention comprise a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 1% w / w to about 10% w / w of the composition. In some embodiments, the compositions of the invention comprise a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 1% w / w to about 8% w / w of the composition. In some embodiments, the compositions of the invention comprise a mixture comprising mi crocry stall ine cellulose and sodium carboxymethyl cellulose in an amount of about 2% w / w to about 6% w / w of the composition. In some embodiments, the compositions of the invention comprise a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 5% w / w of the composition. In some embodiments, the compositions of the invention comprise a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 3% w / w to about 4% w / w of the composition.

[0137] In some embodiments, the mixture comprises about 11% to about 19% sodium carboxy methyl cellulose by weight of the mixture and about 81% to about 89% mi crocry stall ine cellulose by weight of the mixture. In some embodiments, the mixture comprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxymethyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81:19 to about 89:11 by weight. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 85:15 by weight. In some embodiments, not more than 0.1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve as determined by air jet sieving. In some embodiments, not morethan 50% by weight of the mixture’s particles are retained on a 325 mesh (45 micron) sieve as determined by air jet sieving. In some embodiments, not more than 0. 1% by weight of the mixture’s particles are retained on a 60 mesh (250 microns) sieve and not more than 50% by weight of the mixture’s particles are retained on a 325 mesh (45 microns) sieve as determined by air jet sieving. In some embodiments, the mixture has the trademark AVICEL® CL-611.

[0138] In some embodiments, the compositions of the invention comprise an intra-granular phase. In some embodiments, the compositions of the invention comprise APX3330 and an intra-granular phase, and the intra-granular phase comprises the APX3330. In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate and an intra-granular phase, and the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate. In some embodiments, the compositions of the invention comprise APX3330, talc and an intra-granular phase, and the intra-granular phase comprises the APX3330 and talc. In some embodiments, compositions comprise an APX3330 hemi calcium salt monohydrate, talc and an intra-granular phase, and the intra- granular phase comprises the APX3330 hemicalcium salt monohydrate and talc. In some embodiments, the compositions of the invention comprise (i) APX3330, (ii) talc, (iii) crospovidone or low-substituted hydroxypropyl cellulose, and an intra-granular phase, and the intra-granular phase comprises the (i) APX3330, (ii) talc, and (iii) crospovidone or low- substituted hydroxypropyl cellulose. In some embodiments, the compositions of the invention comprise (i) an APX3330 hemicalcium salt monohydrate, (ii) talc, (iii) crospovidone or low- substituted hydroxypropyl cellulose, and an intra-granular phase, and the intra-granular phase comprises the (i) APX3330 hemicalcium salt monohydrate, (ii) talc, and (iii) crospovidone or low-substituted hydroxypropyl cellulose.

[0139] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose, microcrystalline cellulose, magnesium stearate and an intra-granular phase, and the intra- granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose, microcrystalline cellulose, and magnesium stearate.

[0140] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, anhydrous lactose, microcrystalline cellulose, magnesium stearate and an intra-granular phase, and the intra-granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low- substituted hydroxypropyl cellulose, anhydrous lactose, microcrystalline cellulose, and magnesium stearate.

[0141] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose monohydrate, microcrystalline cellulose, magnesium stearate and an intra-granular phase, and the intra-granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low- substituted hydroxypropyl cellulose, lactose monohydrate, microcrystalline cellulose, and magnesium stearate.

[0142] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, di calcium phosphate dihydrate, microcrystalline cellulose, magnesium stearate and an intra-granular phase, and the intra-granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, di calcium phosphate dihydrate, microcrystalline cellulose, and magnesium stearate.

[0143] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose, microcrystalline cellulose, magnesium stearate, an intra-granular phase and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the intra- granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose, microcrystalline cellulose, magnesium stearate and mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the microcrystalline cellulose has an average particle size of less than 50 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 20 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 100 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 10 pm to about 30 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 20 pm to about 60 pm, D50 of about 10 pm to about 30 pm and D10 of about 2 pm to about 10 pm. In some embodiments, the mi crocry stall ine cellulose has a particle size distribution D50 of about 80 pm to about 140 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 170 pm to about 283 pm. D50 of about 80 pm to about 140 pm and D10 of about 15 pm to about 55 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-102. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-105. In some embodiments, the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the mixturecomprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxymethyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81: 19 to about 89:11 by weight. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 85: 15 by weight. In some embodiments, the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose has the trademark AVICEL® CL-611.

[0144] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, anhydrous lactose, microcrystalline cellulose, magnesium stearate, an intra-gr anular phase and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the intra- granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, anhydrous lactose, microcrystalline cellulose, magnesium stearate and mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the microcrystalline cellulose has an average particle size of less than 50 pm. In some embodiments, the microcrystallme cellulose has an average particle size of about 20 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 100 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 10 pm to about 30 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 20 pm to about 60 pm, D50 of about 10 pm to about 30 pm and D10 of about 2 pm to about 10 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 80 pm to about 140 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 170 pm to about 283 pm, D50 of about 80 pm to about 140 pm and D10 of about 15 pm to about 55 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-102. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-105. In some embodiments, the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the mixture comprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxymethyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81: 19 to about 89: 11 by weight. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 85: 15 by weight. In someembodiments, the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose has the trademark AVICEL® CL-611.

[0145] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose monohydrate, microcryslalline cellulose, magnesium stearate, an intra-granular phase and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the intra-granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low- substituted hydroxypropyl cellulose, lactose monohydrate, microcrystalline cellulose, magnesium stearate and mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose. In some embodiments, the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the mixture comprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxymethyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81: 19 to about 89: 11 by weight. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 85: 15 by weight. In some embodiments, the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose has the trademark AVICEL® CL-611.

[0146] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol and an intra- granular phase, and the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, and polyethylene glycol. In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity) in the range of about 85 to about 95. In some embodiments, the polyethylene glycol has an average molecular weight in the range of about 3000 g / mol to about 3500 g / mol. In some embodiments, the polyethylene glycol has an average molecular weight of about 3350 g / mol.

[0147] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, anhydrous lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol and an intra-granular phase, and the intra-granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, anhydrous lactose, partiallypregelatinized maize starch, polyvinylpyrrolidone, and polyethylene glycol. In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity) in the range of about 85 to about 95. In some embodiments, the polyethylene glycol has an average molecular weight in the range of about 3000 g / mol to about 3500 g / mol. In some embodiments, the polyethylene glycol has an average molecular weight of about 3350 g / mol.

[0148] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose monohydrate, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol and an intra-granular phase, and the intra-granular phase comprises the APX3330 hemicalcium salt monohydrate, talc, low-substituted hydroxypropyl cellulose, lactose monohydrate, partially pregelatinized maize starch, polyvinylpyrrolidone, and polyethylene glycol. In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity) in the range of about 85 to about 95. In some embodiments, the polyethylene glycol has an average molecular weight in the range of about 3000 g / mol to about 3500 g / mol. In some embodiments, the polyethylene glycol has an average molecular weight of about 3350 g / mol.

[0149] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition.

[0150] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition;anhydrous lactose in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition.

[0151] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose monohydrate in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition.

[0152] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; dicalcium phosphate dihydrate in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition.

[0153] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystallme cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition.

[0154] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition.

[0155] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg to about 600 mg of APX3330; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition.

[0156] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg. about 150 mg, about 180 mg, about 200 mg. about 240 mg, about 250 mg, about 300 mg, about 350 mg, about 360 mg, about 400 mg, about 420 mg, about 450 mg, about 480 mg, about 500 mg, about 540 mg, about 550 mg, or about 600 mg, of APX3330; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; andmagnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition.

[0157] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose monohydrate in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition.

[0158] In some embodiments, the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose comprises about 11% to about 19% sodium carboxy methyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the mixture comprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxy methyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 85: 15 by weight. In some embodiments, the mixture has the trademark AVICEL® CL-611.

[0159] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular ingredient comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition;low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; lactose in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; and polyethylene glycol in an amount of about 0.1 % w / w to about 0.6% w / w of the composition.

[0160] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular ingredient comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; anhydrous lactose in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; and polyethylene glycol in an amount of about 0.1% w / w to about 0.6% w / w of the composition.

[0161] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular ingredient comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; lactose monohydrate in an amount of about 15% w / w to about 30% w / w of the composition;partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; and polyethylene glycol in an amount of about 0.1% w / w to about 0.6% w / w of the composition.

[0162] In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity) in the range of about 85 to about 95. In some embodiments, the polyethylene glycol has an average molecular weight in the range of about 3000 g / mol to about 3500 g / mol. In some embodiments, the polyethylene glycol has an average molecular weight of about 3350 g / mol.

[0163] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 45% w / w to about 60% w / w of the intra-granular phase; talc in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; low-substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; lactose in an amount of about 10% w / w to about 20% w / w of the intra-granular phase; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the intra-granular phase; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; and magnesium stearate in an amount of about 0.4% w / w to about 1% w / w of the intra-granular phase.

[0164] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 45% w / w to about 60% w / w of the intra-granular phase; talc in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; low-substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 8% w / w of the intra-granular phase;anhydrous lactose in an amount of about 10% w / w to about 20% w / w of the intra- granular phase; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the intra-granular phase; a mixture comprising microcry stalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; and magnesium stearate in an amount of about 0.4% w / w to about 1 % w / w of the intra-granular phase.

[0165] In some embodiments, the compositions of the invention comprise an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 45% w / w to about 60% w / w of the intra-granular phase; talc in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; low-substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; lactose monohydrate in an amount of about 10% w / w to about 20% w / w of the intra-granular phase; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the intra-granular phase; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 8% w / w of the intra-granular phase; and magnesium stearate in an amount of about 0.4% w / w to about 1% w / w of the intra-granular phase.

[0166] In some embodiments, the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose comprises about 11% to about 19% sodium carboxy methyl cellulose by weight of the mixture and about 81% to about 89% microcry stalline cellulose by weight of the mixture. In some embodiments, the mixture comprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxy methyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in themixture is about 85: 15 by weight. In some embodiments, the mixture has the trademark AVICEL® CL-611.

[0167] In some embodiments, the microcrystalline cellulose in an intra-granular phase has an average particle size of less than 50 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 20 pm. In some embodiments, the microcry stalline cellulose has a particle size distribution D50 of about 10 pm to about 30 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 20 pm to about 60 pm, D50 of about 10 pm to about 30 pm and D 10 of about 2 pm to about 10 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH- 105.

[0168] In some embodiments, the compositions of the invention further comprise an extra- granular phase. In some embodiments, the extra-granular phase comprises low-substituted hydroxypropyl cellulose, microcrystalline cellulose, and magnesium stearate. In some embodiments, the extra-granular phase comprises crospovidone, microcry stalline cellulose, and magnesium stearate. In some embodiments, the extra-granular phase comprises crospovidone, microcrystalline cellulose, and sodium stearyl fumarate.

[0169] In some embodiments, the compositions of the invention further comprise an extra- granular phase, wherein the extra-granular phase comprises: low-substituted hydroxypropyl cellulose in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0170] In some embodiments, the compositions of the invention further comprise an extra- granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0171] In some embodiments, the compositions of the invention further comprise an extra- granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and sodium stearyl fumarate in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0172] In some embodiments, the compositions of the invention further comprise an extra- granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 30% w / w to about 45% w / w of the extra- granular phase; microcrystalline cellulose in an amount of about 45% w / w to about 60% w / w of the extra-granular phase; and magnesium stearate in an amount of about 2% w / w to about 15% w / w of the extra-granular phase.

[0173] In some embodiments, the compositions of the invention are formulated for oral administration.

[0174] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: low-substituted hydroxypropyl cellulose in an amount of about 0.2% w / w to about 5% w / w of the composition;microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0175] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: low-substituted hydroxypropyl cellulose in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0176] In some embodiments where microcrystalline cellulose in present in the extra- granular phase, the microcrystalline cellulose has an average particle size of about 100 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 80 pm to about 140 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 170 pm to about 283 pm, D50 of about 80 pm to about 140 pm and D10 of about 15 pm to about 55 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-102.

[0177] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises:an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose monohydrate in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: low-substituted hydroxypropyl cellulose in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0178] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; dicalcium phosphate dihydrate in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.3% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: low-substituted hydroxypropyl cellulose in an amount of about 0.2% w / w to about 5% w / w of the composition;microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0179] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0180] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition;microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0181] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg to about 600 mg of APX3330; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; andmagnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0182] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg, about 150 mg, about 180 mg. about 200 mg, about 240 mg, about 250 mg, about 300 mg, about 350 mg, about 360 mg. about 400 mg. about 420 mg, about 450 mg, about 480 mg, about 500 mg, about 540 mg, about 550 mg, or about 600 mg of APX3330; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0183] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition;lactose monohydrate in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcry stalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0184] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 45% w / w to about 50% w / w of the composition; talc in an amount of about 4% w / w to about 5% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 4% w / w to about 5% w / w of the composition; lactose in an amount of about 11% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 11% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 3% w / w to about 4% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 1% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 6% w / w of the composition; andmagnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0185] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 45% w / w to about 50% w / w of the composition; talc in an amount of about 4% w / w to about 5% w / w of the composition; low -substituted hydroxypropyl cellulose in an amount of about 4% w / w to about 5% w / w of the composition; anhydrous lactose in an amount of about 11% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 1 1% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 3% w / w to about 4% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 1% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0186] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 45% w / w to about 50% w / w of the composition; talc in an amount of about 4% w / w to about 5% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 4% w / w to about 5% w / w of the composition; lactose monohydrate in an amount of about 11% w / w to about 15% w / w of the composition;microcrystalline cellulose in an amount of about 11% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 3% w / w to about 4% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 1% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0187] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 48% w / w to about 52% w / w of the composition; talc in an amount of about 4% w / w to about 5% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 4% w / w to about 5% w / w of the composition; lactose in an amount of about 12% w / w to about 16% w / w of the composition; microcrystalline cellulose in an amount of about 12% w / w to about 16% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 3% w / w to about 5% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.9% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 1% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0188] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 48% w / w to about 52% w / w of the composition; talc in an amount of about 4% w / w to about 5% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 4% w / w to about 5% w / w of the composition; anhydrous lactose in an amount of about 12% w / w to about 16% w / w of the composition; microcrystalline cellulose in an amount of about 12% w / w to about 16% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 3% w / w to about 5% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.9% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 1% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0189] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 48% w / w to about 52% w / w of the composition; talc in an amount of about 4% w / w to about 5% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 4% w / w to about 5% w / w of the composition; lactose monohydrate in an amount of about 12% w / w to about 16% w / w of the composition; microcrystalline cellulose in an amount of about 12% w / w to about 16% w / w of the composition;a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 3% w / w to about 5% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.9% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 1% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

[0190] In some embodiments, the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcry stalline cellulose by weight of the mixture. In some embodiments, the mixture comprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxy methyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight. In some embodiments, the ratio of microcry stalline cellulose to sodium carboxymethyl cellulose in the mixture is about 85: 15 by weight. In some embodiments, the mixture has the trademark AVICEL® CL-611.

[0191] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; lactose in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; andpolyethylene glycol in an amount of about 0.1% w / w to about 0.6% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and sodium stearyl fumarate in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0192] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; anhydrous lactose in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; and polyethylene glycol in an amount of about 0.1% w / w to about 0.6% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and sodium stearyl fumarate in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0193] In some embodiments, the compositions of the invention comprise:(a) an intra-granular phase, wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition;low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; lactose monohydrate in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; and polyethylene glycol in an amount of about 0.1% w / w to about 0.6% w / w of the composition; and(b) an extra-granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and sodium stearyl fumarate in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0194] In some embodiments, the polyvinylpyrrolidone has a K-value (viscosity) in the range of about 85 to about 95. In some embodiments, the polyethylene glycol has an average molecular weight in the range of about 3000 g / mol to about 3500 g / mol. In some embodiments, the polyethylene glycol has an average molecular weight of about 3350 g / mol.

[0195] In some embodiments, the compositions of the invention comprise: an intra-granular phase in an amount of about 80% w / w to about 95% w / w of the composition; and an extra-granular phase in an amount of about 5% w / w to about 20% w / w of the composition.

[0196] In some embodiments, the compositions of the invention comprise: an intra-granular phase in an amount of about 85% w / w to about 95% w / w of the composition; and an extra-granular phase in an amount of about 5% w / w to about 15% w / w of the composition.

[0197] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition;low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 25% w / w of the composition; and magnesium stearate in an amount of about 0.5% w / w to about 1.5% w / w of the composition.

[0198] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 25% w / w of the composition; and magnesium stearate in an amount of about 0.5% w / w to about 1.5% w / w of the composition.

[0199] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose monohydrate in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 25% w / w of the composition; and magnesium stearate in an amount of about 0.5% w / w to about 1.5% w / w of the composition.

[0200] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition;talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 10% w / w of the composition; dicalcium phosphate dihydrate in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition; and magnesium stearate in an amount of about 0.5% w / w to about 1.5% w / w of the composition.

[0201] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 10% w / w of the composition; lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 20% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 1.5% w / w of the composition.

[0202] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 10% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 20% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose in an amount of about 2% w / w to about 6% w / w of the composition; andmagnesium stearate in an amount of about 0.4% w / w to about 1.5% w / w of the composition.

[0203] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg to about 600 mg of APX3330; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 10% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 20% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 1.5% w / w of the composition.

[0204] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg, about 150 mg, about 180 mg. about 200 mg, about 240 mg, about 250 mg, about 300 mg, about 350 mg, about 360 mg. about 400 mg, about 420 mg, about 450 mg, about 480 mg, about 500 mg, about 540 mg, about 550 mg, or about 600 mg of APX3330; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 10% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 20% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 1.5% w / w of the composition.

[0205] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 10% w / w of the composition; lactose monohydrate in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 20% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 1.5% w / w of the composition.

[0206] In some embodiments, the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose comprises about 11% to about 19% sodium carboxy methyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture. In some embodiments, the mixture comprises about 85% microcrystalline cellulose by weight of the mixture and about 15% sodium carboxymethyl cellulose by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxy methyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight of the mixture. In some embodiments, the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 85: 15 by weight of the mixture. In some embodiments, the mixture has the trademark AVICEL® CL-611.

[0207] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; lactose in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition;polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; polyethylene glycol in an amount of about 0.1% w / w to about 0.6% w / w of the composition; crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and sodium stearyl fumarate in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0208] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition; anhydrous lactose in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; polyethylene glycol in an amount of about 0.1% w / w to about 0.6% w / w of the composition; crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and sodium stearyl fumarate in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0209] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 50% w / w to about 65% w / w of the composition; talc in an amount of about 0.2% w / w to about 0.8% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition;lactose monohydrate in an amount of about 15% w / w to about 30% w / w of the composition; partially pregelatinized maize starch in an amount of about 3% w / w to about 10% w / w of the composition; polyvinylpyrrolidone in an amount of about 1% w / w to about 6% w / w of the composition; polyethylene glycol in an amount of about 0. 1% w / w to about 0.6% w / w of the composition; crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition; microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and sodium stearyl fumarate in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0210] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 25% w / w of the composition; magnesium stearate in an amount of about 0.5% w / w to about 1.5% w / w of the composition; and crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0211] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 10% w / w to about 20% w / w of the composition;microcrystalline cellulose in an amount of about 10% w / w to about 25% w / w of the composition; magnesium stearate in an amount of about 0.5% w / w to about 1.5% w / w of the composition; and crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0212] In some embodiments, the compositions of the invention comprise: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; lactose monohydrate in an amount of about 10% w / w to about 20% w / w of the composition; microcrystalline cellulose in an amount of about 10% w / w to about 25% w / w of the composition; magnesium stearate in an amount of about 0.5% w / w to about 1.5% w / w of the composition; and crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition.

[0213] In some embodiments, the compositions of the inventions are in the form of a solution, a suspension, an emulsion, a tablet, a capsule, a powder, a cream, or a gel.

[0214] In some embodiments, the compositions of the invention are in the form of a tablet. In some embodiments, the tablet comprises a coating. In some embodiments, the tablet comprises an outer surface, and the coating coats at least some of the outer surface. In some embodiments, the tablet comprises an outer surface, and the coating coats the entire outer surface. In some embodiments, the coating is applied to the outer surface of the tablet. In some embodiments, the coating is a film coating. In some embodiments, the compositions of the invention comprise a coating, and the coating is present in an amount of about 1% w / w to about 10% w / w of the composition of the invention. In some embodiments, the compositions of the invention comprise a coating, and the coating is present in an amount of about 2% w / w to about 8% w / w of the composition of the invention. In some embodiments, the compositions of the invention comprise a coating, and the coating is present in an amount of about 2% w / w to about 6% w / w of the composition of the invention. In some embodiments, the compositions of the invention comprise a coating, and the coating is present in an amount of about 3% w / w to about 5% w / w of the composition of the invention.

[0215] In some embodiments, the compositions of the invention comprise: an intra-granular phase in an amount of about 80% w / w to about 95% w / w of the composition; an extra-granular phase in an amount of about 5% w / w to about 20% w / w of the composition; and a coating in an amount of about 2% w / w to about 10% w / w of the composition.

[0216] In some embodiments, the compositions of the invention comprise: an intra-granular phase in an amount of about 85% w / w to about 90% w / w of the composition; an extra-granular phase in an amount of about 5% w / w to about 10% w / w of the composition; and a coating in an amount of about 2% w / w to about 6% w / w of the composition.

[0217] In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, and the APX3330 hemi calcium salt monohydrate of the compositions of the invention have a D90 particle size distribution in the range of about 10 pm to about 150 pm. In some embodiments, the compositions of the invention compnse an APX3330 hemi calcium salt monohydrate, and the APX3330 hemicalcium salt monohydrate of the compositions of the invention have a D90 particle size distribution in the range of about 50 pm to about 200 pm. In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, and the APX3330 hemicalcium salt monohydrate of the compositions of the invention have a D90 particle size distribution in the range of about 50 pm to about 150 pm. In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate, and the APX3330 hemi calcium salt monohydrate of the compositions of the invention have a D90 particle size distribution in the range of about 60 pm to about 125 pm. In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate, and the APX3330 hemi calcium salt monohydrate of the compositions of the invention have a D90 particle size distribution in the range of about 10 pm to about 50 pm.

[0218] In some embodiments, the compositions of the invention are in the form of a tablet having a tablet hardness in the range of about 5 kp to about 15 kp. In some embodiments, the tablet hardness is about 5 kp, about 6 kp, about 7 kp, about 8 kp, about 9 kp, about 10 kp, about 11 kp, about 12 kp, about 13 kp, about 14 kp, or about 15 kp. In some embodiments, the tablet hardness is about 6 kp to about 12 kp. In some embodiments, the tablet hardness is about 8 kp to about 14 kp.

[0219] In some embodiments, the compositions of the invention are in the form of a tablet having a tablet thickness in the range of about 3.0 mm to about 7.0 mm. In some embodiments, the tablet thickness is about 3.0 mm, about 3.5 mm, about 4.0 mm, about 4.5 mm, about 5.0 mm, about 5.5 mm, about 6.0 mm, about 6.5 mm, or about 7.0 mm. In some embodiments, the tablet hardness is about 4.0 mm to about 4.3 mm. In some embodiments, the tablet thickness is about 4.0 mm. about 4. 1 mm, about 4.2 mm, or about 4.3 mm. In some embodiments, the tablet hardness is about 4.8 mm to about 5. 1 mm. In some embodiments, the tablet thickness is about 4.8 mm, about 4.9 mm, about 5.0 mm, or about 5. 1 mm.

[0220] In some embodiments, the compositions of the invention are in the form of a tablet having a friabili ty (% weight loss) of less than about 1%. In some embodiments, the tablet's friability is less than about 0.9%. In some embodiments, the tablet’s friability is less than about 0.8%.

[0221] In some embodiments, the compositions of the invention are in the form of a tablet and the tablet has a target weight and an actual weight, wherein the actual weight is ± 10% of the target weight.

[0222] In some embodiments, the compositions of the invention are contained in a capsule. In some embodiments, the capsule comprises hypromellose or gelatin.

[0223] In some embodiments, the compositions of the invention comprise APX3330 in about 20 mg to about 600 mg. In some embodiments, the compositions of the invention comprise APX3330 in about 50 mg to about 600 mg. In some embodiments, the compositions of the invention comprise APX3330 in about 100 mg to about 400 mg. In some embodiments, the compositions of the invention comprise APX3330 in about 120 mg to about 300 mg.

[0224] In some embodiments, the compositions of the invention comprise APX3330 in about 100 mg, about 110 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg, about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg, about 330 mg, about 340 mg, or about 350 mg. In some embodiments, the compositions of the invention comprise APX3330 in about 120 mg or about 300 mg. In some embodiments, the compositions of the invention comprise APX3330 in about 300 mg of APX3330.

[0225] In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 20 mg to about 600 mg of APX3330. In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 50mg to about 600 mg of APX3330. In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 100 mg to about 400 mg of APX3330. In some embodiments, the compositions of the invention comprise an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg to about 300 mg of APX3330.

[0226] In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 100 mg, about 1 10 mg, about 120 mg, about 130 mg, about 140 mg, about 150 mg, about 160 mg, about 170 mg, about 180 mg, about 190 mg, about 200 mg, about 210 mg, about 220 mg, about 230 mg, about 240 mg, about 250 mg, about 260 mg. about 270 mg, about 280 mg, about 290 mg, about 300 mg, about 310 mg, about 320 mg. about 330 mg, about 340 mg, or about 350 mg of APX3330. In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 120 mg or about 300 mg of APX3330. In some embodiments, the compositions of the invention comprise an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 300 mg of APX3330.

[0227] In some embodiments, the compositions of the invention further comprise a stabilizer, binder, filler, diluent, disintegrant, wetting agent, lubricant, glidant, coloring agent, dyemigration inhibitor, sweetening agent, flavoring agent, viscosity modifying agent, pH adjusting agent, buffer, osmotic agent, chelating agent, surfactants, or co-solvent. In some embodiments, the compositions of the invention further comprise a binder, diluent, disintegrant, and / or lubricant.

[0228] In some embodiments, a diluent is sugar, mannitol, lactose, lactose monohy drate, cellulose, microcrystalline cellulose, silicified microcry stalline cellulose, microfine cellulose, or starch. In some embodiments, starch is com starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, or perforated starch. In some embodiments, a diluent is lactose, microcrystalline cellulose, dicalcium phosphate dihydrate, calcium carbonate, or partially pregelatinized maize starch. In some embodiments, the diluent is lactose, and the lactose is lactose monohydrate or anhydrous lactose. In some embodiments, microcrystalline cellulose has an average particle size from about 50 pm to about 200 pm. In some embodiments, microcrystalline cellulose has an average particle size of about 50 pm or about 100 pm. In some embodiments, the microcrystalline cellulose has an average particle size of about 100 pm. In some embodiments, microcrystalline cellulose has an average particle size of less than about 50 pm. In some embodiments, the microcrystalline cellulose has anaverage particle size of about 20 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 10 pm to about 30 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 20 pm to about 60 pm, D50 of about 10 pm to about 30 pm and D10 of about 2 pm to about 10 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D50 of about 80 pm to about 140 pm. In some embodiments, the microcrystalline cellulose has a particle size distribution D90 of about 170 pm to about 283 pm, D50 of about 80 pm to about 140 pm and D10 of about 15 pm to about 55 pm. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-102. In some embodiments, the microcrystalline cellulose has the trademark AVICEL® PH-105.

[0229] In some embodiments, a disintegrant is carboxymethylcellulose, starch, pregelatinized starch, partially pre-gelatinized starch, crospovidone, or hydroxypropyl cellulose. In some embodiments, a disintegrant is carboxymethylcellulose sodium. In some embodiments, a disintegrant is low-substituted hydroxypropyl cellulose.

[0230] In some embodiments, a binder is methylcellulose, hydroxypropyl cellulose, ethyl cellulose, polyvinyl alcohol, powdered acacia, gelatin, or pullulan. In some embodiments, methylcellulose has a viscosity of about 25 cP.

[0231] In some embodiments, a glidant is talc.

[0232] In some embodiments, a lubricant is magnesium stearate, calcium stearate, talc, or sodium stearyl fumarate.

[0233] In some embodiments, a viscosity modifying agent is polyvinyl alcohol, poloxamer, hyaluronic acid, carbomers, and polysaccharides, that is, cellulose derivatives, gellan gum, or xanthan gum.

[0234] In some embodiments, the compositions of the invention comprise lactose, microcrystalline cellulose, starch, carboxymethylcellulose sodium, methylcellulose, and / or magnesium stearate. In some embodiments, starch is partially pregelatinized maize starch.

[0235] In some embodiments, the compositions of the invention comprise anhydrous lactose, microcrystalline cellulose, starch, carboxymethylcellulose sodium, methylcellulose, and / or magnesium stearate. In some embodiments, starch is partially pregelatinized maize starch.

[0236] In some embodiments, the compositions of the invention comprise lactose monohydrate, microcrystalline cellulose, starch, carboxymethylcellulose sodium, methylcellulose, and / or magnesium stearate. In some embodiments, starch is partially pregelatinized maize starch.

[0237] In some embodiments, the compositions of the invention further comprise mannitol or sodium acetate.

[0238] In some embodiments, the compositions of the invention further comprise a preservative. In some embodiments, the preservative is benzalkonium chloride, cetrimide, polyquatemium-1, thimerosal, sodium perborate, stabilized oxy chloro complex, stabilized chlorite peroxide, chlorhexidine. chlorobutanol, phenylethanol or methylparaben.

[0239] In some embodiments, the compositions of the invention do not comprise a preservative. In some embodiments, the compositions of the invention are preservative free.

[0240] In some embodiments, the compositions of the invention are stable at 25 °C / 60% RH for at least 3 months. In some embodiments, the compositions of the invention are stable at 25 °C / 60%RH for at least about 6 months. In some embodiments, the compositions of the invention are stable at 25 °C / 60%RH for at least about 12 months. In some embodiments, the compositions of the invention are stable at 25 °C / 60%RH for at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 18 months, at least about 24 months, at least about 30 months, or at least about 36 months.

[0241] In some embodiments, the compositions of the invention are stable at 40 °C / 75% RH for at least about four weeks. In some embodiments, the compositions of the invention are stable at 40 °C / 75%RH for at least about 3 months. In some embodiments, the compositions of the invention are stable at 40 °C / 75%RH for at least about 6 months. In some embodiments, the compositions of the invention are stable at 40 °C / 75%RH for at least about four weeks, at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 1 1 months, or at least about 12 months. In some embodiments, the compositions of the invention are stored in an open container under stability conditions.

[0242] In some embodiments, the compositions of the invention are stable under light exposure for at least about 1 week. In some embodiments, the compositions of the invention are stable under light exposure for at least about 2 weeks. In some embodiments, the compositions of the invention are stable under light exposure for at least about 3 weeks. In some embodiments, the compositions of the invention are stable under light exposure for at least about 4 weeks. In some embodiments, the compositions of the invention are stable under light exposure for at least about 1 month. In some embodiments, the compositions of theinvention are stable under light exposure for at least about 3 months. In some embodiments, the compositions of the invention are stable under light exposure for at least about 6 months. In some embodiments, the compositions of the invention are stable under visible light exposure for at least about 6 months.

[0243] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM potassium phosphate buffer pH 6.8 at 37 °C ± 0.5 °C, about 70% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0244] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM potassium phosphate buffer pH 6.8 at 37 °C ± 0.5 °C, about 75% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0245] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM potassium phosphate buffer pH 6.8 at 37 °C ± 0.5 °C, about 80% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0246] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM potassium phosphate buffer pH 6.8 at 37 °C ± 0.5 °C, about 85% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0247] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphate buffer pH 6.8 at 37 °C ± 0.5 °C, about 70% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0248] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphatebuffer pH 6.8 at 37 °C ± 0.5 °C, about 75% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0249] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphate buffer pH 6.8 at 37 °C ± 0.5 °C, about 80% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0250] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphate buffer pH 6.8 at 37 °C ± 0.5 °C, about 85% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0251] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphate buffer pH 6.8 and 0.3% w / v sodium lauryl sulfate at 37 °C ± 0.5 °C, about 70% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0252] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphate buffer pH 6.8 and 0.3% w / v sodium lauryl sulfate at 37 °C ± 0.5 °C, about 75% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0253] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphate buffer pH 6.8 and 0.3% w / v sodium lauryl sulfate at 37 °C ± 0.5 °C, about 80% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0254] In some embodiments, where the compositions of the invention are subjected to dissolution testing according to method USP (711 ) DISSOLUTION, using Apparatus 2 (Paddles) at 100 rpm using a dissolution medium consisting of 50 mM sodium phosphate buffer pH 6.8 and 0.3% w / v sodium lauryl sulfate at 37 °C ± 0.5 °C, about 85% to about 98% of APX3330 is detectable in the dissolution medium after 45 minutes.

[0255] In some embodiments, the compositions comprise an APX3330 hemicalcium salt monohydrate, and the dissolution testing comprises using HPLC to detect presence of APX3330 in the dissolution medium. In some embodiments, the dissolution testing comprises using HPLC at 270 nm.

[0256] In some embodiments, the compositions of the invention are contained in a sealed container. In some embodiments, the sealed container further contains an inert gas. In some embodiments, the inert gas is argon or nitrogen.Methods

[0257] The present invention further provides methods for treating or preventing an ocular disease, an inflammatory disease, Barret's esophagus (BE), cancer, a hepatic disease a cardiovascular disease, idiopathic pulmonary fibrosis, a keloid, systemic sclerosis, chemotherapy-induced peripheral neuropathy, stroke, gastro-intestinal dysfunction, chronic gastroesophageal reflux disease, von Hippel-Lindau syndrome or a skin disorder; methods for inhibiting angiogenesis,; methods for inhibiting vascular endothelial grow th factor (VEGF) or VEGF protein expression; methods for inhibiting capillary tube formation; methods for suppressing neuronal sensitivity; methods for treating pain; methods for enhancing DNA base excision repair; and methods for enhancing neuronal DNA repair function, wherein each method comprises administering to a subject in need thereof an effective amount of a composition of the invention.

[0258] In some embodiments, the present invention provides methods for treating or preventing an ocular disease, comprising administering to a subject in need thereof an effective amount of a composition of the invention.

[0259] In some embodiments, the ocular disease is diabetic retinal disease. In some embodiments, diabetic retinal disease is diabetic retinopathy (DR) or diabetic macular edema (DME). In some embodiments, the DR is non-proliferative DR or proliferative DR. In some embodiments, the DR is moderately severe non-proliferative DR or mild proliferative DR. In some embodiments, the DME is DME without loss of central vision.

[0260] In some embodiments, the ocular disease is retinopathy of prematurity, DR, pathological myopia, hypertensive retinopathy, occlusive vasculitis, polypoidal choroidal vasculopathy, diabetic macular edema, uveitic macular edema, retinal vein occlusion, ocular neovascularization, ocular histoplasmosis, neovascular glaucoma, retinoblastoma, macular degeneration, retrolental fibroplasias, retinal angiomatous proliferation, dry eye disease, uveitis, thyroid eye disease, or sickle cell retinopathy. In some embodiments, the oculardisease is DR, and the DR is proliferative diabetic retinopathy. In some embodiments, the ocular disease is macular degeneration, and the macular degeneration is advanced macular degeneration. In some embodiments, the macular degeneration is wet age-related macular degeneration. In some embodiments, the macular degeneration is dry age-related macular degeneration. In some embodiments, the ocular disease is ocular neovascularization, and the ocular neovascularization is comeal neovascularization or retinal neovascularization. In some embodiments, retinal vein occlusion is central retinal vein occlusion or branch retinal vein occlusion.

[0261] In some embodiments, the ocular disease is geographic atrophy, choroidal neovascularization, or comeal graft rejection.

[0262] The present invention further provides methods for treating or preventing Barrett's esophagus, comprising administering to a subject in need thereof an effective amount of a composition of the invention. In some embodiments, the BE is metaplastic BE.

[0263] The present invention further provides methods for treating or preventing cancer, cardiovascular disease, idiopathic pulmonary fibrosis, a keloid, systemic sclerosis, chemotherapy-induced peripheral neuropathy, stroke, gastro-intestinal dysfunction, chronic gastroesophageal reflux disease, von Hippel-Lindau syndrome, or a skin disorder, comprising administering to a subject in need thereof an effective amount of a composition of the invention.

[0264] In some embodiments, the methods of the invention are for treating or preventing cancer, and the cancer is liver cancer, breast cancer, prostate cancer, pancreatic cancer, colon cancer, cervical cancer, germ cell tumor, adult glioma, pediatric glioma, osteosarcoma, rhabdomyosarcoma, non-small cell lung cancer, leukemia, or multiple myeloma. In some embodiments, the cancer is a solid tumor, a blood cancer, a leukemia, or a lymphoma. In some embodiments, the cancer is hepatocellular carcinoma (HCC). In some embodiments, the compound of the invention is useful for treating a solid tumor, comprising administering to a subj ect in need thereof an effective amount of a compound of the invention or a composition of the invention. In some embodiments, the cancer is not liver cancer. In some embodiments, the cancer is breast cancer, prostate cancer, pancreatic cancer, colon cancer, cervical cancer, germ cell tumor, adult glioma, pediatric glioma, osteosarcoma, rhabdomyosarcoma, non- small cell lung cancer, leukemia, or multiple myeloma.

[0265] In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is a solid tumor, and the solid tumor is fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma.lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon cancer, colorectal cancer, kidney cancer, pancreatic cancer, bone cancer, breast cancer, ovarian cancer, prostate cancer, esophogeal cancer, stomach cancer, oral cancer, nasal cancer, throat cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, a papillary adenocarcinoma, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma. choriocarcinoma, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, uterine cancer, testicular cancer, small cell lung carcinoma, bladder carcinoma, lung cancer, epithelial carcinoma, glioma, glioblastoma multiforme, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, skin cancer, melanoma, neuroblastoma, retinoblastoma, or hepatocellular carcinoma (HCC).

[0266] In some embodiments, the cancer is blood cancer, and the blood cancer is leukemia, lymphoma, or myeloma. In some embodiments, the leukemia is acute lymphoblastic B-cell leukemia, acute lymphoblastic T-cell leukemia, acute myeloblastic leukemia, acute promyelocytic leukemia, acute monoblastic leukemia, acute erythroleukemic leukemia, acute megakaryoblastic leukemia, acute myelomonocytic leukemia, acute nonlymphocyctic leukemia, acute undifferentiated leukemia, chronic myelocy tic leukemia, chronic lymphocytic leukemia, or hairy cell leukemia. In some embodiments, the leukemia is an acute leukemia or a chronic leukemia. In some embodiments, the acute leukemia or the chronic leukemia is lymphoblastic leukemia, myelogenous leukemia, lymphocytic leukemia, or myelocytic leukemia. In some embodiments, the lymphoma is Hodgkin's disease, nonHodgkin's lymphoma, Waldenstrom's macroglobulinemia, heavy chain disease, or polycythemia vera. In some embodiments, the myeloma is solitary plasmacytoma, extramedullary plasmacytoma or multiple myeloma.

[0267] In some embodiments, the cancer is ocular cancer. In certain embodiments, the cancer is a solid tumor. In certain embodiments, the cancer is a cancer due to human myeloid leukemia mononuclear cell line (THP-1). In certain embodiments, the cancer is an esophageal adenocarcinoma.

[0268] The present invention further provides methods for treating or preventing a skin disorder, comprising administering to a subject in need thereof an effective amount of a composition of the invention. In some embodiments, the skin disorder is an inflammatoryskin disorder. In some embodiments, the skin disorder is psoriasis, atopic dermatitis, or rosacea.

[0269] The present invention further provides methods for treating or preventing an inflammatory disease, comprising administering to a subject in need thereof an effective amount of a composition of the invention.

[0270] In some embodiments, the inflammatory disease is ankylosing spondylitis, antiphospholipid antibody syndrome, autoimmune encephalitis, chronic recurrent multifocal osteomyelitis, gout, Henoch-Schonlein purpura, idiopathic thrombocytopenic purpura, juvenile dermatomyositis, rheumatoid arthritisjuvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, psoriatic arthritis, reactive arthritis, spondyloarthritis, systemic lupus erythematosus, junvenile lupus, scleroderma, juvenile scleroderma, vasculitis, juvenile vasculitis, mixed connective tissue disease, undifferentiated connective tissue disease, myositis, poststreptococcal inflammatory syndrome, Sjogren’s syndrome, uveitis, vasculitis, colitis, ulcerative colitis, atherosclerosis, cardiac myopathy, Crohn’s disease, celiac disease, dermatitis herpetiformis, autoimmune blistering disease, epidermolysis bullosa, type 1 diabetes, asthma, dermatomyositis, alopecia areata, autoimmune hepatitis, multiple sclerosis, Guillain-Barre syndrome, demyelinating polyneuropathy, psoriasis, Graves’s disease, Hashimoto’s thyroiditis, myasthenia gravis, hemolytic anemia, inflammatory bowel disease, inflammatory myopathy, primary' biliary cirrhosis, or vitiligo.

[0271] In some embodiments, the inflammatory disease is an inflammatory disease of the digestive tract. In some embodiments, the inflammatory disease of the digestive tract is inflammatory bowel disease. In some embodiments, the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

[0272] In some embodiments, the inflammatory disease is a chronic inflammatory disease, rheumatoid arthritis, acute adult respiratory distress syndrome, asthma or endometriosis.

[0273] In some embodiments, the methods for treating comprise delaying progression of the ocular disease, inflammatory' disease, Barrett's esophagus (BE), cancer, hepatic disease, cardiovascular disease, idiopathic pulmonary fibrosis, keloid, systemic sclerosis, chemotherapy-induced peripheral neuropathy, stroke, gastro-intestinal dysfunction, chronic gastroesophageal reflux disease, von Hippel-Lindau syndrome or skin disorder.

[0274] In some embodiments, the methods are for treating an ocular disease, and the ocular disease is non-proliferative retinopathy. In some embodiments, the methods are for treating non-proliferative retinopathy, comprising orally administering to a subject in need thereof an effective amount of a composition of the invention. In some embodiments, the methods arefor treating non-proliferative retinopathy, comprising orally administering to a subject in need thereof an effective amount of a composition of the invention.

[0275] The present invention further provides methods for inhibiting angiogenesis, comprising administering to a subject in need thereof an effective amount of a composition of the invention. In some embodiments, angiogenesis is ocular angiogenesis. In some embodiments, inhibiting angiogenesis results in slowing or stopping tumor growth. In some embodiments, inhibiting angiogenesis results in treating cancer.

[0276] The present invention further provides methods for inhibiting vascular endothelial growth factor (VEGF) or VEGF protein expression, comprising administering to a subject in need an effective amount of a composition of the invention. In some embodiments, inhibiting vascular endothelial growth factor (VEGF) or VEGF protein expression results in inhibiting angiogenesis. In some embodiments, angiogenesis is ocular angiogenesis. In some embodiments, inhibiting vascular endothelial growth factor (VEGF) or VEGF protein expression results in slowing or stopping tumor growth. In some embodiments, inhibiting vascular endothelial growth factor (VEGF) or VEGF protein expression results in treating cancer.

[0277] The present invention further provides methods for inhibiting capillary tube formation, comprising administering to a subject in need thereof an effective amount of a composition of the invention.

[0278] The present invention further provides methods for treating or preventing a hepatic disease, comprising administering to a subject in need thereof an effective amount of a compound of the invention or a composition of the invention. In some embodiments, the hepatic disease is hepatitis, toxic hepatopathy, jaundice, cirrhosis, nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD), or alcoholic steatosis. In some embodiments, the hepatic disease is hepatitis, and the hepatitis is chronic hepatitis, acute hepatitis, viral hepatitis, or alcoholic hepatitis.

[0279] The present invention further provides methods for suppressing neuronal sensitivity, comprising administering to a subject in need thereof an effective amount of a composition of the invention.

[0280] The present invention further provides methods for treating pain, comprising administering to a subject in need thereof an effective amount of a composition of the invention. In some embodiments, the pain is inflammatory or chronic pain.

[0281] The present invention further provides methods for enhancing DNA base excision repair, comprising administering to a subject in need thereof an effective amount of a composition of the invention.

[0282] The present invention further provides methods for enhancing neuronal DNA repair function, comprising administering to a subject in need thereof an effective amount of a composition of the invention.

[0283] In some embodiments of the methods of the invention, the subject has obesity, diabetes, asthma, arthritis, chronic periodontitis, ulcerative colitis, Crohn's disease, chronic sinusitis, chronic active hepatitis, a chronic peptic ulcer, diverticulitis, fibromyalgia, irritable bowel syndrome, irritable bowel disease, Alzheimer's disease, Parkinson's disease, atherosclerosis, or tuberculosis. In some embodiments, the subject has diabetes.

[0284] In some embodiments, the administering is orally administering. In some embodiments, the administering is orally administering a composition of the invention that is in an oral dosage, for example, a tablet or a capsule, form.

[0285] In some embodiments, the effective amount is an amount of a composition of the invention can be administered daily to a subject.

[0286] In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 10 mg to about 1000 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 10 mg to about 800 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 10 mg to about 650 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 120 mg to about 600 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 10 mg, about 20 mg, about 30 mg, about 50 mg, about 60 mg. about 100 mg, about 120 mg, about 150 mg, about 180 mg, about 200 mg, about 240 mg, about 250 mg. about 300 mg, about 350 mg, about 360 mg, about 400 mg, about 420 mg, about 450 mg, about 480 mg, about 500 mg, about 540 mg, about 550 mg, about 600 mg, or about 650 mg.

[0287] In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 600 mg. In some embodiments, the effective amount of a composition of the invention is dailydose of a composition of the invention that comprises APX3330 in an amount of about 480 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 360 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 300 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 240 mg. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises APX3330 in an amount of about 120 mg.

[0288] In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 10 mg to about 1000 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 10 mg to about 800 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 10 mg to about 650 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 120 mg to about 600 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 10 mg, about 20 mg, about 30 mg, about 50 mg, about 60 mg, about 100 mg, about 120 mg, about 150 mg, about 180 mg, about 200 mg, about 240 mg, about 250 mg, about 300 mg, about 350 mg, about 360 mg, about 400 mg, about 420 mg, about 450 mg. about 480 mg, about 500 mg, about 540 mg, about 550 mg, about 600 mg, or about 650 mg of APX3330.

[0289] In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises about 10 mg, about 20 mg, about 30 mg, about 50 mg, about 60 mg, about 100 mg. about 120 mg, about 150 mg, about 180 mg, about 200 mg, about 240 mg, about 250 mg. about 300 mg, about 350 mg, about 360 mg, about 400 mg, about 420 mg, about 450 mg, about 480 mg, about 500 mg, about 540 mg,about 550 mg, about 600 mg, or about 650 mg of an APX3330 hemicalcium salt monohydrate.

[0290] In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 600 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 480 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 360 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 300 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 240 mg of APX3330. In some embodiments, the effective amount of a composition of the invention is daily dose of a composition of the invention that comprises an APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 120 mg of APX3330.

[0291] In some embodiments, the daily dose is divisible among one or more oral dosage forms, e.g., tablets or capsules. In some embodiments, the daily dose is five tablets or capsules, wherein each tablet comprises, or each capsule contains, about 120 mg of APX3330. In some embodiments, the daily dose is five tablets or capsules, wherein each tablet comprises, or each capsule contains, an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg of APX3330.

[0292] In some embodiments, the administering comprises administering to a subject three tablets or capsules in the morning and two tablets or capsules in the evening, wherein each tablet comprises, or each capsule contains, about 120 mg of APX3330. In some embodiments, the daily dose is two tablets or capsules, wherein each tablet comprises, or each capsule contains, about 300 mg of APX3330. In some embodiments, the administering comprises administering to a subject one tablet or capsule in the morning and one tablet or capsule in the evening, where each tablet comprises, or each capsule contains, about 300 mg of APX3330.

[0293] In some embodiments, the administering comprises administering to a subject three tablets or capsules in the morning and two tablets or capsules in the evening, wherein each tablet comprises, or each capsule contains, an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 120 mg of APX3330. In some embodiments, the daily dose is two tablets or capsules, wherein each tablet comprises, or each capsule contains, an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 300 mg of APX3330. In some embodiments, the administering comprises administering to a subject one tablet or capsule in the morning and one tablet or capsule in the evening, wherein each tablet comprises, or each capsule contains, an APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to about 300 mg of APX3330.

[0294] In some embodiments, the effective amount of a composition of the invention is a daily dose. In some embodiments, a composition of the invention is administered once a day, twice a day, or three times a day.

[0295] In some embodiments, the composition is a tablet or a capsule.EXAMPLES

[0296] General Procedures: The X-ray powder diffraction (XRPD) data of Reference Example A were obtained using a Bruker AXS with D2 Phaser 2ndGen configuration (Part Number: A26X1-A2B0B1C) in reflection mode (scan type: Coupled TwoTheta / Theta) scanning the samples at between 3 and 40° 2-theta angles, and using the following measurements characteristics: increment per step was 0.02°, time per step was 0.3 s, and generator voltage / generator amperage was 10 mA / 30 kV to reach 0.3 kW power, detector type LynxEye A17-B60 and a goniometer type Theta / Theta. The XRPD data were collected using DIFFRAC.MEASURMENT 8.6.3.0 software and processed with DIFFRAC.EVA 6.0.0.8 software.

[0297] The XRPD analysis for Reference Example B was obtained using a Bruker D8 Discover diffractometer with DAVINCI configuration, in transmission mode (scan ty pe: TwoTheta or Offset Coupled TwoTheta / Theta) scanning the samples (~2-3 mg) at between 1.5 and 45° 2-theta angles, and using the following measurements characteristics: acquisition time was 7.58 minutes, increment per step was 0.01°, time per step was 0. 1 s, and generator voltage / generator amperage was 40 mA / 40 kV to reach 1.6 kW power. The XRPD system was used in Parallel Beam Geometry (Gobel mirror) with an anode of Cu and a detector type LynxEye. Also, the XRPD system used a goniometer type Theta / Theta with a measuring circle diameter of 560 mm and vertical operating position. For transmission mode, 1 UBCcollimator magnetic holder 1 mm was mounted to primary' optics. The raw XRPD data were imported in the Diffrac.EVA5.0 software and processed using the subsequent parameters: background subtraction and Ka2 stripping were performed before peak determination, and the peak search operation was performed with a threshold of 1 and a peak width of 0.153.

[0298] APX3330 can be obtained according to U.S. Patent No. 5,210,239.Reference Example A. Synthesis of APX3330 Hemi calcium Salt Monohydrate

[0299] About 75 g (0.198 mol) of APX3330 (1 eq.) was charged to a 5 L jacketed reactor. 2025 mL (27.0 vol) of 2:1 EhOMeOH (v / v) was charged to the 5 L jacketed reactor at room temperature. The reaction mixture was agitated for 25 minutes at 25 ± 5 °C to provide a fine suspension. Calcium hydroxide (7.3 g. 0.5 eq.) was charged to the reactor portion- wise over 25 minutes. The resultant mixture was thick but remained stirrable with some shelling observed near the top of the reactor. The shelled material was scraped down. The mixture was agitated at 25 ± 5 °C for 2 hours and the mixture became very' thick. A sample was taken to confirm formation of APX3330 hemicalcium salt monohydrate by an XRPD analysis.

[0300] The resultant solids were collected via vacuum filtration and were washed twice with 2: 1 water / methanol (900 mL, 12.0 vol). The solids were dried under vacuum until they had a water content of about 12% and dried using humidified drying. The humidified dry ing was performed using a vacuum oven attached to a house vacuum system with a small bleed of nitrogen that was saturated with water vapor. The water vapor-saturated nitrogen was obtained by bubbling nitrogen through water and had 100% humidity at 20 ± 5 °C.Humidified dry ing continued until the solids had a water content of 4-6% (Table 1) to provide APX3330 hemicalcium salt monohydrate as an orange solid (80.41 g, 97.2% yield). Purity’ determined by HPLC at 262 nm was 99.9%. HPLC parameters and conditions used are set forth below:Mobile Phase A: 0.1% TFA in WaterMobile Phase B: 0.1% TFA in AcetonitrileDiluent: Acetonitrile and Water; 80:20 v / vSample Concentration: 0.7mg / mL

[0301] The APX3330 hemicalcium salt monohydrate of Reference Example A was analyzed by XRPD (Fig. 1).Table 1. Vacuum Drying Time and Water Content* Inconsistency with this time point due to solids precipitating in the system and sticking to the detector

[0302] Fig. 1 shows an XRPD diffractogram of the APX3330 hemicalcium salt monohydrate obtained by Reference Example A, and Table 2 lists XRPD peaks represented in Fig. 1.Table 2. XRPD Data for APX3330 Hemicalcium Salt MonohydrateReference Example B. Synthesis of APX3330 Hemicalcium Salt Monohydrate

[0303] About 20 g of APX3330 (1 eq.) were weighed and added to a 1 L glass reactor and mixed at room temperature with H20:Me0H (1 :1 v / v) to provide a fine suspension having a concentration of 36.3 g of APX3330 / L of H20:Me0H (1: 1 v / v). The suspension was allowed to stir for 30 minutes with a mechanical stirrer type OS-20 with a rod and PTFE propeller at 300 rpm. Calcium hydroxide (95%; 2.0953 g; 0.5 eq.) was added, and the resultant mixture was allowed to stir at 500 rpm at room temperature for 2 hours. After 2 hours, the resultant precipitate was vacuum filtered, washed with 400 mL of H2O:MeOH (1: 1 v / v). The washedprecipitate was dried in a fume hood at atmospheric pressure at 25 °C for about 45 hours to provide a APX3330 hemi calcium salt monohydrate as a light orange solid (89.06% yield).

[0304] Purity of the APX3330 hemicalcium salt monohydrate was determined by HPLC chromatography using an Agilent 1260 Infinity HPLC device, at 30°C and a HiChrom C 18 column (4.6x100mm, 3.5pm). The HPLC device was coupled with a UV-Vis Diode Array Detector (HPLC-DAD). Analyses were run with a gradient method (as described in Table below) using 0. 1% formic acid in purified MilliQ water (mobile phase A) and 0.1% formic acid in acetonitrile HPLC grade (mobile phase B). A flow rate was 1 mL / min and an injection volume was5 pL. UV detection was run at 236 nm and 266 nm. The sample was dissolved into MilliQ pure water. Purity of the APX3330 hemicalcium salt monohydrate determined by HPLC at 236 nm was 99.7% and at 266 nm was 99.8%.

[0305] The APX3330 hemicalcium salt monohydrate of Reference Example B was analyzed by XRPD. Fig. 2 shows an XRPD diffractogram (background subtracted) of the APX3330 hemicalcium salt monohydrate obtained as described in Reference Example B, and Table 3 lists XRPD peaks represented in Fig. 2.Table 3. XRPD Data for APX3330 hemicalcium salt monohydrate from this ExampleReference Example C. APX3330 Tablet

[0306] Tablets having the composition of Table 4 were prepared and subjected to dissolution testing.Table 4.

[0307] Dissolution test parameters for USP <711) DISSOLUTION:

[0308] HPLC conditions to measure dissolution of APX3330:

[0309] Different batches of the tablets having the composition of Table 4 demonstrated dissolution curves as shown in Fig. 3. Dissolution results are also shown in Table 5.Table 5RSD means relative standard deviation ’■'Batch 3 re-tested at a different timeExample 1. Fluid-Bed Granulation Formulation

[0310] A fluid-bed granulation formulation having the composition of Table 6a was prepared and dried.Table 6a.Intra-Granular

[0311] Compression evaluation of the post-dried granulation composition of Table 6a displayed a sticking issue (granulation sticking to the tablet punch).

[0312] Table 6a tablets comprising an amount of an APX3330 hemicalcium salt monohydrate that is molar equivalent to 120 mg APX3330 were subjected to a dissolution test. The dissolution curves of the 120 mg tablets are shown in Fig. 4. Dissolution results are also shown in Table 6b. The dissolution test conditions were the same as those described in Reference Example C.Table 6b.RSD means relative standard deviationExample 2. Dry Granulation Composition

[0313] Dry granulation via roller compaction was evaluated as a means for increasing granulation density and particle size relative to that of the granulations produced by the fluidbed process. 100 g of a roller compaction blend of the intra-granular ingredients of Table 7 were compounded using a Gerteis Mini-Pactor. The resultant granules were combined with the extra-granular excipients of Table 7 for tableting evaluation using a rotary' tablet press. Table 8 provides the roller compaction parameters used to produce the dry granulation.Table 7Table 8* Due to small size of batch, powder was manually agitated into feed auger. Tamp / Feed auger ratio of 170% was used

[0314] The final blend was used to produce tablets comprising an amount of an APX3330 hemicalcium salt monohydrate of Reference Example A that is molar equivalent to 300 mg APX3330 (300 mg strength tablets) that were compressed using 0.3150” x 0.6063” modified oval tooling and having a tablet weight of 650 mg. The final blend was also used to produce dose / weight proportional tablets comprising an amount of an APX3330 hemicalcium salt monohydrate of Reference Example A that is molar equivalent to 120 mg APX3330 (120 mg strength tablets) that were compressed using 0.2598” x 0.5197” modified oval tablet tooling and having a tablet weight of 260 mg.

[0315] The 120 mg strength tablets (n = 6) were tested for dissolution as shown in Fig. 5 and Table 9. The dissolution test conditions were the same as those described in Reference Example C.Table 9.RSD means relative standard deviationExample 3. Dry Granulation Composition

[0316] Tablets and capsules having the composition of Table 10 were prepared.Table 10f Amount of APX3330 hemicalcium salt monohydrate that is molar equivalent to 300 mg ofAPX3330 accounting for water content of APX3330 hemicalcium salt monohydrate of Reference Example A.{ Theoretical average individual capsule weight per manufacturer's literature. Actual capsule shell weights are determined during batch production.

[0317] Prior to dry granulation, the APX3330 hemicalcium salt monohydrate of Reference Example A was milled (1) using a Model 197 Quadro Comil outfitted with a 024R screen and 1612 impeller and (2) subsequently milled with a 018R screen and 1612 impeller.

[0318] A common granulation batch was prepared at 390 g scale (theoretical 650 dosage units) using a roller compaction process. A roller compaction blend of the intra-granular ingredients was prepared in a 2-quart v-shell diffusional blender and processed on a Gerteis Mini-Pactor. Resultant granules were apportioned into two approximately equal portions and used to prepare the tablet and capsule formulations of Table 10. Extra-granular ingredients were blended with the granulation for each product in a 1 -quart V-shell blender and the resultant blends were either tableted or encapsulated. Tablet cores were prepared using 0.3150” x 0.6360” modified oval tooling on a fully instrumented Elizabeth-Hata ElizaPress EP200L rotary tablet press.

[0319] The tablet cores were coated to a 30 mg (-4.5%) weight gain with Opadry Yellow (03 Al 20009), fully formulated aqueous film coating system from Colorcon. Inc., using aVector LDCS fully perforated pan coater with a 2.5 L pan. Capsules were filled using a Size 00 ProFil hand encapsulation tray.

[0320] The tablets and capsules were manually packaged at 30 counts into high-density polyethylene (HDPE) bottles. The bottles were then induction-sealed using 38 mm White Ribbed CRC caps with foil liners. Packaged samples of each tablet and capsule batch w ere placed at the 25°C / 60% relative humidity (RH) and 40°C / 75%RH storage conditions for analysis after 4 and 8 weeks. Each batch was tested for appearance, purity / impurity, moisture content, dissolution, content uniformity, and x-ray powder diffraction pattern (XRPD) at the beginning of stability' testing (initial time point). Each batch is further tested for appearance, purity / impurity, moisture content, dissolution, and XRPD after 4 and 8 weeks of storage at the respective stability conditions.

[0321] Dissolution test parameters for USP (711) DISSOLUTION:

[0322] HPLC conditions for measuring dissolution of APX3330 hemicalcium salt monohydrate by measuring APX3330:

[0323] Table 11 shows the characteristics of the 300 mg tablets of Table 10 at an initial time point, and Table 12 shows the characteristics of the 300 mg capsules of Table 10 at an initial time point. XRPD analysis of the 300 mg tablet ingredients and the 300 mg capsule ingredients at the initial time point indicated that the APX3330 hemicalcium saltmonohydrate of the tablets and the capsules remained unchanged from the APX3330 hemical ci um salt monohydrate of Reference Example A.Table 11.RSD means relative standard deviation; *%LC = percentage of Label ClaimTable 12.RSD means relative standard deviation; *%LC = percentage of Label ClaimExample 4. Dry Granulation Composition

[0324] Tablets and capsules having the composition of Table 13 were prepared.Table 13(Vegetable Source)t Amount of APX3330 hemicalcium salt monohydrate that is molar equivalent to 300 mg of APX3330 accounting for water content of APX3330 hemicalcium salt monohydrate of Reference Example A.J Theoretical average individual capsule weight per manufacturer's literature. Actual capsule shell weights are determined during batch production.

[0325] Prior to dr7granulation, APX3330 hemicalcium salt monohydrate of Reference Example A was milled (1) using a Model 197 Quadro Comil outfitted with a 156R screen and 1612 impeller then (2) subsequently milled with a 075R screen and 1612 impeller and (3) finally milled with a O24R screen and 1607 impeller.

[0326] A common granulation batch was prepared at 343.2 g scale (theoretical 572 dosage units) using a roller compaction process. A roller compaction blend of the intra-granular ingredients was prepared in a 2-quart v-shell diffusional blender and processed on a Gerteis Mini-Pactor. Resultant granules were apportioned into two approximately equal portions and used to prepare the tablet and capsule formulations of Table 13. Extra-granular ingredients were blended with the granulation for each product in a 1 -quart V-shell blender and the resultant blends were either tableted or encapsulated. Tablet cores were prepared using 0.3543” x 0.6693” modified oval tooling on a fully instrumented Elizabeth-Hata ElizaPress EP200L rotary tablet press.

[0327] The tablet cores were coated to a 30 mg (-4.5%) weight gain with Opadry Yellow (03 Al 20009), fully formulated aqueous film coating system from Colorcon, Inc., using aVector LDCS fully perforated pan coater with a 2.5 L pan. Capsules were filled using a Size 00 ProFil hand encapsulation tray.

[0328] The tablets and capsules were manually packaged at 30 counts into high-density polyethylene (HDPE) bottles. The bottles were then induction-sealed using 38 mm White Ribbed CRC caps with foil liners. Packaged samples of each tablet and capsule batch w ere placed at the 25°C / 60% relative humidity (RH) and 40°C / 75%RH storage conditions for analysis after 4 and 8 weeks. Each batch was tested for appearance, purity / impurity, moisture content, dissolution, content uniformity, and x-ray powder diffraction pattern (XRPD) at the beginning of stability' testing (initial time point). Each batch is further tested for appearance, purity / impurity, moisture content, dissolution, and XRPD after 4 and 8 weeks of storage at the respective stability conditions. Dissolution method is as described in Example 3.

[0329] Table 14 shows the characteristics of the 300 mg tablets at initial time point and Table 15 show s the characteristics of the 300 mg capsules at initial time point. XRPD analysis of the 300 mg tablet ingredients and the 300 mg capsule ingredients at the initial time point indicated that the APX3330 hemicalcium salt monohydrate of the tablets and the capsules remained unchanged from the APX3330 hemicalcium salt monohydrate of Reference Example A.Table 14.RSD means relative standard deviation;*%LC = percentage of Label ClaimTable 15.RSD means relative standard deviation; *%LC = percentage of Label ClaimExample 5. Dry Granulation Composition

[0330] Tablets having the composition of Table 16 were prepared.Table 16f Amount of APX3330 hemicalcium salt monohydrate that is molar equivalent to 300 mg ofAPX3330 accounting for water content of APX3330 hemicalcium salt monohydrate of Reference Example A.

[0331] Prior to dry granulation, the APX3330 hemicalcium salt monohydrate of Reference Example A was milled (1) using a Model 197 Quadro Comil outfitted with a 156R screen and 1612 impeller then (2) subsequently milled with a 075R screen and 1612 impeller and (3) finally milled with a 024R screen and 1612 impeller.

[0332] The dry granulation batch was prepared at 201.6 g scale (theoretical 336 dosage units) using a roller compaction process. A roller compaction blend of the intra-granular ingredients was prepared in a 2-quart v-shell diffusional blender and processed on a Gerteis Mini-Pactor. Extra-granular ingredients were blended with the granulation in a 1 -quart V-shell blender and the resultant blends were tableted. Tablet cores were prepared using 0.3543” x 0.6693” modified oval tooling on a fully instrumented Elizabeth-Hata ElizaPress EP200L rotary tablet press.

[0333] Tablet cores were coated to a 30 mg (-4.5%) weight gain with Opadry Yellow (03 Al 20009), fully formulated aqueous film coating system from Colorcon, Inc., using a Vector LDCS fully perforated pan coater with a 2.5 L pan.

[0334] The tablets were manually packaged at 30 counts into high-density polyethylene (HDPE) bottles. The bottles were then induction-sealed using 38 mm White Ribbed CRC caps with foil liners. Packaged samples were placed at the 25°C / 60%RH and 40°C / 75%RH storage conditions for analysis after 4 and 8 weeks. Tablets were tested for appearance, punty, / impurity, moisture content, dissolution, content uniformity, and x-ray powder diffraction pattern (XRPD) at the beginning of stability testing (initial time point). Tablets were further tested for appearance, purity / impurity, moisture content, dissolution, and XRPD after 4 and 8 weeks of storage at the respective stability conditions. Dissolution method is as described in Example 3.

[0335] Table 17 shows the characteristics of the 300 mg tablets at initial time point. XRPD analysis of the 300 mg tablet ingredients at the initial time point indicated that the APX3330 hemicalcium salt monohydrate in the tablets remained unchanged from the APX3330 hemi calcium salt monohydrate of Reference Example A.Table 17.RSD means relative standard deviation*%LC = percentage of Label ClaimExample 6. Dry Granulation Composition

[0336] Tablets having the composition of Table 18 were prepared.Table 18f Amount of APX3330 hemicalcium salt monohydrate that is molar equivalent to 300 mg ofAPX3330 accounting for water content of APX3330 hemicalcium salt monohydrate of Reference Example A and the % Assay of the Reference Example A lot used.^Amount of anhydrous lactose and microcrystalline cellulose in the intra-granular phase is adjusted based on adjusted amount of APX3330 hemicalcium salt monohydrate.

[0337] Prior to dry granulation, the APX3330 hemicalcium salt monohydrate of Reference Example A was milled (1) using a Model 197 Quadro Comil outfitted with a 156R screen and 1612 impeller at 1600 RPM then (2) subsequently milled with a 075R screen and 1612impeller at 1600 RPM and (3) finally milled with a 024R screen and 1612 impeller at 1600 RPM.

[0338] The dry granulation batch was prepared using 510.72 g of Reference Example A (adjusted scale) (theoretical 500.64 g APX3330 Hemicalcium Salt Monohydrate). 15.6 g talc was passed through a 40-mesh screen then added to MaxiBlend Blender with a 4-quart V- shell with 510.72 g of milled APX3330 hemi calcium salt monohydrate Reference Example A and mixed at 25 RPM for 15 minutes. 133.38 g anhydrous lactose, 133.38 g microcrystalline cellulose, 36.48 g AVICEL® CL-61 1, and 45.6 g low substituted hydroxypropyl cellulose were passed through a 20-mesh screen then added to MaxiBlend Blender with a 4-quart V- shell with the blended mixture of talc and APX3330 hemicalcium salt monohydrate Reference Example A and mixed at 25 RPM for 20 minutes. 6.84 g magnesium stearate was passed through a 40-mesh screen and added to the blender with the other intra-granular blend materials and blended at 25 RPM for 5 minutes to provide intra-granular final blend. The intra-granular final blend was processed on a Gerteis Macro-Pactor with one Smooth Roll (left), one Smooth Roll (right), and the 1.25 mm screen (roller speed: 20 RPM; granular speed 80 RPM) to provide the intra-granular milled granulation.

[0339] Extra-granular ingredients microcrystalline cellulose (36.45g) and crospovidone (26.08 g) were passed through a 20-mesh screen then blended in MaxiBlend Blender with a 4-quart V-shell with the intra-granular milled granulation at 25 RPM for 20 minutes. Pass magnesium stearate (4.35 g) through a 40-mesh screen then add to the blender and mix for 5 minutes at 25 RPM. The resultant blend was tableted.

[0340] Tablet cores were prepared using 0.3543” x 0.6693” modified oval concave tooling on rotary tablet press. Tablet cores were coated to a 30 mg (-4.5%) weight gain with Opadry Yellow (03A120009), fully formulated aqueous film coating system from Colorcon, Inc., using a LDCS Plus Hi-Coater using a 4L coating pan.

[0341] The tablets were manually packaged at 30 counts into high-density polyethylene (HDPE) bottles. The bottles were then induction-sealed using 38 mm SecuRx® Ribbed Side Text Closure with FS M-1 / .035 Pulp Print SFYP White Ink Induction Seal Liner. Table 19 shows the characteristics of the 300 mg tablets at initial time point. XRPD analysis of the 300 mg tablet ingredients at the initial time point indicated that the APX3330 hemicalcium salt monohydrate in the tablets remained unchanged from the APX3330 hemicalcium salt monohydrate of Reference Example A.Table 19.RSD means relative standard deviation ; *%LC = percentage of Label Claim

[0342] Tablet samples prepared according to this Example were placed at the 25°C / 60%RH and 40°C / 75%RH storage conditions for analysis after 4 and 8 weeks. Tablets were tested for appearance, purity / impurity, moisture content, dissolution, content unifonnity. and x-ray powder diffraction pattern (XRPD) at the beginning of stability testing (initial time point). Tablets were further tested for appearance, purity / impurity, moisture content, dissolution, and XRPD after 4 and 8 weeks of storage at the respective stability conditions. Dissolution method is as described in Example 3.

[0343] Table 20 shows the characteristics of the 300 mg tablets prepared according to this Example at initial time point (different lot than Table 19 sample). XRPD analysis of the 300 mg tablet ingredients at the initial time point indicated that the APX3330 hemicalcium salt monohydrate in the tablets remained unchanged from the APX3330 hemicalcium salt monohydrate of Reference Example A.Table 20.RSD means relative standard deviation; *%LC = percentage of Label Claim

[0344] Table 21 shows the characteristics of the 300 mg tablets prepared according to this Example after 4 weeks at the 25°C / 60%RH storage conditions. These results are for the same lot of tablets whose characteristics at initial time point are provided in Table 20. XRPD analysis of the 300 mg tablet ingredients after 4 weeks at the 25°C / 60%RH storage conditions indicated that the APX3330 hemicalcium salt monohydrate in the tablets remained unchanged from the APX3330 hemicalcium salt monohydrate of Reference Example A.Table 21.RSD means relative standard deviation; *%LC = percentage of Label Claim

[0345] Table 22 shows the characteristics of the 300 mg tablets prepared according to this Example after 4 weeks at the 40°C / 75%RH storage conditions. These results are for the same lot of tablets whose characteristics at initial time point are provided in Table 20. XRPD analysis of the 300 mg tablet ingredients after 4 weeks at the 40°C / 75%RH storage conditions indicated that the APX3330 hemicalcium salt monohydrate in the tablets remained unchanged from the APX3330 hemicalcium salt monohydrate of Reference Example A.Table 22.RSD means relative standard deviation; *%LC = percentage of Label Claim

[0346] Table 23 shows the characteristics of the 300 mg tablets prepared according to this Example after 8 weeks at the 25°C / 60%RH storage conditions. These results are for the same lot of tablets whose characteristics at initial time point are provided in Table 20.XRPD analysis of the 300 mg tablet ingredients after 8 weeks at the 25°C / 60%RH storage conditions indicated that the APX3330 hemicalcium salt monohydrate in the tablets remained unchanged from the APX3330 hemicalcium salt monohydrate of Reference Example A.Table 23.RSD means relative standard deviation; *%LC = percentage of Label Claim

[0347] Table 24 shows the characteristics of the 300 mg tablets prepared according to this Example after 8 weeks at the 40°C / 75%RH storage conditions. These results are for the same lot of tablets whose characteristics at initial time point are provided in Table 20. XRPD analysis of the 300 mg tablet ingredients after 8 weeks at the 40°C / 75%RH storage conditions indicated that the APX3330 hemicalcium salt monohydrate in the tablets remained unchanged from the APX3330 hemicalcium salt monohydrate of Reference Example A.Table 24.RSD means relative standard deviation; *%LC = percentage of Label ClaimExample 7. Dry Granulation Composition. One- and Six-Month Storage Stability.

[0348] Tablet samples prepared according to Example 6 were placed at the 25°C / 60%RH and 40°C / 75%RH storage conditions for analysis after 1 month and 6 months. Tablets were tested for appearance, purity / impurity, moisture content, dissolution, content uniformity’, and x-ray powder diffraction pattern (XRPD) at the beginning of stability testing (initial time point). Results for these tests are provided in Table 19, in Example 6, above. Tablets were further tested for appearance, purity / impurity. moisture content, and dissolution after 1 month and 6 months of storage at the respective stability conditions. Tablets were further tested for XRPD only after 6 months of storage at the respective stability conditions. Dissolution method is as described in Example 3.

[0349] Table 25 shows the characteristics of the 300 mg tablets prepared according to this Example after 1 month at the 25°C / 60%RH storage conditions.Table 25.*%LC = percentage of Label Claim

[0350] Table 26 shows the characteristics of the 300 mg tablets prepared according to this Example after 1 month at the 40°C / 75%RH storage conditions.Table 26.*%LC = percentage of Label Claim

[0351] Table 27 shows the characteristics of the 300 mg tablets prepared according to this Example after 6 months at the 25°C / 60%RH storage conditions. XRPD analysis of the 300 mg tablet ingredients after 6 months at the 25°C / 60%RH storage conditions indicated that the APX3330 hemi calcium salt monohydrate in the tablets remained unchanged from the APX3330 hemi calcium salt monohydrate of Reference Example A.Table 27.*%LC = percentage of Label Claim

[0352] Table 28 shows the characteristics of the 300 mg tablets prepared according to this Example after 6 months at the 40°C / 75%RH storage conditions. XRPD analysis of the 300 mg tablet ingredients after 6 months at the 40°C / 75%RH storage conditions indicated that the APX3330 hemi calcium salt monohydrate in the tablets remained unchanged from the APX3330 hemi calcium salt monohydrate of Reference Example A.Table 28.*%LC = percentage of Label ClaimExample 8. Safety and Efficacy Study of an APX3330 Hemicalcium Salt Monohydrate in Patients with an Ocular Disease

[0353] This study is randomized, placebo-controlled, double-masked study of the safety and efficacy of an APX3330 hemicalcium salt monohydrate composition prepared according toany one of Examples 1-6 orally administered twice daily for 24 weeks in subjects having an ocular disease as described herein, such as moderately severe to severe non-proliferative diabetic retinopathy (NPDR) or mild proliferative diabetic retinopathy (PDR).

[0354] The study has a 1: 1 randomization (placebo: APX3330 hemicalcium salt monohydrate). Randomization is stratified by level of disease severity.

[0355] APX3330 hemicalcium salt monohydrate arm (APX3330 hemi calcium salt monohydrate amounts are molar equivalent to the APX3330 amounts referenced below):600 mg / day: Five 120 mg tablets comprising or capsules containing a composition of any one of Examples 1-6 are divided as three 120 mg morning doses and two 120 mg evening doses (e.g., 360 mg even' morning and 240 mg every evening), or two 300 mg tablets comprising or capsules containing a composition of any one of Examples 1-6 are divided as one 300 mg morning dose and one 300 mg evening dose. The tablets or capsules are taken orally.Placebo arm: placebo tablets are identical to APX3330 hemicalcium salt monohydrate tablets except for the absence of APX3330 hemicalcium salt monohydrate. Five placebo tablets are taken by mouth as follows: 3 tablets every morning and 2 tablets even' evening.

[0356] Study medication is taken at approximately the same time each day and may be taken with or without food. If a subject is considering discontinuing the study due to an adverse event, a daily dose reduction from 600 mg to 480 mg per day as an alternative can be offered (e.g., 2 120 mg tablets every morning and 2 120 mg tablets every evening). The Screening Visit (Visit 1) occurs 1 to 21 days prior to Qualification / Baseline Visit (Visit 2), which occurs before dosing on Day 1. There are 3 scheduled treatment site visits: Visit 4 Week 4 (± 2 days), Visit 6 Week 12 (± 2 days), and Visit 9 Week 24 (± 2 days). In between these visits, subjects are contacted by telephone on Visit 3 Week 1 (± 2 days). Visit 5 Week 8 (± 2 days). Visit 7 Week 16 (± 2 days), and Visit 8 Week 20 (± 2 days) for a safety’ assessment to include adverse events (AEs), concomitant medications, and drug compliance.

[0357] Analysis of efficacy: For the analysis of the primary efficacy endpoint, appropriate imputation techniques are performed for missing observations or for subjects requiring rescue if applicable. If the analysis using the per-protocol (PP) population shows a positive effect for APX3330 hemi calcium salt monohydrate at the 0.05 level of significance, the primary endpoint is considered met. Confirmatory analyses may be performed using the all randomized population, with imputation performed for missing data. If warranted,confirmatory analyses with imputation for missing data or subjects requiring rescue are also performed for the secondary efficacy endpoints.

[0358] For all efficacy endpoints, baseline values are defined as the last observation prior to randomization. The primary efficacy endpoint is the difference between treatment groups in percent of subjects with a > 2-step improvement from baseline in disease severity score, such as diabetic retinopathy severity score, in the study eye at Week 24. The primary efficacy endpoint is analyzed using a logistic regression model with treatment as factor and the baseline severity score as a covariate. The percent of subjects in each treatment group meeting the criteria, the odds ratio (OR) with 95% confidence interval (CI), and p-value are provided.INCORPORATION BY REFERENCE

[0359] The entire disclosure of each of the patent documents and scientific articles referred to herein is incorporated by reference for all purposes.EQUIVALENTS

[0360] The invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The foregoing embodiments are therefore to be considered in all respects illustrative rather than limiting the invention described herein. Scope of the invention is thus indicated by the appended claims rather than by the foregoing description, and all changes that come within the meaning and range of equivalency of the claims are intended to be embraced therein.

Claims

Claims:

1. A composition comprising: an APX3330 hemicalcium salt monohydrate; talc; and crospovidone or low-substituted hydroxypropyl cellulose.

2. The composition of claim 1 , wherein the composition comprises crospovidone and low-substituted hydroxypropyl cellulose.

3. The composition of claim 1 or 2. wherein the composition further comprises lactose, microcrystalline cellulose, dicalcium phosphate dihydrate, or calcium carbonate.

4. The composition of any one of claims 1-3, wherein the composition further comprises partially pregelatinized maize starch.

5. The composition of any one of claims 1-4, wherein the composition further comprises D-a-tocopheryl polyethylene glycol succinate.

6. The composition of any one of claims 1-5. wherein the composition further comprises sodium stearyl fumarate or magnesium stearate.

7. The composition of claim 1, wherein the composition further comprises lactose, microcrystalline cellulose, dicalcium phosphate dihydrate, calcium carbonate, partially pregelatimzed maize starch, sodium stearyl fumarate, polyethylene glycol, D-a-tocopheryl polyethylene glycol succinate, or magnesium stearate.

8. The composition of any one of claims 1-7, wherein the composition further comprises a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose.

9. The composition of claim 8, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture.

10. The composition of claim 8, wherein the ratio of microcrystalline cellulose to sodium carboxy methyl cellulose in the mixture is about 81 : 19 to about 89: 11 by weight of the mixture.

11. The composition of any one of claims 1-10, wherein the composition comprises low- substituted hydroxypropyl cellulose.

12. The composition of claim 1 , wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, microcrystalline cellulose, or magnesium stearate.

13. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, microcrystalline cellulose, and magnesium stearate.

14. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises di calcium phosphate dihydrate, mi crocry stall ine cellulose, or magnesium stearate.

15. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises dicalcium phosphate dihydrate, microcrystalline cellulose, and magnesium stearate.

16. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, microcrystalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, or crospovidone.

17. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, microcrystalline cellulose, sodium carboxymethyl cellulose, magnesium stearate, and crospovidone.

18. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, magnesium stearate, or crospovidone.

19. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, magnesium stearate, and crospovidone.

20. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol, microcrystalline cellulose, crospovidone, or sodium stearyl fumarate.

21. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, polyethylene glycol, microcrystalline cellulose, crospovidone, and sodium steary l fumarate.

22. The composition of any one of claims 3-13 and 16-21, wherein the composition comprises lactose, and the lactose is lactose monohydrate or anhydrous lactose.

23. The composition of claim 1, wherein the composition comprises low-substituted hydroxypropyl cellulose and further comprises anhydrous lactose, a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, microcrystalline cellulose, magnesium stearate, and crospovidone.

24. The composition of any one of claims 1-23, wherein the composition comprises an intra-granular phase.

25. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate.

26. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate and talc.

27. The composition of claim 24, wherein the intra-granular phase comprises (i) the APX3330 hemi calcium salt monohydrate, (ii) talc, and (iii) crospovidone or low-substituted hydroxypropyl cellulose.

28. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises lactose, microcrystalline cellulose, or magnesium stearate.

29. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises lactose, microcrystalline cellulose, and magnesium stearate.

30. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises dicalcium phosphate dihydrate, microcrystalline cellulose, or magnesium stearate.

31. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises dicalcium phosphate dihydrate, microcrystalline cellulose, and magnesium stearate.

32. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises lactose, microcrystalline cellulose, magnesium stearate or a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose.

33. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises lactose, microcrystalline cellulose, magnesium stearate and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose.

34. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose.and further comprises lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, or polyethylene glycol.

35. The composition of claim 24, wherein the intra-gr anular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises lactose, partially pregelatinized maize starch, polyvinylpyrrolidone, and polyethylene glycol.

36. The composition of any one of claims 18, 19, 32, and 33, wherein the mixture comprises about 11% to about 19% sodium carboxymethyl cellulose by weight of the mixture and about 81% to about 89% microcrystalline cellulose by weight of the mixture.

37. The composition of any one of claims 18, 19, 32, and 33, wherein the ratio of microcrystalline cellulose to sodium carboxymethyl cellulose in the mixture is about 81: 19 to about 89: 11 by weight.

38. The composition of any one of 28, 29, and 32-37, wherein the lactose is lactose monohydrate or anhydrous lactose.

39. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises anhydrous lactose, microcrystalline cellulose, magnesium stearate or a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose.

40. The composition of claim 24, wherein the intra-granular phase comprises the APX3330 hemi calcium salt monohydrate, talc, and low-substituted hydroxypropyl cellulose, and further comprises anhydrous lactose, microcrystalline cellulose, magnesium stearate and a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose.

41. The composition of any one of claims 24-40 further comprising an extra-granular phase.

42. The composition of claim 41, wherein the extra-granular phase comprises low- substituted hydroxypropyl cellulose, microcrystalline cellulose, or magnesium stearate.

43. The composition of claim 41, wherein the extra-granular phase comprises low- substituted hydroxypropyl cellulose, microcrystalline cellulose, and magnesium stearate.

44. The composition of claim 41, wherein the extra-granular phase comprises crospovidone, microcrystalline cellulose, or magnesium stearate.

45. The composition of claim 41, wherein the extra-granular phase comprises crospovidone, microcrystalline cellulose, and magnesium stearate.

46. The composition of claim 41, wherein the extra-granular phase comprises crospovidone, microcrystalline cellulose, or sodium stearyl fumarate.

47. The composition of claim 41, wherein the extra-granular phase comprises crospovidone, microcrystalline cellulose, and sodium stearyl fumarate.

48. The composition of any one of claims 1-47, wherein the APX3330 hemicalcium salt monohydrate exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 8.0 ± 0.2 degrees 2-theta and a peak at 10.1 ± 0.2 degrees 2-theta.

49. The composition of claim 48, wherein the XRPD pattern further comprises a peak at 13.3 ± 0.2 degrees 2-theta or a peak at 14.6 degrees 2-theta.

50. The composition of any one of claims 1-47, wherein the APX3330 hemicalcium salt monohydrate exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 5. 1 ± 0.2 degrees 2-theta, a peak at 8.0 ± 0.2 degrees 2-theta, a peak at 10.1 ± 0.2 degrees 2-theta, a peak at 13.3 ± 0.2 degrees 2-theta, a peak at 14.6 ± 0.2 degrees 2-theta, and a peak at 18.5 ± 0.2 degrees 2-theta.

51. The composition of any one of claims 1-47, wherein the APX3330 hemicalcium salt monohydrate exhibits an XRPD pattern that is substantially the same as that depicted in Fig. 1.

52. The composition of any one of claims 1-47, wherein the APX3330 hemicalcium salt monohydrate exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 5.8 ± 0.2 degrees 2-theta and a peak at 6.3 ± 0.2 degrees 2-theta.

53. The composition of claim 52, wherein the XRPD pattern further comprises a peak at 13.7 ± 0.2 degrees 2-theta or a peak at 14.1 ± 0.2 degrees 2-theta.

54. The composition of any one of claims 1 -47, wherein the APX3330 hemicalcium salt monohydrate exhibits an X-ray powder diffraction (XRPD) pattern comprising a peak at 4.1 ± 0.2 degrees 2-theta, a peak at 5.3 ± 0.2 degrees 2-theta, a peak at 5.8 ± 0.2 degrees 2-theta, a peak at 6.3 ± 0.2 degrees 2-theta, a peak 13.7 ± 0.2 degrees 2-theta, and a peak at 14.1 ± 0.2 degrees 2-theta.

55. The composition of any one of claims 1-47, wherein the APX3330 hemicalcium salt monohydrate exhibits an X-ray powder diffraction (XRPD) pattern that is substantially the same as that depicted in Fig. 2.

56. The composition of any one of claims 1-55, wherein the composition comprises the APX3330 hemi calcium salt monohydrate in an amount of about 35% w / w to about 65% w / w of the composition.

57. The composition of claim 56, wherein the composition comprises the APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition.

58. The composition of any one of claims 1-57, wherein the composition comprises the talc in an amount of about 0.3% w / w to about 10% w / w of the composition.

59. The composition of claim 58, wherein the composition comprises the talc in an amount of about 3% w / w to about 8% w / w of the composition.

60. The composition of any one of claims 1-59, wherein the composition comprises the low-substituted hydroxypropyl cellulose in an amount of about 2% w / w to about 15% w / w of the composition.

61. The composition of claim 60, wherein the composition comprises the low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 8% w / w of the composition.

62. The composition of any one of claims 3-13 and 16-61, wherein the composition comprises lactose in an amount of about 5% w / w to about 30% w / w of the composition.

63. The composition of claim 62, wherein the composition comprises lactose in an amount of about 10% w / w to about 16% w / w of the composition.

64. The composition of claim 62 or 63, wherein the lactose is lactose monohydrate or anhydrous lactose.

65. The composition of claim 62, wherein the lactose is anhydrous lactose.

66. The composition of claim 63, wherein the lactose is anhydrous lactose.

67. The composition of any one of claims 3-66, wherein the composition comprises microcrystalline cellulose in an amount of about 5% w / w to about 30% w / w of the composition.

68. The composition of claim 67, wherein the composition comprises microcrystalline cellulose in an amount of about 10% w / w to about 20% w / w of the composition.

69. The composition of any one of claims 6-19 and 24-68, wherein the composition comprises magnesium stearate in an amount of about 0.5% w / w to about 5% w / w of the composition.

70. The composition of claim 69, wherein the composition comprises magnesium stearate in an amount of about 0.5% w / w to about 2% w / w of the composition.

71. The composition of any one of claims 3-11, 14, 15, and 24-70, wherein the composition comprises dicalcium phosphate dihydrate in an amount of about 5% w / w to about 30% w / w of the composition.

72. The composition of any one of claims 1-11 and 16-71, wherein the composition comprises crospovidone in an amount of about 0.5% w / w to about 5% w / w of the composition.

73. The composition of any one of claims 8-11, 18, 19, and 24-72, wherein the composition comprises the mixture comprising microcrystalline cellulose and sodium carboxy methyl cellulose in an amount of about 1 % w / w to about 10% w / w of the composition.

74. The composition of claim 73, wherein the composition comprises the mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose in an amount of about 2% w / w to about 6% w / w of the composition.

75. The composition of any one of claims 24 and 48-55. wherein the intra-granular phase comprises: an APX3330 hemicalcium salt monohydrate in an amount of about 40% w / w to about 55% w / w of the composition; talc in an amount of about 3% w / w to about 6% w / w of the composition; low-substituted hydroxypropyl cellulose in an amount of about 3% w / w to about 6% w / w of the composition; anhydrous lactose in an amount of about 8% w / w to about 15% w / w of the composition; microcrystalline cellulose in an amount of about 8% w / w to about 15% w / w of the composition; a mixture comprising microcrystalline cellulose and sodium carboxymethyl cellulose, wherein the mixture is in an amount of about 2% w / w to about 6% w / w of the composition; and magnesium stearate in an amount of about 0.4% w / w to about 0.8% w / w of the composition.

76. The composition of claim 75, wherein the composition further comprises an extra- granular phase, wherein the extra-granular phase comprises: crospovidone in an amount of about 0.2% w / w to about 5% w / w of the composition;microcrystalline cellulose in an amount of about 2% w / w to about 10% w / w of the composition; and magnesium stearate in an amount of about 0.2% w / w to about 0.8% w / w of the composition.

77. The composition of any one of claims 1-76, wherein the composition is a tablet.

78. The composition of claim 77, wherein the tablet comprises the APX3330 hemicalcium salt monohydrate in an amount that is molar equivalent to 120 mg or 300 mg of APX3330.

79. The composition of claim 77 or 78, wherein the tablet comprises the APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to 300 mg of APX3330.

80. The composition of any one of claims 77-79, wherein the tablet comprises a film coating.

81. The composition of claim 80, wherein the film coating is present in an amount of about 2% w / w to about 6% w / w of the composition.

82. The composition of any one of claims 1-76, wherein the composition is contained in a capsule.

83. The composition of claim 82, wherein the capsule contains the APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 120 mg or about 300 mg of APX3330.

84. The composition of claim 82 or 83, wherein the capsule contains the APX3330 hemi calcium salt monohydrate in an amount that is molar equivalent to about 300 mg of APX3330.

85. The composition of any one of claims 82-84, wherein the capsule comprises hypromellose or gelatin.

86. A method for treating or preventing an ocular disease or an inflammatory disease, comprising administering to a subject in need thereof an effective amount of the composition of any one of claims 1-85.

87. The method of claim 86, wherein the method is for treating or preventing an ocular disease, and the ocular disease is diabetic retinal disease.

88. The method of claim 86, wherein the method is for treating or preventing an ocular disease, and the ocular disease is diabetic retinopathy (DR).

89. The method of claim 86 wherein the method is for treating or preventing an ocular disease, and the ocular disease is diabetic macular edema (DME).

90. The method of claim 88, wherein the DR is non-proliferative DR or proliferative DR.

91. The method of claim 88. wherein the DR is moderately severe non-proliferative DR or mild proliferative DR.

92. The method of claim 89, wherein the DME is DME without loss of central vision.

93. The method of claim 86, wherein the method is for treating or preventing an inflammatory' disease, and the inflammatory disease is anky losing spondylitis, antiphospholipid antibody syndrome, autoimmune encephalitis, chronic recurrent multifocal osteomyelitis, gout, Henoch-Schonlein purpura, idiopathic thrombocytopenic purpura, juvenile dermatomyositis, rheumatoid arthritisjuvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, psoriatic arthritis, reactive arthritis, spondyloarthritis, systemic lupus erythematosus, junvenile lupus, scleroderma, juvenile scleroderma, vasculitis uvenile vasculitis, mixed connective tissue disease, undifferentiated connective tissue disease, myositis, poststreptococcal inflammatory syndrome, Sjogren’s syndrome, uveitis, vasculitis, colitis, atherosclerosis, cardiac myopathy, Crohn’s disease, celiac disease, dermatitis herpetiformis, autoimmune blistering disease, epidermolysis bullosa, ty pe 1 diabetes, asthma, dermatomyositis, alopecia areata, autoimmune hepatitis, multiple sclerosis, Guillain-Barre syndrome, demyelinating polyneuropathy, psoriasis, Graves’s disease, Hashimoto’sthyroiditis, myasthenia gravis, hemolytic anemia, inflammatory bowel disease, inflammatory- myopathy, primary biliary cirrhosis, or vitiligo.

94. The method of claim 86, wherein the method is for treating or preventing an inflammatory' disease, and the inflammatory' disease is an inflammatory' disease of the digestive tract.

95. The method of claim 94, wherein the inflammatory disease of the digestive tract is inflammatory' bowel disease.

96. The method of claim 95, wherein the inflammatory bowel disease is Crohn's disease or ulcerative colitis.

97. The method of any one of claims 86-96, wherein the subject has diabetes.

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