WO2006009549A1

WO2006009549A1 - Novel crystalline forms of compositions of matter including the elements gallium, nitrogen, and oxygen

Info

Publication number: WO2006009549A1
Application number: PCT/US2004/019968
Authority: WO
Inventors: Valeriya N. Smolenskaya; Jeffrey S. Stults
Original assignee: Genta Incorporated
Priority date: 2004-06-21
Filing date: 2004-06-21
Publication date: 2006-01-26

Abstract

Provided are crystalline forms of compositions of matter including the elements Ga, N, and O and, in particular, crystalline forms of gallium nitrate that are hydrates. Also provided is amorphous gallium nitrate.

Description

NOVEL CRYSTALLINE FORMS OF COMPOSITIONS QF MATTER INCLUDING THE ELEMENTS GALLIUM, NITROGEN. AND OXYGEN

FIELD OF THE INVENTION The present invention relates to crystalline and amorphous forms of compositions of matter that include the elements Ga, N₅ and O and especially to crystalline or amorphous forms of gallium nitrate that are hydrates.

BACKGROUND OF THE INVENTION

The use of gallium administered in a variety of gallium-containing compounds to treat mammalian and human disease is well known. Gallium was initially identified as an antineoplastic agent by Hart, et al. (Proc Natl Acad Sci USA, Vol. 68, 1971, pp. 1623- 1626), and has subsequently been reported to be effective against a variety of cancers, including particularly hematological malignancies such as leukemias, lymphomas (e.g., non-Hodgkin's lymphoma), multiple myeloma and Hodgkin's Disease. See, e.g., D. J. Straus, Semin Oncol Vol. 30(2 Suppl 5), April 2003, pp. 25-33; E. A. Van Leeuwen-Stok, et al., Leuk Lymphoma, Vol. 31(5-6), November 1998, pp. 533-544; R. P. Warrell, et al., Cancer Treat Rep, Vol. 71, 1987, pp. 47-51 ; M. S. Myette, et al., Cancer Lett, Vol. 129(2), July 17, 1998, pp. 199-204; C. R. Chitambar, et al., Am J Clin Oncol, Vol. 20(2), April 1997, pp. 173-178. Warrell, Jr. et al. have shown that gallium salts, especially gallium nitrate, are useful in treatments for regulating calcium resorption from bone in certain bone disease and hypercalcemia, United States Patent No. 4,529,593.

It has also been reported that gallium is a potent inhibitor of bone resorption, leading to its use to treat hypercalcemia associated with cancer (R. P. Warrell, et al., J Clin Invest, Vol. 73, May 1984, pp. 1487-1490) as well as other diseases characterized by accelerated bone loss, such as multiple myeloma (R. P. Warrell, et al., J Bone Mineral Res, Vol. 5 (Suppl 2), August 28, 1990, pp. S 106; R. P. Warrell, et ύ., JClin Oncol, Vol. 11(12), December 1993, pp. 2443-2450), bone metastases (R. P. Warrell, Cancer, Vol. 80, 1997, pp. 1680-1685), hyperparathyroidism (US Patent No. 4,529,593; C. R. Chitambar, Semin Oncol, Vol. 30(2 Suppl 5), April 2003, pp. 1-4), Paget's disease (R. P. Warrell, et al., Ann Ira Med, Vol. 113, 1990, pp. 847-851) and osteoporosis (US Patent No. 4,529,593; R. Bockman, Semin Oncol Vol. 30(2 Suppl 5), April 2003, pp. 5-12). The actions of gallium on bone are different from bisphosphonates, and appear to be mediated by inhibition of the ATPase-dependent proton pump of osteoclasts, which decreases acid secretion (R. Bockman, Semin Oncol Vol. 30(2 Suppl 5), April 2003, pp. 5-12). Gallium is reported to accumulate at sites of inflammation and infection and has well-known immunosuppressive properties. Macrophages in particular have been shown to accumulate gallium, possibly as a result of their ability to engulf protein-iron complexes, resulting in inhibition of the release of inflammatory mediators from the cells. See N. Makkonen, et al. Inflamm Res, Vol. 44(12), December 1995, pp. 523-528. Gallium has reported efficacy in animal models of autoimmune disease and hypersensitivity, including type 1 diabetes, experimental autoimmune encephalomyelitis, experimental pulmonary inflammation, cardiac allograft rejection, experimental autoimmune uveitis, endotoxic shock, and systemic lupus erythematosus (G. Apseloff, Am JTher, Vol. 6(6), November 1999, pp. 327-339). Gallium, therefore, holds particular promise as a therapy for disorders involving the immune system, in particular autoimmune diseases and conditions or diseases involving a cell-mediated (e.g., macrophage-mediated) immune response.

As evidenced by the foregoing, the therapeutic utility of gallium as a component of a variety of compounds and complexes is established. The compounds of the present invention, comprising, inter alia, Ga¹¹¹ will therefore exhibit a similar range of therapeutic activities and utilities as described above. However, gallium compounds that are better tolerated and have better bioavailability are needed. The compositions of matter including the elements Ga, N, and O of the present invention were developed in part to address these needs. It is known that crystalline inorganic and organic compounds can sometimes crystallize with more than one type of molecular packing resulting in different crystal structures. This phenomenon - a single crystalline substance having different crystal structures - is often referred to as polymorphism. Reported examples of inorganic compounds that are polymorphic, that is they can crystallize in different crystal structures (forms), include CaCO₃, TiO₂ and SiO₂.

It is also known that some inorganic and some organic compounds can crystallize with atoms or molecules of a foreign substance, especially a solvent such as water, such that atoms or molecules of both substances are incorporated in the crystal structure. Crystalline materials in which a solvent molecule is incorporated in the crystal structure are often referred to as solvates or pseudopolymorphs. When the solvent is water, these materials are often referred to as hydrates. Several types of hydrates are known. Crystalline hydrates have been divided into three classes according to whether (1) the water molecules are associated with a metal ion, (2) they are isolated from each other, or (3) engage in hydrogen bonding with other water molecules. Brittian, H.G., Polymorphism in Pharmaceutical , Solids p. 202 (Marcel Dekker 1999) (hereafter Brittian). In metal ion hydrates, the water is thought to be associated with the metal ion of a salt through the electron lone pair of oxygen. The association is best described as electrostatic and does not obey the rules of atomic valency. (See e.g. Brittian, pp. 135 and 156-57 in which four waters are associated with Ca^2*). Crystal packing can be an important factor in determining what levels of hydration are possible, (Brittian, p. 135). Metal ion hydrates typically require high temperatures to dehydrate because of the binding strength between the water molecules and the metal ion. Metal ion hydrates reportedly exhibit sharp weight loss and endotherms in thermal analysis. (Brittian, p. 163).

In isolated site hydrates, water molecules (or collections of water molecules) are isolated from hydrogen bonding with the water molecules in an adjacent unit cell. Site hydrates typically have high dehydration temperatures because the water molecules ire trapped, in the crystal lattice and because evaporation of a water molecule from a site does not destabilize other water molecules in the crystal (c.f. channel hydrates, below). Dehydration of site hydrates often disrupts the repeat arrangement of the organic compound. The disrupted lattice may remain disrupted, in which case the dehydrated compound is amorphic (Brittian, p. 215), Alternatively; the dehydrated compound may reorganize into the same polymorphic form or a different polymorphic form (Brittian, 199-200). Site hydrates typically exhibit sharp O-H stretching frequencies due w the lack of hydrogen bonding and, like metal ion hydrates, reportedly undergo a sharp weight loss and endotherm under thermal analysis (Brittian, p. 163).

In channel hydrates, water molecules form a hydrogen bonded network spanning more than one unit cell. Since the unit cell repeats, the network spans the lattice of a 2004/019968

perfect crystal. The network may be one dimensional, in which case the crystal is spanned by closely-spaced parallel tunnels. Or, the network may be two dimensional in which case the crystal is spanned by planar gaps occupied by water molecules. When such hydrogen bonding is possible, the gaps in the lattice are typically great enough that water molecules can migrate through the tunnel or plane without disrupting the arrangement, of the organic compound in the lattice. A channel hydrate undergoes incremental, stoichiometric hydration at low levels of hydration. Some channel hydrates are capable of expanding to absorb water continuously upon exposure to higher humidity, in which case they can absorb water in non-stoichiometric amounts. The expansion is, in principle, detectable by increased d-spacings in the x-ray diffraction pattern (Brittian, p. 150).

Crystalline hydrates of gallium nitrate. Ga(NO₃)₂* N H₂O, have been reported in the literature. C2 Gmelin Handbook of Inorganic and Organometallic Chemistry — Ga Gallium, 208 (Hartmut Katscher and Brigitte Hohsin, eds., 8^th edition). The discovery of a new crystalline form (polymorph or pseudopolymorph) of a pharmaceutically useful compound provides an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for designing, for example, a pharmaceutical dosage form of a drug with a targeted release profile or other desired characteristic. It is clearly advantageous when this repertoire is enlarged by the discovery of new crystalline forms of a useful compound. For a general review of polymorphs and the pharmaceutical applications of polymorphs see G.M. Wall, Pharm Manuf. 3,33 (1986); J.K. Haleblian and W. McCrone, J. Pharm. ScI, 58, 911 (1969), and J.K. Haleblian, J. Pharm. Set, 64, 1269 (1975), all of which are incorporated herein by reference. The solid state physical properties of crystalline forms of a pharmaceutically useful compound can be influenced by controlling the conditions under which the compound is obtained in solid form. Solid state physical properties include, for example, the flowability of the milled solid. Flowability affects the ease with which the material is handled during processing into a pharmaceutical product. When particles of the powdered compound do not flow past each other easily, a formulation specialist must take that fact into account in developing a tablet or capsule formulation, which may necessitate the use of glidants such as colloidal silicon dioxide, talc, starch or tribasic calcium phosphate. Another important solid state property of a pharmaceutical compound that can vary from one polymorph or pseudopolymorph to the next is its rate of dissolution in aqueous media, e.g., gastric fluid. The rate of dissolution of an active ingredient in a patient's stomach fluid can have therapeutic consequences since it imposes an upper limit on the rate at which an orally-administered active ingredient can reach the patient's bloodstream. The rate of dissolution is also a consideration in formulating syrups, elixirs and other liquid medicaments. The solid state form of a compound may also affect its behavior on compaction and its storage stability.

Clearly, discovery of new crystalline forms of an active pharmaceutical ingredient provides the pharmaceutical formulator with new and useful options in the manufacture of dosage forms, especially solid oral dosage forms.

SUMMARY OF THE INVENTION

In one aspect, the present invention relates to a crystalline form of gallium nitrate that is a hydrate (form Al) characterized by x-ray reflections at about 13.4°, 14.2°, 19.7°, 21.6°, 22.1°, 22.4°, 23.5°, 24.6°, 27.5°, 29.8°, and 24.5° ± 0.2° 2Θ.

In another aspect, the present invention relates to a crystalline form of gallium nitrate that is a hydrate (form B) characterized by x-ray reflections at about 37.7°, 38.0°, and 44.5° ± 0.2° 2θ. Form be can be further characterized by x-ray reflections at about 17.6°, 19.5°, 23.0°, 25.5 and 26.2°± 0.2°2θ. In another aspect, the present invention relates to a crystalline form of gallium nitrate that is a hydrate (form Bl) characterized by x-ray reflections at about 37.7°, 38.0°, and 44.5° ± 0.2° 2Θ. Form Bl can be further characterized by x-ray reflections at about 17.6°, 19.5°, 23.0°, 25.5 and 26.2°± 0.2°2 Θ.

In another aspect, the present invention relates to a crystalline form of gallium nitrate that is a hydrate (form C) characterized by x-ray reflections at about 24.4°and

41.7° ± 0.2° 20. Form C can be further characterized by x-ray reflections at about 12.7°, 19.0 and 25.4° ± 0.2° 2θ.

In a further aspect, the present invention relates to a crystalline form of gallium nitrate that is a hydrate (form E) characterized by x-ray reflections at about 10.9°, 14.8°, 32.7°, 32.9 and 35.0°± 0.2° 20. Form E can be further characterized by x-ray reflections at about 12.7°, 21.8°, 22.0°, 25.5°, 26.9°, and 29.7° ± 0.2° 20. In another aspect, the present invention relates to a crystalline form of gallium nitrate that is a hydrate (form N) characterized by either x-ray reflections at about 18.2°, 40.3°, 47.6°, 49.5°, and 54.9°± 0.2° 2Θ, or by FTIR bands at about 1383.97, 1356.04, 3338.19, 570.80, 832.70, 1042.12, 403.58, 2398.13, and 1765.37 cm^'1, or both. FormN can be further characterized by x-ray reflections at about 12.9°, 22.3°, 25.9°, 31.8°, 35.7°, and 43.6° ± 0.2° 20.

In yet another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form G) characterized either by x-ray reflections at about 10.0°, 12.6°, 15.4°, 19.9 20.4°, 24.1°, 25.2°, 27.0°, 29.7°, 32.8°, and 28.2° ± 0.2° 2Θ; or FTIR bands at about 493, 686, 724, 829, 935, 960, 1001, 1046, 1303, 1345, 1384, 1424, 1439, 1750, 2383, 2920, 2962, and 3010 cm^'1, or both.

In another aspect, the present invention relates to A crystalline composition of matter comprising the elements Ga, N, and O (form D) characterized by x-ray reflections at about 14.5°, 27.6° and 28.8° ± 0.2° 2Θ. Form D can be further characterized by x-ray reflections at about 7.0°, 10.9°, 14.0°, 14.3°, 17.0°, 17.6° and 21.9 ± 0.2° 2Θ.

In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form Dl) characterized by x-ray reflections at about 7.0°, 10.9°, 14.0°, 14.4°, 16.9°, 17.6°, 20.0°, 21.8°, 27.5°, and 34.1° ± 0.2° 2Θ. In yet a further aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form H) characterized by x-ray reflections at about 13.0°and 18.7° ± 0.2° 2Θ. Form H can be further characterized by x-ray reflections at about 10.9°, 18.3°, 29.7°, and 37.6° ± 0.2° 29.

In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form I) characterized by x-ray reflections at about 22.2°and 24.6° ± 0.2° 20. Form I can be further characterized by reflections at about 8.0°, 9.0°, 9.8°, 14.0°, 18.4°, and 24.0° ± 0.2°2θ.

In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form II) characterized by x-ray reflections at 9.2°, 22.7°, 27.5°, and 34.0° ± 0.2° 2Θ. Form Il can be further characterized by x-ray reflections at about 7.0°, 8.0°, 9.0°, 10.9°, 21.8°, and 03.1° ± 0.2° 2Θ. In still yet another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form J) characterized by x- ray reflections at about 11.5°, 14.2°, 17.6°, 19.6°, 23.1°, 25.5°, 26.2°, 26.9°, 31.7°, and 34.8° ± 0.2°2θ. In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form Jl) characterized by x-ray reflections at about 10.9°, 11.5°, 13.1°, 14.3°, 17.6°, 19.6°, 21.7°, 22.3°, 23.1°, 25.0°, 25.6° 26.2°, 26.9°, 31.8°, 34.8°, and 37.6° ± 0.2° 2Θ.

In a further aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga₅ N, and O (form K) characterized by x-ray reflections at about 25.9° and 35.7° ± 0.2° 2Θ. Form K can be further characterized by x-ray reflections at about 7.0 10.9°, 11.5°, 12.9°, 14.2°, 17.6°, 19.6°, 22.3°, 23.1°, 25.5°, 26.2°, 26.9°, and 31.8° ± 0.2° 2Θ.

In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form L) characterized by either x-ray reflections at about 7.0°, 10.9°, 11.5°, 14.2°, 17.6°, 19.6°, 21.9°, 23.1°, and 25.6°± 0.2° 2Θ; or FTIR bands at about 410, 578, 824, 1040, 1384, 1566, 1672, 1762, 2395, and 3424 cm^"1, or both.

In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form M) characterized by either x-ray reflections at about 6.3°, 10.2°, 11.9°, 12.2°, 21.2°, and 27.1 ° ± 0.2° 20; or by FTIR bands at about 422, 430, 573, 819, 1358, 1384, 1661, and 3295 cm^"1, or both. Form M can be further characterized by x-ray reflections at about 6.6°, 7.0°, 10.9°, 14.1°, and 26.8° ± 0.2° 2Θ. In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form 1) characterized by x-ray reflections at about 7.0° and 10.4° ± 0.2° 20.

In still yet another aspect, the present invention relates to a crystalline composition of matter including the elements Ga, N, and O (form 2) characterized by x- ray reflections at about 13.4° and 18.9° ± 0.2° 2Θ.

In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N₅ and O (form 3) and characterized by x-ray reflections at about 15.2°, 17.0°, 20.4°, 21.6°, 23.4°, 24.1°, 26.1°, 26.8 and 32.0° ± 0.2°2θ.

In yet another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N and O (form 4) characterized by x-ray reflections at about 8.0°, 9.8°, and 12.8° ± 0.2° 2Θ.

In another aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form 5) characterized by x-ray reflections at about 6.8°, 7.4°, and 9.7° ± 0.2° 2Θ.

In another aspect, the present invention relates to a crystalline composition of matter including the elements Ga, N, and O (form 6) characterized by x-ray reflections at about 15.8°, 17.9°, 29.0°, 32.9°, 39.1°, and 40.1° ± 0.2° 2Θ.

In a further aspect, the present invention relates to a crystalline composition of matter comprising the elements Ga, N, and O (form 7) characterized by an x-ray reflection at about 5.8° ± 0.2° 2Θ. In still yet a further aspect, the present invention relates to pharmaceutical compositions, especially in the form of solid oral dosage forms, including at least one of the compositions of matter including the elements Ga, N, and O of the present invention, especially crystalline forms of gallium nitrate that are hydrates, and at least one pharmaceutically acceptable excipient. In yet another aspect, the present invention relates to the use of at least one of the compositions of matter including the elements Ga, N, and O of the present invention, especially crystalline forms of gallium nitrate that are hydrates, for the manufacture of pharmaceutical compositions for parenteral administration.

BRIEF DESCRIPTION OF THE FIGURES Figure 1 is a representative x-ray diffraction diagram of form A

Figure 2 is a representative x-ray diffraction diagram of gallium nitrate form Al.

Figure 3 is a representative x-ray diffraction diagram gallium nitrate form B.

Figure 4 is a representative x-ray diffraction diagram of gallium nitrate form Bl.

Figure 5 is a representative x-ray diffraction diagram of gallium nitrate form C. Figure 6 is a representative x-ray diffraction diagram of gallium nitrate form E. Figure 7 is a representative x-ray diffraction diagram of gallium nitrate form N. Figure 8 is an FTIR spectrum of gallium nitrate form N.

Figure 9 is an x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form. G. Figure 10 is a FTIR spectrum of a crystalline composition of matter including the elements Ga, N, and O denominated form D.

Figure 11 is an x-ray diffraction diagram of crystalline composition of matter including the elements Ga, N, and O denominated form D.

Figure 12 is an x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form D 1.

Figure 13 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form H.

Figure 14 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form I. Figure 15 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form Il .

Figure 16 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form J.

Figure 17 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form Jl .

Figure 18 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form K.

Figure 19 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form L. Figure 20 is a representative FTIR spectrum of a crystalline composition of matter including the elements Ga, N, and O denominated form L.

Figure 21 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form M. Figure 22 is a representative FTIR spectrum of a crystalline composition of matter including the elements Ga, N, and O denominated form M.

Figure 23 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form 1. Figure 24 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form 2.

Figure 25 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form 3.

Figure 26 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form 4.

Figure 27 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form 5.

Figure 28 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form 6. Figure 29 is a representative x-ray diffraction diagram of a crystalline composition of matter including the elements Ga, N, and O denominated form 7.

Figure 30 is a representative combined DSC - TGA thermogram of a crystalline form of gallium nitrate denominated form Al.

Figure 31 is a representative combined DSC - TGA thermogram of an amorphous form of gallium nitrate denominated form F.

Figure 32 is a representative x-ray diffraction diagram of an amorphous form of gallium nitrate denominated form F.

Figure 33 is a representative DSC thermogram of a crystalline composition of matter including the elements Ga, N, and O denominated form G. Figure 34 is a representative combined DSC - TGA thermogram of a crystalline composition of matter including the elements Ga, N, and O denominated form D.

Figure 35 is a representative combined DSC - TGA thermogram of a crystalline composition of matter including the elements Ga, N, and O denominated form Dl. Figure 36 is a combined DSC - TGA thermogram of a crystalline composition of matter including the elements Ga, N, and O denominated form M.

SUMMARY OF THE INVENTION

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides crystalline compositions of matter including the elements gallium (Ga), nitrogen (N), and oxygen, especially in the atomic ratio of about 0.5:1:3. In preferred embodiments, these compositions of matter are crystalline forms of Gallium nitrate [Ga(NO₃ )₂] that are crystalline hydrates. Crystalline hydrates of organic and inorganic compounds are well known in the art. Crystalline hydrates are crystalline compounds that have water of crystallization. The hydrates can be "regular", wherein the water occupies regular positions in the unit sell, or they can be so-called channel hydrates as known in the art.

Crystalline forms of gallium nitrate that are hydrates share the characteristic of converting to gallium nitrate hydrate form A, now commercially available and useful as a starting material for the preparation of the novel crystalline compositions of matter of the present invention. This conversion (interconversion) can be effected in the presence of water, especially by suspending or dissolving a crystalline form of gallium nitrate that is a hydrate in water under ambient conditions As used herein, ambient conditions refers to ambient or room temperature (about

22° to about 27° C) and ambient pressure, which the skilled artisan knows varies about a mean of 760 mm Hg.

As used herein, low humidity or low humidity conditions refers to a relative humidity of less than about 14%, typically 12% to 14 RH. Gallium nitrate form A is now available commercially and is thought to be a hydrate of gallium nitrate. Crystalline gallium nitrate form A is characterized by x-ray reflections at about 13.5°, 14.2°, 19.7°, 21.7°, 22.1°, 22.4°, 23.5°, 24.6°, 29.8°, and 34.5°± 0.2° 2Θ. A representative x-ray diffraction diagram of gallium nitrate form A is shown in Figure 1. The crystalline compositions of matter including Ga, N, and O of the present invention, especially crystalline forms of gallium nitrate that are hydrates, can be characterized by the well-known technique of x-ray diffraction, in particular powder x-ray diffraction. The various compositions of matter can be characterized by, among other things, their characteristic reflections in x-ray diffraction analysis.

X-ray powder diffraction (XRPD) analyses were performed using a Shimadzu XRD-6000 X-ray powder diffractometer using Cu Ka radiation. The instrument is equipped with a long fine focus X-ray tube. The tube voltage and amperage were set to 40 kV and 40 mA, respectively. The divergence and scattering slits were set at 1° and the receiving slit was set at 0.15 mm. Diffracted radiation was detected by a NaI scintillation detector. A theta-two theta continuous scan at 3 °/min (0.4 sec/0.02° step) from 2.5 to 40 °2Θ was used. A silicon standard was analyzed to check the instrument alignment. Data were collected and analyzed using XRD-6000 v. 4.1. Samples were prepared for analysis by placing them in an aluminum holder with silicon insert.

X-ray powder diffraction (XRPD) analyses were alternatively performed using an Inel XRG-3000 diffractometer equipped with a CPS (Curved Position Sensitive) detector with a 2Θ range of 120°. Real time data were collected using Cu-Ka radiation starting at approximately 4 °2Θ at a resolution of 0.03 °2Θ. The tube voltage and amperage were set to 40 kV and 30 mA, respectively. The monochromator slit was set at 5 mm by 80 or 160 μm. The pattern is displayed from 2.5-60 °2Θ or 2.5-80 °2Θ. An aluminum sample holder with silicon insert was used. Samples were also prepared for analysis by packing them into thin-walled glass capillaries. Each capillary was mounted onto a goniometer head that is motorized to permit spinning of the capillary during data acquisition. The samples were analyzed for 5-60 min. Instrument calibration was performed using a silicon reference standard.

X-ray powder diffraction (XRPD) analyses were also performed using a Bruker D8 Discover diffractometer using Cu Ka radiation. The instrument is equipped with a fine focus X-ray tube. The tube voltage and amperage were set to 40 kV and 40 mA, respectively. The X-ray beam is focused using a Gδbel mirror, and is then passed through a 0.5-mm slit and a 0.5-mm collimator. Diffracted radiation was detected by a Seimens position-sensitive area detector located approximately 15 cm from the sample which provides an effective 20 range of ~37°. Samples were prepared for analysis by placing them in a capillary tube. Typically, samples are analyzed with the X-ray source positioned at an incident angle (B₁) of 0°. The detector angle (O₂) is 22°. During the data collection O₁ and θ₂ are moved in tandem over a 5-10° range, while keeping the difference between them constant (ω scan). Analysis times range from 3 to 20 minutes, with the specific analysis time depending primarily on sample size, and slit and collimator configuration). A silicon standard was analyzed to check the instrument alignment. A 2-θ position check was performed using a silicon standard, and a source intensity check using a specific position on the aluminum stage as the target. Data were collected using GADDS (General Area Diffraction Software) v. 4.1.14. The 2D diffraction data acquired is integrated from 5 to 39 °2Θ with a χ range of -140 to -40°. The diffraction patterns are integrated with a step size of 0.05 °2Θ and the intensity is normalized by solid angle. The integrated data is imported into EVA v.7.0 rev.O for further processing.

Variable-temperature XRPD (VT-XRPD) was performed on a Shimadzu XRD- 6000 X-ray powder diffractometer equipped with an Anton Paar HTK 1200 high temperature stage. Samples were packed in a ceramic holder and analyzed from 2.5 to 80 °2Θ at 3 °/min (0.4 sec/0.02° step. A silicon standard was analyzed to check the instrument alignment. Temperature calibration was performed using vanillin and sulfapyridine standards. Data were collected and analyzed using XRD-6000 v. 4.1.

Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) can also be applied to the analysis and, in certain embodiments, characterization of the crystalline compositions of matter including Ga, N, and O of the present invention. Thermogravimetric (TG) analyses (TGA) were performed using a TA Instruments

2050 or 2950 thermogravimetric analyzer. Samples were placed in an aluminum sample pan and inserted into the TG furnace. Samples were first equilibrated at 25 ⁰C, and then heated under nitrogen at a rate of 10 °C/min, up to a final temperature of 350°C. Nickel and Alumel™ were used as the calibration standards. Differential scanning calorimetry (DSC) was performed using a TA Instruments differential scanning calorimeter 2920. The sample was placed into an aluminum DSC pan, and the weight accurately recorded. The pan was covered with a lid and then crimped. In some analyses the pan was covered with a lid perforated with a laser pinhole to allow for pressure release, and then hermetically sealed (see tables for pan types and scan rates). The sample cell was equilibrated at ambient or 25°C and heated under a nitrogen purge at a rate of 10°C/min, up to a final temperature of 200 or 350⁰C. Indium metal was used as the calibration standard. Reported temperatures are at the transition maxima (i.e. peak maxima).

Thermogravimetric infrared (TG-IR) analyses were acquired on a TA Instruments thermogravimetric (TG) analyzer model 2050 interfaced to a Magna 560^® Fourier transform infrared (FT-IR) spectrophotometer (Thermo Nicolet) equipped with an Ever- GIo mid/far IR source, a potassium bromide (KBr) beamsplitter, and a deuterated triglycine sulfate (DTGS) detector. The TG instrument was operated under a flow of helium at 90 and 10 cc/min for the purge and balance, respectively. Samples were placed in a platinum sample pan, inserted into the TG furnace, accurately weighed by the instrument, and the furnace was heated from ambient to 150- 175° C at a rate of

20 °C/min. The TG instrument was started first, immediately followed by the FT-IR instrument. Each IR spectrum represents 8 co-added scans collected at a spectral resolution of 4 cm^"1. IR spectra were collected every 8 seconds for 7.5-8 minutes. A background scan was collected before the beginning of the experiment. Wavelength calibration was performed using polystyrene. The TG calibration standards were nickel and Alumel™. Volatiles were identified from a search of the High Resolution Nicolet TGA Vapor Phase spectral library (Notebook 1489-42, 44).

Vibrational spectroscopy (infra red or "IR" spectroscopy) can also be applied to the analysis, and in certain embodiments the characterization of the crystalline compositions of matter including the elements Ga, N, and O of the present invention.

Infrared spectra were acquired on a Magna-IR 860^® Fourier transform infrared (FT-IR) spectrophotometer (Thermo Nicolet) equipped with an Ever-Glo mid/far IR source, an extended range potassium bromide (KBr) beamsplitter, and a deuterated triglycine sulfate (DTGS) detector. A diffuse reflectance accessory (the Collector™, Thermo Spectra-Tech) was used for sampling. Each spectrum represents 128 or 256 co- added scans collected at a spectral resolution of 4 cm^"1. Sample preparation consisted of placing the sample into either a 3 -mm or 13 -mm diameter sample cup (KBr-diluted samples were mixed with KBr) and leveling the material. A background data set was acquired with air or an alignment mirror (for samples diluted in KBr). A Log \/R (R = reflectance) spectrum was acquired by taking a ratio of these two data sets against each other and then converted to Kubelka-Munk units for KBr-diluted samples. Wavelength calibration was performed using polystyrene. FT-Raman spectra were acquired on an FT-Raman 960 or 860 spectrometer (Thermo Nicolet). This spectrometer uses an excitation wavelength of 1064 nm. Approximately 0.5-1.1 W of Nd: YVO₄ laser power was used to irradiate the sample. The Raman spectra were measured with an indium gallium arsenide (InGaAs) detector. The samples were prepared for analysis by placing the material in a glass tube and positioning the tube in a gold-coated tube holder in the accessory. A total of 128 or 256 sample scans were collected from 3704 or 3600 to 100 cm^'1 at a spectral resolution of 4 or 8 cm^"1, using Happ-Genzel apodization. Wavelength calibration was performed using sulfur and, cyclohexane Depending on the objective of the analysis, moisture content was determined by one of several techniques, principally the well-known Karl Fisher method.

Coulometric Karl-Fischer (KF) analysis for water determination was performed using a Mettler Toledo DL39 Karl Fischer titrator. Approximately 2.2 to 3.9 mg of sample was placed in the KF titration vessel containing approximately 100 mL of Hydranal® - Coulomat AD and mixed for 60 seconds to ensure dissolution. The sample was then titrated by means of a generator electrode which produces iodine by electrochemical oxidation: 2 I- => I₂ + 2e. Three or four replicates were obtained to ensure reproducibility.

Volumetric Karl-Fischer (KF) analysis for water determination was performed using a Mettler Toledo DL38 Karl Fischer titrator. Approximately 77 to 98 mg of sample was placed in the KF titration vessel containing Hydranal® Methanol dry and mixed to ensure dissolution. The sample was then titrated with Hydranal® Composite 5 titrant to an appropriate endpoint. Three replicates were obtained to ensure reproducibility. The titrant was standardized with Hydranal Water Standard 10.0. Moisture sorption/desorption data were collected on a VTI SGA-100 Vapor

Sorption Analyzer. Sorption and desorption data were collected over a range of 5% to 95% relative humidity (RH) at 10% RH intervals under a nitrogen purge. Samples were not dried prior to analysis. Equilibrium criteria used for analysis were less than 0.0100% weight change in 2 minutes, with a maximum equilibration time of 3 hours if the weight criterion was not met. Data were not corrected for the initial moisture content of the samples. NaCl and PVP were used as calibration standards. The behavior of the crystalline compositions of matter including the elements Ga, N, and O of the present invention was also observed by hot stage microscopy. Hot stage microscopy was performed using a Linkam hot stage (model FTIR 600) mounted on a Leica DM LP microscope. Samples were observed using a 2Ox or 4Ox objective with a lambda plate with crossed polarizers. Samples were placed on a coverslip; another coverslip was then placed over the sample. Each sample was visually observed as the stage was heated. Images were captured using a SPOT Insight™ color digital camera with SPOT Software v. 3.5.8. The hot stage was calibrated using USP melting point standards. Moisture sorption/desorption data for the crystalline compositions of matter of the present invention was collected on a VTI SGA-100 Vapor Sorption Analyzer. Sorption and desorption data were collected over a range of 5% to 95% relative humidity (RH) at 10% RH intervals under a nitrogen purge. Samples were not dried prior to analysis. Equilibrium criteria used for analysis were less than 0.0100% weight change in 2 minutes, with a maximum equilibration time of 3 hours if the weight criterion was not met. Data were not corrected for the initial moisture content of the samples. NaCl and PVP were used as calibration standards.

The crystalline compositions of matter including the elements Ga, N, and O, especially those that that are crystalline forms of gallium nitrate that are hydrates, can be made by one or more of the following techniques.

One technique useful in making the crystalline compositions of matter of the present invention is the crystallization method. In one modification of the crystallization method, a suitable gallium nitrate (i.e. gallium nitrate of commerce; form A) is dissolved in the desired amount of the chosen solvent. Thereafter crystallization of the crystalline composition of matter including the elements Ga, N, and O can be effected by slow evaporation, preferably at ambient conditions, or by combining the solution with an anti- solvent, which can also be referred to as a precipitant. Anti-solvents are liquids, preferably freely miscible with the solvent chosen to prepare the solution, in which the desired crystalline composition of matter is at best sparingly soluble. Anti-solvent can be combined with solution at ambient temperature, or cold (crash precipitation).

For crash precipitation, a sample of gallium nitrate hydrate was dissolved in an appropriate solvent at ambient and filtered into an antisolvent cooled in a dry ice bath to approximately -2 to -7 °C (crash precipitation, CP). This procedure can also be carried out using both ambient solvent and anti-solvent (crash precipitation, CP(RT)). In certain embodiments, an antisolvent at ambient was added to a hot solution (HCP). Any solids formed in any variation of the crystallization method were removed (recovered) by filtration. If no solids were present, solutions were allowed to stand at room temperature to effect crystallization.

In any variation of the crystallization method, any solid materials formed were recovered by filtration and analyzed. For some samples the wet solid was allowed to dry under ambient conditions before the analysis. Solids obtained were analyzed by X-ray powder diffraction (XRPD).

In another modification of the crystallization method, solvent is allowed to slowly evaporate from a solution of gallium nitrate in the desired amount of the chosen solvent.

In yet a further modification of the crystallization method that can be referred to as the slurry method, gallium nitrate starting material (e.g. form A) is combined, with agitation, with a slurry solvent in which gallium nitrate is at best sparingly soluble.

Selected results of the crystallization method in several of its modifications are given below in Table 1.

TABLE 1

Certain embodiments of the crystalline compositions of matter that include the elements Ga, N, and O can be made by the capillary method. Solutions of gallium nitrate hydrate, form A {see starting material, infra), were prepared by treating the compound with enough solvent to provide a solution concentration of approximately 20-40 mg/mL. The solutions of gallium nitrate hydrate prepared in a given solvent or solvent mixture were filtered prior to adding the solution to an XRPD-quality capillary. The solvent was allowed to evaporate from the capillaries under various conditions (examples, Table 00 infra). The resulting samples were analyzed by optical microscopy and/or XRPD. Certain experiments were conducted by treating solid material that was placed in capillaries under various thermal, humidity, or solvent stress (vapor stress) conditions. In one embodiment, the present invention provides a crystalline form of gallium nitrate [Ga(NO₃)₂] that is a hydrate, and here denominated form Al. Form Al is characterized by x- ray reflections at about 13.4°, 14.2°, 19.7°, 21.6°, 22.1°, 22.4°, 23.5°, 24.6°, 27.5°, 29.8°, and 24.5° ± 0.2° 2Θ. A representative x-ray diffraction diagram of form Al is shown in Figure 2. Representative DSC and TGA thermograms of form Al are shown in Figure 30.

When examined by hot stage microscopy, form Al liquefies at about 51° to 52° C. The water content of form Al (Karl Fisher) corresponds to about 7 moles water per mole GaN(O₃)₂.

Form Al can be made by, for example, grinding form A under ambient conditions. Form Al can also be made in admixture with form G of the crystalline form of Ga(NO₃)₂ that is a hydrate by freeze drying (lyophilizing) an aqueous solution of GaN(Os)₂ having a slight excess of nitric acid.

In another embodiment the present invention provides a crystalline form of gallium nitrate that is a hydrate, denominated form B that can be characterized by x ray reflections at about 37.7°, 38.0°, and 44.5° ± 0.2° 26. Form B can be further characterized by x-ray reflection at about 17.6°, 19.5°, 23.0°, 25.5°, and 26.2° ±0.2°. 2θ. A typical x-ray diffraction diagram of form B is shown in Figure 3.

Form B can be made by concentrating an aqueous solution of a gallium nitrate hydrate. Form B so prepared had a water content corresponding to about 7.4 mole water per mole GaN(O₃)₂, but the water content can be as low as about 6.2 mole/mole GaN(O₃)₂.

Form B can also be prepared by concentrating an aqueous solution of a gallium nitrate hydrate, e.g. Form A, (150 mg/mL; 0.6 M excess HNO₃) .

Form B can convert to form Bl {infra) upon storage, but typically converts to form A. In another embodiment, the present invention provides a crystalline form of gallium nitrate that is a hydrate, denominated form Bl, characterized by an x-ray reflection at about 11.5° ±0.2° 20. Form Bl can be further characterized by x-ray reflections at about 12.9°, 17.6°, 19.6°, 23.1°, 25.6°, 25.9°, 26.2°, 26.9°, 31.8°, and 35.7° ±0.2° 2Θ. A representative x-ray diffraction diagram of form B 1 is shown in Figure 4.

In another embodiment, the present invention provides a crystalline form of gallium nitrate that is a hydrate, denominated from C, characterized by x-ray reflections at about 24.4° and 41.7° ±0.2° 2Θ. Form C can be further characterized by x-ray reflections at about 12.7°, 19.0°, and 25.4° ±0.2° 2Θ. A representative x-ray diffraction diagram of form C is shown in Figure 5.

Form C can be made by, for example, concentrating at room temperature an aqueous solution of gallium nitrate (15 mg/niL; 0.6M excess HNO₃) to about one-half its initial volume and isolating form C from the slurry so obtained.

Form C converts to form A upon prolonged storage at low relative humidity (12%-14%).

In a further embodiment, the present invention provides a crystalline form of gallium nitrate that is a hydrate, denominated form E, characterized by x-ray reflection at about 10.9°, 14.8°, 32.7°, 32.9°, and 35.0° ±0.2° 2Θ. Form E is further characterized by x-ray reflections at about 12.7°; 21.8°, 22.0°, 25.5°, 26.9°, and 29.7° ±0.2° 2Θ. A representative x-ray diffraction diagram of form E is shown in Figure 6.

Form E can be made by, for example, a crystallization method in which gallium nitrate hydrate form A is slurried with methylene chloride. Form E converts to form Al upon prolonged storage at low relative humidity (12%- 14%).

In another embodiment, the present invention provides a crystalline form of gallium nitrate that is a hydrate, denominated form N, characterized by either x-ray reflections at about 18.2°, 40.3°, 47.6°, 49.5°, and 54.9° ±0.2° 2Θ; or by FTIR bands at about 1383.97, 1356.04, 3338.19, 570.80, 832.70, 1042.12, 403.58, 2398.13, and 1765.37 cm^'1. Form N can be further characterized by x-ray reflections at about 12.9°, 22.3°, 25.9°, 31.8°, 35.7°, and 43.6° ±0.2° 20. A representative x-ray diffraction diagram of form N is shown in Figure 7. A representative FTIR spectrum of form N is shown in Figure 8. In yet another embodiment the present invention provides an amorphous form of gallium nitrate, denominated form F. Some characteristics of form F are collected in Table 2.

Table 2

Representative DSC and TGA thermograms of Form F are shown in Figure 31.

The DSC thermogram of form F shows a broad endotherm at ca. 138°, overlapping with decomposition. The weight loss at 55⁰C was ca. 3.49%. Based on hot stage microscopy the sample was not birefringent and shrank at ca. 160⁰C. Therefore the endothermic transition in DSC is thought to be due to dehydration-decomposition of the sample.

A representative x-ray diffraction diagram of form F is shown in Figure 32.

Form F can be made by, for example, the slurry method using a slurry solvent selected from acetone, diethyl ether, ethyl acetate, and mixtures of ethyl acetate and methanol.

In a further embodiment, the present invention provides a crystalline composition of matter that includes the elements gallium (Ga), nitrogen (N),and oxygen (O), and here designated simply form G, characterized by either x-ray reflections at 10.0°, 12.6°, 15.4°, 19.9°, 20.4°, 24.1°, 25.2°, 27.0°, 29.7°, 32.8°, and 38.2° ±0.2° 29 or FTIR bands at about 493, 686, 724, 829, 935, 960, 1001, 1046, 1303, 1345, 1384, 1424, 1439, 1750, 2383, 2920, 2962, and 3010 cm^"1. A representative x-ray diffraction diagram of form G is shown in Figure 9. A representative FTIR spectrum form G is shown in figure 10.

Further characterization of four G is given in Table 3.

Table 3

The DSC thermogram of form G, Figure 33, shows an endotherm at about 123°C, followed by decompositions. Minimal weight loss (TGA) was observed at about 55⁰C (0.14%) and 125°C (1.9%). In hot-stage microscopy, the material was found in loose birefringence at about 126°C. The broad intensive band in the region of 3300 to 3500 Cm_-1 (H₂O stretching) is not observed in the IR spectrums of form G, indicative of a lower state of hydration. Raman spectroscopy indicated that form G is not a hydrate of gallium nitrate.

From G can be made by, for example, a slurry method using DMSO or other slurry solvent. In another embodiment, the present invention provides a crystalline composition of matter that includes the elements Ga, N, and O, here simply denoted form D, that is characterized by x-ray reflection at about 14.5°, 27.6°, and 28.8° ±0.2° 29. Form D can be further characterized by x-ray reflection at about 7.0°, 10.9°, 14.0°, 14.3°, 17.0°, 17.6° and 21.9° ±0.2° 2Θ. A representative x-ray diffraction diagram of form D is shown in Figure 11. Further characteristics of form D are given in Table 4.

Table 4

Representative DSC and TGA thermograms of form D are shown in Figure 34. The DSC shows a broad endotherm with a minimum at about 115°C followed by decomposition. The TGA thermogram shows a weight loss of about 3.8% at about 55°C. In hot-stage microscopy, a sample of form D lost birefringence at about 82°C.

Form D can be made by, for example, a slurry method using diethyl ether as the slurry solvent. In a further embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, here simply denominated form Dl, and characterized by x-ray reflections at about 7.0°, 10.9°, 14.0°, 14.4°, 16.9°, 17.6°. 20.0°, 21.8°, 27.5°, and 34.1° ±0.2° 2Θ. A representative x-ray diffraction diagram of form Dl is shown in Figure 12. Representative DSC and TGA thermograms of form Dl are shown in Figure 35.

The DSC shows a broad endotherm peaking at about 115°C, followed by decomposition. In hot-stage microscopy, a sample of form Dl lost birefringence at about 82°C.

Form Dl can be prepared by, for example, a slurry method using acetonitrile, methyl ethyl ketone, or ethyl acetate as slurry solvent. Form Dl can also be prepared by a crystallization method where gallium nitrate is dissolved in ethanol and slowly evaporating the solvent at low relative humidity (12%-

O ).

In another embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, here simply designated form H, characterized by x-ray reflections at about 13.0° and 18.7° ±0.2° 20. Form H can be further characterized by x-ray reflections at about 10.9°, 18.3°, 29.7°, and 37.6° ±0.2° 20. A representative x-ray diffraction diagram is shown in Figure 13.

Form H can be prepared by , for example, a slurry method in which mixed hexanes are the slurry solvents for about one week. Upon storage at low relative humidity (12%-14%), form H converts to form J. Further storage results in transformation to form Jl .

In yet a further embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, here simply described as form I, characterized by x-ray reflections at about 22.2° and 24.6° ±0.2° 2Θ. Form I can be further characterized by x-ray reflections at about 8.0°, 9.0°, 9.8°, 14.0°, 18.4°, and 24.0° ±0.2° 2Θ. A representative x-ray diffraction diagram of form I is shown in Figure 14.

Form I can be prepared by, for example, slow evaporation, under ambient conditions, of ethanolic or methanolic solutions of gallium nitrate (modification of the crystallization method).

In another embodiment, the present invention relates to a crystalline composition of matter including the elements, Ga, N, and O, here denominated simply as form II, characterized by x-ray reflections at about 9.2°, 22.7°. 27.5° and 34.0° +1-0.2° 2Θ. Form Il can be further characterized by x-ray reflections at about 7.0°, 8.0°, 9.0°, 10.9°, 21.8°, and 30.1° +1-0.2° 20. A representative x-ray diffraction diagram of form Il is shown in Figure 15.

Form Il was not birefringent when viewed between crossed polars.

In another embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N and O, here simply denominated form J, characterized by x-ray reflections as about 11.5°, 14.2°, 17.6°, 19.6°, 23.1°, 25.5°, 26.2°, 26.9°, 31.7°, and 34.8° +1-0.2 20.

A representative x-ray diffraction diagram of form J is shown in Figure 16. Representative DSC and TGA thermograms of Figure J. In another embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N and O, and here designated form Jl, characterized by x-ray reflections at about 10.9°, 11.5°, 13.1°, 14.3°, 17.6°, 19.6°, 21.7°, 22.3°, 23.1°, 25.0°, 25.6°, 26.2°, 26.9°, 31.8°, 34.8°, and 37.6° +1-0.2° 2Θ. A representative x-ray diffraction diagram of form Jl is shown in Figure 17.

Form Jl can be obtained by storage of form J at low relative humidity (12% - 14%).

In a further embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N and O, and herein denominated form K, characterized by x-ray reflections at about 25.9° and 35.7° +1-0.2° 2Θ. Form K can be further characterized by x-ray reflections at about 7.0°, 10.9°, 11.5°, 12.9°, 14.2°, 17.6°, 19.6°, 22.3°, 23.1°, 25.5°, 26.2°, 26.9° and 31.8° +1-02° 20. A representative x-ray diffraction diagram of form K is shown in Figure 18.

Form K can be obtained by treatment of form A in a moisture determination apparatus (moisture balance).

In another embodiment, the present invention provides a crystalline composition of matter comprising the elements Ga, N, and O, and herein denominated form L, characterized by either x-ray reflections at about 7.0°, 10.9°, 11.5°, 14.2°, 17.6°, 19.6°, 21.9°, 23.1°, and 25.6° +1-0.2° 2Θ; or by FTIR bands at about 410, 578, 824, 1040, 1384, 1566, 1672, 1762, 2395, and 3424 cm^"1.

A representative x-ray diffraction diagram of form L is shown in Figure 19. A representative FTIR spectrum of form L is shown in Figure 20.

The DSC thermograms of form L exhibits an endotherm at about 45°C, followed by decomposition, a weight loss of about 4.5° at about 55°C in thermogravemetric analysis.

A sample of form L lost birefringence without liquefying at about 44°C when observed by hot stage microscopy.

Form L can be made by, for example, slow evaporation of a solution of gallium nitrate in tetrahydrofuran (THF).

In yet another embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, and here denominated from M, characterized by either x-ray reflections at about 6.3°, 10.2°, 11.9°, 12.2°, 21.2°, and 27.1° +1-0.2° 2Θ; or by FTIR bands at about 422, 430, 573, 819, 1358, 1384, 1661, and 3295 cm^'1.

A representative x-ray diffraction diagram of form M is shown in Figure 21. A representative FTIR spectrum of form M is shown in Figure 8. Representative DSC and TGA thermograms of form M are shown in Figure 36.

The DSC thermogram of form M exhibits broad, overlapping endotherms at about 86°, 104°, and 121°C. A weight loss of about 1.8% was observed at about 55⁰C in TGA.

When observed by hot-stage microscopy, a sample of form M remained unchanged to a temperature of about 96⁰C, at which point it lost birefringence. The IR band in the region of 3300 to 3500cm-l suggested a relatively lower state of hydration compared to that of form A.

Form M can be obtained by, for example, slow evaporation of a methanolic solution of Ga(NO3)2 at low humidity (e.g., 12% - 14% relative humidity).

In a further embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, and here denominated form 1 (form one), characterized by x-ray reflections at about 7.0° and 10.4° +1-0.2° 2Θ. A representative x- ray diffraction diagram of form 1 is shown in Figure 23.

Form 1 can be obtained by the capillary method using methanol solvent (vacuum oven). In a further embodiment, the present invention provides a crystalline composition of matter comprising the elements Ga, N, and O, here denominated form 2, characterized by x-ray reflections at about 13.4° and 18.9° +1-02° 2Θ. Form 2 can be further characterized by x-ray reflections at about 7.8°, 19.4°, 20.4°, 21.6°, 23.4°, 24.1°, 24.5°, and 30.2° +1-0.2° 2Θ. A representative x-ray diffraction diagram of form 2 is shown in Figure 24.

Form 2 can be made by, for example, a capillary method in which form A is vapor stressed with acetone at ambient conditions.

In a further embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, and here simply denominated form 3, characterized by x-ray reflections at about 15.2°, 17.0°, 20.4°, 21.6°, 23.4°, 24.1°, 24.5° and 30.2° +1-0.2° 2Θ. A representative x-ray diffraction diagram of form 3 is shown in Figure 25.

Form 3 can be obtained by a capillary method using a 1 :2 mixture of water and trifluoroethanol as the solvent. In a further embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, and here denominated form 4, characterized by x-ray reflections at about 8.0°, 9.8°, and 12.8° +1-0.2° 2Θ. A representative x-ray diffraction diagram of form 4 is shown in Figure 26.

Form 4 can be prepared by a capillary method. In yet another embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, and here denominated form 5, characterized by x-ray reflections at about 6.8°, 7.4°, and 9.7° +1-0.2° 2Θ. A representative x-ray diffraction diagram of form 5 is shown in Figure 27.

Form 5 can be obtained by a capillary method in which form A is vapor stressed with vapors of acetonitrile .

In another embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, and here simply denominated form 6, characterized by x-ray reflections at about 15.8°, 17.9°, 29.0°, 32.9°, 39.1°, and 40.1° +1- 0.2° 20. A representative x-ray diffraction diagram of form 6 is shown in Figure 28. Form 6 can be prepared by a capillary method in which form A is stressed with vapors of acetonitrile.

In still yet another embodiment, the present invention provides a crystalline composition of matter including the elements Ga, N, and O, and here simply denominated form 7, characterized by an x-ray reflection at about 5.8° +1-0.2° 20. Form 7 can be further characterized by x-ray reflections at about 8.1 ° and 10.1° +1 -0.2° 2Θ.

In still yet another embodiment, the present invention provides pharmaceutical compositions, especially for oral administration that include at least one of the novel crystalline forms of gallium nitrate that are hydrates, i.e., gallium nitrate forms Al, B, Bl, C, E, and N; and at least one pharmaceutically acceptable excipient.

Pharmaceutically acceptable excipients are non-toxic in the amounts used and do not significantly interfere with the bioavailability or efficacy of the active pharmaceutical ingredient with which they are used. Excipients are used in pharmaceutical compositions for a variety of purposes.

Diluents increase the bulk of a solid pharmaceutical composition and may make a pharmaceutical dosage form containing the composition easier for the patient and caregiver to handle. Diluents for solid compositions include, for example, microcrystalline cellulose (e.g. AVICEL®, microfme cellulose, lactose, starch, pregelitinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, polymethacrylates (e.g. Eudragit®), potassium chloride, powdered cellulose, sodium chloride, sorbitol and talc.

Solid pharmaceutical compositions that are to be compacted into a solid dosage form, especially a solid oral dosage form like a tablet, can and usually do include pharmaceutically acceptable excipients whose functions include helping to bind the active ingredient and other excipients together after compression. Binders for solid pharmaceutical compositions include acacia, alginic acid, carbomer (e.g. carbopol), carboxymethylcellulose sodium, dextrin, ethyl cellulose, gelatin, guar gum, hydrogenated vegetable oil, hydroxyethyl cellulose, hydroxypropyl cellulose (e.g. KLUCEL®), hydroxypropyl methyl cellulose (e.g. METHOCEL®), liquid glucose, magnesium aluminum silicate, maltodextrin, methylcellulose, polymethacrylates, povidone (e.g. KOLLIDON®, PLASDONE®), pregelatinized starch, sodium alginate and starch.

The dissolution rate of a compacted solid pharmaceutical composition in the patient's stomach may be increased by the addition of a disintegrant to the composition which aid in the break-up of the solid oral dosage form in the alimentary tract. Disintegrants include alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium (e.g. Ac-DI-SOL®, PRIMELLOSE®), colloidal silicon dioxide, croscarmellose sodium, crospovidone (e.g. KOLLIDON®, POLYPLASDONE®), guar gum, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, polacrilin potassium, powdered cellulose, pregelatinized starch, sodium alginate, sodium starch glycolate (e.g. EXPLOTAB®) and starch.

Glidants can be added to improve the flow properties of non-compacted solid compositions and improve the accuracy of dosing in tableting equipment. Excipients that may function as glidants include colloidal silicon dioxide, magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate, to mention just a few. When a solid dosage form such as a tablet is made by compaction of a powdered composition, the composition is subjected to pressure from a punch and dye. Some excipients and active ingredients have a tendency to adhere to the surfaces of the punch and dye, which can cause the product to have pitting and other surface irregularities. A lubricant can be added to the composition to reduce adhesion and ease release of the product from the dye. Lubricants include magnesium stearate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulfate, sodium stearyl fumarate, stearic acid, talc and zinc stearate.

Flavoring agents and flavor enhancers make the oral dosage form more palatable to the patient. Common flavoring agents and flavor enhancers for pharmaceutical products that may be included in the composition of the present invention include maltol, vanillin, ethyl vanillin, menthol, citric acid, fumaric acid ethyl maltol, and tartaric acid.

Compositions may also be colored using any pharmaceutically acceptable colorant to improve their appearance and/or facilitate patient identification of the product and unit dosage level.

Selection of excipients and the amounts to use may be readily determined by the formulation scientist based upon experience and consideration of standard procedures and reference works in the field.

The solid pharmaceutical compositions of the present invention include powders, granulates, aggregates and compacted compositions. The dosages include dosages suitable for oral, buccal, rectal, parenteral (including subcutaneous, intramuscular, and intravenous), inhalant and ophthalmic administration. Although the most suitable route in any given case will depend on the nature and severity of the condition being treated, the most preferred route of the present invention is oral. The dosages may be conveniently presented in unit dosage form and prepared by any of the methods well-known in the pharmaceutical arts.

The crystalline compositions of matter including the elements Ga, N, and O of the present invention are also well suited for the formulation and preparation of pharmaceutical compositions for parenteral administration, especially by subcutaneous or intravenous injection. The formulation and manufacture of pharmaceutical compositions for parenteral administration is well known in the art. Dosage forms include solid dosage forms like tablets, powders, capsules, suppositories, sachets, troches and lozenges as well as liquid syrups, suspensions and elixirs. An especially preferred dosage form of the present invention is a tablet.

The present invention, in certain of its embodiments, is illustrated by the following nonlimiting examples.

EXAMPLES

Starting materials:

The gallium nitrate hydrate form A used as starting material for the preparation of the novel crystalline compositions of matter that include the elements Ga, N, and O, and

10 in particular crystalline gallium nitrates that are hydrates, are described in Table 5 below.

Table 5 Starting Materials

a. weight loss (%) at given temperature (°C)

15 b. endo = endotherm, temperatures reported are transition maxima. Temperatures are rounded to the nearest degree.

Example 1 Form Al

Two hundred fifty one mg of 1 was dissolved in 1 mL of isopropanol. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate to dryness at 20 -12-14% RH in a vial covered with perforated Al foil. A solid material formed after 6 days and was stored at -12-14 % RH. Example 2 Form B

Starting material 4, 5 mL ,was rotary evaporated to dryness for -25-30 min at 45 to 50 °C. The resulting solid material was stored at -12-14% RH. The XRPD of the sample after 20 days indicated a new crystalline form (Bl, infra).

Example 3 Form Bl

The material resulted from pattern B material upon storing at -12-14 % RH as detected by XRPD.

Example 4 Form C Starting material 4, 16 mL, was rotary evaporated to approx. 8 ml (concentrated by a factor of 2) at ambient conditions. Small crystals formed in solution. Rapid crystallization occurred upon transferring the material to a vial. The resulting thick slurry was stored in a desiccator. After storing overnight, 2 spatulas of the material were vacuum filtered, analyzed by XRPD and returned to the desiccator. Conversion of the retained material to form A was detected by XRPD after 18 days.

Example 5 Form D

Starting material 1, 555.1 mg, was slurried in 12 mL of diethyl ether for 1 week. The resulting material was isolated by vacuum filtration, stored at -12-14% RH.

Example 6 Form Dl a) Starting material 1, 78.3 mg, was slurried in 11 mL of acetonitrile for 8 days. The sample was vacuum filtered and stored at -12-14% RH. b) Starting material 1, 79.5 mg, was slurried in 11 mL of methyl ethyl ketone for 8 days. The sample was vacuum filtered and stored at -12-14% RH. c) Starting material 1, 77.3 mg, was slurried in 11 mL of ethyl acetate for 8 days.

The sample was vacuum filtered and stored at -12-14% RH. d) Starting material 1, 243.4 mg, was dissolved in 2 mL of ethanol. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate to dryness at -12-14% RH in a vial covered with perforated Al foil. A solid material formed after 1 month and 1 week and was stored at -12-14 % RH.

Example 7 Form E

Starting material 1, 82.2 mg, of 1 was slurried in 11 mL of methylene chloride for 8 days, the resulting material was vacuum filtered. Conversion to pattern A +peaks upon storing at -12-14% RH was detected by XRPD after 18 days.

Example 8 Form F

Starting material 1, 3.205 g, of 1 was added to 182 mL of diethyl ether. The suspension was stirred for 4 days. The resulting material was isolated by vacuum filtration and stored at -12-14% RH. Form F was found to be amorphous.

Example 9 Form G

Starting material 1, 163.1 mg, was slurried in 9 mL of DMSO for 1 week. The suspension was vacuum filtered. The resulting wet solid was dried at -12-14 % RH for 11 days.

Example 10, Form H

Starting material 1, 79.4 mg, was slurried in 11 mL of hexanes for 8 days. The resulting material was vacuum filtered and stored at -12-14% RH. XRPD of the sample after 18 days indicated a new pattern , form J, infra. New peaks were detected by XRPD after 48 days (Form Jl) .

Example 11 Form I a) Starting material 1, 73.5 mg, was dissolved in 0.5 mL of ethanol. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate in a vial covered with perforated Al foil. A small amount of solvent had remained upon evaporation overnight, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed upon drying for 10 days and was stored at -12-14 % RH. XRPD of the sample after 35 days indicated a low crystalline pattern I with a new peak (form II). b) Starting material 1, 85.5 mg, was dissolved in 0.5 mL of methanol. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate in a vial covered with perforated Al foil. A small amount of solvent had remained upon evaporation overnight, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed after drying for 10 days and was stored at -12-14 % RH. XRPD of the sample after 40 days indicated a low crystalline pattern I with a new peak (form II). c) Starting material 1, 86.6 mg, was dissolved in 0.1 mL of water. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate in a vial covered with perforated Al foil. A small amount of solvent had remained upon evaporation overnight, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed after drying for 10 days and was stored at -12-14 % RH.

Example 12 Form Il a) The material upon storing form I at -12-14 % RH as detected by XRPD (see pattern I). b) The material resulted upon storing form I at -12-14 % RH as detected by

XRPD (see pattern I). c) Starting material 1, 84.7 mg, was dissolved in 0.5 mL of THF. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate in a vial covered with perforated Al foil. A small amount of solvent had remained upon evaporation overnight, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed after drying for 10 days and was stored at -12-14 % RH. d) Starting material 1, 99.6 mg, was dissolved in 0.6 mL of CH₃CN:H₂O (85:15). A 2-layer mixture formed and was allowed to evaporate in a vial covered with perforated Al foil. A small amount of solvent had remained upon evaporation overnight, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed after drying for 9 days and stored at -12-14 % RH. XRPD of the sample after 35 days indicated a new crystalline form. f) Starting material 1, 97.7 mg, was dissolved in 1 mL of i-PrOH:H₂O (9:1). The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate in a vial covered with perforated Al foil. A small amount of solvent had remained upon evaporation overnight, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed after drying for 9 days and was stored at -12-14 % RH. g) Starting material 1, 82.7 mg, was dissolved in 0.4 mL of EtOH:H₂O (95:5). The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate in a vial covered with perforated Al foil. A small amount of solvent had remained upon evaporation overnight, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed after drying for 9 days and was stored at -12-14 % RH.

Example 13 Form J Form H was stored -12-14 % RH as detected by XRPD (see pattern H) to yield form J. XRPD of the sample after 48 days indicated a new crystalline form (Jl).

Example 14 Form Jl

The material resulted from form J material upon storing at -12-14% RH as detected by XRPD (see pattern J).

Example 15 Form K

Post-MB material of gallium nitrate lot.

Post-MB material of gallium nitrate lot D0926-020701

Example 16 Form L

Starting material 1, 206.2 mg, was dissolved in 1.5 mL of THF. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate until no solvent was left at -14-17% RH in a flask covered with perforated Al foil. A solid material formed after 18 days and was stored at -12-17% RH. Example 17 Form M

Starting material 1, 228.4 mg, was dissolved in 1.5 mL of methanol. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate to dryness at -14-17% RH in a flask covered with perforated Al foil. A solid material formed after 37 days and was stored at -12-17% RH. Example 17 Form N a) Starting material 1, 3.54 g, was dissolved in 21 mL of methanol. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate in the hood in a flask covered with perforated Al foil. A small amount of solvent had remained upon evaporation for 9 days, no crystallization was observed. The sample was placed in a vacuum oven at ambient temperature. A solid material formed upon drying for 12 days and was stored at -12-14 % RH. b) Starting material 3, 315.7 mg, was dissolved in 1 mL of THF. The solution was filtered through a 0.2 μm nylon filter and allowed to evaporate to dryness at -12-14 % RH in a vial covered with perforated Al foil. A solid material formed after lweek and was stored at -12-14% RH.

Tabulated Results:

TABLE 6

Example 18 Capillary Experiments

The capillary screen is summarized in Table 7 below. The representative capillary screen experiments for gallium nitrate hydrate are listed in Table 7. They resulted in 2 known and 7 new XRPD patterns. An amorphous pattern material was generated by evaporating a solution in 2:1 methanol :acetonitrile at ambient temperature followed by vacuum drying. A low crystalline pattern D material, form Dl, resulted from evaporation of an aqueous solution at 60°C followed by vacuum drying.

The new XRPD patterns 1 to 7 are shown in the Figures. They resulted from evaporations or vapor stress (7-12 days) experiments (Table 7). Form 1 and 2 materials were generated using ambient conditions: evaporation of a methanol solution (1) and acetone vapor stress (2). Forms 3, 4, 5, 6 and 7 materials were obtained from evaporations or stress experiments at 58 or 60°C. Temperature stress conditions possibly resulted in dehydration of the gallium nitrate hydrate.

Form 1, 2, 6 and 7 materials were analyzed by Raman spectroscopy. The Raman 0 spectrum of form 2 indicated a different composition compared to the gallium nitrate hydrate. None of the spectra exhibited splitting of the band at —1050 cm^"1.

Table 7

Claims

What is claimed is:

1. A crystalline form of gallium nitrate that is a hydrate characterized by x-ray reflections at about 13.4°, 14.2°, 19.7°, 21.6°, 22.1°, 22.4°, 23.5°, 24.6°, 27.5°, 29.8°, and 24.5° ± 0.2° 2Θ.

2. The crystalline form of gallium nitrate of claim 1 having an x-ray diffraction diagram substantially as shown in Figure 2.

3. A crystalline form of gallium nitrate that is a hydrate characterized by x-ray reflections at about 37.7°, 38.0°, and 44.5° ± 0.2° 2Θ.

4. The crystalline form of gallium nitrate of claim 3 further characterized by x- ray reflections at about 17.6°, 19.5°, 23.0°, 25.5° and 26.2° ± 0.2° 2Θ. ^'

5. The crystalline form of gallium nitrate of claim 4 having an x-ray diffraction diagram substantially as shown in Figure 3.

6. A crystalline form of gallium nitrate that is a hydrate characterized by an x-ray reflection at about 11.5° ± 0.2° 2Θ.

7. The crystalline form of gallium nitrate of claim 6 further characterized by x- ray reflections at about 12.9°, 17.6°, 19.6°, 23.1°, 25.6°, 25.9°, 26.2°, 26.9°, 31.8°, and 35.7° ± 0.2° 2Θ.

8. The crystalline form of gallium nitrate of claim 7 having an x-ray diffraction diagram substantially as shown in Figure 4.

9. A crystalline form of gallium nitrate that is a hydrate characterized by x-ray reflections at about 24.4°and 41.7° ± 0.2° 2Θ.

10. The crystalline form of gallium nitrate of claim 9 further characterized by x- ray reflections at about 12.7°, 19.0° and 25.4° ± 0.2° 2Θ.

11. The crystalline form of gallium nitrate of claim 10 having an x-ray diffraction diagram substantially as shown in Figure 5.

12. A crystalline form of gallium nitrate that is a hydrate characterized by x-ray reflections at about 10.9°, 14.8°, 32.7°, 32.9 and 35.0°± 0.2° 2Θ.

13. The crystalline form of gallium nitrate of claim 12 further characterized by x- ray reflections at about 12.7°, 21.8°, 22.0° , 25.5°, 26.9°, and 29.7° ± 0.2° 2Θ.

14. The crystalline form of gallium nitrate of claim 13 having an x-ray diffraction diagram substantially as shown in Figure 6.

15. A crystalline form of gallium nitrate that is a hydrate characterized by x-ray reflections at about 18.2°, 40.3°, 47.6°, 49.5°, and 54.9°± 0.2° 2Θ, or by FTIR bands at about 1383.97, 1356.04, 3338.19, 570.80, 832.70, 1042.12, 403.58, 2398.13, and 1765.37 cm^"1.

16. The crystalline form of gallium nitrate of claim 15 characterized by x-ray reflections at about 18.2°, 40.3°, 47.6°, 49.5°, and 54.9°± 0.2° 2Θ.

17. The crystalline form of gallium nitrate of claim 16 further characterized by x- ray reflections at about 12.9°, 22.3°, 25.9°, 31.8°, 35.7°, and 43.6° ± 0.2° 2Θ.

18. The crystalline form of gallium nitrate of claim 17 having an x-ray diffraction diagram substantially as shown in Figure 7.

19. The crystalline form of gallium nitrate of claim 15 having FTIR bands at about 1383.97, 1356.04, 3338.19, 570.80, 832.70, 1042.12, 403.58, 2398.13, and 1765.37 cm^"1.

20. The crystalline form of gallium nitrate of claim 19 having an FTIR spectrum substantially as shown in Figure 8.

21. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 10.0°, 12.6°, 15.4°, 19.9° 20.4°, 24.1°, 25.2°, 27.0°, 29.7°, 32.8°, and 38.2° ± 0.2° 2Θ; or FTIR bands at about 493, 686, 724, 829, 935, 960, 1001, 1046, 1303, 1345, 1384, 1424, 1439, 1750, 2383, 2920, 2962, and 3010 cm^"1.

22. The crystalline composition of matter of claim 21 characterized by x-ray reflections at about 10.0°, 12.6°, 15.4°, 19.9 20.4°, 24.1°, 25.2°, 27.0°, 29.7°, 32.8°, and 28.2° ± 0.2°2Θ.

23. The crystalline composition of matter of claim 22 having an x-ray diffraction diagram substantially as shown in Figure 9.

24. The crystalline composition of matter of claim 21 characterized by FTIR bands at about 493, 686, 724, 829, 935, 960, 1001, 1046, 1303, 1345, 1384, 1424, 1439, 1750, 2383, 2920, 2962, and 3010 cm^"1.

25. The crystalline composition of matter of claim 24 having an FTIR spectrum substantially as shown in Figure 10.

26. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 14.5°, 27.6° and 28.8° ± 0.2° 2Θ.

27. The crystalline composition of matter of claim 26 further characterized by x- ray reflections at about 7.0°, 10.9°, 14.0°, 14.3°, 17.0°, 17.6° and 21.9 ± 0.2° 2Θ.

28. The crystalline composition of matter of claim 27 having an x-ray diffraction diagram substantially as shown in Figure 11.

29. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 7.0°, 10.9°, 14.0°, 14.4°, 16.9°, 17.6°, 20.0°, 21.8°, 27.5°, and 34.1° ± 0.2° 2Θ.

30. The crystalline composition of matter of claim 29 having an x-ray diffraction diagram substantially as shown in Figure 12.

31. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 13.0° and 18.7° ± 0.2° 2Θ.

32. The crystalline composition of matter of claim 31 further characterized by x- ray reflections at about 10.9°, 18.3°, 29.7°, and 37.6° ± 0.2° 2Θ.

33. The crystalline composition of matter of claim 32 having an x-ray diffraction diagram substantially as shown in Figure 13.

34. A crystalline composition of matter comprising the elements Ga, N₅ and O characterized by x-ray reflections at about 22.2° and 24.6° ± 0.2° 2Θ.

35. The crystalline composition of matter of claim 34 further characterized by reflections at about 8.0°, 9.0°, 9.8°, 14.0°, 18.4°, and 24.0° ± 0.2°2Θ.

36. The crystalline composition of matter of claim 35 having an x-ray diffraction diagram substantially as shown in Figure 14.

37. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at 9.2°, 22.7°, 27.5°, and 34.0° ± 0.2° 2Θ.

38. The crystalline composition of matter of claim 37 further characterized by x- ray reflections at about 7.0°, 8.0°, 9.0°, 10.9°, 21.8°, and 30.1° ± 0.2° 2Θ.

39. The crystalline composition of matter of claim 38 having an x-ray diffraction diagram substantially as shown in Figure 15.

40. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 11.5°, 14.2°, 17.6°, 19.6°, 23.1°, 25.5°, 26.2°, 26.9°, 31.7°, and 34.8° ± 0.2°2Θ.

41. The crystalline composition of matter of claim 40 having an x-ray diffraction diagram substantially as shown in Figure 16.

42. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 10.9°, 11.5°, 13.1°, 14.3°, 17.6°, 19.6°, 21.7°, 22.3°, 23.1°, 25.0°, 25.6° 26.2°, 26.9°, 31.8°, 34.8°, and 37.6° ± 0.2° 2Θ.

43. The crystalline composition of matter of claim 42 having an x-ray diffraction diagram substantially as shown in Figure 17.

44. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 25.9° and 35.7° ± 0.2° 2Θ.

45. The crystalline composition of matter of claim 44 further characterized by x- ray reflections at about 7.0° 10.9°, 11.5°, 12.9°, 14.2°, 17.6°, 19.6°, 22.3°, 23.1°, 25.5°,

26.2°, 26.9°, and 31.8° ± 0.2° 2Θ.

46. The crystalline composition of matter of claim 45 having an x-ray diffraction diagram substantially as shown in Figure 18.

47. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 7.0°, 10.9°, 11.5°, 14.2°, 17.6°, 19.6°, 21.9°, 23.1°, and 25.6°± 0.2° 2Θ; or FTIR bands at about 410, 578, 824, 1040, 1384, 1566, 1672, 1762, 2395, and 3424 cm^"1.

48. The crystalline composition of matter of claim 47 characterized by x-ray reflections at about 7.0°, 10.9°, 11.5°, 14.2°, 17.6°, 19.6°, 21.9°, 23.1°, and 25.6°± 0.2°

49. The crystalline composition of matter of claim 48 having an x-ray diffraction diagram substantially as shown in Figure 19.

50. The crystalline composition of matter of claim 47 characterized by FTIR bands at about 410, 578, 824, 1040, 1384, 1566, 1672, 1762, 2395, and 3424 cm^"1.

51. The crystalline composition of matter of claim 50 having a FTIR spectrum substantially as shown in Figure 20.

52. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 6.3°, 10.2°, 11.9°, 12.2°, 21.2°, and 27.1° ± 0.2° 2Θ; or by FTIR bands at about 422, 430, 573, 819, 1358, 1384, 1661, and 3295 cm^"1.

53. The crystalline composition of matter of claim 52 further characterized by x- ray reflections at about 6.3°, 10.2°, 11.9°, 12.2°, 21.2°, and 27.1° ± 0.2° 2Θ.

54. The crystalline composition of matter of claim 53 further characterized by x- ray reflections at about 6.6°, 7.0°, 10.9°, 14.1°, and 26.8° ± 0.2° 2Θ.

55. The crystalline composition of matter of claim 54 having an x-ray diffraction diagram substantially as shown in Figure 21.

56. The crystalline composition of matter of claim 52 characterized by FTIR bands at about 422, 430, 573, 819, 1358, 1384, 1661, and 3295 cm^"1.

57. The crystalline composition of matter of claim 56 having a FTIR spectrum substantially as shown in Figure 22.

58. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 7.0° and 10.4° ± 0.2° 2Θ.

59. The crystalline composition of matter of claim 58 having an x-ray diffraction diagram substantially as shown in Figure 23.

60. A crystalline composition of matter comprising the elements Ga, N, and O, characterized by x-ray reflections at about 13.4° and 18.9° ± 0.2° 2Θ.

61. The crystalline composition of matter of claim 60 further characterized by x- ray reflections at about 7.8°, 15.4°, 20.4°, 21.6°, 23.4°, 24.1°, 24.5°, and 30.2° ± 0.2° 2Θ.

62. The crystalline composition of matter of claim 61 having an x-ray diffraction diagram substantially as shown in Figure 24.

63. A crystalline composition of matter comprising the elements Ga, N, and O and characterized by x-ray reflections at about 15.2°, 17.0° , 20.4°, 21.6°, 23.4°, 24.1°, 26.1°, 26.8 and 32.0° ± 0.2°2Θ.

64. The crystalline composition of matter of claim 63 having an x-ray diffraction diagram substantially as shown in Figure 25.

65. A crystalline composition of matter comprising the elements Ga, N and O characterized by x-ray reflections at about 8.0°, 9.8°, and 12.8° ± 0.2° 2Θ.

66. The crystalline composition of matter of claim 65 having an x-ray diffraction diagram substantially as shown in Figure 26.

67. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 6.8°, 7.4°, and 9.7° ± 0.2° 2Θ.

68. The crystalline composition of matter of claim 67 having an x-ray diffraction diagram substantially as shown in Figure 27.

69. A crystalline composition of matter comprising the elements Ga, N, and O characterized by x-ray reflections at about 15.8°, 17.9°, 29.0°, 32.9°, 39.1°, and 40.1° ± 0.2° 2Θ.

70. The crystalline composition of matter of claim 69 further characterized by x- ray reflections at about 6.7°, 7.4°, 21.6°, and 26.0° ± 0.2° 2Θ.

71. The crystalline composition of matter of claim 70 having an x-ray diffraction diagram substantially as shown in Figure 28.

72. A crystalline composition of matter comprising the elements Ga, N, and O characterized by an x-ray reflection at about 5.8° ± 0.2° 2Θ.

73. The crystalline composition of claim 72 further characterized by x-ray reflections at about 8.1° and 10.1° ± 0.2° 2Θ.

74. The crystalline composition of matter of claim 73 having an x-ray diffraction diagram substantially as shown in Figure 29.

75. Amorphous gallium nitrate.

76. A pharmaceutical composition for oral administration comprising one or more of the crystalline forms of gallium nitrate that is a hydrate of any of claims 1 to 20 and at least one pharmaceutically acceptable excipient.

77. A pharmaceutical composition for oral administration comprising one or more of the crystalline compositions of matter comprising the elements Ga, N, and O of any of claims 21 to 75 and at least one pharmaceutically acceptable excipient.

78. Use of at least one of the crystalline forms of gallium nitrate that is a hydrate of any of claims 1 to 20 for the manufacture of a pharmaceutical formulation for parenteral administration.

79. Use of at least one of the crystalline compositions of matter comprising the elements Ga, N, and O of any of claims 21 to 74 for the manufacture of a pharmaceutical formulation for parenteral administration.