COMPLEXING AGENT SALT FORMULATIONS OF PHARMACEUTICAL COMPOUNDS
Provided herein are pharmaceutical formulations and pharmaceutical compound salts which utilize complexing agents as counterions. Such formulations and salts are useful for treating a variety of disease and disorders.
1 . An amorphous solid salt comprising:
(i) at least one cationic pharmaceutical compound; and
(ii) an anionic substituted cyclodextrin,
wherein the anionic substituted cyclodextrin is a counter-anion to the at least one cationic pharmaceutical compound, and
wherein the amorphous solid salt is substantially free of crystalline material.
2 . The amorphous solid salt of claim 1 , wherein the anionic substituted cyclodextrin is substituted with at least one anionic functional group.
3 . The amorphous solid salt of claim 2 , wherein the at least one anionic functional group is a conjugate base.
4 . The amorphous solid salt of claim 3 , wherein the at least one anionic functional group is a conjugate base of a carboxylic acid, a sulfonic acid, a sulfinic acid, a phosphonic acid, or a phosphinic acid.
5 . The amorphous solid salt of claim 1 , wherein the amorphous solid salt comprises at least two cationic pharmaceutical compounds.
6 . The amorphous solid salt of claim 1 , wherein the molar ratio of the cationic pharmaceutical compound to the anionic substituted cyclodextrin is greater than 1:1.
7 . The amorphous solid salt of claim 6 , wherein the molar ratio of the cationic pharmaceutical compound to the anionic substituted cyclodextrin is from about 2:1 to about 8:1.
8 . The amorphous solid salt of claim 1 , wherein the at least one cationic pharmaceutical compound has an ionizable nitrogen.
9 . The amorphous solid salt of claim 1 , wherein the amorphous solid salt is characterized by scanning electron microscopy, IR spectral analysis, differential scanning calorimetry, or nuclear magnetic resonance (NMR) spectroscopy.
10 . The amorphous solid salt of claim 1 , wherein the amorphous solid salt is free of crystalline material.
11 . The amorphous solid salt of claim 1 , wherein the amorphous solid salt is at least 98% free of impurities.
12 . An amorphous solid salt comprising the formula:
[pharmaceutical compound] n [substituted cyclodextrin];
wherein
the pharmaceutical compound is a cation;
the substituted cyclodextrin comprises a plurality of anionic conjugate bases which are counter-anions to the pharmaceutical compound;
n is the number of pharmaceutical compound molecules per molecule of substituted cyclodextrin;
n is at least 1; and
wherein the amorphous solid salt is substantially free of crystalline material.
13 . The amorphous solid salt of claim 12 , wherein n is at least 2.
14 . The amorphous solid salt of claim 12 , wherein n is 6, 7, or 8.
15 . The amorphous solid salt of claim 12 , wherein the pharmaceutical compound is an antibiotic, an anti-coagulant, an anti-diabetic, an antifungal, an anti-inflammatory, an anti-migraine, an anti-neoplastic, an antiviral, a piperazine, a naphthylpropylamine, or a phenidate, or a combination thereof.
16 . The amorphous solid salt of claim 12 , wherein the amorphous solid salt is formulated for oral administration.
17 . The amorphous solid salt of claim 12 , wherein the amorphous solid salt is formulated as a powder, tablet, pill, dragee, capsule, lozenge, gel, suppository or a cachet.
18 . The amorphous solid salt of claim 12 , wherein the amorphous solid salt is characterized by scanning electron microscopy, IR spectral analysis, differential scanning calorimetry, or nuclear magnetic resonance (NMR) spectroscopy.
19 . A method of dissolving an amorphous solid salt, comprising:
dissolving an amorphous solid salt in a solution, the amorphous solid salt comprising the formula:
[pharmaceutical compound] n [substituted cyclodextrin];
wherein
the pharmaceutical compound is a cation;
the substituted cyclodextrin comprises a plurality of anionic conjugate bases which are counter-anions to the pharmaceutical compound;
n is the number of pharmaceutical compound molecules per molecule of substituted cyclodextrin;
n is at least 1; and
wherein the amorphous solid salt is substantially free of crystalline material.
20 . The method of claim 19 , wherein the amorphous solid salt is characterized by increased solubility compared to a corresponding crystalline form of the solid salt.