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 . A stable 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.
2 . The stable solid salt of claim 1 , wherein the anionic substituted cyclodextrin is substituted with at least one anionic functional group.
3 . The stable solid salt of claim 2 , wherein the at least one anionic functional group is a conjugate base.
4 . The stable 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 stable solid salt of claim 1 , wherein the at least one cationic pharmaceutical compound of the stable solid salt has improved stability when compared to the same pharmaceutical compound in a formulation without an anionic substituted cyclodextrin.
6 . The stable solid salt of claim 1 , wherein the stable solid salt comprises at least two cationic pharmaceutical compounds.
7 . The stable solid salt of claim 1 , wherein the molar ratio of the cationic pharmaceutical compound to the anionic substituted cyclodextrin is greater than 1:1.
8 . The stable solid salt of claim 7 , wherein the molar ratio of the cationic pharmaceutical compound to the anionic substituted cyclodextrin is from about 2:1 to about 8:1.
9 . The stable solid salt of claim 1 , wherein the at least one cationic pharmaceutical compound has an ionizable nitrogen.
10 . A stable 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; and
n is at least 1.
11 . The stable solid salt of claim 10 , wherein n is at least 2.
12 . The stable solid salt of claim 10 , wherein n is 6, 7, or 8.
13 . The stable solid salt of claim 10 , 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.
14 . The stable solid salt of claim 10 , wherein the stable solid salt is formulated for oral administration.
15 . The stable solid salt of claim 10 , wherein the solid salt is formulated as a powder, tablet, pill, dragee, capsule, lozenge, gel, troche, film, suppository or a cachet.
16 . The stable solid salt of claim 10 , wherein the solid salt is formulated as a liquid, syrup, slurry, emulsion, suspension, or a gel.
17 . The stable solid salt of claim 10 , wherein the at least one cationic pharmaceutical compound of the stable solid salt has improved stability when compared to the same pharmaceutical compound in a formulation without the substituted cyclodextrin.
18 . The stable solid salt of claim 10 , wherein the stable solid salt is stable for at least one month, as determined by High Performance Liquid Chromatography (HPLC).
19 . A method of dissolving a stable solid salt, comprising:
dissolving a stable solid salt in a solution,
the stable solid salt comprising the formula:
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; and
n is the number of pharmaceutical compound molecules per molecule of substituted cyclodextrin, and wherein n is at least 1.
20 . The method of claim 19 , wherein the stable solid salt has an osmolality that is at least about 10% less than a corresponding solid salt prepared from a salt of the complexing agent.