Formulations containing acetaminophen and sulfoalkyl ether cyclodextrin
Pharmaceutical formulations containing acetaminophen and sulfoalkyl ether cyclodextrin are described. The formulation includes acetaminophen; and sulfoalkyl ether cyclodextrin, wherein the molar ratio of sulfoalkyl ether cyclodextrin to acetaminophen is in the range of about 0.01 to about 2. The formulations can be prepared in an injectable form for mitigating or treating fever or alleviating pain in a patient.
1 . A pharmaceutical formulation, comprising:
acetaminophen; and
a sulfoalkyl ether cyclodextrin,
wherein the sulfoalkyl ether cyclodextrin is a compound having the structure:
wherein each R is independently —H or —(CH 2 ) 4 SO 3 Na and the average degree of substitution with —(CH 2 ) 4 SO 3 Na groups is between 6 and 7.1;
wherein the molar ratio of the sulfoalkyl ether cyclodextrin to acetaminophen is in the range of about 0.05 to about 1.5, and wherein the formulation does not contain N-acetylcysteine, L-methionine, L-cysteine, cysteine hydrochloride, or mixtures thereof;
wherein the formulation is an aqueous solution;
wherein the concentration of acetaminophen is in the range of about 8 mg/ml to about 12 mg/ml; and
wherein the sulfoalkyl ether cyclodextrin has a concentration of about 50 mM to about 100 mM.
2 . The formulation of claim 1 , wherein the molar ratio of sulfoalkyl ether cyclodextrin to acetaminophen is about 1.5.
3 . The formulation of claim 1 , wherein the molar ratio of sulfoalkyl ether cyclodextrin to acetaminophen is in the range of about 0.05 to less than 1.
4 . The formulation of claim 1 , wherein the concentration of acetaminophen is about 10 mg/ml.
5 . The formulation of claim 1 , further comprises less than 2.6 μg/ml of p-aminophenol.
6 . The formulation of claim 1 , further comprises less than 0.05 μg/ml of p-aminophenol.
7 . The formulation of claim 1 , further comprises less than 0.015% of p-aminophenol by weight based on the total amount of acetaminophen in the formulation.
8 . The formulation of claim 5 , wherein the amount of p-aminophenol is determined after the formulation is stored at 25° C. for 12 months.
9 . The formulation of claim 1 , wherein the formulation is scrubbed of oxygen.
10 . The formulation of claim 1 , wherein the formulation is not scrubbed of oxygen.
11 . The formulation of claim 1 , wherein the formulation does not contain a corticosteroid.
12 . The formulation of claim 1 , wherein the formulation does not contain an androgen.
13 . The formulation of claim 1 , wherein the formulation does not contain a clopidogrel.
14 . The formulation of claim 1 , wherein the formulation does not contain a fluoroquinolone.
15 . The formulation of claim 1 , wherein the formulation does not contain a benzhydrylpiperazine.
16 . The formulation of claim 1 , wherein the formulation does not contain a cetirizine.
17 . The formulation of claim 1 , wherein the formulation does not contain a nicotine.
18 . The formulation of claim 1 , wherein the formulation does not contain a 17α-ethynyl-5α-androstane-3α, 17β-diol.
19 . The formulation of claim 1 , wherein the formulation does not contain a pyrone analog.
20 . The formulation of claim 1 , wherein the formulation does not contain a flavonoid.
21 . The formulation of claim 1 , wherein the formulation does not contain a quercetin.
22 . The formulation of claim 1 , further comprising one or more pharmaceutically acceptable excipient.
23 . The formulation of claim 1 , further comprising a buffer.
24 . The formulation of claim 23 , wherein the buffer is a phosphate buffer.
25 . The formulation of claim 23 , wherein the buffer is an acetate buffer.
26 . The formulation of claim 23 , wherein the buffer has a concentration in the range of 1 mM to about 100 mM.
27 . The formulation of claim 1 , wherein the formulation has a pH in the range of about 5 to about 10.
28 . The formulation of claim 27 , wherein the pH of the formulation is in the range of about 5.8 to about 7.4.
29 . The formulation of claim 1 , wherein the formulation has a pH greater than 5.8.
30 . The formulation of claim 1 , further comprising a salt.
31 . The formulation of claim 30 , wherein the salt is sodium chloride.
32 . The formulation of claim 1 , wherein the formulation has an osmolality in the range of about 100 mOsm/kg to about 500 mOsm/kg.
33 . The formulation of claim 32 , wherein the osmolality of the formulation is in the range of about 200 mOsm/kg to about 300 mOsm/kg.
34 . An aqueous pharmaceutical formulation, consisting of:
acetaminophen;
a sulfoalkyl ether cyclodextrin, and
a buffer;
wherein the sulfoalkyl ether cyclodextrin is a compound having the structure:
wherein each R is independently —H or —(CH 2 ) 4 SO 3 Na and the average degree of substitution with —(CH 2 ) 4 SO 3 Na groups is between 6 and 7.1;
wherein the molar ratio of the sulfoalkyl ether cyclodextrin to acetaminophen is in the range of about 0.05 to about 1.5,
wherein the concentration of acetaminophen is in the range of about 8 mg/ml to about 12 mg/ml; and
wherein the sulfoalkyl ether cyclodextrin has a concentration of about 50 mM to about 100 mM.
35 . An aqueous pharmaceutical formulation, consisting essentially of:
acetaminophen; and
a sulfoalkyl ether cyclodextrin,
wherein the sulfoalkyl ether cyclodextrin is a compound having the structure:
wherein each R is independently —H or —(CH 2 ) 4 SO 3 Na and the average degree of substitution with —(CH 2 ) 4 SO 3 Na groups is between 6 and 7.1;
wherein the molar ratio of the sulfoalkyl ether cyclodextrin to acetaminophen is in the range of about 0.05 to about 1.5,
wherein the concentration of acetaminophen is in the range of about 8 mg/ml to about 12 mg/ml; and
wherein the sulfoalkyl ether cyclodextrin has a concentration of about 50 mM to about 100 mM.
36 . The aqueous pharmaceutical formulation of claim 35 , further comprising a buffer.