INJECTABLE FORMULATION
Described herein are pharmaceutical formulations, methods for their production, and uses thereof. The pharmaceutical formulations comprise a salt of an optionally substituted dimethyltryptamine compound, a buffer, which is separate to the salt, and water. The formulations have pH values of from about 3.5 to about 6.5 and osmolalities of about 250 to about 350 mOsm/Kg. Such formulations are suitable for injection, being both stable and clinically acceptable, and have potential uses in the treatment of psychiatric or neurological disorders.
1 . An injectable pharmaceutical formulation, comprising:
a salt of a dimethyltryptamine compound, wherein the dimethyltryptamine compound is optionally substituted with one or more of deuterium, acetoxy, methoxy, or monohydrogen phosphate;
a buffer which is other than the salt; and
water,
wherein the formulation has a pH of about 3.5 to about 6.5 and an osmolality of about 250 to about 350 mOsm/Kg.
2 . The formulation of claim 1 , wherein the dimethyltryptamine compound is unsubstituted dimethyltryptamine.
3 . The formulation of claim 1 , wherein the dimethyltryptamine compound is substituted with deuterium.
4 . The formulation of claim 1 , wherein the dimethyltryptamine compound is substituted at position 4 or 5 with acetoxy or methoxy.
5 . The formulation of claim 1 , wherein the dimethyltryptamine compound is substituted at position 4 with monohydrogen phosphate.
6 . The formulation of claim 1 , wherein the salt comprises a Brønsted acid having a pKa of from about 3 to about 5, and a compound of Formula I:
wherein:
R 4 and R 5 are both H and each x H and each Y H is independently selected from H and D, or
one of R 4 and R 5 is H and the other is acetoxy or methoxy, each Y H is H and each x H is independently selected from H and D, or
the salt comprises a compound of Formula I wherein R 4 is monohydrogen phosphate, R 5 is H and each Y H and each x H is H.
7 . The formulation of claim 6 , wherein R 4 and R 5 are both H.
8 . The formulation of claim 6 , wherein R 4 is acetoxy and R 5 is H.
9 . The formulation of claim 6 , wherein R 4 is H and R 5 is methoxy.
10 . The formulation of claim 1 , wherein the salt formed by an acid selected from the group consisting of fumaric acid, tartaric acid, citric acid, acetic acid, lactic acid, and gluconic acid.
11 . The formulation of claim 1 , wherein the concentration of the optionally substituted dimethyltryptamine is about 2.5 mg/mL.
12 . The formulation of claim 1 , wherein the buffer comprises an acetate salt and acetic acid, sodium acetate and acetic acid, or potassium acetate and acetic acid.
13 . The formulation of claim 12 , wherein the buffer is present in a concentration of about 15 mM to about 75 mM.
14 . The formulation of claim 11 , further comprising a tonicity agent comprising sodium chloride.
15 . The formulation of claim 14 , wherein the formulation consists essentially of the salt, the buffer, water, and the tonicity agent.
16 . The formulation of claim 1 , wherein the formulation has an oxygen content of less than 2 ppm.
17 . A kit, comprising:
formulation of claim 6 , and
a container adapted to prevent penetration of ultraviolet light.
18 . A method of treating a psychiatric or neurological disorder in a patient, comprising:
administering to a patient in need thereof a formulation of claim 1 or a formulation of claim 6 .
19 . The method of claim 18 , wherein the psychiatric or neurological disorder is selected from the group consisting of (i) an obsessive compulsive disorder, (ii) a depressive disorder, (iii) an anxiety disorder, (iv) substance abuse, and (v) an avolition disorder.
20 . The method of claim 18 , wherein the formulation of claim 1 is a N,N-dimethyltryptamine fumarate salt.