WO2022256545A1

WO2022256545A1 - Injectable pregabalin formulations

Info

Publication number: WO2022256545A1
Application number: PCT/US2022/031982
Authority: WO
Inventors: Ronald DOMALAON; Jinjiang Li; Tushar HINGORANI; Kumaresh Soppimath
Original assignee: Nevakar Injectables Inc.
Priority date: 2021-06-04
Filing date: 2022-06-02
Publication date: 2022-12-08

Abstract

The present disclosure is directed to novel injectable pregabalin compositions and methods for treating pain.

Description

INJECTABLE PREGAB ALIN FORMULATIONS

FIELD AND BACKGROUND OF THE INVENTION

[0001] The present disclosure relates to injectable pharmaceutical compositions comprising pregabalin. In some aspects, the composition is suitable for parenteral administration. The present disclosure also relates to methods for treating pain in a subject in need thereof.

[0002] Anticonvulsant agents such as pregabalin have been used to treat pain in patients, but parenteral administration of an injectable pregabalin composition is challenging due to the instability of aqueous pregabalin solutions, which form decomposition products and adducts when stored over time.

[0003] Thus, there is a need to develop injectable pregabalin compositions that are stable over long periods of time and under various conditions.

BRIEF SUMMARY OF THE INVENTION

Pharmaceutical Compositions

[0004] The present disclosure provides pharmaceutically acceptable injectable compositions comprising pregabalin and pharmaceutically acceptable excipients.

[0005] In some aspects, the pharmaceutical composition comprises from about 0.01 to about 30 mg/mL pregabalin.

[0006] In some aspects, the pharmaceutical composition comprises from about 3 to about

6 mg/mL sodium chloride.

[0007] In some aspects, the pharmaceutical composition comprises from about 0.1 to about 2.5 mg/mL of a buffer.

[0008] In some aspects, the pharmaceutical composition comprises a pH-adjusting agent.

[0009] In some aspects, the pharmaceutical composition comprises an aqueous carrier.

[0010] In some aspects, the pharmaceutical composition has a pH of from about 5 to about 7.

[0011] In some aspects, the pharmaceutical composition does not contain acetaminophen.

[0012] In some aspects, the pharmaceutical composition comprises less than 0.5 wt % pregabalin citrate adduct. [0013] In some aspects, the pharmaceutical composition comprises about 0.01 mg/mL pregabalin.

[0014] In some aspects, the pharmaceutical composition comprises about 0.05 mg/mL pregabalin.

[0015] In some aspects, the pharmaceutical composition comprises about 0.1 mg/mL pregabalin.

[0016] In some aspects, the pharmaceutical composition comprises about 0.5 mg/mL pregabalin.

[0017] In some aspects, the pharmaceutical composition comprises about 1 mg/mL pregabalin.

[0018] In some aspects, the pharmaceutical composition comprises about 1.5 mg/mL pregabalin.

[0019] In some aspects, the pharmaceutical composition comprises about 5 mg/mL pregabalin.

[0020] In some aspects, the pharmaceutical composition comprises about 10 mg/mL pregabalin.

[0021] In some aspects, the pharmaceutical composition comprises about 15 mg/mL pregabalin.

[0022] In some aspects, the pharmaceutical composition comprises about 20 mg/mL pregabalin.

[0023] In some aspects, the pharmaceutical composition comprises about 25 mg/mL pregabalin.

[0024] In some aspects, the pharmaceutical composition comprises about 30 mg/mL pregabalin.

[0025] In some aspects, the pharmaceutical composition comprises about 3 mg/mL sodium chloride.

[0026] In some aspects, the pharmaceutical composition comprises about 4 mg/mL sodium chloride.

[0027] In some aspects, the pharmaceutical composition comprises about 5 mg/mL sodium chloride.

[0028] In some aspects, the pharmaceutical composition comprises about 6 mg/mL sodium chloride. [0029] In some aspects, the pharmaceutical composition comprises a buffer, wherein the buffer comprises an acid, a conjugate base of an acid, both the acid and the conjugate base of the acid, pharmaceutically acceptable derivatives thereof, or combinations thereof.

[0030] In some aspects, the pharmaceutical composition comprises an acid selected from the group consisting of citric acid, acetic acid, phosphoric acid, and combinations thereof.

[0031] In some aspects, the pharmaceutical composition comprises about 0.1 mg/mL buffer.

[0032] In some aspects, the pharmaceutical composition comprises about 0.5 mg/mL buffer.

[0033] In some aspects, the pharmaceutical composition comprises about 1 mg/mL buffer.

[0034] In some aspects, the pharmaceutical composition comprises about 1.5 mg/mL buffer.

[0035] In some aspects, the pharmaceutical composition comprises about 2 mg/mL buffer.

[0036] In some aspects, the pharmaceutical composition comprises about 2.5 mg/mL buffer.

[0037] In some aspects, the pharmaceutical composition comprises sodium hydroxide.

[0038] In some aspects, the pharmaceutical composition comprises hydrochloric acid.

[0039] In some aspects, the pharmaceutical composition has a pH of about 5.

[0040] In some aspects, the pharmaceutical composition has a pH of about 5.5.

[0041] In some aspects, the pharmaceutical composition has a pH of about 6.

[0042] In some aspects, the pharmaceutical composition has a pH of about 6.5.

[0043] In some aspects, the pharmaceutical composition has a pH of about 7.

[0044] In some aspects, the pharmaceutical composition comprises pregabalin, about 5 mg/mL sodium chloride, about 0.4 mg/mL buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

[0045] In some aspects, the pharmaceutical composition consists essentially of pregabalin, about 5 mg/mL sodium chloride, about 0.4 mg/mL buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

[0046] In some aspects, the pharmaceutical composition consists of pregabalin, about 5 mg/mL sodium chloride, about 0.4 mg/mL buffer, and an aqueous carrier, wherein the composition has a pH of about 6, and wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %.

[0047] In some aspects, the pharmaceutical composition comprises from about 0.01 to about 30 wt % pregabalin, from about 3 to about 6 wt % sodium chloride, from about 0.1 to about 2.5 wt % buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

[0048] In some aspects, the pharmaceutical composition consists essentially of from about 0.01 to about 30 wt % pregabalin, from about 3 to about 6 wt % sodium chloride, from about 0.1 to about 2.5 wt % buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

[0049] In some aspects, the pharmaceutical composition consists of from about 0.01 to about 30 wt % pregabalin, from about 3 to about 6 wt % sodium chloride, from about 0.1 to about 2.5 wt % buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, and wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %.

[0050] In some aspects, the pharmaceutical composition comprises about 0.01 wt % pregabalin.

[0051] In some aspects, the pharmaceutical composition comprises about 0.05 wt % pregabalin.

[0052] In some aspects, the pharmaceutical composition comprises about 0.1 wt % pregabalin.

[0053] In some aspects, the pharmaceutical composition comprises about 0.5 wt % pregabalin. [0054] In some aspects, the pharmaceutical composition comprises about 1 wt % pregabalin.

[0055] In some aspects, the pharmaceutical composition comprises about 1.5 wt % pregabalin.

[0056] In some aspects, the pharmaceutical composition comprises about 5 wt % pregabalin.

[0057] In some aspects, the pharmaceutical composition comprises about 10 wt % pregabalin.

[0058] In some aspects, the pharmaceutical composition comprises about 15 wt % pregabalin.

[0059] In some aspects, the pharmaceutical composition comprises about 20 wt % pregabalin.

[0060] In some aspects, the pharmaceutical composition comprises about 25 wt % pregabalin.

[0061] In some aspects, the pharmaceutical composition comprises about 30 wt % pregabalin.

[0062] In some aspects, the pharmaceutical composition comprises about 3 wt % sodium chloride.

[0063] In some aspects, the pharmaceutical composition comprises about 4 wt % sodium chloride.

[0064] In some aspects, the pharmaceutical composition comprises about 5 wt % sodium chloride.

[0065] In some aspects, the pharmaceutical composition comprises about 6 wt % sodium chloride.

[0066] In some aspects, the pharmaceutical composition comprises about 0.1 wt % buffer.

[0067] In some aspects, the pharmaceutical composition comprises about 0.5 wt % buffer.

[0068] In some aspects, the pharmaceutical composition comprises about 1 wt % buffer.

[0069] In some aspects, the pharmaceutical composition comprises about 1.5 wt % buffer.

[0070] In some aspects, the pharmaceutical composition comprises about 2 wt % buffer. [0071] In some aspects, the pharmaceutical composition comprises about 2.5 wt % buffer.

[0072] In some aspects, the pharmaceutical composition comprises pregabalin, about 5 wt

% sodium chloride, about 0.4 wt % buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

[0073] In some aspects, the pharmaceutical composition consists essentially of pregabalin, about 5 wt % sodium chloride, about 0.4 wt % buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

[0074] In some aspects, the pharmaceutical composition consists of pregabalin, about 5 wt % sodium chloride, about 0.4 wt % buffer, and an aqueous carrier, wherein the composition has a pH of about 6, and wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %.

[0075] In some aspects, the pharmaceutical composition comprises less than 5 wt % of a decomposition product of pregabalin.

[0076] In some aspects, the pharmaceutical composition comprises less than 5 wt % of 4-

(2-methylpropyl)pyrrolidin-2-one (MPP).

[0077] In some aspects, the pharmaceutical composition is packaged in a unit dosage form.

[0078] In some aspects, the pharmaceutical composition is packaged in a bag.

[0079] In some aspects, the pharmaceutical composition is packaged in a glass vial.

[0080] In some aspects, the pharmaceutical composition is packaged in a prefilled syringe.

[0081] In some aspects, the pharmaceutical composition is packaged in a polymer bag.

[0082] In some aspects, the pharmaceutical composition is packaged in a polypropylene polymer bag further packaged in an aluminum over-pouch.

[0083] In some aspects, the pharmaceutical composition is packaged in a polypropylene polymer bag further packaged in an aluminum over-pouch, wherein the aluminum over pouch contains an oxygen scavenger. [0084] In some aspects, the pharmaceutical composition has a volume of about 1 mL.

[0085] In some aspects, the pharmaceutical composition has a volume of about 10 mL.

[0086] In some aspects, the pharmaceutical composition has a volume of about 100 mL.

[0087] In some aspects, the pharmaceutical composition has a volume of about 1000 mL.

[0088] In some aspects, the pharmaceutical composition is stable after being stored for at least three months at 40 °C and 75% relative humidity.

[0089] In some aspects, the pharmaceutical composition comprises less than 5 wt % 4-(2- methylpropyl)pyrrolidin-2-one (MPP) after storage for at least three months at 40 °C and 75% relative humidity.

[0090] In some aspects, the pharmaceutical composition has a pH of about 6 after storage for at least three months at 40 °C and 75% relative humidity.

Methods of Treatment

[0091] The present disclosure also provides methods of treating pain in a subject, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising pregabalin and pharmaceutically acceptable excipients.

[0092] In some aspects, the pharmaceutical composition comprises about from about 10 to about 30 mg/mL pregabalin.

[0093] In some aspects, the pharmaceutical composition comprises about from about 3 to about 6 mg/mL sodium chloride.

[0094] In some aspects, the pharmaceutical composition comprises about from about 0.1 to about 2.5 mg/mL buffer.

[0095] In some aspects, the pharmaceutical composition comprises a pH-adjusting agent.

[0096] In some aspects, the liquid unit dosage has a pH of from about 5 to about 7.

[0097] In some aspects, the pharmaceutical composition does not contain acetaminophen.

[0098] In some aspects, the pharmaceutical composition comprises less than 0.5 wt % pregabalin citrate adduct.

[0099] In some aspects, the pharmaceutical composition comprises about 0.01 mg/mL pregabalin.

[0100] In some aspects, the pharmaceutical composition comprises about 0.05 mg/mL pregabalin. [0101] In some aspects, the pharmaceutical composition comprises about 0.1 mg/mL pregabalin.

[0102] In some aspects, the pharmaceutical composition comprises about 0.5 mg/mL pregabalin.

[0103] In some aspects, the pharmaceutical composition comprises about 1 mg/mL pregabalin.

[0104] In some aspects, the pharmaceutical composition comprises about 1.5 mg/mL pregabalin.

[0105] In some aspects, the pharmaceutical composition comprises about 5 mg/mL pregabalin.

[0106] In some aspects, the pharmaceutical composition comprises about 10 mg/mL pregabalin.

[0107] In some aspects, the pharmaceutical composition comprises about 15 mg/mL pregabalin.

[0108] In some aspects, the pharmaceutical composition comprises about 20 mg/mL pregabalin.

[0109] In some aspects, the pharmaceutical composition comprises about 25 mg/mL pregabalin.

[0110] In some aspects, the pharmaceutical composition comprises about 30 mg/mL pregabalin.

[0111] In some aspects, the pharmaceutical composition comprises about 3 mg/mL sodium chloride.

[0112] In some aspects, the pharmaceutical composition comprises about 4 mg/mL sodium chloride.

[0113] In some aspects, the pharmaceutical composition comprises about 5 mg/mL sodium chloride.

[0114] In some aspects, the pharmaceutical composition comprises about 6 mg/mL sodium chloride.

[0115] In some aspects, the pharmaceutical composition comprises a buffer, wherein the buffer comprises an acid, a conjugate base of an acid, both the acid and the conjugate base of the acid, pharmaceutically acceptable derivatives thereof, or combinations thereof. [0116] In some aspects, the pharmaceutical composition comprises an acid selected from the group consisting of citric acid, acetic acid, phosphoric acid, and combinations thereof.

[0117] In some aspects, the pharmaceutical composition comprises about 0.1 mg/mL buffer.

[0118] In some aspects, the pharmaceutical composition comprises about 0.5 mg/mL buffer.

[0119] In some aspects, the pharmaceutical composition comprises about 1 mg/mL buffer.

[0120] In some aspects, the pharmaceutical composition comprises about 1.5 mg/mL buffer.

[0121] In some aspects, the pharmaceutical composition comprises about 2 mg/mL buffer.

[0122] In some aspects, the pharmaceutical composition comprises about 2.5 mg/mL buffer.

[0123] In some aspects, the pharmaceutical composition comprises sodium hydroxide.

[0124] In some aspects, the pharmaceutical composition comprises hydrochloric acid.

[0125] In some aspects, the pharmaceutical composition has a pH of about 5.

[0126] In some aspects, the pharmaceutical composition has a pH of about 5.5.

[0127] In some aspects, the pharmaceutical composition has a pH of about 6.

[0128] In some aspects, the pharmaceutical composition has a pH of about 6.5.

[0129] In some aspects, the pharmaceutical composition has a pH of about 7.

[0130] In some aspects, the pharmaceutical composition can be a liquid unit dosage form.

[0131] In some aspects, the pharmaceutical composition comprises pregabalin, about 5 mg/mL sodium chloride, about 0.4 mg/mL buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

[0132] In some aspects, the pharmaceutical composition comprises less than 5 wt % of a decomposition product of pregabalin.

[0133] In some aspects, the pharmaceutical composition comprises less than 5 wt % 4-(2- methylpropyl)pyrrolidin-2-one (MPP). [0134] In some aspects, the pharmaceutical composition is administered to the subject within 24 hours prior to the subject undergoing a surgical procedure.

[0135] In some aspects, the pharmaceutical composition is administered to the subject simultaneously with the subject undergoing a surgical procedure.

[0136] In some aspects, the pharmaceutical composition is administered to the subject within 24 hours after the subject has undergone a surgical procedure.

[0137] In some aspects, the administering is parenteral.

[0138] In some aspects, the administering is intravenous .

[0139] In some aspects, the administering is intramuscular .

[0140] In some aspects, the administering is subcutaneous .

[0141] In some aspects, the administering is performed via injection.

[0142] In some aspects, the pharmaceutical composition is administered in combination with a second active agent.

[0143] In some aspects, the pharmaceutical composition is stable after storage for at least three months at 40 °C and 75% relative humidity.

[0144] In some aspects, the pharmaceutical composition comprises less than 5 wt % 4-(2- methylpropyl)pyrrolidin-2-one (MPP) after storage for at least three months at 40 °C and 75% relative humidity.

[0145] In some aspects, the pharmaceutical composition comprises less than 0.5 wt % pregabalin citrate adduct after storage for at least three months at 40 °C and 75% relative humidity.

[0146] In some aspects, the pharmaceutical composition has a pH of about 6 after storage for at least three months at 40 °C and 75% relative humidity.

[0147] In some aspects, the pain is selected from the group consisting of angina pain, bone injury pain, central pain, chronic lower back pain, cluster headaches, dental pain, genitourinary tract-related pain including cystitis and nociceptive pain, herpes neuralgia, migraine, neuropathic pain, pain during labor and delivery, pain resulting from bums, phantom limb pain, postoperative pain, postpartum pain, surgical pain, visceral pain, and combinations thereof. DETAILED DESCRIPTION OF THE INVENTION

Definitions

[0148] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present application including the definitions will control. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. All publications, patents and other references mentioned herein are incorporated by reference in their entireties for all purposes as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

[0149] Although methods and materials similar or equivalent to those described herein can be used in practice or testing of the present disclosure, suitable methods and materials are described below. The materials, methods and examples are illustrative only and are not intended to be limiting. Other features and advantages of the disclosure will be apparent from the detailed description and from the claims.

[0150] In order to further define this disclosure, the following terms and definitions are provided.

[0151] The singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. The terms "a" (or "an"), as well as the terms "one or more," and "at least one" can be used interchangeably herein. In certain aspects, the term "a" or "an" means "single." In other aspects, the term "a" or "an" includes "two or more" or "multiple."

[0152] The term "about" is used herein to mean approximately, roughly, around, or in the regions of. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" is used herein to modify a numerical value above and below the stated value by a variance of 10 percent, up or down (higher or lower).

[0153] The term "and/or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term "and/or" as used in a phrase such as "A and/or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and/or" as used in a phrase such as "A, B, and/or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0154] The term "pharmaceutically acceptable" as used herein refers to those compounds, materials, compositions, formulations, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

[0155] The term "excipient" refers to any substance, not itself a therapeutic agent, which may be used in a composition for delivery of an active therapeutic agent to a subject or combined with an active therapeutic agent (e.g., to create a pharmaceutical composition) to improve its handling or storage properties or to permit or facilitate formation of a dose unit of the composition. The excipient can be an inert substance, an inactive substance, and/or a not medicinally active substance.

[0156] The terms "effective amount" or "pharmaceutically effective amount" or

"therapeutically effective amount" as used herein refer to the amount or quantity of a drug or pharmaceutically active substance which is sufficient to elicit the required or desired therapeutic response, or in other words, the amount which is sufficient to elicit an appreciable biological response when administered to a patient.

[0157] "Administration", or "to administer" means the step of giving (i.e. providing) a pharmaceutical composition to a subject. The pharmaceutical compositions disclosed herein can be "locally administered", that is administered at or in the vicinity of the site at which a therapeutic result or outcome is desired. For example to treat an ocular condition such as corneal pain, topical administration, directly to the eye of a subject, of an ophthalmic formulation can be carried out, and is an example of local administration.

[0158] The term "pharmaceutically acceptable salts" is art-recognized, and includes relatively non-toxic, inorganic and organic acid addition salts of compounds and relatively non-toxic, inorganic and organic base addition salts of compounds.

[0159] The term "unit dosage form" or "unit dose composition" as used herein refers to a quantity of a compound, such as a drop or a droplet, said quantity being such that one or more predetermined units may be provided as a single therapeutic administration.

[0160] As used herein, "treat," "treatment", and "treating" refer to the reduction or amelioration of the progression, severity, and/or duration of a given disease resulting from the administration of one or more therapies (including, but not limited to, the administration of an ophthalmic formulation). In certain aspects, the terms refer to the reduction of pain associated with one or more diseases or conditions.

[0161] The term "wt %" or "weight/volume" as used herein refers to the ratio between two components with respect to volume. For example, a 5 wt % ethanol in water solution would represent a solution comprising 5 g ethanol for every 100 mL water.

[0162] The term "mg/mL" as used herein refers to the ratio between a solute, generally an active pharmaceutical ingredient or excipient, and a solvent, generally but not necessarily water. For example, a 50 mg/mL sodium chloride aqueous solution would represent a solution comprising 50 mg sodium chloride for every 1 mL water.

[0163] The term "stable" is used herein to describe a composition in which most or all of the active pharmaceutical ingredient does not degrade or transform over a specific time period and under specific conditions.

Pharmaceutical Compositions

[0164] Pharmaceutical compositions of this disclosure include an effective amount of a pregabalin or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients formulated for parenteral administration. In some aspects, the pharmaceutical compositions and methods are useful in the treatment of pain. In some aspects, the pharmaceutical composition comprises from about 10 to about 30 mg/mL pregabalin and one or more pharmaceutically acceptable excipients. In some aspects, the pharmaceutical composition comprises from about 3 to about 6 mg/mL sodium chloride, from about 0.1 to about 2.5 mg/mL buffer, a pH adjusting agent, and an aqueous carrier.

[0165] In some aspects, the pharmaceutical composition does not contain a non-opioid analgesic. In some aspects, the pharmaceutical composition does not contain acetaminophen.

[0166] In other aspects, composition comprises less than 0.5 wt % pregabalin citrate adduct.

[0167] In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of from about 0.01 to about 30 mg/mL. In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of from about 10 to about 12.5 mg/mL, from about 10 to about 15 mg/mL, from about 10 to about 17.5 mg/mL, from about 10 to about 20 mg/mL, from about 10 to about 22.5 mg/mL, from about 10 to about 25 mg/mL, from about 10 to about 27.5 mg/mL, from about 10 to about 30 mg/mL, from about 12.5 to about 15 mg/mL, from about 12.5 to about 17.5 mg/mL, from about 12.5 to about 20 mg/mL, from about 12.5 to about 22.5 mg/mL, from about 12.5 to about 25 mg/mL, from about 12.5 to about 27.5 mg/mL, from about 12.5 to about 30 mg/mL, from about 15 to about 17.5 mg/mL, from about 15 to about 20 mg/mL, from about 15 to about 22.5 mg/mL, from about 15 to about 25 mg/mL, from about 15 to about 27.5 mg/mL, from about 15 to about 30 mg/mL, from about 17.5 to about 20 mg/mL, from about 17.5 to about 22.5 mg/mL, from about 17.5 to about 25 mg/mL, from about 17.5 to about 27.5 mg/mL, from about 17.5 to about 30 mg/mL, from about 20 to about 22.5 mg/mL, from about 20 to about 25 mg/mL, from about 20 to about 27.5 mg/mL, from about 20 to about 30 mg/mL, from about 22.5 to about 25 mg/mL, from about 22.5 to about 27.5 mg/mL, from about 22.5 to about 30 mg/mL, from about 25 to about 27.5 mg/mL, from about 25 to about 30 mg/mL, or from about 27.5 to about 30 mg/mL.

[0168] In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of from about 0.01 to about 0.05 mg/mL, from about 0.01 to about 0.1 mg/mL, from about 0.01 to about 0.5 mg/mL, from about 0.01 to about 1 mg/mL, from about 0.01 to about 1.5 mg/mL, from about 0.01 to about 5 mg/mL, from about 0.01 to about 10 mg/mL, from about 0.05 to about 0.1 mg/mL, from about 0.05 to about 0.5 mg/mL, from about 0.05 to about 1 mg/mL, from about 0.05 to about 1.5 mg/mL, from about 0.05 to about 5 mg/mL, from about 0.05 to about 10 mg/mL, from about 0.1 to about 0.5 mg/mL, from about 0.1 to about 1 mg/mL, from about 0.1 to about 1.5 mg/mL, from about 0.1 to about 5 mg/mL, from about 0.1 to about 10 mg/mL, from about 0.5 to about 1 mg/mL, from about 0.5 to about 1.5 mg/mL, from about 0.5 to about 5 mg/mL, from about 0.5 to about 10 mg/mL, from about 1 to about 1.5 mg/mL, from about 1 to about 5 mg/mL, from about 1 to about 10 mg/mL, from about 1.5 to about 5 mg/mL, from about 1.5 to about 10 mg/mL, or from about 5 to about 10 mg/mL.

[0169] In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of about 20 mg/mL. In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of about 10 mg/mL, about 12.5 mg/mL, about 15 mg/mL, about 17.5 mg/mL, about 22.5 mg/mL, about 25 mg/mL, about 27.5 mg/mL, or about 30 mg/mL. In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of about 0.01 mg/mL, about 0.05 mg/mL, about 0.1 mg/mL, about 0.5 mg/mL, about 1 mg/mL, about 1.5 mg/mL, or about 5 mg/mL.

[0170] In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of from about 0.01 to about 30 wt %. In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of from about 10 to about

12.5 wt %, from about 10 to about 15 wt %, from about 10 to about 17.5 wt %, from about 10 to about 20 wt %, from about 10 to about 22.5 wt %, from about 10 to about 25 wt %, from about 10 to about 27.5 wt %, from about 10 to about 30 wt %, from about

12.5 to about 15 wt %, from about 12.5 to about 17.5 wt %, from about 12.5 to about 20 wt %, from about 12.5 to about 22.5 wt %, from about 12.5 to about 25 wt %, from about

12.5 to about 27.5 wt %, from about 12.5 to about 30 wt %, from about 15 to about 17.5 wt %, from about 15 to about 20 wt %, from about 15 to about 22.5 wt %, from about 15 to about 25 wt %, from about 15 to about 27.5 wt %, from about 15 to about 30 wt %, from about 17.5 to about 20 wt %, from about 17.5 to about 22.5 wt %, from about 17.5 to about 25 wt %, from about 17.5 to about 27.5 wt %, from about 17.5 to about 30 wt %, from about 20 to about 22.5 wt %, from about 20 to about 25 wt %, from about 20 to about 27.5 wt %, from about 20 to about 30 wt %, from about 22.5 to about 25 wt %, from about 22.5 to about 27.5 wt %, from about 22.5 to about 30 wt %, from about 25 to about 27.5 wt %, from about 25 to about 30 wt %, or from about 27.5 to about 30 wt %.

[0171] In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of from about 0.01 to about 0.05 wt %, from about 0.01 to about 0.1 wt %, from about 0.01 to about 0.5 wt %, from about 0.01 to about 1 wt %, from about 0.01 to about 1.5 wt %, from about 0.01 to about 5 wt %, from about 0.01 to about 10 wt %, from about 0.05 to about 0.1 wt %, from about 0.05 to about 0.5 wt %, from about 0.05 to about 1 wt %, from about 0.05 to about 1.5 wt %, from about 0.05 to about 5 wt %, from about 0.05 to about 10 wt %, from about 0.1 to about 0.5 wt %, from about 0.1 to about 1 wt %, from about 0.1 to about 1.5 wt %, from about 0.1 to about 5 wt %, from about 0.1 to about 10 wt %, from about 0.5 to about 1 wt %, from about 0.5 to about 1.5 wt %, from about 0.5 to about 5 wt %, from about 0.5 to about 10 wt %, from about 1 to about 1.5 wt %, from about 1 to about 5 wt %, from about 1 to about 10 wt %, from about 1.5 to about 5 wt %, from about 1.5 to about 10 wt %, or from about 5 to about 10 wt %. [0172] In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of about 20 wt %. In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of about 10 wt %, about 12.5 wt %, about 15 wt %, about 17.5 wt %, about 22.5 wt %, about 25 wt %, about 27.5 wt %, or about 30 wt %. In some aspects, the pharmaceutical composition comprises pregabalin present at a concentration of about 0.01 wt %, about 0.05 wt %, about 0.1 wt %, about 0.5 wt %, about 1 wt %, about 1.5 wt %, or about 5 wt %.

[0173] In some aspects, the aqueous carrier is water. In some aspects, the aqueous carrier is water and one or more pharmaceutically acceptable excipients.

[0174] In some aspects, the pharmaceutical composition comprises one or more pharmaceutically acceptable excipients. In some aspects, the excipient is a preservative, a buffer, a penetration enhancer, a viscosity agent, a tonicity regulator, a chelating agent, a polymer, a lipid, or a combination of excipients thereof. The excipient can serve various purposes. A person skilled in the art can select one or more excipients with respect to the particular desired properties by routine experimentation and without any undue burden. The amount of each excipient used can vary within ranges conventional in the art. Techniques and excipients which can be used to formulate dosage forms are described in Handbook of Pharmaceutical Excipients, 6th edition, Rowe et ah, Eds., American Pharmaceuticals Association and the Pharmaceutical Press, publications department of the Royal Pharmaceutical Society of Great Britain (2009); and Remington: the Science and Practice of Pharmacy, 21th edition, Gennaro, Ed., Lippincott Williams & Wilkins (2005).

[0175] In some aspects, the pharmaceutical composition comprises at least one tonicity regulator in an amount effective to control the tonicity or osmolarity of the composition. Non-limiting examples of tonicity regulators include salts, particularly sodium chloride, potassium chloride, glycerin, mannitol, dextrose, and other sugar alcohols, and other suitable pharmaceutically acceptable tonicity regulators and mixtures thereof. In some aspects, the pharmaceutical composition comprises sodium chloride.

[0176] In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of from about 3 to about 6 mg/mL. In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of from about 3 to about 3.5 mg/mL, from about 3 to about 4 mg/mL, from about 3 to about 4.5 mg/mL, from about 3 to about 5 mg/mL, from about 3 to about 5.5 mg/mL, from about

3.5 to about 4 mg/mL, from about 3.5 to about 4.5 mg/mL, from about 3.5 to about 5 mg/mL, from about 3.5 to about 5.5 mg/mL, from about 3.5 to about 6 mg/mL, from about 4 to about 4.5 mg/mL, from about 4 to about 5 mg/mL, from about 4 to about 5.5 mg/mL, from about 4 to about 6 mg/mL, from about 4.5 to about 5 mg/mL, from about

4.5 to about 5.5 mg/mL, from about 4.5 to about 6 mg/mL, from about 5 to about 5.5 mg/mL, from about 5 to about 6 mg/mL, or from about 5.5 to about 6 mg/mL.

[0177] In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of about 5 mg/mL. In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of about 3 mg/mL, about 3.5 mg/mL, about 4 mg/mL, about 4.5 mg/mL, about 5.5 mg/mL, or about 6 mg/mL.

[0178] In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of from about 3 to about 6 wt %. In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of from about 3 to about 3.5 wt %, from about 3 to about 4 wt %, from about 3 to about 4.5 wt %, from about 3 to about 5 wt %, from about 3 to about 5.5 wt %, from about 3.5 to about 4 wt %, from about 3.5 to about 4.5 wt %, from about 3.5 to about 5 wt %, from about 3.5 to about 5.5 wt %, from about 3.5 to about 6 wt %, from about 4 to about 4.5 wt %, from about 4 to about 5 wt %, from about 4 to about 5.5 wt %, from about 4 to about 6 wt %, from about 4.5 to about 5 wt %, from about 4.5 to about 5.5 wt %, from about 4.5 to about 6 wt %, from about 5 to about 5.5 wt %, from about 5 to about 6 wt %, or from about 5.5 to about 6 wt %.

[0179] In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of about 5 wt %. In some aspects, the pharmaceutical composition comprises sodium chloride present at a concentration of about 3 wt %, about

3.5 wt %, about 4 wt %, about 4.5 wt %, about 5.5 wt %, or about 6 wt %.

[0180] In some aspects, the pharmaceutical composition has an osmolarity of from about

260 to about 365 mOsm/L. In some aspects, the pharmaceutical composition has an osmolarity of from about 285 mOsm/L to about 295 mOsm/L, from about 285 mOsm/L to about 305 mOsm/L, from about 285 mOsm/L to about 315 mOsm/L, from about 285 mOsm/L to about 325 mOsm/L, from about 285 mOsm/L to about 335 mOsm/L, from about 285 mOsm/L to about 345 mOsm/L, from about 285 mOsm/L to about 355 mOsm/L, from about 285 mOsm/L to about 365 mOsm/L, from about 295 mOsm/L to about 305 mOsm/L, from about 295 mOsm/L to about 315 mOsm/L, from about 295 mOsm/L to about 325 mOsm/L, from about 295 mOsm/L to about 335 mOsm/L, from about 295 mOsm/L to about 345 mOsm/L, from about 295 mOsm/L to about 355 mOsm/L, from about 295 mOsm/L to about 365 mOsm/L, from about 305 mOsm/L to about 315 mOsm/L, from about 305 mOsm/L to about 325 mOsm/L, from about 305 mOsm/L to about 335 mOsm/L, from about 305 mOsm/L to about 345 mOsm/L, from about 305 mOsm/L to about 355 mOsm/L, from about 305 mOsm/L to about 365 mOsm/L, from about 315 mOsm/L to about 325 mOsm/L, from about 315 mOsm/L to about 335 mOsm/L, from about 315 mOsm/L to about 345 mOsm/L, from about 315 mOsm/L to about 355 mOsm/L, from about 315 mOsm/L to about 365 mOsm/L, from about 325 mOsm/L to about 335 mOsm/L, from about 325 mOsm/L to about 345 mOsm/L, from about 325 mOsm/L to about 355 mOsm/L, from about 325 mOsm/L to about 365 mOsm/L, from about 335 mOsm/L to about 345 mOsm/L, from about 335 mOsm/L to about 355 mOsm/L, from about 335 mOsm/L to about 365 mOsm/L, from about 345 mOsm/L to about 355 mOsm/L, from about 345 mOsm/L to about 365 mOsm/L, from about 355 mOsm/L to about 365 mOsm/L, from about 260 mOsm/L to about 265 mOsm/L, from about 260 mOsm/L to about 275 mOsm/L, from about 260 mOsm/L to about 285 mOsm/L, from about 260 mOsm/L to about 295 mOsm/L, from about 260 mOsm/L to about 305 mOsm/L, from about 260 mOsm/L to about 315 mOsm/L, from about 260 mOsm/L to about 325 mOsm/L, from about 260 mOsm/L to about 335 mOsm/L, from about 260 mOsm/L to about 345 mOsm/L, from about 260 mOsm/L to about 355 mOsm/L, from about 260 mOsm/L to about 365 mOsm/L, from about 265 mOsm/L to about 275 mOsm/L, from about 265 mOsm/L to about 285 mOsm/L, from about 265 mOsm/L to about 295 mOsm/L, from about 265 mOsm/L to about 305 mOsm/L, from about 265 mOsm/L to about 315 mOsm/L, from about 265 mOsm/L to about 325 mOsm/L, from about 265 mOsm/L to about 335 mOsm/L, from about 265 mOsm/L to about 345 mOsm/L, from about 265 mOsm/L to about 355 mOsm/L, from about 265 mOsm/L to about 365 mOsm/L, from about 275 mOsm/L to about 285 mOsm/L, from about 275 mOsm/L to about 295 mOsm/L, from about 275 mOsm/L to about 305 mOsm/L, from about 275 mOsm/L to about 315 mOsm/L, from about 275 mOsm/L to about 325 mOsm/L, from about 275 mOsm/L to about 335 mOsm/L, from about 275 mOsm/L to about 345 mOsm/L, from about 275 mOsm/L to about 355 mOsm/L, from about 275 mOsm/L to about 365 mOsm/L.

[0181] In some aspects, the pharmaceutical composition has an osmolarity of about 260 mOsm/L, about 265 mOsm/L, about 275 mOsm/L, about 285 mOsm/L, about 295 mOsm/L, about 305 mOsm/L, about 315 mOsm/L, about 325 mOsm/L, about 335 mOsm/L, about 345 mOsm/L, about 355 mOsm/L, or about 365 mOsm/L

[0182] In some aspects, the pharmaceutical composition is isotonic. In some aspects, the pharmaceutical composition is hypotonic. In some aspects, the pharmaceutical composition is hypertonic.

[0183] In some aspects, the pharmaceutical composition comprises one or more buffers in an amount effective to control and/or maintain the pH of the composition. The buffer may comprise an acid, a conjugate base of an acid, both the acid and the conjugate base of the acid, or pharmaceutically acceptable derivatives thereof. In some aspects, the acid is citric acid, acetic acid, or phosphoric acid. Non-limiting examples of buffers include citrate buffers, acetate buffers, phosphate buffers, borate buffers, borate-polyol buffers, carbonate buffers, organic buffers, amino acid buffers, TRIS buffers, and combinations thereof. The amount of buffer employed preferably is sufficient to maintain the pH of the composition in a range of from about 5 to about 5.5, from about 5 to about 6, from about 5 to about 6.5, from about 5 to about 7, from about 5.5 to about 6, from about 5.5 to about 6.5, from about 5.5 to about 7, from about 6 to about 6.5, from about 6 to about 7, or from about 6.5 to about 7.

[0184] In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of from about 0.1 to about 2.5 mg/mL. In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of from about 0.1 to about 0.5 mg/mL, from about 0.1 to about 1 mg/mL, from about 0.1 to about

1.5 mg/mL, from about 0.1 to about 2 mg/mL, from about 0.5 to about 1 mg/mL, from about 0.5 to about 1.5 mg/mL, from about 0.5 to about 2 mg/mL, from about 0.5 to about

2.5 mg/mL, from about 1 to about 1.5 mg/mL, from about 1.5 to about 2 mg/mL, from about 2 to about 2.5 mg/mL, from about 1.5 to about 2 mg/mL, from about 1.5 to about

2.5 mg/mL, or from about 2 to about 2.5 mg/mL. [0185] In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of about 0.4 mg/mL. In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of about 0.1 mg/mL, about 0.5 mg/mL, about 1 mg/mL, about 1.5 mg/mL, about 2 mg/mL, or about 2.5 mg/mL.

[0186] In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of from about 0.1 to about 2.5 wt %. In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of from about 0.1 to about 0.5 wt %, from about 0.1 to about 1 wt %, from about 0.1 to about 1.5 wt %, from about 0.1 to about 2 wt %, from about 0.5 to about 1 wt %, from about 0.5 to about 1.5 wt %, from about 0.5 to about 2 wt %, from about 0.5 to about 2.5 wt %, from about 1 to about 1.5 wt %, from about 1.5 to about 2 wt %, from about 2 to about 2.5 wt %, from about 1.5 to about 2 wt %, from about 1.5 to about 2.5 wt %, or from about 2 to about 2.5 wt %.

[0187] In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of about 0.4 wt %. In some aspects, the pharmaceutical composition comprises a citrate buffer present at a concentration of about 0.1 wt %, about 0.5 wt %, about 1 wt %, about 1.5 wt %, about 2 wt %, or about 2.5 wt %.

[0188] In some aspects, the pharmaceutical composition has a pH of from about 5 to about 7. In some aspects, the pharmaceutical composition has a pH of from about 5 to about 5.5, from about 5 to about 6, from about 5 to about 6.5, from about 5.5 to about 6, from about 5.5 to about 6.5, from about 5.5 to about 7, from about 6 to about 6.5, from about 6 to about 7, or from about 6.5 to about 7.

[0189] In some aspects, the pharmaceutical composition has a pH of about 6. In some aspects, the pharmaceutical composition has a pH of about 5, about 5.5, about 6, about 6.5, or about 7.

[0190] In some aspects, the pharmaceutical composition comprises one or more pH- adjusting agents. A pH-adjusting agent can be any pharmaceutically acceptable agent that can alter the pH of the composition. Non-limiting examples of pH-adjusting agents include hydrochloric acid and sodium hydroxide.

[0191] In some aspects, the pharmaceutical composition comprises pregabalin citrate adduct. Pregabalin citrate adduct is formed when pregabalin undergoes a Maillard reaction with citrate. In some aspects, the pharmaceutical composition comprises less than 0.5 wt % pregabalin citrate adduct. In some aspects, the pharmaceutical composition comprises less than 0.4 wt %, less than 0.3 wt %, less than 0.2 wt %, or less than 0.1 wt % pregabalin citrate adduct. In some aspects, the pharmaceutical composition comprises less than 0.5 wt % pregabalin citrate adduct after being stored for at least three months at 40 °C and 75% relative humidity.

[0192] In some aspects, the pharmaceutical composition comprises a decomposition product of pregabalin. In some aspects, the decomposition product is 4-(2- methylpropyl)pyrrolidin-2-one (MPP). In some aspects, the pharmaceutical composition comprises less than 5 wt % of a pregabalin decomposition product. In some aspects, the pharmaceutical composition comprises less than 4 wt %, less than 3 wt %, less than 2 wt %, or less than 1 wt % of a pregabalin decomposition product. In some aspects, the pharmaceutical composition comprises less than 5 wt % of a decomposition product after being stored for at least three months at 40 °C and 75% relative humidity.

[0193] In some aspects, the pharmaceutical composition is packaged in a unit dosage form. Non-limiting examples of unit dosage forms include bags, polymer bags, polypropylene or polyvinyl chloride polymer bags, glass vials, and prefilled syringes. In some aspects, a bag may be further packaged in an aluminum over-pouch. In some aspects, the aluminum over-pouch comprises an oxygen scavenger.

[0194] In some aspects, the volume of the pharmaceutical composition packaged in a unit dosage form is about 1 mL, about 10 mL, about 100 mL, or about 1000 mL. In some aspects, the volume is from about 0.5 to about 1.5 mL, from about 5 to about 15 mL, or from about 500 to about 1500 mL.

[0195] In some aspects, the pharmaceutical composition is stable after being stored for at least three months at 40 °C and 75% relative humidity. In some aspects, the pharmaceutical composition is stable after being stored for at least three months at 25 °C and 60% relative humidity. In some aspects, the pharmaceutical composition is stable after being stored for at least three months at 4 °C. In some aspects, the pH remains constant after being stored for at least three months at 40 °C and 75% relative humidity.

[0196] In some aspects, the pharmaceutical composition comprises an alcohol as an excipient. Non-limiting examples of alcohols include ethanol, propylene glycol, glycerol, polyethylene glycol, chlorobutanol, isopropanol, xylitol, sorbitol, maltitol, erythritol, threitol, arabitol, ribitol, mannitol, galactilol, fucitol, lactitol, or any combination thereof.

[0197] In some aspects, the pharmaceutical composition comprises polyethylene glycol

(PEG) as an excipient. PEGs with molecular weights ranging from about 300 g/mol to about 10,000,000 g/mol can be used. Non-limiting examples of PEGs include PEG 200, PEG 300, PEG 400, PEG 540, PEG 550, PEG 600, PEG 1000, PEG 1450, PEG 1500, PEG 2000, PEG 3000, PEG 3350, PEG 4000, PEG 4600, PEG 6000, PEG 8000, PEG 10,000, and PEG 20,000.

[0198] Further excipients that can be used in a pharmaceutical composition described herein include, for example, benzalkonium chloride, benzethonium chloride, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorobutanol, dehydroacetic acid, ethylenediamine, ethyl vanillin, glycerin, hypophosphorous acid, phenol, phenylethyl alcohol, phenylmercuric nitrate, potassium benzoate, potassium metabi sulfite, potassium sorbate, sodium bisulfite, sodium metabi sulfite, sorbic acid, thimerasol, acetic acid, aluminum monostearate, boric acid, calcium hydroxide, calcium stearate, calcium sulfate, calcium tetrachloride, cellulose acetate pthalate, microcrystalline celluose, chloroform, citric acid, edetic acid, and ethylcellulose.

[0199] In some aspects, the pharmaceutical composition provided herein comprises an aprotic solvent as an excipient. Non-limiting examples of aprotic solvents include perfluorohexane, a,a,a-trifluorotoluene, pentane, hexane, cyclohexane, methylcyclohexane, decalin, dioxane, carbon tetrachloride, freon-11, benzene, toluene, carbon disulfide, diisopropyl ether, diethyl ether, t-butyl methyl ether, ethyl acetate, 1,2- dimethoxyethane, 2-methoxyethyl ether, tetrahydrofuran, methylene chloride, pyridine, 2- butanone, acetone, N-methylpyrrolidinone, nitromethane, dimethylformamide, acetonitrile, sulfolane, dimethyl sulfoxide, and propylene carbonate.

[0200] In some aspects, the pharmaceutical composition is a liquid formulation. In some aspects, the pharmaceutical composition is formulated for parenteral administration. In some aspects, the pharmaceutical composition is formulated for intravenous administration. In some aspects, the pharmaceutical composition is formulated for intramuscular administration. In some aspects, the pharmaceutical composition is formulated for subcutaneous administration. In some aspects, the pharmaceutical composition is formulated to comprise a single dose. In some aspects, the pharmaceutical composition is formulated to comprise multiple doses.

Methods of Treatment

[0201] The present disclosure also provides a method for treating pain in a subject in need thereof, the method comprising administration to the subject a therapeutically effective amount of a pharmaceutical composition comprising from about 10 to about 30 mg/mL pregabalin, from about 3 to about 6 mg/mL sodium chloride, from about 0.1 to about 2.5 mg/mL of a buffer, a pH-adjusting agent, and an aqueous carrier. In some aspects, the pharmaceutical composition has a pH of from about 5 to about 7. In some aspects, the pharmaceutical composition does not contain acetaminophen. In some aspects, the amount of pregabalin citrate adduct present in the pharmaceutical composition is less than 0.5 wt %.

[0202] In some aspects, the pharmaceutical composition comprises about 20 mg/mL pregabalin, about 4 mg/mL sodium chloride, about 0.4 mg/mL buffer, a pH adjusting agent, and an aqueous carrier. In some aspects, the pharmaceutical composition has a pH of about 6. In some aspects, the pharmaceutical composition does not contain acetaminophen. In some aspects, the amount of pregabalin citrate adduct present in the pharmaceutical composition is less than 0.5 wt %.

[0203] In some aspects, the pharmaceutical composition is administered to the subject within about 24 hours prior to the subject undergoing a surgical procedure. In some aspects, the pharmaceutical composition is administered to the subject within about 48 hours, about 36 hours, about 16 hours, or about 8 hours prior to the subject undergoing a surgical procedure.

[0204] In some aspects, the pharmaceutical composition is administered to the subject simultaneously with the subject undergoing a surgical procedure.

[0205] In some aspects, the pharmaceutical composition is administered to the subject within about 24 hours after the subject has undergone a surgical procedure. In some aspects, the pharmaceutical composition is administered to the subject within about 8 hours, about 16 hours, about 36 hours, or about 48 hours after the subject has undergone a surgical procedure.

[0206] In some aspects, the pharmaceutical composition is administered via parenteral administration. In some aspects, the pharmaceutical composition is administered via injection. In some aspects, the pharmaceutical composition is administered via intravenous administration. In some aspects, the pharmaceutical composition is administered via intravenous injection. In some aspects, the pharmaceutical composition is administered via intramuscular administration. In some aspects, the pharmaceutical composition is administered via intramuscular injection. In some aspects, the pharmaceutical composition is administered via subcutaneous administration. In some aspects, the pharmaceutical composition is administered via subcutaneous injection.

[0207] In some aspects, the pharmaceutical composition is administered in combination with a second active agent. In some aspects, the pharmaceutical composition is administered without any additional active agents.

[0208] In some aspects, the pain being treated can be, for example, mild, moderate, severe, or agonizing. The pain of a subject can be assessed using a numeric scale, in which a patient can self-report pain on a scale from 0-10, where 0 indicates no pain, 1-3 suggests mild pain, 4-6 indicates moderate pain, and 7-10 suggests severe and disabling pain. Non-limiting examples of pain include angina pain, bone injury pain, central pain, chronic lower back pain, cluster headaches, dental pain, genitourinary tract-related pain including cystitis and nociceptive pain, herpes neuralgia, migraine, neuropathic pain, pain during labor and delivery, pain resulting from bums, phantom limb pain, postoperative pain, postpartum pain, surgical pain, or visceral pain.

[0209] In some aspects, the pain is postoperative pain.

[0210] The pain can be chronic or acute. Postoperative pain can describe that occurs after a surgery, and can be a direct or indirect result of the surgery.

[0211] In some aspects, the pharmaceutical composition can be administered to a subject during or prior to surgery to treat, for example, acute postoperative pain. The postoperative pain can be reduced by at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 99%. The reduction in postoperative pain can happen after about 10 minutes, about 20 minutes, about 30 minutes, about 40 minutes, about 50 minutes, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 8 hours, about 10 hours, or about 12 hours after the surgery. [0212] In some aspects, the subject is a mammal. In some aspects, the pharmaceutical composition is suitable for veterinary use. In some aspects, the subject is a human. [0213] The following examples are illustrative and do not limit the scope of the claimed aspects.

EXAMPLES

Example 1

[0214] Table 1 provides an exemplary formulation of the pharmaceutical compositions described herein.

[0215] Table 2 provides the stability results of the formulation described in Table 1.

Example 2

[0216] Table 3 provides an exemplary formulation of the pharmaceutical compositions described herein.

[0217] Table 4 provides the stability results of the formulation described in Table 3.

NR - Not Reportable (NR = <0.05%); CCL: Clear and Colorless Liquid Example 3

[0218] Tables 5 and 6 provide exemplary formulations of the pregabalin pharmaceutical compositions described herein.

Table 5

Table 6

[0219] Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

[0220] All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

Claims

WHAT IS CLAIMED IS:

1. An injectable pharmaceutical composition comprising from about 0.01 to about 30 mg/mL pregabalin, from about 3 to about 6 mg/mL sodium chloride, from about 0.1 to about 2.5 mg/mL of a buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

2. An injectable pharmaceutical composition consisting essentially of from about 0.01 to about 30 mg/mL pregabalin, from about 3 to about 6 mg/mL sodium chloride, from about 0.1 to about 2.5 mg/mL of a buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

3. An injectable pharmaceutical composition consisting of from about 0.01 to about 30 mg/mL pregabalin, from about 3 to about 6 mg/mL sodium chloride, from about 0.1 to about 2.5 mg/mL of a buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, and wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %.

4. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 0.01 mg/mL pregabalin.

5. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 0.05 mg/mL pregabalin.

6. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 0.1 mg/mL pregabalin. 7. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 0.5 mg/mL pregabalin.

8. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 1 mg/mL pregabalin.

9. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 1.5 mg/mL pregabalin.

10. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 5 mg/mL pregabalin.

11. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 10 mg/mL pregabalin.

12. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 15 mg/mL pregabalin.

13. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 20 mg/mL pregabalin.

14. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 25 mg/mL pregabalin.

15. The pharmaceutical composition of any one of claims 1 to 3, wherein the composition comprises about 30 mg/mL pregabalin.

16. The pharmaceutical composition of any one of claims 1 to 15, wherein the composition comprises about 3 mg/mL sodium chloride. 17. The pharmaceutical composition of any one of claims 1 to 15, wherein the composition comprises about 4 mg/mL sodium chloride.

18. The pharmaceutical composition of any one of claims 1 to 15, wherein the composition comprises about 5 mg/mL sodium chloride.

19. The pharmaceutical composition of any one of claims 1 to 15, wherein the composition comprises about 6 mg/mL sodium chloride.

20. The pharmaceutical composition of any one of claims 1 to 19, wherein the buffer comprises an acid, a conjugate base of an acid, both the acid and the conjugate base of the acid, pharmaceutically acceptable derivatives thereof, or combinations thereof.

21. The pharmaceutical composition of claim 20, wherein the acid is selected from the group consisting of citric acid, acetic acid, phosphoric acid, and combinations thereof.

22. The pharmaceutical composition of any one of claims 1 to 21, wherein the composition comprises about 0.1 mg/mL buffer.

23. The pharmaceutical composition of any one of claims 1 to 21, wherein the composition comprises about 0.5 mg/mL buffer.

24. The pharmaceutical composition of any one of claims 1 to 21, wherein the composition comprises about 1 mg/mL buffer.

25. The pharmaceutical composition of any one of claims 1 to 21, wherein the composition comprises about 1.5 mg/mL buffer.

26. The pharmaceutical composition of any one of claims 1 to 21, wherein the composition comprises about 2 mg/mL buffer. 27. The pharmaceutical composition of any one of claims 1 to 21, wherein the composition comprises about 2.5 mg/mL buffer.

28. The pharmaceutical composition of any one of claims 1 to 27, wherein the pH-adjusting agent is sodium hydroxide.

29. The pharmaceutical composition of any one of claims 1 to 27, wherein the pH-adjusting agent is hydrochloric acid.

30. The pharmaceutical composition of any one of claims 1 to 27, wherein the pH is about 5.

31. The pharmaceutical composition of any one of claims 1 to 27, wherein the pH is about

5.5.

32. The pharmaceutical composition of any one of claims 1 to 27, wherein the pH is about 6.

33. The pharmaceutical composition of any one of claims 1 to 27, wherein the pH is about

6.5.

34. The pharmaceutical composition of any one of claims 1 to 27, wherein the pH is about 7.

35. An injectable pharmaceutical composition comprising pregabalin, about 5 mg/mL sodium chloride, about 0.4 mg/mL buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

36. An injectable pharmaceutical composition consisting essentially of pregabalin, about 5 mg/mL sodium chloride, about 0.4 mg/mL buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen. 37. An injectable pharmaceutical composition consisting of pregabalin, about 5 mg/mL sodium chloride, about 0.4 mg/mL buffer, and an aqueous carrier, wherein the composition has a pH of about 6, and wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %.

38. An injectable pharmaceutical composition comprising from about 0.01 to about 30 wt % pregabalin, from about 3 to about 6 wt % sodium chloride, from about 0.1 to about 2.5 wt % of a buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

39. An injectable pharmaceutical composition consisting essentially of from about 0.01 to about 30 wt % pregabalin, from about 3 to about 6 wt % sodium chloride, from about 0.1 to about 2.5 wt % of a buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

40. An injectable pharmaceutical composition consisting of from about 0.01 to about 30 wt % pregabalin, from about 3 to about 6 wt % sodium chloride, from about 0.1 to about 2.5 wt % of a buffer, a pH-adjusting agent, and an aqueous carrier, wherein the composition has a pH of from about 5 to about 7, and wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %.

41. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 0.01 wt % pregabalin.

42. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 0.05 wt % pregabalin. 43. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 0.1 wt % pregabalin.

44. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 0.5 wt % pregabalin.

45. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 1 wt % pregabalin.

46. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 1.5 wt % pregabalin.

47. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 5 wt % pregabalin.

48. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 10 wt % pregabalin.

49. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 15 wt % pregabalin.

50. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 20 wt % pregabalin.

51. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 25 wt % pregabalin.

52. The pharmaceutical composition of any one of claims 38 to 40, wherein the composition comprises about 30 wt % pregabalin. 53. The pharmaceutical composition of any one of claims 38 to 52, wherein the composition comprises about 3 wt % sodium chloride.

54. The pharmaceutical composition of any one of claims 38 to 52, wherein the composition comprises about 4 wt % sodium chloride.

55. The pharmaceutical composition of any one of claims 38 to 52, wherein the composition comprises about 5 wt % sodium chloride.

56. The pharmaceutical composition of any one of claims 38 to 52, wherein the composition comprises about 6 wt % sodium chloride.

57. The pharmaceutical composition of any one of claims 38 to 56, wherein the buffer comprises an acid, a conjugate base of an acid, both the acid and the conjugate base of the acid, pharmaceutically acceptable derivatives thereof, or combinations thereof.

58. The pharmaceutical composition of claim 57, wherein the acid is selected from the group consisting of citric acid, acetic acid, phosphoric acid, and combinations thereof.

59. The pharmaceutical composition of any one of claims 38 to 57, wherein the composition comprises about 0.1 wt % buffer.

60. The pharmaceutical composition of any one of claims 38 to 57, wherein the composition comprises about 0.5 wt % buffer.

61. The pharmaceutical composition of any one of claims 38 to 57, wherein the composition comprises about 1 wt % buffer.

62. The pharmaceutical composition of any one of claims 38 to 57, wherein the composition comprises about 1.5 wt % buffer. -se es The pharmaceutical composition of any one of claims 38 to 57, wherein the composition comprises about 2 wt % buffer.

64. The pharmaceutical composition of any one of claims 38 to 57, wherein the composition comprises about 2.5 wt % buffer.

65. The pharmaceutical composition of any one of claims 38 to 64, wherein the pH-adjusting agent is sodium hydroxide.

66. The pharmaceutical composition of any one of claims 38 to 64, wherein the pH-adjusting agent is hydrochloric acid.

67. The pharmaceutical composition of any one of claims 38 to 66, wherein the pH is about 5.

68. The pharmaceutical composition of any one of claims 38 to 66, wherein the pH is about

5.5.

69. The pharmaceutical composition of any one of claims 38 to 66, wherein the pH is about 6.

70. The pharmaceutical composition of any one of claims 38 to 66, wherein the pH is about

6.5.

71. The pharmaceutical composition of any one of claims 38 to 66, wherein the pH is about 7.

72. An injectable pharmaceutical composition comprising pregabalin, about 5 wt % sodium chloride, about 0.4 wt % buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

73. An injectable pharmaceutical composition consisting essentially of pregabalin, about 5 wt % sodium chloride, about 0.4 wt % buffer, and an aqueous carrier, wherein the composition has a pH of about 6, wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %, and wherein the composition does not contain acetaminophen.

74. An injectable pharmaceutical composition consisting of pregabalin, about 5 wt % sodium chloride, about 0.4 wt % buffer, and an aqueous carrier, wherein the composition has a pH of about 6, and wherein the amount of pregabalin citrate adduct present in the composition is less than 0.5 wt %.

75. The pharmaceutical composition of any one of claims 1 to 74, wherein the composition comprises a decomposition product of pregabalin at a level of less than 5 wt %.

76. The pharmaceutical composition of claim 75, wherein the decomposition product of pregabalin is 4-(2-methylpropyl)pyrrolidin-2-one (MPP).

77. The pharmaceutical composition of any one of claims 38 to 76, wherein the composition is packaged in a unit dosage form.

78. The pharmaceutical composition of claim 77, wherein the unit dosage form is a bag, a glass vial, or a prefilled syringe.

79. The pharmaceutical composition of claim 78, wherein the bag is a polymer bag.

80. The pharmaceutical composition of claim 79, wherein the polymer bag is a polypropylene bag, further packaged in an aluminum over-pouch.

81. The pharmaceutical composition of claim 80, wherein the aluminum over-pouch contains an oxygen scavenger.

82. The pharmaceutical composition of any one of claims 77 to 81, wherein the volume of the composition is about 1 mL. 83. The pharmaceutical composition of any one of claims 77 to 81, wherein the volume of the composition is about 10 mL.

84. The pharmaceutical composition of any one of claims 77 to 81, wherein the volume of the composition is about 100 mL.

85. The pharmaceutical composition of any one of claims 77 to 81, wherein the volume of the composition is about 1000 mL.

86. The pharmaceutical composition of any one of claims 1 to 85, wherein the composition is stable after being stored for at least three months at 40 °C and 75% relative humidity.

87. The pharmaceutical composition of any one of claims 1 to 85, wherein the composition comprises less than 5 wt % 4-(2-methylpropyl)pyrrolidin-2-one (MPP) after storage for at least three months at 40 °C and 75% relative humidity.

88. The pharmaceutical composition of any one of claims 1 to 85, wherein the composition comprises less than 0.5 wt % pregabalin citrate adduct after storage for at least three months at 40 °C and 75% relative humidity.

89. The pharmaceutical composition of any one of claims 1 to 85, wherein the pH of the composition is about 6 after storage for at least three months at 40 °C and 75% relative humidity.

90. A method of treating pain in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of any one of claims 1 to 3 or 38 to 40.

91. The method of claim 90, wherein the pharmaceutical composition comprises about 0.01 mg/mL pregabalin. 92. The method of claim 90, wherein the pharmaceutical composition comprises about 0.05 mg/mL pregabalin.

93. The method of claim 90, wherein the pharmaceutical composition comprises about 0.1 mg/mL pregabalin.

94. The method of claim 90, wherein the pharmaceutical composition comprises about 0.5 mg/mL pregabalin.

95. The method of claim 90, wherein the pharmaceutical composition comprises about 1 mg/mL pregabalin.

96. The method of claim 90, wherein the pharmaceutical composition comprises about 1.5 mg/mL pregabalin.

97. The method of claim 90, wherein the pharmaceutical composition comprises about 5 mg/mL pregabalin.

98. The method of claim 90, wherein the pharmaceutical composition comprises about 10 mg/mL pregabalin.

99. The method of claim 90, wherein the pharmaceutical composition comprises about 15 mg/mL pregabalin.

100. The method of claim 90, wherein the pharmaceutical composition comprises about 20 mg/mL pregabalin.

101. The method of claim 90, wherein the pharmaceutical composition comprises about 25 mg/mL pregabalin. 102. The method of claim 90, wherein the pharmaceutical composition comprises about 30 mg/mL pregabalin.

103. The method of any one of claims 90 to 102, wherein the pharmaceutical composition comprises about 3 mg/mL sodium chloride.

104. The method of any one of claims 90 to 102, wherein the pharmaceutical composition comprises about 4 mg/mL sodium chloride.

105. The method of any one of claims 90 to 102, wherein the pharmaceutical composition comprises about 5 mg/mL sodium chloride.

106. The method of any one of claims 90 to 102, wherein the pharmaceutical composition comprises about 6 mg/mL sodium chloride.

107. The method of any one of claims 90 to 106, wherein the buffer comprises an acid, a conjugate base of an acid, both the acid and the conjugate base of the acid, pharmaceutically acceptable derivatives thereof, or combinations thereof.

108. The method of claim 107, wherein the acid is selected from the group consisting of citric acid, acetic acid, phosphoric acid, and combinations thereof.

109. The method of any one of claims 90 to 108, wherein the pharmaceutical composition comprises about 0.1 mg/mL buffer.

110. The method of any one of claims 90 to 108, wherein the pharmaceutical composition comprises about 0.5 mg/mL buffer.

111. The method of any one of claims 90 to 108, wherein the pharmaceutical composition comprises about 1 mg/mL buffer. 112. The method of any one of claims 90 to 108, wherein the pharmaceutical composition comprises about 1.5 mg/mL buffer.

113. The method of any one of claims 90 to 108, wherein the pharmaceutical composition comprises about 2 mg/mL buffer.

114. The method of any one of claims 90 to 108, wherein the pharmaceutical composition comprises about 2.5 mg/mL buffer.

115. The method of any one of claims 90 to 114, wherein the pH-adjusting agent is sodium hydroxide.

116. The method of any one of claims 90 to 114, wherein the pH-adjusting agent is hydrochloric acid.

117. The method of any one of claims 90 to 116, wherein the pharmaceutical composition has a pH of about 5.

118. The method of any one of claims 90 to 116, wherein the pharmaceutical composition has a pH of about 5.5.

119. The method of any one of claims 90 to 116, wherein the pharmaceutical composition has a pH of about 6.

120. The method of any one of claims 90 to 116, wherein the pharmaceutical composition has a pH of about 6.5.

121. The method of any one of claims 90 to 116, wherein the pharmaceutical composition has a pH of about 7. 122. A method of treating pain in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the composition of any one of claims 35 to 37 or 72 to 74.

123. The method of any one of claims 90 to 122, wherein the pharmaceutical composition comprises a decomposition product of pregabalin at a level of less than 5 wt %.

124. The method of claim 123, wherein the decomposition product of pregabalin is 4-(2- methylpropyl)pyrrolidin-2-one (MPP).

125. The method of any one of claims 90 to 124, wherein the pharmaceutical composition is administered to the subject within 24 hours prior to the subject undergoing a surgical procedure.

126. The method of any one of claims 90 to 124, wherein the pharmaceutical composition is administered to the subject simultaneously with the subject undergoing a surgical procedure.

127. The method of any one of claims 90 to 124, wherein the pharmaceutical composition is administered to the subject within 24 hours after the subject has undergone a surgical procedure.

128. The method of any one of claims 90 to 127, wherein the administering is parenteral.

129. The method of any one of claims 76 to 128, wherein the administering is intravenous.

130. The method of any one of claims 76 to 128, wherein the administering is intramuscular .

131. The method of any one of claims 76 to 128, wherein the administering is subcutaneous . 132. The method of any one of claims 76 to 131, wherein the administering is performed via injection.

133. The method of any one of claims 76 to 132, wherein the pharmaceutical composition is administered in combination with a second active agent.

134. The method of any one of claims 76 to 133, wherein the pharmaceutical composition is stable after storage for at least three months at 40 °C and 75% relative humidity.

135. The method of any one of claims 76 to 134, wherein the pharmaceutical composition comprises less than 5 wt % 4-(2-methylpropyl)pyrrolidin-2-one (MPP) after storage for at least three months at 40 °C and 75% relative humidity.

136. The method of any one of claims 76 to 135, wherein the pharmaceutical composition comprises less than 0.5 wt % pregabalin citrate adduct after storage for at least three months at 40 °C and 75% relative humidity.

137. The method of any one of claims 76 to 136, wherein the pH of the pharmaceutical composition is about 6 after storage for at least three months at 40 °C and 75% relative humidity.

138. The method of any one of claims 76 to 137, wherein the pain is selected from the group consisting of angina pain, bone injury pain, central pain, chronic lower back pain, cluster headaches, dental pain, genitourinary tract-related pain including cystitis and nociceptive pain, herpes neuralgia, migraine, neuropathic pain, pain during labor and delivery, pain resulting from bums, phantom limb pain, postoperative pain, postpartum pain, surgical pain, visceral pain, and combinations thereof.