Patent Application

App. No. 17/996,995

Abstract

Claims (51)

1 - 263 . (canceled)

264 . A stable pharmaceutically acceptable formulation comprising a microsphere, the microsphere comprising:

a biodegradable polymer selected from the group consisting of 60LP2L20-D27, 10LP10L20-GLL40, and 20LP10L20-GLL-40; and

an active drug load of bupivacaine free base or a pharmaceutically acceptable salt of bupivacaine.

265 . The stable pharmaceutically acceptable formulation of claim 264 , further comprising one or more antioxidants.

266 . The stable pharmaceutically acceptable formulation of claim 264 , further comprising a diluent.

267 . The stable pharmaceutically acceptable formulation of claim 264 , wherein the active drug load of bupivacaine free base or a pharmaceutically acceptable salt of bupivacaine in the microsphere is about 10% to about 80% w/w.

268 . The stable pharmaceutically acceptable formulation of claim 264 , wherein the formulation is sterile.

269 . The stable pharmaceutically acceptable formulation of claim 264 , wherein the formulation has a shelf life of about 14 days at 25° C. following refrigeration.

270 . The stable pharmaceutically acceptable formulation of claim 264 , wherein the formulation has a shelf life of about 24 months at 25° C.

271 . The stable pharmaceutically acceptable formulation of claim 264 , wherein the formulation is provided in an injector.

272 . A method of producing a stable pharmaceutically acceptable formulation comprising

a microsphere, the method comprising:

providing a first phase comprising:

a first biodegradable polymer selected from the group consisting of 60LP2L20-D27, 10LP10L20-GLL40, and 20LP10L20-GLL-40; and

an active drug load of bupivacaine free base or a pharmaceutically acceptable salt of bupivacaine;

adding a second phase comprising an aqueous surfactant continuously into the first phase to form an emulsion;

adding a quench solution to the emulsion to produce a volume comprising a microsphere; and

washing, filtering, and drying the microsphere to reduce solvent content.

273 . A method of producing the stable pharmaceutically acceptable formulation of claim 264 , the method comprising:

providing a first phase comprising:

the first biodegradable polymer;

the active drug load of bupivacaine free base or a pharmaceutically acceptable salt of bupivacaine; and

a solvent system suitable to dissolve the polymer and bupivacaine;

emulsifying the first phase with a second phase, thereby forming an emulsion;

wherein the second phase comprises an aqueous solution which comprises a surfactant; and

removing a substantial portion of the solvent system from the emulsion, thereby obtaining the microsphere.

274 . A method of treating pain in a subject, comprising administering to the subject:

a stable pharmaceutically acceptable formulation comprising a microsphere,

the microsphere comprising a first biodegradable polymer selected from a group consisting of 60LP2L20-27, 10LP10L20-GLL40, and 20LP10L20-GLL-40 and about 200 mg to about 8000 mg of bupivacaine free base or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical formulation effects a therapeutically acceptable effective concentration of bupivacaine free base or a pharmaceutically acceptable salt thereof for about 2 days to about 14 days following administration to the subject.

275 . A pre-filled injector comprising the stable pharmaceutically acceptable formulation of claim 264 .

276 . A method of manufacturing a pre-filled injector comprising a stable pharmaceutically acceptable formulation, the method comprising:

preparing the stable pharmaceutically acceptable formulation of claim 264 ;

loading a sterile cartridge with the stable pharmaceutically acceptable formulation; and

attaching the sterile cartridge operably to an injector.

277 . A long-acting dosage form comprising:

the stable pharmaceutically acceptable formulation of claim 264 , comprising

the microsphere comprising:

the biodegradable polymer; and

the drug load of bupivacaine free base or a pharmaceutically acceptable salt thereof;

wherein administration of a single dose of the long-acting dosage form to a subject results in at least one of the pharmacokinetic parameters selected from the group consisting of:

a steady state plasma profile of bupivacaine from day 1 to day 7 following administration exhibiting a mean C max value no greater than the steady state plasma level of bupivacaine provided by 100 mg of immediate release subcutaneous injection of bupivacaine hydrochloride;

a bupivacaine elimination half-life of 2 hours to about 4 hours; and

a release profile corresponding to about 1% to about 50% release of the total administered dose of bupivacaine or a pharmaceutically acceptable salt thereof per day.

278 . A kit comprising:

a first vial comprising a concentrated form of the stable pharmaceutically acceptable formulation of claim 264 ;

a second vial comprising a pharmaceutically acceptable diluent;

a first syringe suitable for withdrawing the pharmaceutically acceptable diluent from the second vial;

an adapter which can operably attach to the first syringe and is suitable for dispensing the pharmaceutically acceptable diluent into the first vial;

a second syringe suitable for withdrawing a liquid from the second vial and for injecting the liquid into a subject; and

instructions for diluting the concentrated form and for administering the stable pharmaceutically acceptable formulation or the long-acting dosage form to a patient in need thereof.

Assignments (12)