Sustained release formulations using non-aqueous emulsions

Patent metadata

Field	Value
Publication number	US-11730793-B2
Application number	US-202017104566-A
Country	US
Kind code	B2
Filing date	Nov 25, 2020
Priority date	Nov 25, 2019
Publication date	Aug 22, 2023
Grant date	Aug 22, 2023

Abstract

Non-aqueous emulsion methods for producing polymeric or polymer-coated microparticles are provided. One method produces a sustained release microparticle composition by combining protein powder and a polymer into a hydrocarbon solvent to form a non-aqueous first solution and adding the first solution to a second solution, wherein the second solution comprises a fluorocarbon liquid and a fluorosurfactant to form a non-aqueous emulsion comprising multiple emulsion hydrocarbon droplets in the fluorocarbon liquid. The subsequent microparticle hardening process includes the steps of removing the hydrocarbon solvent from the formed emulsion droplets, which can be achieved through evaporation the hydrocarbon at ambient condition under stirring, or accelerated hardening through vacuum, or through adding hydrofluoroester into the fluorocarbon as a cosolvent. Removing the fluorocarbon liquid and washing with extra fluorocarbon liquid to isolate the sustained release microparticles, wherein the sustained release microparticles comprise one or more cores of protein and a cortex of polymer.

First claim

We claim:

1. Encapsulated protein microparticles produced by a method comprising the steps of:
(a) combining spray-dried protein powder and a polymer into a hydrocarbon solvent to form a non-aqueous first solution;
(b) adding the first solution to a second solution, wherein the second solution comprises a fluorocarbon liquid and a fluorosurfactant;
(c) agitating the combined solutions to form a non-aqueous emulsion comprising multiple emulsion hydrocarbon droplets in the fluorocarbon liquid;
(d) removing the hydrocarbon solvent; and
(e) removing the fluorocarbon liquid to isolate the microparticles, wherein the microparticles comprise protein encapsulated within a matrix of polymer, wherein the microparticles are sustained release microparticles, wherein the microparticles comprise a polymer cortex devoid of pores or channels.

2. A sustained release composition produced by the method of claim 1 , comprising the microparticles.

3. Encapsulated protein microparticles produced by a method comprising the steps of:
(a) combining a hydrocarbon solution comprising dissolved polymer and spray-dried protein powder to produce a dispersed phase;
(b) combining the dispersed phase with a continuous phase to produce non-aqueous emulsion droplets of the dispersed phase in the continuous phase, wherein the continuous phase comprises a fluorocarbon liquid and 0.1 to 5.0% w/v of a fluorosurfactant; and
(c) harvesting the polymer-coated microparticles, wherein the microparticles are sustained release microparticles, wherein the microparticles comprise a polymer cortex devoid of pores or channels.

4. A pharmaceutical composition produced by the method of claim 3 , comprising the microparticles.

5. The pharmaceutical composition produced by the method of claim 4 , further comprising one or more excipients.

6. The pharmaceutical composition produced by the method of claim 4 , wherein the pharmaceutical composition is a sustained release composition.

7. The pharmaceutical composition produced by the method of claim 4 , wherein the pharmaceutical composition is formulated for parenteral administration.

8. Encapsulated protein microparticles produced by a method comprising the steps of:
(a) combining a non-aqueous first solution comprising a spray-dried protein powder and a polymer in a hydrocarbon solvent with a second solution comprising a fluorocarbon solvent and a fluorosurfactant;
(b) agitating the combined solutions to produce a non-aqueous emulsion;
(c) removing the hydrocarbon solvent under vacuum while stirring the combined solutions to harden the microparticles;
(d) harvesting the microparticles; and
(e) drying the microparticles, wherein the microparticles are sustained release microparticles, wherein the microparticles comprise a polymer cortex devoid of pores or channels.

9. The microparticles produced by the method of claim 8 , further comprising the step of:
(f) washing the microparticles prior to drying.

Assignees

• Regeneron Pharma

Inventors

• Zhao Yiming
• Chen Hunter

Classifications

• A61K9/5015

  Organic compounds, e.g. fats, sugars · CPC title

• A61K9/5031

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide) · CPC title

• A61K9/1617

  Organic compounds, e.g. phospholipids, fats · CPC title

• A61K9/1647 Primary

  Polyesters, e.g. poly(lactide-co-glycolide) · CPC title

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title