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US 2003/0118660 A1Published application
Residual solvent extraction method and microparticles produced thereby
AssigneeAlkermes Controlled Therapeutics Inc. II
InventorsMichael E. Rickey, J. Michael Ramstack, Rajesh Kumar
Life of this patent
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Abstract
Methods for preparing microparticles having reduced residual solvent levels. Microparticles are contacted with a non-aqueous washing system to reduce the level of residual solvent in the microparticles. Preferred non-aqueous washing systems include 100% ethanol and a blend of ethanol and heptane. A solvent blend of a hardening solvent and a washing solvent can be used to harden and wash microparticles in a single step, thereby eliminating the need for a post-hardening wash step.
Claims87
A method for preparing microparticles, comprising:
- preparing an emulsion comprising an aqueous peptide solution and a biodegradable, biocompatible polymer dissolved in a halogenated solvent;
- combining the emulsion with a coacervating agent that is free from solvents for the polymer to form a combined phase;
- extracting the halogenated solvent from the combined phase with an extraction medium that is a non-solvent for the polymer and a solvent for the halogenated solvent and the coacervating agent, whereby microparticles precipitate out of the extraction medium;
- and
- washing the precipitated microparticles in a non-aqueous washing system that is either (1) 100% ethanol or (2) a blend of ethanol and heptane to thereby reduce a level of residual halogenated solvent.
2 more elements
A method for preparing microparticles, comprising:
- contacting microparticles comprising a biodegradable, biocompatible polymer matrix comprising a peptide and a halogenated solvent with a non-aqueous washing system to thereby reduce a level of residual halogenated solvent in the microparticles, wherein the washing system is either (1) 100% ethanol or (2) a blend of ethanol and heptane;
- and
- recovering the microparticles from the washing system.
A method for preparing microparticles, comprising:
- contacting microparticles comprising a biodegradable, biocompatible polymer matrix comprising goserelin and a halogenated solvent with a non-aqueous washing system to thereby reduce a level of residual halogenated solvent to less than about 0.06% by weight of the microparticles, wherein the washing system is either (1) 100% ethanol or (2) a blend of ethanol and heptane;
- and
- recovering the microparticles from the washing system.
A method for preparing microparticles, comprising:
- preparing a first phase comprising a biodegradable, biocompatible polymer and a halogenated solvent;
- preparing an aqueous second phase comprising a peptide;
- combining the first phase and the second phase under the influence of a mixer to form an emulsion;
- combining the emulsion with a coacervating agent that is free from solvents for the polymer to form a combined phase;
- extracting the halogenated solvent from the combined phase with an extraction medium that is a non-solvent for the polymer and a solvent for the halogenated solvent and the coacervating agent, whereby microparticles precipitate out of the extraction medium;
- and
- washing the precipitated microparticles in a non-aqueous washing system that is either (1) 100% ethanol or (2) a blend of ethanol and heptane to thereby reduce a level of residual halogenated solvent.
4 more elements
A method for preparing microparticles, comprising:
- preparing an emulsion comprising an aqueous peptide solution and a biodegradable, biocompatible polymer dissolved in a halogenated solvent;
- combining the emulsion with a coacervating agent that is free from solvents for the polymer to form a combined phase;
- extracting the halogenated solvent from the combined phase with an extraction medium that is a non-solvent for the polymer and a solvent for the halogenated solvent and the coacervating agent, whereby microparticles precipitate out of the extraction medium;
- and
- washing the precipitated microparticles in a non-aqueous washing system that comprises ethanol.
2 more elements
A method for preparing microparticles, comprising:
- contacting microparticles comprising a biodegradable, biocompatible polymer matrix containing an active agent and an organic solvent with a non-aqueous washing system to thereby reduce a level of residual organic solvent in the microparticles, wherein the non-aqueous washing system is either (1) 100% ethanol or (2) a blend of ethanol and heptane;
- and
- recovering the microparticles from the non-aqueous washing system.
A method for preparing microparticles, comprising:
- preparing a first phase, the first phase comprising an active agent, a biodegradable, biocompatible polymer, and a solvent;
- preparing a second phase, wherein the first phase is substantially immiscible with the second phase;
- combining the first phase and the second phase to form an emulsion;
- extracting solvent from the emulsion using an extraction liquid to thereby form microparticles containing the active agent;
- and
- washing the microparticles with a non-aqueous washing system to thereby reduce the level of residual solvent in the microparticles, wherein the non-aqueous washing system comprises ethanol.
3 more elements
A method for preparing microparticles, comprising:
- preparing an emulsion comprising an aqueous peptide solution and a biodegradable, biocompatible polymer dissolved in a solvent;
- combining the emulsion with a coacervating agent that is free from solvents for the polymer to form a combined phase;
- extracting solvent from the combined phase in an extraction medium that is a non-solvent for the polymer and a solvent for the solvent and the coacervating agent, whereby microparticles precipitate out of the extraction medium;
- and
- washing the precipitated microparticles in 100% ethanol.
2 more elements
A method for preparing microparticles, comprising:
- contacting microparticles comprising a biodegradable, biocompatible polymer matrix containing an active agent and an organic solvent with a non-aqueous washing system to thereby reduce a level of residual organic solvent in the microparticles, wherein the non-aqueous washing system is either (1) 100% alcohol or (2) a blend of alcohol and a liquid alkane;
- and
- recovering the microparticles from the non-aqueous washing system.
A method for preparing microparticles, comprising:
- preparing an emulsion comprising an active agent and a biodegradable, biocompatible polymer dissolved in a solvent;
- combining the emulsion with a coacervating agent that is free from solvents for the polymer to form a combined phase;
- and
- extracting the solvent from the combined phase with a solvent blend of a hardening solvent and a washing solvent, to thereby form hardened microparticles.
1 more element
Dependencies are inferred from the claim text.