METHOD AND APPARATUS FOR PURIFYING PHARMACEUTICAL COMPOSITIONS USING SUPERCRITICAL FLUIDS
The present invention provides a method and an apparatus for removing impurities from biodegradable polymers and/or pharmaceutical compounds. In accordance with the method, a stream of supercritical fluid and, optionally, a modifying co-solvent, is used to dissolve the impurities. The pressure and temperature of the supercritical fluid or supercritical fluid/co-solvent mixture is controlled such that the supercritical fluid or mixture acts as a solvent for the impurities, but not for the biodegradable polymers and/or pharmaceutical compounds.
1 . A method of purifying a pharmaceutical composition comprising:
providing a pharmaceutical composition that comprises a biologically active substance and at least a first impurity;
loading the pharmaceutical composition into an extraction chamber;
flowing a supercritical fluid through the extraction chamber in contact the pharmaceutical composition at a first temperature and at a first pressure in which the first impurity is soluble in the supercritical fluid but the biologically active substance is not;
monitoring the concentration of the first impurity dissolved in the supercritical fluid in an exit stream flowing from the extraction chamber;
stopping the flow of supercritical fluid through the extraction chamber when the concentration of the dissolved first impurity in the exit stream is at or below a predetermined level; and
depressurizing the extraction chamber to collect a purified pharmaceutical composition.
2 . The method according to claim 1 wherein the pharmaceutical composition further comprises a biodegradable polymer.
3 . The method according to claim 1 wherein the supercritical fluid is supercritical carbon dioxide.
4 . The method according to claim 1 wherein the pharmaceutical composition further comprises a second impurity and wherein after the first impurity is extracted from the pharmaceutical composition, supercritical fluid is flowed through the extraction chamber in contact the pharmaceutical composition at a second temperature and at a second pressure in which the second impurity is soluble in the supercritical fluid but the biologically active substance is not.
5 . The method according to claim 1 wherein the pharmaceutical composition is in the form of discrete particles.
6 . The method according to claim 1 wherein the pharmaceutical composition is supported by a tray inside the extraction chamber.
7 . The method according to claim 1 wherein the first impurity is selected from the group consisting of residual monomers, unreacted reagents and residual organic solvents.
8 . The method according to claim 1 wherein the concentration of the first impurity in the exit stream is monitored using a photo diode array detector.
9 . A purified pharmaceutical composition formed in accordance with the method of claim 1 .
10 . The method according to claim 1 wherein the supercritical fluid flowing through the extraction chamber in contact the pharmaceutical composition is mixed with one or more modifying co-solvents that are at least partially miscible with the supercritical fluid.
11 . The method according to claim 10 wherein the pharmaceutical composition further comprises a biodegradable polymer.
12 . The method according to claim 10 wherein the supercritical fluid is supercritical carbon dioxide.
13 . The method according to claim 10 wherein the pharmaceutical composition further comprises a second impurity and wherein after the first impurity is extracted from the pharmaceutical composition, supercritical fluid is flowed through the extraction chamber in contact the pharmaceutical composition at a second temperature and at a second pressure in which the second impurity is soluble in the supercritical fluid but the biologically active substance is not.
14 . The method according to claim 10 wherein the pharmaceutical composition is in the form of discrete particles.
15 . The method according to claim 10 wherein the pharmaceutical composition is supported by a tray inside the extraction chamber.
16 . The method according to claim 10 wherein the first impurity is selected from the group consisting of residual monomers, unreacted reagents and residual organic solvents.
17 . The method according to claim 10 wherein the concentration of the first impurity in the exit stream is monitored using a photo diode array detector.
18 . A purified pharmaceutical composition formed in accordance with the method of claim 10 .
19 . An apparatus for purifying a pharmaceutical composition comprising:
an extraction chamber for receiving a pharmaceutical composition comprising a biologically active substance and at least a first impurity;
a source of supercritical fluid connected to the extraction chamber for flowing supercritical fluid into the extraction chamber;
a valve for adjusting the pressure within the extraction chamber;
a heating jacket disposed on the extraction chamber for adjusting the temperature within the extraction chamber;
a plurality of trays disposed within the extraction chamber for supporting the pharmaceutical composition; and
a photo diode array detector connected to an exit flow from the extraction chamber for monitoring the concentration of the first impurity dissolved in the supercritical fluid.
20 . An apparatus for purifying a pharmaceutical composition comprising:
an extraction chamber for receiving a pharmaceutical composition comprising a biologically active substance and at least a first impurity;
a source of supercritical fluid connected to the extraction chamber for flowing supercritical fluid into the extraction chamber;
a source of at least one co-solvent connected to the extraction chamber for mixing with the supercritical fluid and modifying the solvating power of the supercritical fluid;
a valve for adjusting the pressure within the extraction chamber;
a heating jacket disposed on the extraction chamber for adjusting the temperature within the extraction chamber;
a plurality of trays disposed within the extraction chamber for supporting the pharmaceutical composition; and
a photo diode array detector connected to an exit flow from the extraction chamber for monitoring the concentration of the first impurity dissolved in the supercritical fluid/co-solvent mixture.