Continuous Production of Active Pharmaceutical Ingredients
AssigneeNew Jersey Institute of Technology
InventorKamalesh Sirkar
Life of this patent
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Abstract
The present invention is directed to a method of producing active pharmaceutical ingredients (APIs). The method includes subjecting a reaction mixture with an API precursor to solvent extraction to produce a reactant stream with the API precursor. The method includes concentrating the API precursor in the reactant stream using at least one membrane. The method includes carrying out a reaction in a membrane reactor. The method includes separating the API precursor from the reaction stream using a separator. The method includes crystallizing the API precursor using a crystallizer to produce APIs.
Claims43
A method of producing active pharmaceutical ingredients (APIs), comprising:
- (a) subjecting a reaction mixture with an API precursor to solvent extraction to produce a reactant stream with the API precursor;
- (b) concentrating the API precursor in the reactant stream using at least one membrane;
- (c) carrying out a reaction in a membrane reactor;
- (d) separating the API precursor from the reaction stream using a separator;
- and
- (e) crystallizing the API precursor using a crystallizer to produce APIs.
A method for solvent exchange and nanofiltration or reverse osmosis, comprising:
- (a) adding a solvent to a reaction mixture;
- and
- (b) removing preexisting solvent from the reaction mixture through a membrane by organic solvent nanofiltration or organic solvent reverse osmosis.
A method to immobilize catalysts in pores of polymeric or ceramic planar, tubular or hollow fiber membranes for carrying out two-phase based reactions in this membrane reactor for gas-liquid systems as well as liquid-liquid systems.
A method to immobilize a catalyst using membrane-based devices in enzyme catalysis, comprising:
- (a) directing a reaction mixture containing small molecule substrates and products through a membrane reactor lined with charged nanofiltration membranes;
- and
- (b) segregating a catalyst and cofactor in the reactor and immobilizing the catalyst in a membrane.
A method for continuous manufacturing of prexasertib monolactate monohydrate, said method comprising the steps of:
- (a) combining compound 7 with hydrazine in the presence of acetic acid in methanol and THF at the temperature of about 130° C. to produce compound 8:
- (b) combining compound 8 with compound 9 in the presence of N-ethylmorpholine in DMSO at the temperature of about 85° C. to produce compound 10:
- (c) deprotecting compound 10 by combining it with formic acid at the temperature of about 25° to produce compound 1:
- and
- (d) subjecting compound 1 to lactic acid distillation in THF/water to produce compound 12:
- wherein each of steps (a)-(d) is carried out in a series of units connected to each other to support continuous flow;
- and
- wherein said series of units comprises at least one membrane-based unit.
A method for continuous manufacturing of fluoxetine hydrochloride, said method comprising
- (a) reacting compound 13 with diisobutylaluminium hydride (DIBALH) in water/hydrochloric acid at a temperature of about 25° C. to produce compound 14:
- (b) combining compound 14 with methylamine at a temperature of about 135° C. to produce compound 15:
- and
- (c) combining compound 15 with compound 16 in the presence of potassium tert-butoxide and a crown ether at a temperature of about 140° C. to produce compound 17:
- wherein each of steps (a)-(c) is carried out in a series of units connected to each other to support continuous flow;
- and
- wherein said series of units comprises at least one membrane-based unit.
Dependencies are inferred from the claim text.