Method for formation of micro-prilled polymers

Abstract

A method for formation of micro-prilled poloxamer particles is disclosed. The particles find special use in pharmaceutical formulations. The process involves use of atomizing nozzles at higher than normal pressure atomizing gas, high atomizing gas temperature, use of high feed temperatures to reduce the viscosity of the poloxamer and optionally sieving after prill formation in prilling towers. The poloxamer particles are spherical and preferably have an average nominal diameter of less than or equal to 106 microns. The process is very cost effective and rapid.

1 . A plurality of micro-prilled poloxamer particles comprising:
 one or more copolymers of ethylene oxide and propylene oxide each having a general formula of HO(C2H4O)a(C3H6O)b(C2H4O)aH, wherein a value of a is from about 60 to about 150 and a value of b is from about 25 to about 60;   said particles being spherical, solid at 25° C., and said plurality of particles having an average nominal diameter of less than or equal to 106 microns.   
     
     
         2 . The plurality of micro-prilled poloxamer particles as recited in  claim 1 , wherein at least 50% of said plurality of particles have an average nominal diameter of less than or equal to 53 microns. 
     
     
         3 . The plurality of micro-prilled poloxamer particles as recited in  claim 1 , wherein said one or more copolymers each have a number average molecular weight of from about 6000 to about 18000 Daltons. 
     
     
         4 . The plurality of micro-prilled poloxamer particles as recited in  claim 1 , wherein said one or more copolymers are selected from the group consisting of HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 80 and with b having a value of about 27; HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 64 and with b having a value of about 37; HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 141 and with b having a value of about 44; HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 101 and with b having a value of about 56; and mixtures thereof. 
     
     
         5 . The plurality of micro-prilled poloxamer particles as recited in  claim 1 , further comprising a medicament. 
     
     
         6 . The plurality of micro-prilled poloxamer particles as recited in  claim 5 , wherein said plurality of micro-prilled poloxamer particles are present in an amount of from about 10 to about 50% by weight based on the total weight. 
     
     
         7 . The plurality of micro-prilled poloxamer particles as recited in  claim 5 , wherein said medicament is selected from the group consisting of carbamazepine, methadone, propranolol, metoprolol, carvedilol, timolol, atenol, meperidine, cocaine, amphetamine, phenmetrazine, methylphenidate, diltiazem, amlodipine, verapamil, benzodiazepine, and chloral hydrate. 
     
     
         8 . A method for formation of a plurality of micro-prilled poloxamer particles comprising the steps of:
 a) providing at least one copolymer of ethylene oxide and propylene oxide having a general formula of HO(C2H4O)a(C3H6O)b(C2H4O)aH, wherein a value of a is from about 60 to about 150 and a value of b is from about 25 to about 60;   b) heating the at least one copolymer of step a) to a temperature sufficient to reduce its viscosity to less than or equal to 1300 cps;   c) atomizing the heated at least one copolymer from step b) by passing it through an atomizing nozzle and into one of a co-current or a counter-current prilling tower thereby forming a plurality of particles of said at least one copolymer, said plurality of particles having an average nominal diameter of less than or equal to 106 microns; and optionally   d) sieving said plurality of particles formed in step c) and retaining the particles passing through a mesh screen having openings of about 106 microns.   
     
     
         9 . The method as recited in  claim 8 , wherein step a) comprises providing at least one copolymer of ethylene oxide and propylene oxide having a number average molecular weight of from about 6000 to about 18000 Daltons. 
     
     
         10 . The method as recited in  claim 8 , wherein step a) comprises providing at least one copolymer selected from the group consisting of HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 80 and with b having a value of about 27; HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 64 and with b having a value of about 37; HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 141 and with b having a value of about 44; HO(C2H4O)a(C3H6O)b(C2H4O)aH with a having a value of about 101 and with b having a value of about 56; and mixtures thereof. 
     
     
         11 . The method as recited in  claim 8 , wherein step b) comprises heating the at least one copolymer to a temperature of from about 120° C. to about 205° C. 
     
     
         12 . The method as recited in  claim 8 , wherein step b) comprises heating the at least one copolymer to a temperature of from about 125° C. to about 195° C. 
     
     
         13 . The method as recited in  claim 8 , wherein step c) comprises passing the copolymer of step b) through one of a two fluid atomizing nozzle or a three fluid atomizing nozzle. 
     
     
         14 . The method as recited in  claim 13  wherein the nozzle is selected to be a two fluid atomizing nozzle and the pressure of the outer gas is set at from about 100 to about 150 psig. 
     
     
         15 . The method as recited in a  claim 14 , further comprising setting the outer gas at a temperature of from about 80 to about 140° C. 
     
     
         16 . The method as recited in  claim 14 , wherein the outer gas is selected from the group consisting of nitrogen, air, oxygen, helium, and argon. 
     
     
         17 . The method as recited in  claim 8 , further comprising the step of mixing the particles retained in step d) with a medicament. 
     
     
         18 . The method as recited in  claim 17 , comprising mixing the particles in an amount of from 10 to 50% by weight based on the total weight. 
     
     
         19 . The method as recited in  claim 17 , comprising selecting the medicament from the group consisting of carbamazepine, methadone, propranolol, metoprolol, carvedilol, timolol, atenol, meperidine, cocaine, amphetamine, phenmetrazine, methylphenidate, diltiazem, amlodipine, verapamil, benzodiazepine, and chloral hydrate. 
     
     
         20 . The method as recited in  claim 13  wherein the nozzle is selected to be a three fluid atomizing nozzle and the pressure of the inner gas is set at from about 100 to about 150 and the pressure of the outer gas is set at from about 100 to about 150 psig. 
     
     
         21 .- 22 . (canceled)