1. A polyolefin production system, comprising:
a first fractionation column configured to fractionate a feed stream comprising a diluent and an olefin monomer recovered from a polymerization reactor, wherein the first fractionation column is configured to discharge:
a side product stream comprising a majority of the diluent,
an overhead vapor stream comprising components lighter than the diluent, and
a bottoms stream comprising components heavier than the diluent;
a condenser configured to receive and partially condense the overhead vapor stream into a condensed liquid comprising a quantity of the monomer from the feed stream; and
wherein a first portion the condensed liquid is transported to the polymerization reactor.
2. The polyolefin production system as recited in claim 1, comprising a diluent feed system configured to transport the side product stream to the polymerization reactor.
3. The polyolefin production system as recited in claim 1, comprising an accumulator vessel configured to receive and collect the condensed liquid from the condenser.
4. The polyolefin production system as recited in claim 1, wherein a second portion of the condensed liquid is delivered as a reflux to the first fractionation column.
5. The polyolefin production system as recited in claim 1, wherein a third portion of the condensed liquid is delivered to a second fractionation column configured to produce substantially olefin-free diluent.
6. The polyolefin production system as recited in claim 1, wherein the uses of the substantially olefin-free diluent comprise a motive fluid for delivery of a catalyst to the polymerization reactor, a fluid to dilute a catalyst, or a flush for at least one pressure safety valve.
7. The polyolefin production system as recited in claim 3, comprising:
a diluent vessel disposed between the accumulator vessel and the polymerization reactor, wherein the diluent vessel is configured to receive the first portion of the condensed liquid from the accumulator vessel, wherein the first portion of the condensed liquid is delivered from the diluent vessel to the polymerization reactor.
8. The polyolefin production system as recited in claim 1, wherein the side product stream from the first fractionation column is transported to a diluent vessel.
9. The polyolefin production system as recited in claim 1, wherein the diluent comprises isobutane and the olefin monomer comprises ethylene, and wherein the first fractionation column is configured to operate at a pressure in the range of 125-225 psig (861-1551 kPa) and at a temperature in the range of 100-350\xb0 F. (37-176\xb0 C.).
10. The polyolefin production system as recited in claim 1, comprising a flash chamber configured to receive an effluent from the polymerization reactor and to discharge a flash overhead stream comprising substantially vapor to the first fractionation column.
11. A method for operating a polyolefin production process, the method comprising the acts of:
separating diluent from a stream comprising diluent and monomer in a first fractionation column in a fractionation system;
transmitting the separated diluent to a polymerization reactor;
separating light components comprising monomer from the stream and at least partially condensing the light components; and
combining a portion of the condensed light components with the separated diluent being transmitted to the polymerization reactor.
12. The method as recited in claim 11, comprising the act of processing an effluent from the polymerization reactor to generate the stream comprising diluent and monomer.
13. The method as recited in claim 11, wherein the polymerization reactor comprises a polyethylene loop slurry reactor, and the stream comprising diluent and monomer comprises isobutane and ethylene.
14. The method as recited in claim 11, comprising the act of reducing a flow rate of a vent stream comprising monomer from the fractionation system to recover additional monomer within the fractionation system.
15. The method as recited in claim 14, comprising the act of feeding the recovered additional monomer to the polymerization reactor.
16. The method as recited in claim 11, comprising the act of regulating a flow rate of the portion of the condensed light components to avoid upset of operation of the fractionation system.
17. The method as recited in claim 16, comprising the acts of:
monitoring a concentration of olefin comonomer in an overhead stream of the first fractionation column, wherein the olefin comonomer is heavier than the diluent; and
regulating the flow rate of the portion of the condensed light components inversely with the concentration of the olefin comonomer in the overhead stream.
18. The method as recited in claim 16, comprising the acts of:
monitoring a concentration of olefin comonomer in a bottoms stream of a second fractionation column disposed fluidically downstream of the first fractionation column, wherein the olefin comonomer is heavier than the diluent, and wherein the second fractionation column is configured to produce substantially olefin-free diluent in the bottoms stream; and
regulating the flow rate of the portion of the condensed light components inversely with the concentration of the olefin comonomer in the bottoms stream of the second fractionation column.
19. A process for manufacturing a product comprising a polyolefin, the process comprising the acts of:
manufacturing a product at least a portion of which comprises a polyolefin, wherein the polyolefin is produced by a method comprising the acts of:
polymerizing monomer in the presence of catalyst in a polymerization reactor to form the polyolefin;
processing an effluent from the polymerization reactor to generate a stream comprising diluent and monomer;
separating diluent from the stream comprising diluent and monomer in a fractionation system;
transmitting the separated diluent to the polymerization reactor;
separating light components comprising monomer from the stream comprising diluent and monomer;
partially condensing the light components; and
combining a portion of the condensed light components with the separated diluent being transmitted to the polymerization reactor.
20. The process as recited in claim 19, wherein the act of manufacturing comprises the act of processing the polyolefin to form the product or to form a polyolefin component of the product, or a combination thereof.
21. The process as recited in claim 20, wherein the act of processing comprises the act of blending, heating, melting, compounding, extruding, injection molding, precision molding, blow molding, forming a film, forming a coating, or incorporating an additive, or any combination thereof.
22. The process as recited in claim 19, wherein the act of manufacturing comprises the act of assembling a component formed from the polyolefin into the product.
23. The process as recited in claim 19, wherein the polyolefin comprises high density polyethylene (HDPE), medium density polyethylene (MDPE), low density polyethylene (LDPE), linear low density polyethylene (LLDPE), isotactic polypropylene (iPP), or syndiotactic polypropylene (sPP), or any combination thereof.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A process for preparing a particulate pharmaceutical formulation from core particles comprising an active pharmaceutical ingredient, comprising the step of:
mixing the core particles, water soluble andor water swellable coating material particles, and substantially water insoluble polymer particles, to produce the particulate pharmaceutical formulation comprising coated core particles;
wherein a volume averaged median particle size of the core particles is at least three times greater than a median particle size of both the water soluble andor water swellable coating material particles and the substantially water insoluble polymer particles;
less than 0.1% of the API dissolves in a dissolution test indicative of taste-release in the mouth in 60 seconds; and
at least 90% of an amount of the API that would have been released from uncoated core particles of a same composition and size in a USP dissolution test indicative of dissolution in the GI tract is released within 30 minutes.
2. The process of claim 1, wherein the active pharmaceutical ingredient is completely released from the particulate pharmaceutical formulation in 30 minutes in the USP Dissolution Test.
3. The process of claim 1, wherein the volume averaged median particle size of the core particles is in a range of from 10 \u03bcm to 1000 \u03bcm.
4. The process of claim 3, wherein the volume averaged median particle size of the core particles is in a range of from 40 \u03bcm to 500 \u03bcm.
5. The process of claim 1, wherein the median particle size for the water soluble andor water swellable material particles and the substantially water insoluble polymer particles is independently selected to be in a range of from 1 \u03bcm to 20 \u03bcm.
6. The process of claim 1, wherein the soluble andor water swellable coating material particles are hydrophilic polymer particles comprising a polymer selected from the group consisting of hydroxypropylmethylcellulose, hydroxypropylcellulose, poly-(ethylene oxide), polymethacrylates, lactose and combinations thereof.
7. The process of claim 1, wherein the substantially water insoluble polymer particles comprise a polymer selected from the group consisting of polyethylene, polypropylene, polytetrafluoroethylene, carnauba wax, castor wax, polyamide wax, and combinations thereof.
8. The process of claim 1, wherein a ratio between the median particle size of the substantially water insoluble polymer particles and the median particle size of the water soluble andor water swellable material particles is in a range of from 1:1.5 to 1:6.
9. The process of claim 1, wherein the water soluble andor water swellable material particles comprise from 0.1 wt % to 25 wt. % of the total weight of the core particles, the substantially water insoluble particles and water soluble andor water swellable material particles in the mixing step.
10. The process of claim 9, wherein the water soluble andor water swellable material particles comprise from 0.5 wt. % to 20 wt. % of the total weight of the core particles, the substantially water insoluble particles and water soluble andor water swellable material particles in the mixing step.
11. The process of claim 1, wherein the substantially water insoluble polymer particles comprise from 0 wt. % to 50 wt. % of the total weight of the core particles, the substantially water insoluble particles and water soluble andor water swellable material particles in the mixing step.
12. The process of claim 1, wherein the substantially water insoluble polymer particles comprise from 5 wt % to 25 wt % of the total weight of the core particles, the substantially water insoluble particles and water soluble andor water swellable material particles in the mixing step.
13. The process of claim 1, wherein the particle number ratio between the water soluble andor water swellable material particles and the hydrophobic polymer particles of the mixing step is in a range of from 1:10 to 1:100.
14. The process of claim 1, wherein the particle number ratio between the water soluble andor water swellable material particles and the hydrophobic polymer particles of the mixing step is in a range of from 1:20 to 1:80.
15. The process of claim 1, further comprising a step of dry coating the water soluble andor water swellable material particles with a hydrophobic silica having a median particle size not greater than 100 \u03bcm, prior to the mixing step.
16. The process of claim 15, wherein the hydrophobic silica has a median particle size not greater than 20 nm.
17. The process of claim 1, wherein the mixing step comprises steps of:
1) preblending the water soluble andor water swellable coating material particles and substantially water insoluble polymer particles;
2) mixing the pre-blended water soluble andor water swellable coating material particles and substantially water insoluble polymer particles with core particles to produce the coated core particles.
18. The process of claim 1, wherein the water soluble andor water swellable material particles are added stepwise to the core particles and substantially water insoluble polymer particles during the mixing step.
19. The process of claim 1, wherein the substantially water insoluble polymer particles are added stepwise the core particles and water soluble andor swellable material particles during the mixing step.
20. The process of claim 1, wherein media particles are present during the mixing step and the media particles have a volume averaged median particle size that is in sufficiently different from the volume averaged median particle size of the coated core particles to permit separation of the media particles from the core particles by sieving.
21. The process of claim 20, wherein the media particles have a median particle size in a range of from 10 \u03bcm to 1000 \u03bcm.
22. The process of claim 20, wherein the media particles have a median particle size in a range of from 50 \u03bcm to 500 \u03bcm.
23. The process of claim 1, wherein the core particles comprise a mixture of core particles of sufficiently different sizes to permit at least one fraction of coated core particles to be separated from at least another fraction of coated core particles.
24. The process of claim 20, wherein the particle number ratio between the core particles and the media particles in the mixing step is in a range of from 1:30 to 1:300.
25. The process of claim 20, wherein the particle number ratio between the core particles and the media particles in the ingredients of the mixing step is in a range of from 1:50 to 1:200.
26. The process of claim 1, further comprising a step of curing the coated core particles.
27. The process of claim 1, further comprising a step of dry coating the coated core particles with a hydrophobic silica having a median particle size in a range of from 20 nm to 500 nm.
28. The process of claim 27, wherein the hydrophobic silica has a median particle size in a range of from 50 nm to 200 nm.
29. The process of claim 1, wherein at least 95% of an amount of the API that would have been released from uncoated core particles of a same composition and size in a USP dissolution test indicative of dissolution in the GI tract is released within 30 minutes.
30. The process of claim 1, wherein at least 99% of an amount of the API that would have been released from uncoated core particles of a same composition and size in a USP dissolution test indicative of dissolution in the GI tract is released within 30 minutes.
31. The process of claim 1, wherein less than 1% of the API dissolves in a dissolution test indicative of taste-release in the mouth in 120 seconds.
32. The process of claim 1, wherein less than 0.5% of the API dissolves in a dissolution test indicative of taste-release in the mouth in 120 seconds.