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put capacity and does not require premixing; it is fairly inexpensive and suitable for continuous operation. Major drawbacks to this equipment are its lack of availability, the need for special heating and cooling control systems, no available laboratory model, and the need for many trial-and-error runs in order to scale-up to production. 8. Static Mixers A true low-shear and low-energy requirement device for emulsifying immiscible liq-uid mixtures is the static mixer. Sometimes called a pipeline mixer, this device is ac-tually a series of specially designed baffles in a cylindrical pipe as shown in Fig. 42. These simple devices are used extensively for the preparation of unstable emulsions for liquid-liquid extraction purposes. Droplet sizes, obtainable using static mixers, have been studied extensively and vary with viscosity, interfacial tension, pressure drop, and static mixer design [45]. Size distributions obtainable range from 1000-100 |am. Hence, al-though there are very few emulsions stable in this region, the static mixer has seen application as an in-line premixer in continuous processes or in recirculation loops to batch-processing equipment. F. Nonmechanical Disperse Processing Recently a new processing technique became available for the production of stable and uniform liposomes. It uses the physico-chemical properties of the supercritical liquids rather than the mechanical forces of the pumps. One such a process technology is pre-sented in this section. 1. Critical Fluids Liposome Process Near-critical or supercritical fluid solvents with or without polar cosolvents (SuperFluids™) (Aphios, Corp., Woburn, MA) for the formation of uniform and stable liposomes having high encapsulation efficiencies has been used [46-48]. Supercritical or near-critical fluids as shown by the pressure-temperature diagram in Fig. 43, are gases such as carbon dioxide and propane that have been processed under ambient conditions. When compressed at conditions above their critical temperature and pres-sure, these substances become fluids with liquidlike density and the ability to dissolve other materials, and gaslike properties of low viscosity and high diffusivity. The gas-eous characteristics increase mass transfer rates, thereby significantly reducing process-ing time. Small added amounts of miscible polar cosolvents, such as alcohol, can be used to adjust polarity and to maximize the selectivity and capacity of the solvent. Fig. 42 Static mixer. (From Ref. 44.)
DOI link for put capacity and does not require premixing; it is fairly inexpensive and suitable for continuous operation. Major drawbacks to this equipment are its lack of availability, the need for special heating and cooling control systems, no available laboratory model, and the need for many trial-and-error runs in order to scale-up to production. 8. Static Mixers A true low-shear and low-energy requirement device for emulsifying immiscible liq-uid mixtures is the static mixer. Sometimes called a pipeline mixer, this device is ac-tually a series of specially designed baffles in a cylindrical pipe as shown in Fig. 42. These simple devices are used extensively for the preparation of unstable emulsions for liquid-liquid extraction purposes. Droplet sizes, obtainable using static mixers, have been studied extensively and vary with viscosity, interfacial tension, pressure drop, and static mixer design [45]. Size distributions obtainable range from 1000-100 |am. Hence, al-though there are very few emulsions stable in this region, the static mixer has seen application as an in-line premixer in continuous processes or in recirculation loops to batch-processing equipment. F. Nonmechanical Disperse Processing Recently a new processing technique became available for the production of stable and uniform liposomes. It uses the physico-chemical properties of the supercritical liquids rather than the mechanical forces of the pumps. One such a process technology is pre-sented in this section. 1. Critical Fluids Liposome Process Near-critical or supercritical fluid solvents with or without polar cosolvents (SuperFluids™) (Aphios, Corp., Woburn, MA) for the formation of uniform and stable liposomes having high encapsulation efficiencies has been used [46-48]. Supercritical or near-critical fluids as shown by the pressure-temperature diagram in Fig. 43, are gases such as carbon dioxide and propane that have been processed under ambient conditions. When compressed at conditions above their critical temperature and pres-sure, these substances become fluids with liquidlike density and the ability to dissolve other materials, and gaslike properties of low viscosity and high diffusivity. The gas-eous characteristics increase mass transfer rates, thereby significantly reducing process-ing time. Small added amounts of miscible polar cosolvents, such as alcohol, can be used to adjust polarity and to maximize the selectivity and capacity of the solvent. Fig. 42 Static mixer. (From Ref. 44.)
put capacity and does not require premixing; it is fairly inexpensive and suitable for continuous operation. Major drawbacks to this equipment are its lack of availability, the need for special heating and cooling control systems, no available laboratory model, and the need for many trial-and-error runs in order to scale-up to production. 8. Static Mixers A true low-shear and low-energy requirement device for emulsifying immiscible liq-uid mixtures is the static mixer. Sometimes called a pipeline mixer, this device is ac-tually a series of specially designed baffles in a cylindrical pipe as shown in Fig. 42. These simple devices are used extensively for the preparation of unstable emulsions for liquid-liquid extraction purposes. Droplet sizes, obtainable using static mixers, have been studied extensively and vary with viscosity, interfacial tension, pressure drop, and static mixer design [45]. Size distributions obtainable range from 1000-100 |am. Hence, al-though there are very few emulsions stable in this region, the static mixer has seen application as an in-line premixer in continuous processes or in recirculation loops to batch-processing equipment. F. Nonmechanical Disperse Processing Recently a new processing technique became available for the production of stable and uniform liposomes. It uses the physico-chemical properties of the supercritical liquids rather than the mechanical forces of the pumps. One such a process technology is pre-sented in this section. 1. Critical Fluids Liposome Process Near-critical or supercritical fluid solvents with or without polar cosolvents (SuperFluids™) (Aphios, Corp., Woburn, MA) for the formation of uniform and stable liposomes having high encapsulation efficiencies has been used [46-48]. Supercritical or near-critical fluids as shown by the pressure-temperature diagram in Fig. 43, are gases such as carbon dioxide and propane that have been processed under ambient conditions. When compressed at conditions above their critical temperature and pres-sure, these substances become fluids with liquidlike density and the ability to dissolve other materials, and gaslike properties of low viscosity and high diffusivity. The gas-eous characteristics increase mass transfer rates, thereby significantly reducing process-ing time. Small added amounts of miscible polar cosolvents, such as alcohol, can be used to adjust polarity and to maximize the selectivity and capacity of the solvent. Fig. 42 Static mixer. (From Ref. 44.)
ABSTRACT
In still another procedure, supercritical fluids can be uniquely used to encapsulate very hydrophobic molecules such as potent anticancer drugs, for example, paclitaxel, camptothecin, (a very effective topoisomerase-I inhibitor), and other anti-infective (antiHIV) agents [49]. In this case, the hydrophobic drug and the phospholipids are directly solubilized in the supercritical fluids prior to their injection into a phosphate buffered saline (PBS) or some other biocompatible solvents. After decompression through a nozzle, the supercritical fluids evaporate leaving an aqueous dispersion of liposomes containing hydrophobic molecules entrapped within their lipid bilayer.