WO2023059210A1 - Procédé de préparation de particules par atomisation - Google Patents
Procédé de préparation de particules par atomisation Download PDFInfo
- Publication number
- WO2023059210A1 WO2023059210A1 PCT/PT2022/050026 PT2022050026W WO2023059210A1 WO 2023059210 A1 WO2023059210 A1 WO 2023059210A1 PT 2022050026 W PT2022050026 W PT 2022050026W WO 2023059210 A1 WO2023059210 A1 WO 2023059210A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- mixture
- solution
- particles
- frozen
- liquid solution
- Prior art date
Links
- 239000002245 particle Substances 0.000 title claims abstract description 92
- 238000000889 atomisation Methods 0.000 title claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 title description 10
- 239000000203 mixture Substances 0.000 claims abstract description 117
- 238000000034 method Methods 0.000 claims abstract description 57
- 239000012530 fluid Substances 0.000 claims abstract description 51
- 239000007787 solid Substances 0.000 claims abstract description 49
- 239000006193 liquid solution Substances 0.000 claims abstract description 48
- 238000000859 sublimation Methods 0.000 claims abstract description 32
- 230000008022 sublimation Effects 0.000 claims abstract description 32
- 238000004108 freeze drying Methods 0.000 claims abstract description 29
- 238000000926 separation method Methods 0.000 claims abstract description 16
- 238000001035 drying Methods 0.000 claims abstract description 11
- 230000005484 gravity Effects 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 86
- 239000012716 precipitator Substances 0.000 claims description 20
- 239000007864 aqueous solution Substances 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 230000008018 melting Effects 0.000 claims description 5
- 238000002844 melting Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 238000009834 vaporization Methods 0.000 claims description 5
- 230000008016 vaporization Effects 0.000 claims description 5
- 230000009477 glass transition Effects 0.000 claims description 4
- -1 cell Substances 0.000 claims description 3
- 102000039446 nucleic acids Human genes 0.000 claims description 2
- 108020004707 nucleic acids Proteins 0.000 claims description 2
- 150000007523 nucleic acids Chemical class 0.000 claims description 2
- 102000004169 proteins and genes Human genes 0.000 claims description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 2
- 238000001816 cooling Methods 0.000 abstract description 9
- 239000002105 nanoparticle Substances 0.000 description 15
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 11
- 229930195725 Mannitol Natural products 0.000 description 11
- 239000000594 mannitol Substances 0.000 description 11
- 235000010355 mannitol Nutrition 0.000 description 11
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- 229940098773 bovine serum albumin Drugs 0.000 description 8
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 8
- 238000010438 heat treatment Methods 0.000 description 7
- 238000004626 scanning electron microscopy Methods 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 238000010943 off-gassing Methods 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 239000005720 sucrose Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 229960000278 theophylline Drugs 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 3
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 description 3
- 239000001569 carbon dioxide Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical class C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 3
- 238000007711 solidification Methods 0.000 description 3
- 230000008023 solidification Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000012792 lyophilization process Methods 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 229920002101 Chitin Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 238000012382 advanced drug delivery Methods 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000005315 distribution function Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012520 frozen sample Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000001878 scanning electron micrograph Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000001808 supercritical antisolvent technique Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5192—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D1/00—Evaporating
- B01D1/16—Evaporating by spraying
- B01D1/18—Evaporating by spraying to obtain dry solids
Definitions
- the depressurization takes place at the sublimation temperature of the dry ice under the existing pressure conditions, and the depressurization temperature is controlled by the depressurization of the supercritical CO 2 fluid itself, which leads to the cooling of the system.
- the depressurization takes place at a temperature of at least -80°C; preferably -78.5 ° C,
- the liquid solution/mixture and the supercritical CO 2 fluid are depressurized separately. [0030] In one embodiment, the liquid solution/mixture and the supercritical CO 2 fluid are depressurized in separate injectors. In another embodiment, the liquid solution/mixture and the supercritical CO 2 fluid are depressurized in separate injectors, where the solution/mixture is atomized by an ultrasonic injector.
- freeze-drying takes place at a pressure ranging from 1 to 1000 Pa, preferably from 10 to 100 Pa. In one embodiment, freeze-drying takes place at a temperature ranging from -80°C to 25°C, preferably from -40 to 20°C; in yet another embodiment, lyophilization takes place for 24 to 120 hours, preferably for 72 hours. Preferably, lyophilization takes place at 10 Pa and -40 °C for 12 h followed by a heating ramp to -10 °C (1 °C/min) followed by a hold at -10 °C for 20 h, followed by a heating ramp of 0.15 °C/min to 25 °C, followed by 12 h at 25 °C.
- the present disclosure also describes a nebulizer, tablets or suspension characterized by comprising the described nanoparticle.
- the suspension is parenterally administrable.
- the supercritical CO 2 fluid can be depressurized in an injector different from the injector in which the liquid solution/mixture is depressurized.
- the supercritical CO 2 fluid can be depressurized in co-current, in which both injectors are located at the top of the precipitator, or in counter-current, with, for example, the supercritical CO 2 fluid being depressurized through an injector located at the bottom of the precipitator and the solution/mixture depressurized through an injector located at the top of the precipitator.
- the depressurization of the supercritical CO 2 fluid or the mixture of the supercritical CO 2 fluid with the liquid solution should preferably be greater than 12 MPa so that the cooling causes the sublimation of the CO 2 to the state solid and form a macrostructure that surrounds and captures the droplets resulting from the solution/mixture after its atomization.
- depressurisations lower than 12 MPa and higher than 8 MPa, using higher ratios of CO 2 flow per solution flow, preferably between 20 and 50.
- Supercritical CO 2 from a pressure of 12 MPa to atmospheric pressure, through an injector with a channel 0.15 mm in diameter and 0.25 mm in length.
- the solution and the supercritical CO 2 were mixed immediately before the injector at a temperature of 40°C, in a volume of less than 0.1 ml.
- the supercritical CO 2 fluid flow rate was 35 g/min and the solution flow rate was 2.2 g/min.
- the solid was captured in a cylindrical precipitator of 0.2 L volume and 50 mm diameter.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Physical Or Chemical Processes And Apparatus (AREA)
- Glanulating (AREA)
- Medicinal Preparation (AREA)
Abstract
La présente invention concerne un procédé pour obtenir des particules ayant des dimensions inférieures à 1 micromètre par atomisation à partir d'une solution/d'un mélange liquide. Ledit procédé est caractérisé en ce qu'il comprend les étapes suivantes consistant à atomiser la solution/le mélange liquide et un fluide de CO2 supercritique par élimination de la pression au moyen d'au moins un injecteur, avec au moins un canal, et à refroidir la solution/le mélange liquide et le fluide à pression éliminée jusqu'à la congélation de la solution et la solidification d'au moins 10% en poids de CO2; pour obtenir des particules atomisées de la solution/du mélange congelé dans lequel le CO2 à pression éliminée implique les particules atomisées de la solution/du mélange congelé; séparer les particules atomisées de la solution/du mélange congelé et le CO2 solide du CO2 gazeux au moyen de la séparation gravitationnelle, d'un cyclone et/ou d'un filtre; séparer le CO2 solide des particules atomisées de la solution/du mélange congelé par sublimation du CO2; et sécher les particules atomisées de la solution/du mélange congelé par lyophilisation.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PT117503A PT117503B (pt) | 2021-10-07 | 2021-10-07 | Método de preparação de particulas por atomização |
| PT117503 | 2021-10-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2023059210A1 true WO2023059210A1 (fr) | 2023-04-13 |
Family
ID=84365724
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/PT2022/050026 WO2023059210A1 (fr) | 2021-10-07 | 2022-10-06 | Procédé de préparation de particules par atomisation |
Country Status (2)
| Country | Link |
|---|---|
| PT (1) | PT117503B (fr) |
| WO (1) | WO2023059210A1 (fr) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101869282A (zh) * | 2010-06-12 | 2010-10-27 | 嘉吉烯王生物工程（武汉）有限公司 | 一种喷雾冷冻干燥制备多不饱和脂肪酸油脂微胶囊的方法 |
| WO2013139384A1 (fr) * | 2012-03-21 | 2013-09-26 | Dorkoosh, Farid Abedin | Congélation de solutions en aérosol (fas): système de production continue de particules |
| WO2016184576A2 (fr) * | 2015-05-20 | 2016-11-24 | Curevac Ag | Composition de poudre sèche comprenant de l'arn à chaîne longue |
-
2021
- 2021-10-07 PT PT117503A patent/PT117503B/pt active IP Right Grant
-
2022
- 2022-10-06 WO PCT/PT2022/050026 patent/WO2023059210A1/fr unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101869282A (zh) * | 2010-06-12 | 2010-10-27 | 嘉吉烯王生物工程（武汉）有限公司 | 一种喷雾冷冻干燥制备多不饱和脂肪酸油脂微胶囊的方法 |
| WO2013139384A1 (fr) * | 2012-03-21 | 2013-09-26 | Dorkoosh, Farid Abedin | Congélation de solutions en aérosol (fas): système de production continue de particules |
| WO2016184576A2 (fr) * | 2015-05-20 | 2016-11-24 | Curevac Ag | Composition de poudre sèche comprenant de l'arn à chaîne longue |
Non-Patent Citations (1)
| Title |
|---|
| SHOYELE S A ET AL: "Particle engineering techniques for inhaled biopharmaceuticals", ADVANCED DRUG DELIVERY REVIEWS, ELSEVIER, AMSTERDAM , NL, vol. 58, no. 9-10, 31 October 2006 (2006-10-31), pages 1009 - 1029, XP024892116, ISSN: 0169-409X, [retrieved on 20061031], DOI: 10.1016/J.ADDR.2006.07.010 * |
Also Published As
| Publication number | Publication date |
|---|---|
| PT117503B (pt) | 2024-03-20 |
| PT117503A (pt) | 2023-04-10 |
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