CN110960504A - Hollow particle preparation method and dry powder inhalation preparation - Google Patents
Hollow particle preparation method and dry powder inhalation preparation Download PDFInfo
- Publication number
- CN110960504A CN110960504A CN201911051074.7A CN201911051074A CN110960504A CN 110960504 A CN110960504 A CN 110960504A CN 201911051074 A CN201911051074 A CN 201911051074A CN 110960504 A CN110960504 A CN 110960504A
- Authority
- CN
- China
- Prior art keywords
- flow channel
- liquid flow
- hollow particles
- organic phase
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
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
- A61K9/5005—Wall or coating material
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
- A61J3/02—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of powders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- 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
- A61K9/5089—Processes
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to a preparation method of hollow particles and a dry powder inhalation preparation, wherein the preparation method of the hollow particles comprises the following steps: providing a spray head, wherein the spray head is provided with a spray opening, a first liquid flow channel, a second liquid flow channel and an air flow channel which are communicated with the spray opening; introducing an organic phase into the first liquid flow channel, introducing a water phase into the second liquid flow channel, and introducing gas into the gas flow channel, so that the organic phase of the first liquid flow channel and the water phase of the second liquid flow channel are subjected to spray drying under the action of the gas while being contacted with each other through the jet orifice, and hollow particles are prepared; wherein one of the organic phase and the aqueous phase is dissolved with a drug, and the other is dissolved with a carrier for coating the drug. The preparation method of the hollow particles can greatly reduce the use of auxiliary materials and provide possibility for inhalation administration prescriptions with large dose.
Description
Technical Field
The invention relates to the technical field of dry powder preparation, in particular to a preparation method of hollow particles and a dry powder inhalation preparation.
Background
Pulmonary drug delivery is a simple, direct, effective, noninvasive mode of administration, and pulmonary drug delivery can achieve local and systemic therapeutic effects, and an important mode of pulmonary drug delivery is dry powder inhalation administration at present. Because the hollow particles have larger geometric diameter and smaller density, the aerodynamic diameter of the particles can be improved, and then good lung deposition rate is obtained, the absorption of the medicine is ensured, and the hollow particles are more and more favored by research personnel.
The current method of preparing hollow particles is to mix the nanoparticle solution with excipients (such as lactose, glucose, etc.) to form a mixed solution for spray drying. When the particle size of the medicine is below 10 mu m, the fluidity of the medicine powder can be reduced, so that the method needs to greatly increase the dosage of the auxiliary materials in the micronized medicine so as to achieve the aims of flow aid, powder fluidity improvement and accurate dosage quantification, and the addition amount of the auxiliary materials reaches 50-100 times of the medicine quality generally. However, the addition of large amounts of excipients limits the use of bolus formulations in inhalation delivery systems.
Disclosure of Invention
Based on this, there is a need for a method for preparing hollow particles and a dry powder inhalation formulation. The preparation method of the hollow particles can greatly reduce the use amount of the auxiliary materials, and provides possibility for a large-dose inhalation administration prescription.
A method of making hollow particles comprising the steps of:
providing a spray head, wherein the spray head is provided with a spray opening, a first liquid flow channel, a second liquid flow channel and an air flow channel which are communicated with the spray opening;
introducing an organic phase into the first liquid flow channel, introducing an aqueous phase into the second liquid flow channel, and introducing gas into the gas flow channel, so that the organic phase of the first liquid flow channel and the aqueous phase of the second liquid flow channel are subjected to spray drying under the action of the gas while being in contact with each other through the jet orifice, and the hollow particles are prepared;
wherein, one of the organic phase and the water phase is dissolved with a drug, and the other is dissolved with a carrier for coating the drug.
In one embodiment, the second flow passage communicates with a middle portion of the injection port, and the first flow passage and the gas flow passage communicate with an edge portion of the injection port around the middle portion.
In one embodiment, the flow rate of the organic phase is 1mL/min to 5mL/min, and the flow rate of the aqueous phase is 1mL/min to 10 mL/min.
In one embodiment, the outlet temperature of the first liquid flow channel and the second liquid flow channel of the spray head is 60-100 ℃; and/or
The evaporation solvent amount of the injection opening is 400L/h-100L/h.
In one embodiment, the gas introduced into the gas flow channel is air, and the air flux in the gas flow channel is 160m3/h～330m3/h。
In one embodiment, the carrier is a hydrophobic amino acid; and/or
The drug is a glucocorticoid drug.
In one embodiment, the hydrophobic amino acid is selected from: one or more of leucine, tryptophan, phenylalanine, valine, isoleucine, alanine and methionine.
In one embodiment, the glucocorticoid drug is selected from the group consisting of: one or more of budesonide, prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
In one embodiment, the mass percentage of the drug in the organic phase is 1-10%; and/or
The mass percentage of the carrier in the water phase is 0.1-10%.
A dry powder inhalation preparation comprises the hollow particles prepared by the method.
The preparation method of the hollow particles adopts a multi-channel nozzle, one channel is communicated with an organic phase, the other channel is communicated with a water phase, the hollow particles are formed by utilizing the principle of anti-solvent and spray drying under the action of air flow, the content of auxiliary materials in the hollow particles can be greatly reduced, the hollow particles containing a small amount of auxiliary materials or pure medicinal hollow particles without auxiliary materials are prepared, the particle size of the hollow particles prepared by the method can reach less than 10 mu m, the hollow particles have proper aerodynamic particle size (can reach less than 5 mu m), and the possibility is provided for a large-dose inhalation administration prescription.
Drawings
Fig. 1 is a schematic structural diagram of a showerhead according to an embodiment of the present invention.
Detailed Description
In order that the invention may be more fully understood, a more particular description of the invention will now be rendered by reference to specific embodiments thereof that are illustrated in the appended drawings. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The invention provides a preparation method of hollow particles, which comprises the following steps:
s101, providing a spray head, wherein as shown in FIG. 1, the spray head 10 of the present invention has a spray opening A, and a first liquid flow passage 211, a second liquid flow passage 212 and a gas flow passage 220 which are all communicated with the spray opening A.
In one embodiment, the nozzle 10 includes an outer casing 100 having a nozzle opening A, the first flow path 211, the second flow path 212 and the air flow path 220 are disposed in the outer casing 100, and the outlets of the first flow path 211, the second flow path 212 and the air flow path 220 converge at the nozzle opening A of the outer casing 100. Wherein the first flow path 211 is for circulating the organic phase, and the second flow path 212 is for circulating the aqueous phase.
It is understood that the number of the gas flow path 220, the first liquid flow path 211 and the second liquid flow path 212 in the present invention is not particularly limited, and may be any integer greater than or equal to 1. In one embodiment, the spray head 10 is a three-channel spray head, i.e., includes a first fluid flow channel 211, a second fluid flow channel 212, and a gas flow channel 220.
Further, the end of the head 10 where the ejection opening a is provided gradually tapers from the air flow passage 220 toward the ejection opening a.
Further, the second flow passage 212 communicates with the middle portion of the injection port a, and the first flow passage 211 and the gas flow passage 220 communicate with the side portion of the injection port a around the middle portion.
Further, the second liquid flow channel 212 is disposed between the first liquid flow channel 211 and the air flow channel 220 to facilitate the air flow to sequentially wrap the liquid droplets and to rapidly volatilize the solvent in the liquid droplets, thereby achieving rapid spray drying.
Further, the central axis of the second flow path 212 overlaps the central axis of the outer sleeve 100, and the first flow path 211 and the gas flow path 220 are disposed on both sides of the second flow path 212 in an axisymmetric manner with the central axis of the second flow path 212 as a symmetry axis.
Further, the central axis of the second flow path 212 and the central axis of the injection port are on the same line, and the first flow path 211 and the gas flow path 220 each include a parallel section spaced apart from and arranged in parallel with the second flow path 212 and a bent section communicating with the parallel section, the bent section communicating with the injection port a.
S102: introducing an organic phase into the first liquid flow channel 211, introducing a water phase into the second liquid flow channel 212, and introducing gas into the gas flow channel 220, so that the organic phase of the first liquid flow channel 211 and the water phase of the second liquid flow channel 212 are subjected to spray drying under the action of the gas while being in contact with each other at the injection port A, and hollow particles are prepared; wherein, one of the organic phase and the water phase is dissolved with the drug, and the other is dissolved with the carrier for wrapping the drug.
On the basis of the spray head, the organic phase and the water phase are respectively introduced into the two liquid flow channels, and the anti-solvent principle is utilized, so that the addition of a large amount of auxiliary materials in the traditional method can be effectively avoided, the fluidity of the hollow particle powder is further improved, and the possibility is provided for a large-dose inhalation administration prescription.
Further, the flow rate of the organic phase and the flow rate of the aqueous phase are greater than or equal to 1mL/min, so that the organic phase and the aqueous phase can collide at a high speed at the jet orifice, and the particle size of the hollow particles is reduced.
Furthermore, the flow rate of the organic phase is 1mL/min to 5mL/min, and the flow rate of the aqueous phase is 1mL/min to 10 mL/min.
It should be noted that, when the head includes a plurality of first flow channels, the flow rates of the organic phase in the plurality of first flow channels may be the same or different; similarly, when the head has a plurality of second liquid flow passages, the flow rates of the aqueous phases in the plurality of second liquid flow passages may be the same or different.
Further, the gas introduced into the gas flow channel is air, and the air flux of the gas flow channel is more than or equal to 150m3H, to promote the formation of hollow particles of smaller particle size while ensuring that spray drying is carried out.
Further, it is preferable that the air flux is 160m3/h～330m3/h。
Further, the outlet temperature of the first liquid flow channel and the second liquid flow channel is 60-100 ℃, and/or the evaporation solvent amount of the injection port is 400-100L/h, so as to ensure that the spray drying is fully carried out.
In addition, in the invention, one phase of the organic phase and the water phase is dissolved with the drug, and the other phase is dissolved with the carrier for wrapping the drug. In one embodiment, the drug is dissolved in an organic phase and the carrier is dissolved in an aqueous phase. Wherein, the solvent of the organic phase can be DMF, methanol, ethanol and other organic solvents, and the solvent of the water phase is water.
Further, the drug is a glucocorticoid drug, including but not limited to one or more of budesonide, prednisone, methylprednisolone, betamethasone, beclomethasone dipropionate, prednisolone, hydrocortisone, and dexamethasone.
Furthermore, the carrier is hydrophobic amino acid, and the surface diffusivity is improved by adopting the hydrophobic amino acid, so that the amino acid can rapidly move to the surface under the action of a hydrophobic group, the curing speed is accelerated, and the formation of hollow particles is further ensured.
Still further, it is preferred that the hydrophobic amino acid is selected from: one or more of leucine, tryptophan, phenylalanine, valine, isoleucine, alanine and methionine.
In addition, the concentration of the drug and the carrier can be adjusted according to the specific type and production requirement of the drug, and in one embodiment, the mass percentage content of the drug in the organic phase is 1-10%; and/or the mass percentage of the carrier in the water phase is 0.1-10%.
The invention also provides a dry powder inhalation preparation which comprises the hollow particles prepared by the preparation method, and the preparation method of the hollow particles is the same as the above and is not repeated.
The present invention will be described below with reference to specific examples.
Example 1
The preparation method comprises the following steps:
(1) providing a showerhead 10, as shown in fig. 1, the showerhead 10 having an injection port a and a first liquid flow passage 211, a second liquid flow passage 212 and a gas flow passage 220 all communicating with the injection port a; the first flow path 211 and the gas flow path 220 are disposed on both sides of the second flow path 212 in an axisymmetrical manner with the center axis of the second flow path 212 as a symmetry axis.
(2) Introducing an organic phase into the first liquid flow channel, introducing a water phase into the second liquid flow channel, and introducing gas into the gas flow channel, so that the organic phase in the first liquid flow channel 211 and the water phase in the second liquid flow channel 212 are in contact with each other in the jet opening A and are subjected to spray drying under the action of the gas to prepare hollow particles;
wherein the organic phase is a methanol solution of budesonide (1g/mL) with a flow rate of 5mL/min, the aqueous phase is an aqueous solution of leucine (0.1g/mL) with a flow rate of 1mL/min, see Table 1 for details, and see Table 2 for other parameter settings.
Example 2
The preparation method comprises the following steps:
(1) providing a showerhead 10, as shown in fig. 1, the showerhead 10 having an injection port a and a first liquid flow passage 211, a second liquid flow passage 212 and a gas flow passage 220 all communicating with the injection port a; the first flow path 211 and the gas flow path 220 are disposed on both sides of the second flow path 212 in an axisymmetrical manner with the center axis of the second flow path 212 as a symmetry axis.
(2) Introducing an organic phase into the first liquid flow channel, introducing a water phase into the second liquid flow channel, and introducing gas into the gas flow channel, so that the organic phase in the first liquid flow channel 211 and the water phase in the second liquid flow channel 212 are in contact with each other in the jet opening A and are subjected to spray drying under the action of the gas to prepare hollow particles;
wherein the organic phase is a methanol solution (3g/mL) of betamethasone, the flow rate is 4mL/min, the aqueous phase is an aqueous solution (0.6g/mL) of tryptophan, the flow rate is 6mL/min, see Table 1 specifically, and see Table 2 for other parameter settings.
Example 3
The preparation method comprises the following steps:
(1) providing a showerhead 10, as shown in fig. 1, the showerhead 10 having an injection port a and a first liquid flow passage 211, a second liquid flow passage 212 and a gas flow passage 220 all communicating with the injection port a; the first flow path 211 and the gas flow path 220 are disposed on both sides of the second flow path 212 in an axisymmetrical manner with the center axis of the second flow path 212 as a symmetry axis.
(2) Introducing an organic phase into the first liquid flow channel, introducing a water phase into the second liquid flow channel, and introducing gas into the gas flow channel, so that the organic phase in the first liquid flow channel 211 and the water phase in the second liquid flow channel 212 are in contact with each other in the jet opening A and are subjected to spray drying under the action of the gas to prepare hollow particles;
wherein the organic phase is a methanol solution of hydrocortisone (4g/mL) at a flow rate of 3mL/min, the aqueous phase is an aqueous solution of valine (0.8g/mL) at a flow rate of 8mL/min, see Table 1 for details, and other parameter settings see Table 2.
Example 4
The preparation method comprises the following steps:
(1) providing a showerhead 10, as shown in fig. 1, the showerhead 10 having an injection port a and a first liquid flow passage 211, a second liquid flow passage 212 and a gas flow passage 220 all communicating with the injection port a; the first flow path 211 and the gas flow path 220 are disposed on both sides of the second flow path 212 in an axisymmetrical manner with the center axis of the second flow path 212 as a symmetry axis.
(2) Introducing an organic phase into the first liquid flow channel, introducing a water phase into the second liquid flow channel, and introducing gas into the gas flow channel, so that the organic phase in the first liquid flow channel 211 and the water phase in the second liquid flow channel 212 are in contact with each other in the jet opening A and are subjected to spray drying under the action of the gas to prepare hollow particles;
wherein the organic phase is dexamethasone in methanol (5g/mL) at a flow rate of 1mL/min, the aqueous phase is alanine in water (1.0g/mL) at a flow rate of 10mL/min, see Table 1 for details, and other parameter settings see Table 2.
Table 1:
table 2:
| parameters of the instrument | Parameter setting |
| Outlet temperature | 60-100℃ |
| Amount of evaporated solvent | 400-100L/h |
| Dry air flux | 160-330m3/h |
Comprehensive performance testing
The overall performance of the center granules prepared by the methods of examples 1-4 was determined, and the test criteria included: particle size, compression, angle of repose and flow rate, the test results are shown in table 3.
The test method comprises the following steps:
particle size: referring to the third method of the pharmacopoeia 2015 year edition general rule 0982 for light scattering
Degree of compression: powder flowability requirements according to the European pharmacopoeia section 2.9.36
Angle of repose: powder flowability requirements according to section U European pharmacopoeia 2.9.36
Flow rate: powder flowability requirements of the European pharmacopoeia section 2.9.36
Table 3: summary of test results for examples 1-4 (n ═ 3)
As can be seen from table 3, the hollow particle powders of examples 1 to 4 all had a small particle diameter and excellent flowability.
Characterization of aerodynamic parameters
Aerodynamic characterization of hollow particles prepared by the methods of examples 1-4 was determined using a drug impactor. The test method is USP 601, and the results are as follows:
table 4: results of the drug impactor measurements of examples 1-4 (n ═ 3)
As can be seen from Table 4, the Mass Median Aerodynamic Diameter (MMAD) of examples 1 to 4 is less than 5 μm, and the fine particle specific gravity (FPD) is high, so that the hollow particles prepared by the method of the present invention can be applied to inhalation formulations.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. A method for preparing hollow particles, which is characterized by comprising the following steps:
providing a spray head, wherein the spray head is provided with a spray opening, a first liquid flow channel, a second liquid flow channel and an air flow channel which are respectively communicated with the spray opening;
introducing an organic phase into the first liquid flow channel, introducing an aqueous phase into the second liquid flow channel, and introducing gas into the gas flow channel, so that the organic phase of the first liquid flow channel and the aqueous phase of the second liquid flow channel are subjected to spray drying under the action of the gas while being in contact with each other through the jet orifice, and the hollow particles are prepared;
wherein, one of the organic phase and the water phase is dissolved with a drug, and the other is dissolved with a carrier for coating the drug.
2. The method of producing hollow particles according to claim 1, wherein the second liquid flow passage communicates with a middle portion of the ejection port, and the first liquid flow passage and the gas flow passage communicate with an edge portion of the ejection port around the middle portion.
3. The method of claim 2, wherein the flow rate of the organic phase is 1 to 5mL/min and the flow rate of the aqueous phase is 1 to 10 mL/min.
4. The method for producing hollow particles according to claim 1, wherein the outlet temperature of the first and second liquid flow passages of the shower head is 60 ℃ to 100 ℃; and/or
The evaporation solvent amount of the injection opening is 400L/h-100L/h.
5. The method for producing hollow particles according to claim 1, wherein the gas introduced into the gas flow channel is air, and the air flux in the gas flow channel is 160m3/h～330m3/h。
6. The method for producing hollow particles according to any one of claims 1 to 5, wherein the carrier is a hydrophobic amino acid; and/or
The drug is a glucocorticoid drug.
7. The method for producing hollow particles according to claim 6, wherein the hydrophobic amino acid is selected from the group consisting of: one or more of leucine, tryptophan, phenylalanine, valine, isoleucine, alanine and methionine.
8. The method of claim 6, wherein the glucocorticoid drug is selected from the group consisting of: one or more of budesonide, prednisone, methylprednisolone, betamethasone, beclomethasone propionate, prednisolone, hydrocortisone, and dexamethasone.
9. The method for preparing hollow particles according to claim 1, wherein the drug is dissolved in the organic phase, and the mass percentage of the drug in the organic phase is 1% to 10%; and/or
The carrier is dissolved in the water phase, and the mass percentage of the carrier in the water phase is 0.1-10%.
10. A dry powder inhalation formulation comprising the hollow particles produced by the production method according to any one of claims 1 to 9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911051074.7A CN110960504A (en) | 2019-10-31 | 2019-10-31 | Hollow particle preparation method and dry powder inhalation preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911051074.7A CN110960504A (en) | 2019-10-31 | 2019-10-31 | Hollow particle preparation method and dry powder inhalation preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110960504A true CN110960504A (en) | 2020-04-07 |
Family
ID=70030223
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911051074.7A Pending CN110960504A (en) | 2019-10-31 | 2019-10-31 | Hollow particle preparation method and dry powder inhalation preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110960504A (en) |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002045690A1 (en) * | 2000-12-08 | 2002-06-13 | Unisearch Limited | Synthesis of small particles |
| CN1409627A (en) * | 1999-11-03 | 2003-04-09 | 葛兰素集团有限公司 | Novel apparatus and process for preparing crystalline particles |
| CN2841040Y (en) * | 2005-11-14 | 2006-11-29 | 朱建军 | Jet-flow medical atomizing apparatus |
| CN1973827A (en) * | 2006-12-15 | 2007-06-06 | 北京化工大学 | Prepn process of superfine inhaled glucocorticoid medicine powder |
| CN103328089A (en) * | 2010-12-21 | 2013-09-25 | 哈佛学院院长等 | Spray drying techniques |
| CN107320460A (en) * | 2017-08-04 | 2017-11-07 | 北京化工大学 | A kind of nilotinib oral administration nanometer preparation and preparation method thereof |
| CN107960055A (en) * | 2015-03-31 | 2018-04-24 | 好利安科技有限公司 | The continuous preparation of particle |
| CN209735001U (en) * | 2019-01-29 | 2019-12-06 | 洛阳中超新材料股份有限公司 | Spray nozzle for spray dryer |
-
2019
- 2019-10-31 CN CN201911051074.7A patent/CN110960504A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1409627A (en) * | 1999-11-03 | 2003-04-09 | 葛兰素集团有限公司 | Novel apparatus and process for preparing crystalline particles |
| WO2002045690A1 (en) * | 2000-12-08 | 2002-06-13 | Unisearch Limited | Synthesis of small particles |
| CN2841040Y (en) * | 2005-11-14 | 2006-11-29 | 朱建军 | Jet-flow medical atomizing apparatus |
| CN1973827A (en) * | 2006-12-15 | 2007-06-06 | 北京化工大学 | Prepn process of superfine inhaled glucocorticoid medicine powder |
| CN103328089A (en) * | 2010-12-21 | 2013-09-25 | 哈佛学院院长等 | Spray drying techniques |
| CN107960055A (en) * | 2015-03-31 | 2018-04-24 | 好利安科技有限公司 | The continuous preparation of particle |
| CN107320460A (en) * | 2017-08-04 | 2017-11-07 | 北京化工大学 | A kind of nilotinib oral administration nanometer preparation and preparation method thereof |
| CN209735001U (en) * | 2019-01-29 | 2019-12-06 | 洛阳中超新材料股份有限公司 | Spray nozzle for spray dryer |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Zeng et al. | The influence of lactose carrier on the content homogeneity and dispersibility of beclomethasone dipropionate from dry powder aerosols | |
| US7267813B2 (en) | Inhalation particles incorporating a combination of two or more active ingredients | |
| KR100951750B1 (en) | Spray drying methods and compositions thereof | |
| US20080029084A1 (en) | Device for improved peptide delivery | |
| JP4728558B2 (en) | Method for producing nanoparticles | |
| EP2983645B1 (en) | Composition comprising at least two dry powders obtained by spray drying to increase the stability of the formulation | |
| MXPA05006322A (en) | Novel dry powder inhalation system for transpulmonary administration. | |
| US7172752B2 (en) | Combination particles for the treatment of asthma | |
| KR20130140358A (en) | Dry powder for inhalation formulation comprising salmeterol xinafoate, fluticasone propionate and tiotropium bromide, and method for preparing the same | |
| US20150202156A1 (en) | Dry powder pharmaceutical composition, its preparation process and stable aqueous suspension obtained from such composition | |
| US20100183725A1 (en) | Multiple active pharmaceutical ingredients combined in discrete inhalation particles and formulations thereof | |
| US10517828B2 (en) | Composition comprising at least one dry powder obtained by spray drying to increase the stability of the formulation | |
| EP1242048B2 (en) | INHALATION PARTICLES: method of preparation | |
| EP2821061B1 (en) | Novel inhalation formulations | |
| CN110960504A (en) | Hollow particle preparation method and dry powder inhalation preparation | |
| US20220409831A1 (en) | Inhaler devices, medication formulations used therewith and methods of manufacture | |
| Pilicheva et al. | Flowability evaluation of dry powder inhalation formulations intended for nasal delivery of Betahistine Dihydrochloride | |
| CN108721219A (en) | A kind of bioadhesive lung inhales Nano Composite Particles and preparation method thereof | |
| CN100428938C (en) | Glucocorticoid capsule type inhaling atomized powder and preparation method | |
| CN112933047A (en) | Preparation method of ultrafine pulverized salmeterol ticasone | |
| WO2017053409A1 (en) | Pulmonary delivery of progestogen | |
| Vartiainen et al. | Development of Inhalable Drug Formulations for Idiopathic Pulmonary Fibrosis | |
| CN116421585A (en) | Suspension budesonide inhalation aerosol and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200407 |