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WO2022116792A1 - Produit à inhaler à base de poudre sèche d'isoniazide pour le traitement de la tuberculose pulmonaire - Google Patents

Produit à inhaler à base de poudre sèche d'isoniazide pour le traitement de la tuberculose pulmonaire Download PDF

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Publication number
WO2022116792A1
WO2022116792A1 PCT/CN2021/130116 CN2021130116W WO2022116792A1 WO 2022116792 A1 WO2022116792 A1 WO 2022116792A1 CN 2021130116 W CN2021130116 W CN 2021130116W WO 2022116792 A1 WO2022116792 A1 WO 2022116792A1
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Prior art keywords
isoniazid
dry powder
powder inhaler
leucine
lactose
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English (en)
Chinese (zh)
Inventor
张桐桐
王实强
曲伟
张涛
张国立
颜携国
李勇
梁民彩
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Shenzhen Sciencare Medical Industries Co Ltd
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Shenzhen Sciencare Medical Industries Co Ltd
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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis

Definitions

  • the invention belongs to the field of pharmaceutical preparations, and in particular relates to an isoniazid dry powder inhaler for treating pulmonary tuberculosis, a preparation method thereof, and its use in preparing medicines for treating various types of pulmonary tuberculosis.
  • Pulmonary tuberculosis is a highly contagious lung disease, which is highly destructive to the lungs and takes a long time to treat, usually more than half a year.
  • the current clinical treatment of pulmonary tuberculosis often adopts oral administration of isoniazid, rifampicin, ethambutol and pyrazinamide.
  • isoniazid has strong antibacterial activity against Mycobacterium tuberculosis, and is a very effective and rapid Mycobacterium tuberculosis fungicide.
  • conventional oral preparations have strong hepatotoxicity, and it is difficult to achieve and maintain effective or high drug concentrations in the trachea, bronchi and alveolar secretions.
  • isoniazid injection can assist in the treatment of pulmonary tuberculosis after inhalation by atomization.
  • CN1102093A discloses an isoniazid aerosol, a spray and a preparation method thereof, wherein the content of the aerosol is composed of the drug isoniazid; diluent and specific gravity regulator anhydrous sodium sulfate or anhydrous lactose; Agent Span-85, ethyl oleate; latent solvent trichloromonofluoromethane; propellant dichlorodifluoromethane, dichlorotetrachloroethane, etc., wherein the content of the spray is the drug isoniazid; pH Regulator boric acid (salt), phosphate; osmotic pressure regulator sodium chloride, glucose, solvent water, etc.
  • the defects of isoniazid aerosols and sprays are that the process is cumbersome and the delivery rate is very low, with only 2-5 mg of drug per swipe, while dry powder inhalers can deliver 10-50
  • CN101684116A discloses an isoniazid lipid derivative and a composition thereof, characterized in that the structure of the isoniazid lipid derivative is: INH-THTT-R, wherein INH is isoniazid and THTT is thiadiazine thione , R is a long aliphatic chain with 6-20 carbon atoms. Tablets, capsules, injections, aerosols, dry powder inhalers and highly dispersible dosage forms can be prepared from isoniazid lipid derivatives.
  • This application chemically synthesizes isoniazid and modifies it as a lipid derivative to improve the absorption of isoniazid in vivo, but this method has complicated preparation process, poor preparation stability, and difficulty in scaling up the process production.
  • CN103110633A relates to a dry powder inhaler that can prevent the respiratory tract transmission of Mycobacterium tuberculosis. 5%, firstly mix isoniazid sustained-release microspheres, rifampicin sustained-release microspheres, and glidant together, and put them in gelatin, plastic capsules or aluminum-plastic blister, or in the form of storage Packaged in a multi-dose dry powder inhaler device.
  • this application uses a large amount of gelatin excipients.
  • the gelatin is derived from animals and may have some immunogenicity when it enters the lung, so the safety cannot be guaranteed.
  • the amount of added excipients is large, and the drug load will decrease.
  • the present inventor prepared an isoniazid dry powder inhaler with high stability and high drug loading by using modern formulation technology. Department to treat various types of tuberculosis.
  • the isoniazid dry powder inhalation prepared by the method of the invention is especially suitable for treating pulmonary tuberculosis and bronchial tuberculosis in patients with impaired liver function.
  • the present invention relates to an isoniazid dry powder inhaler for treating pulmonary tuberculosis, characterized in that: the dry powder inhaler comprises isoniazid micropowder, and with or without carrier micropowder, by fluidizing
  • the carrier micro-powder is prepared by adding excipients inside, and the excipients are amino acids, mannitol or phospholipids, and the dry powder inhaler also includes adjuvants selected from amino acids, phospholipids, sugars or magnesium stearate. one or more.
  • the amino acid is selected from leucine, valine, glycine or isoleucine, preferably leucine.
  • the saccharide is selected from mannitol, lactose, maltose, trehalose or sucrose, preferably lactose or mannitol.
  • the type of lactose is one or more of Inhalac 120, Inhalac 140, Inhalac 230 or Inhalac 400.
  • the internal adjuvant is leucine
  • the added amount of the leucine accounts for 0-30%, preferably 2-10%, of the total weight of the dry powder inhaler.
  • the adjuvant is leucine and/or lactose and/or magnesium stearate and/or mannitol
  • the added amount of the leucine accounts for 5% of the total weight of the dry powder inhaler 0-30%, preferably 2-10%
  • the added amount of the lactose accounts for 0-50% of the total weight of the dry powder inhaler, preferably 10-30%.
  • the addition amount of the magnesium stearate accounts for 0-10% of the total dry powder inhaler, preferably 1-5%
  • the addition of the mannitol accounts for 0-50% of the total dry powder inhaler, preferably 10-30%. %. .
  • the present invention relates to a method for preparing the above-mentioned isoniazid dry powder inhaler for treating pulmonary tuberculosis, the method comprising the steps of: passing the isoniazid through a fluidized bed supersonic jet pulverization method To prepare isoniazid micropowder, take isoniazid micropowder, mix lactose and isoniazid micropowder according to a certain proportion, add leucine after mixing, and then pack the mixed powder in a capsule or blister, or in the form of a reservoir Packaged in a multi-dose dry powder inhalation device, or the method includes the following steps: dissolving isoniazid in a certain amount of solvent, adding leucine to prepare a clear and transparent solution, spray-drying the above solution, collecting cyclone separation drying Continue to dry the micropowder in the container for a period of time, add lactose and/or magnesium stearate and continue to mix for a period of time, and then pack the
  • the solvent is selected from purified water, propylene glycol or ethanol, preferably purified water.
  • the spray drying air inlet temperature is 100°C-180°C, preferably 120°C-150°C; the fan frequency is 30Hz-40Hz, preferably 34Hz-38Hz; the rotational speed is 5rpm-40rpm, preferably 8rpm-20rpm ; Atomization pressure 0.20MPa-0.30MPa, preferably 0.24MPa-0.28MPa; orifice size 0.5mm-1.2mm, preferably 0.8mm-1mm.
  • the drying time is 5h-48h; the mixing time is 0.5h-1h.
  • the present invention relates to the use of the above-mentioned dry powder inhaler or the dry powder inhaler prepared by the above-mentioned preparation method in the preparation of a medicine for treating pulmonary tuberculosis.
  • the pulmonary tuberculosis is pulmonary tuberculosis in a patient with poor liver function, or the pulmonary tuberculosis is bronchial tuberculosis.
  • the present invention has the following beneficial effects:
  • the present invention adopts a dry powder inhalation dosage form, which has a high drug delivery rate, and can deliver a dose of 10-50 mg each time.
  • the dry powder inhaler of the present invention has a relatively high drug load, and more than 50% or even more than 75% of the pharmaceutical preparation is the active ingredient isoniazid.
  • the dry powder inhaler of the present invention has higher formulation stability, and the preparation process is simple, can quickly prepare the isoniazid dry powder inhaler, and can meet the requirements of scale-up production.
  • the isoniazid dry powder inhaler prepared by the method of the present invention is especially suitable for treating pulmonary tuberculosis and bronchial tuberculosis in patients with impaired liver function.
  • Figure 1 shows the scanning electron microscope results of the isoniazid dry powder inhaler of Example 6.
  • the large block in the picture is lactose, on which the isoniazid active pharmaceutical ingredient (API) raw material is adsorbed.
  • API active pharmaceutical ingredient
  • Figure 2 shows the scanning electron microscope results of the isoniazid dry powder inhaler of Example 8. The figure shows that after adding magnesium stearate, the particles are more dispersed and the agglomeration is reduced.
  • test materials used in the following examples are all commercially available products unless otherwise specified.
  • the application has prepared the following isoniazid dry powder inhalers, and used them in various effect experiments described below.
  • Example 4 Dissolve 10.0 g of isoniazid in 200 mL of purified water, add leucine with a concentration of 5% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 150°C
  • the rotational speed was 15rpm
  • the fan frequency was 35Hz
  • the outlet air temperature was 135°C
  • the particles in the cyclone were collected.
  • Inhalac 120 lactose and mix for 30min and lactose accounts for 30% of the total preparation weight.
  • Example 5 Dissolve 10.0 g of isoniazid in 200 mL of purified water, add leucine with a concentration of 10% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 150°C
  • the rotational speed was 10rpm
  • the fan frequency was 35Hz
  • the outlet air temperature was 135°C
  • the particles in the cyclone were collected.
  • Inhalac 120 lactose and mix for 30min lactose accounts for 30% of the total weight of the preparation.
  • Example 6 Dissolve 10.0 g of isoniazid in 200 mL of purified water, add leucine at a concentration of 8% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 150°C
  • the rotational speed was 10rpm
  • the fan frequency was 35Hz
  • the outlet air temperature was 130°C
  • the particles in the cyclone were collected.
  • Inhalac 140 lactose and mix for 30min lactose accounts for 30% of the total weight of the preparation.
  • Example 7 Dissolve 10.0 g of isoniazid in 300 mL of purified water, add leucine at a concentration of 8% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 150°C
  • the rotational speed was 10rpm
  • the fan frequency was 35Hz
  • the outlet air temperature was 130°C
  • the particles in the cyclone were collected.
  • Inhalac 140 lactose and mix for 30min lactose accounts for 30% of the total weight of the preparation.
  • Example 8 Dissolve 10.0 g of isoniazid in 300 mL of purified water, add leucine at a concentration of 8% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 150°C
  • the rotational speed was 10rpm
  • the fan frequency was 35Hz
  • the outlet air temperature was 130°C
  • the particles in the cyclone were collected.
  • magnesium stearate and mix for 30min add magnesium stearate accounts for 2.5% of the total weight of the preparation.
  • Example 9 Dissolve 10.0 g of isoniazid in 200 mL of purified water, add leucine at a concentration of 8% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 150°C
  • the rotational speed was 25rpm
  • the fan frequency was 35Hz
  • the outlet air temperature was 130°C
  • the particles in the cyclone were collected.
  • Inhalac 140 lactose and mix for 30min lactose accounts for 30% of the total weight of the preparation.
  • Example 10 Dissolve 10.0 g of isoniazid in 200 mL of purified water, add leucine with a concentration of 10% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 150°C
  • the rotational speed was 25rpm
  • the fan frequency was 45Hz
  • the outlet air temperature was 130°C
  • the particles in the cyclone were collected.
  • Inhalac 140 lactose and mix for 30min lactose accounts for 30% of the total weight of the preparation.
  • Example 11 Dissolve 10.0 g of isoniazid in 200 mL of purified water, add leucine at a concentration of 8% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 120°C
  • the rotational speed was 10rpm
  • the fan frequency was 45Hz
  • the outlet air temperature was 130°C
  • the particles in the cyclone were collected. Continue to dry for 5h.
  • Example 12 Dissolve 10.0 g of isoniazid in 200 mL of purified water, add leucine at a concentration of 8% (w/v, g/mL) to prepare a clear and transparent solution, spray-dry the above solution, and prepare the solution.
  • the air temperature was set to 120°C
  • the rotational speed was 10rpm
  • the fan frequency was 45Hz
  • the outlet air temperature was 130°C
  • magnesium stearate accounts for 2.5% of the total preparation weight and lactose accounts for 30% of the total preparation weight
  • the shape of the isoniazid micropowder particles was observed by scanning electron microscope, the particle size of the powder was determined by the dry method, and the fine particle dose of the isoniazid micropowder particles was determined by the NGI method.
  • the SEM results of Example 6 and Example 8 are shown in Figure 1 and Figure 2, respectively. The results are shown in Table 1.
  • Example 3 shows that adding a certain amount of fine-grained lactose has a certain advantage over adding large-grained lactose, but when the amount of lactose is excessive, the FPD value will drop significantly, which may be due to the fact that when the amount of lactose is too large, a large amount of fine-grained raw materials are sucked into the surface, causing Fine particles are deposited in the throat along with lactose, reducing FPD.
  • the change of spray drying process parameters can cause the change of particle size.
  • the rotation speed is selected lower, the FPD value of the particles increases.
  • the concentration of API is low, the FPD value of the particles increases.
  • the addition of magnesium stearate can The significant increase in the FPD value of the particles may be related to their good lubrication and flow-assisting effects, and the interaction between particles decreases.
  • Example 9 and Example 10 when the rotation speed is too high, adjusting other parameters has little effect on the FPD effect of the particles, and the rotation speed is closely related to the size of the particles obtained by the pursuit.
  • Example 11 and Example 12 were placed in a stability test chamber, under the conditions of 40°C ⁇ 2°C 5%, and the particle size of the powder was measured by dry method in 0, January, February, and March, respectively.
  • NGI measures the particle size of fine particles, and measures the moisture content of the powder by the loss-on-drying method. The results are shown in Table 2 and Table 3, respectively.
  • the particles prepared by this method are more uniform than those prepared by the fluidized bed supersonic jet pulverization method.
  • the addition of an antistatic agent can enhance the spheroidization of the raw material, reduce the particle size of the drug, and make the distribution of the drug and the excipients uniform.
  • the prepared powder is more stable and easy to fill.
  • Table 5 Drug concentrations of isoniazid in isoniazid dry powder inhaler and isoniazid tablet in rat lung tissue
  • the results of drug concentration in plasma show that the change of drug concentration in plasma of inhaled powder is similar to that of injection, and it is quickly absorbed into the blood, and the Cmax is higher than the Cmax of the gavage group, and it has a fast blood entry.
  • the results of drug concentration in lung tissue show that the change of drug concentration in lung tissue of inhaled powder is also similar to that of injection, but Cmax can reach about 3 times of Cmax of gavage group, indicating that isoniazid powder After the aerosol is inhaled, it can quickly reach a higher concentration in the lung tissue and kill the Mycobacterium tuberculosis in the lungs.
  • the results of drug concentration in liver tissue showed that the drug concentration of inhaled powder in liver tissue did not change much compared with the gavage group, but the retention time in liver tissue of gavage group was relatively long, >1 ⁇ g /mL group, the gavage group lasted from 10min to 6h, while the inhalation group only lasted from 10min to 2h. Isoniazid has the potential advantage of reducing liver toxicity after inhalation.
  • Aerosol infection of acute mouse tuberculosis model diluted with PBS+0.04% Tween 80 cryopreserved Mycobacterium tuberculosis H37Rv (storage concentration should be > 10 8 cfu/mL), diluted cryopreserved Mycobacterium tuberculosis H37Rv to a concentration of 5 ⁇ 10 6 cfu/mL.
  • the 24 BALB/C mice (18-20 g) to be infected were loaded into the nebulizer chamber, the chamber was closed, and the bacterial liquid was sucked into the nebulizer.
  • mice were kept in separate cages in the negative pressure infection animal room. On the 3rd day after the infection, 3 mice were dissected, and the viable bacteria were counted to determine whether the infection was successful. Three mice were dissected on day 10 post-infection to provide basal values for lung viable counts at the start of treatment.
  • the treatment was started on the 10th day after infection.
  • the mice were administered once a day for 4 consecutive weeks, and the next day after 28 doses, the mice in each group were sacrificed, the mice were weighed, and the viable lung bacteria were counted. The results are shown in Table 7.
  • the dry powder inhaler of the present invention has a relatively high drug load, and 80% or even more than 95% of the pharmaceutical preparation is the active ingredient isoniazid.
  • the dry powder inhalant of the invention has high formulation stability and simple preparation process, can rapidly prepare the isoniazid dry powder inhalant, and can meet the requirements of scaled production.
  • the isoniazid dry powder inhaler prepared by the method of the invention is especially suitable for treating pulmonary tuberculosis and bronchial tuberculosis in patients with impaired liver function, and has important clinical significance.

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Abstract

La présente invention concerne un produit à inhaler à base de poudre sèche d'isoniazide pour le traitement de la tuberculose pulmonaire, ayant une stabilité élevée, contenant une micro-poudre d'isoniazide, et contenant ou ne contenant pas de micro-poudre d'excipient. La taille des particules de la micro-poudre d'isoniazide est traitée à 0,1-10 µm au moyen d'un procédé de broyage à jet supersonique à lit fluidisé ou d'un procédé de séchage par pulvérisation. De préférence, un adjuvant tel que la leucine, le mannitol ou un phospholipide peut être ajouté au produit à inhaler à base de poudre sèche pour améliorer la vitesse de granulation des particules, et un adjuvant tel que le stéarate de magnésium, le mannitol, la leucine et/ou le lactose est également ajouté pour améliorer la fluidité du médicament et réduire l'agglomération des particules. Le produit à inhaler à base de poudre sèche convient au traitement des patients atteints de tuberculose pulmonaire et présentant un dysfonctionnement hépatique.
PCT/CN2021/130116 2020-12-04 2021-11-11 Produit à inhaler à base de poudre sèche d'isoniazide pour le traitement de la tuberculose pulmonaire Ceased WO2022116792A1 (fr)

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CN202011412789.3 2020-12-04
CN202011412789.3A CN112336703B (zh) 2020-12-04 2020-12-04 一种用于治疗肺结核的异烟肼干粉吸入剂

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CN112336703B (zh) * 2020-12-04 2022-03-11 深圳善康医疗健康产业有限公司 一种用于治疗肺结核的异烟肼干粉吸入剂
CN115581688B (zh) * 2022-11-25 2023-03-10 山东国邦药业有限公司 一种替米考星干粉吸入剂及其制备方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101422457A (zh) * 2007-10-31 2009-05-06 江苏正大天晴药业股份有限公司 噻托溴铵吸入用干粉组合物
CN103110633A (zh) * 2013-02-28 2013-05-22 郑州大学 一种可预防结核杆菌呼吸道传播的干粉吸入剂
CN106692116A (zh) * 2015-11-15 2017-05-24 复旦大学 一种含异佛司可林的胶囊型吸入粉雾剂
CN112336703A (zh) * 2020-12-04 2021-02-09 深圳善康医疗健康产业有限公司 一种用于治疗肺结核的异烟肼干粉吸入剂

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101422457A (zh) * 2007-10-31 2009-05-06 江苏正大天晴药业股份有限公司 噻托溴铵吸入用干粉组合物
CN103110633A (zh) * 2013-02-28 2013-05-22 郑州大学 一种可预防结核杆菌呼吸道传播的干粉吸入剂
CN106692116A (zh) * 2015-11-15 2017-05-24 复旦大学 一种含异佛司可林的胶囊型吸入粉雾剂
CN112336703A (zh) * 2020-12-04 2021-02-09 深圳善康医疗健康产业有限公司 一种用于治疗肺结核的异烟肼干粉吸入剂

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LIANG CHAOFENG , LU KEWEI , LUO HUIHONG , LIU YING , SU SHINA , GUANGDONG LINGNAN: "Research Progress of Dry Powder Inhalant", PHARMACY TODAY, vol. 29, no. 4, 3 April 2019 (2019-04-03), pages 283 - 288, XP055935991, ISSN: 1674-229X, DOI: 10.12048/j.issn.1674-229X.2019.04.017 *
SIBUM IMCO, HAGEDOORN PAUL, FRIJLINK HENDERIK W., GRASMEIJER FLORIS: "Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation", PHARMACEUTICS, vol. 11, no. 5, 1 January 2019 (2019-01-01), pages 1 - 15, XP055935987, DOI: 10.3390/pharmaceutics11050233 *

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