EP4232046A1 - Durch trockenmahlverfahren hergestellte pharmazeutische zusammensetzungen mit celecoxib mit erhöhter auflösungsgeschwindigkeit - Google Patents

Durch trockenmahlverfahren hergestellte pharmazeutische zusammensetzungen mit celecoxib mit erhöhter auflösungsgeschwindigkeit

Info

Publication number
EP4232046A1
EP4232046A1 EP21803262.1A EP21803262A EP4232046A1 EP 4232046 A1 EP4232046 A1 EP 4232046A1 EP 21803262 A EP21803262 A EP 21803262A EP 4232046 A1 EP4232046 A1 EP 4232046A1
Authority
EP
European Patent Office
Prior art keywords
celecoxib
composition according
milling
povidone
mannitol
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
Application number
EP21803262.1A
Other languages
English (en)
French (fr)
Other versions
EP4232046A4 (de
Inventor
Levent ÖNER
Hakan EROGLU
Aslihan Arslan
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hacettepe Ueniversitesi
Original Assignee
Hacettepe Ueniversitesi
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Hacettepe Ueniversitesi filed Critical Hacettepe Ueniversitesi
Publication of EP4232046A1 publication Critical patent/EP4232046A1/de
Publication of EP4232046A4 publication Critical patent/EP4232046A4/de
Pending legal-status Critical Current

Links

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
    • A61K9/14—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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
    • A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
    • 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
    • A61K9/146—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 macromolecular compounds

Definitions

  • the invention relates to a pharmaceutical composition prepared by dry milling containing celecoxib or pharmaceutically acceptable salt or hydrate thereof, povidone, mannitol and at least one pharmaceutically acceptable excipient and the celecoxib particle size in this composition and the dissolution rate of the composition.
  • Non-steroidal anti-inflammatory drugs are the most commonly prescribed drug class worldwide for the treatment of various diseases and relief of their symptoms.
  • NSAIDs are non-steroidal drug class used to reduce pain and stiffness due to arthritis in diseases such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and used in the treatment of acute musculoskeletal pain, post-operative pain and dysmenorrhea.
  • Celecoxib has been described in the patent numbered US5466823 with a class of 1,5-diaryl pyrazoles and their salts and processes for the preparation of such substances.
  • Celebrex® is a product in oral capsule form containing celecoxib in strengths of 50 mg, 100 mg, 200 mg and 400 mg for use in the treatment of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, ankylosing spondylitis, acute musculoskeletal pain, chronic pain and post-operative pain.
  • Concensi® is a product in tablet form containing celecoxib and amlodipine besylate providing the treatment of pain from osteoarthritis and hypertension with a combined product. It has strengths of 200 mg/2.5 mg, 200 mg/5 mg, and 200 mg/10 mg, where 200 mg of celecoxib is combined with 2.5 mg, 5 mg, and 10 mg of amlodipine besylate, respectively.
  • the fixed dose combination of celecoxib-amlodipine, which was licensed in 2018, is mentioned in detail in the patent numbered US9662315B2.
  • ElyxybTM is a product in oral solution form in 25 mg/mL strength, indicated for the treatment of acute migraine with or without aura.
  • the celecoxib oral solution form which was developed and licensed in 2020 for celecoxib to be absorbed quickly and reach the maximum plasma concentration much faster than the Celebrex® product, is mentioned in detail in the patent numbered US9795620B2.
  • celecoxib is combined with ibuprofen and this combined product can be administered by oral, rectal, intranasal, sublingual administration or by intravenous, intramuscular, intrastemal or subcutaneous injection. It has been mentioned that 25 mg to 200 mg strength of celecoxib can be combined with 50 mg to 800 mg strength of ibuprofen in this fixed dose combination.
  • celecoxib may be effective in different diseases as well as its efficacy in symptomatic treatment of diseases such as osteoarthritis, rheumatoid arthritis and ankylosing spondylitis, acute pain, and the pharmacological effect of celecoxib continues to be investigated. For this reason, it is an important need to introduce pharmaceutical celecoxib compositions will be developed for any proven indication of celecoxib, to the use of patients as innovative products with new inventions.
  • NS AIDs are generally used to provide symptomatic treatment, they reduce radiological progression without increasing toxicity when used continuously in the treatment of chronic diseases such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis. For this reason, patients must take NS AIDs continuously instead of using them only to reduce the signs and symptoms of the disease.
  • NSAIDs besides the benefits of NSAIDs, they have undesirable especially gastrointestinal side effects.
  • the Food and Drug Administration (FDA) recommends the use of drugs at the lowest effective dose in the shortest time, in accordance with the target, in the treatments with all NSAIDs, so that patients do not encounter too many side effects while benefiting from NSAIDs.
  • NSAIDs that are frequently used in the clinic are molecules in the Class 2 group of the Biopharmaceutical Classification System (BCS), with very low water solubility but high permeability.
  • cryogenic spraying method creation of nano-structured amorphous drug particles with high porosity at very low temperatures
  • crystalline engineering obtaining metastable polymorph, high-energy amorphous forms, ultra-thin particles by controlled crystallization process
  • the mechanical particle size reduction method is the most suitable method for the industry. For this reason, there are many molecules whose particle size is reduced, and their bioavailability is increased by this method.
  • wet milling method is used in order to obtain more effective and positive results in order to reduce the particle size.
  • the wet milling process is a laborious and long process in the production of solid dosage forms. Because the particles produced by the wet method must be converted into solid state by a technique such as spray drying or lyophilization.
  • Dry milling system can be used to facilitate the milling process, but in this case, the possibility of re-agglomeration of the milled particles arise.
  • dry milling method with using excipients having function as stabilizer and surfactant is also preferred as an effective method.
  • Excipients such as lactose, sorbitol, sodium lauryl sulfate, polyoxyl stearate, polyethylene glycol were used in dry milling compositions made for celecoxib in patents numbered US8808751B2 (EP2054042A1 and A4), US8735450B2, EP2421525B1, US9095496B2, US9526734B2.
  • the particle size of celecoxib was reduced by milling with the mentioned excipients.
  • Celecoxib is a BCS Class 2 molecule that is practically insoluble in water, is hydrophobic, and has high permeability. The very low water solubility of celecoxib results in high variation in absorption and low bioavailability after oral administration.
  • celecoxib When celecoxib is taken orally in the form of capsule or tablet, it is not well absorbed, as it does not quickly distribute and dissolve in the gastrointestinal system. Therefore, it may take approximately 3 hours to reach the maximum plasma concentration following oral administration and delaying plasma concentration in this way causes the pharmacological effect to occur later. However, in cases such as migraines, acute pain, arthritis pain, dysmenorrhea, rapid pain relief effect is desired. In order to enable celecoxib to act more rapidly and to increase its bioavailability, it is necessary to improve its solubility and dissolution properties.
  • the medium in which celecoxib has the highest solubility is the pH 12 medium that does not simulate any physiological medium. Therefore, the dissolution method recommended by the FDA for the Celebrex® product is pH 12 medium containing 1% sodium lauryl sulfate. In order to improve the solubility and dissolution properties of celecoxib, it is not sufficient to increase its solubility only in the pH 12 medium.
  • the gastrointestinal system pH values that celecoxib will be exposed to when taken orally are in the range of pH 1.2-6.8 and its solubility in these media should also be increased.
  • co-milling the hydrophobic active ingredients with hydrophilic excipients can increase the solubility more compared to milling the active ingredient alone.
  • ibuprofen was milled in a planetary ball mill with excipients such as povidone, microcrystalline cellulose, hydroxypropyl methylcellulose, soluplus. Compared to ibuprofen milled alone; the solubility increased more as a result of milling ibuprofen with soluplus (Amjad Hussain et ak, Poster presentation, 2013).
  • a pharmaceutical composition comprising celecoxib active substance, which is practically insoluble in water, whose solubility is increased by using the dry milling method with povidone, mannitol and at least one pharmaceutically acceptable excipient, and whose particle size is reduced to submicron size by co-milling with pharmaceutical excipients is mentioned.
  • Celecoxib is a hydrophobic substance and has very low solubility and wettability in water.
  • a pharmaceutical composition has been developed that will allow rapid distribution and then dissolution in the gastrointestinal tract when it is taken orally as a solid dosage form such as a tablet or capsule.
  • Dry milling method which is the most suitable method for the industry, was chosen for the particle size reduction of celecoxib. However, only celecoxib was not milled in the dry milling method. By taking advantage of dry co-milling, both the milling performance of celecoxib particles were increased and the solubility increased much more than the amount that would increase depending on the particle size reduction, by means of the pharmaceutical excipients in the milling composition.
  • solubility of the composition which is specified for celecoxib in the patents numbered US8808751B2 (EP2054042A1 and A4), US8735450B2, EP2421525B1, US9095496B2, US9526734B2 and obtained as a result of dry milling of celecoxib with lactose monohydrate, sodium lauryl sulfate, polyoxyl stearate, at physiological pH is considerably lower than the composition presented in the invention.
  • the solubility did not increase to the same extent at the pH values in the range of pH 1.2-6.8. Therefore, the ratio by weight of povidone and mannitol presented in the invention is very critical for increasing solubility.
  • the solubility of celecoxib at physiological pH values was increased.
  • povidone and mannitol excipients in specific ratio in the pharmaceutical composition of celecoxib prepared by dry milling method increased the solubility at all pH physiological values in addition to pH 12 medium. It is not known in the art how or weather the ratio by weight of povidone and mannitol in the milling composition affect solubility at physiological pHs.
  • the ratio by weight of povidone and mannitol in the milling composition directly affects the solubility at physiological pHs.
  • the highest solute amount was obtained at 1:1:2 and 1:2:1 ratios when the milling parameters were kept constant at 500 rpm, 1 hour and 10:1 ball ratio.
  • the highest solute amounts were obtained at 1 : 1 : 1, 1:1.5:1.5, 1:0.5:1.5 and 1:1.5:0.5 ratios.
  • the weight ratio of celecoxib and sodium lauryl sulfate was 1 and 0.2, respectively.
  • celecoxib with an average particle size of 5-10 micrometers was milled in a planetary ball mill or high-energy ball mill.
  • the pharmaceutical composition obtained at the end of dry milling was dispersed in water and the particle size was measured. Since povidone, mannitol and sodium lauryl sulfate in the pharmaceutical composition dissolve very well in water, the only insoluble substance in the prepared dispersion is celecoxib. As a result of the particle size measurement, the average particle size of celecoxib was found in the range of 200 nm-1500 nm.
  • solubility values were determined by preparing saturated solutions of the pharmaceutical composition prepared by dry milling from pH 1.2, pH 4.5 and pH 6.8 media containing 0.2% sodium lauryl sulfate. At the same time, the solubility values of raw celecoxib and Celebrex® were determined by preparing saturated solutions from pH 1.2, pH 4.5 and pH 6.8 media containing 0.2% sodium lauryl sulfate. Solubility values were given in Table 1.
  • the developed pharmaceutical composition had a dissolution rate such that at least 40% of celecoxib was dissolved in 30 minutes in dissolution media in the range of pH 1.2-pH 6.8 containing USP Apparatus 2 (Paddle), 50 rpm rotational speed, 1000 mL, 37°C, 0.2% sodium lauryl sulfate; at least 70% of celecoxib is dissolved in 30 minutes in dissolution media in the range of pH 1.2-pH 6.8 containing 0.5% sodium lauryl sulfate.
  • the dissolution profiles of the Celebrex® product and the test product were evaluated within the scope of the invention, of the dissolution test performed without maintaining the sink condition are given in Figures 7, 8 and 9.
  • the dry milling method which is known and widely used in the field of pharmaceutical technology, is used not only for the purpose of reducing the particles by creating a mechanical effect, but also used as a solid dispersion preparation method in addition to the mechanical effect in the presented invention.
  • methods such as spray drying, solvent evaporation, hot melt extrusion, co-precipitation, electrospinning method, lyophilization method are generally used to prepare solid dispersion.
  • co-milling method is not preferred as a solid dispersion preparation method, it is the most applicable to industry.
  • stable solid dispersions with increased solubility were produced by using the dry milling method.
  • the developed production method is designed in way to be applied to the industry.
  • the method specified in this invention is much less costly, contains less risk factors and is the most compatible with the industry than other methods applied to increase solubility known in the art.
  • Celecoxib used in dry milling in the invention is in the form of crystalline form-III.
  • the solid dispersion of celecoxib with povidone is prepared, the crystalline form in beginning turns into an amorphous structure. It has been stated that when a solid dispersion of amorphous celecoxib is prepared with mannitol, mannitol can induce celecoxib crystalline growth. (Bhatt V et al., 2015, International Journal of Pharmaceutics, 495/1, 132-139).
  • Figure 2 SEM image of celecoxib particles in the composition obtained as a result of dry co-milled of celecoxib, povidone and sodium lauryl sulfate.
  • Figure 3 SEM image of celecoxib particles in the composition obtained as a result of co-milled of celecoxib, povidone, mannitol and sodium lauryl sulfate (PVP ⁇ MAN).
  • Figure 4 Dissolution rate profile of Celebrex® and the test product in the pH 1.2+0.2% SLS medium of the dissolution test by maintaining the sink condition
  • Figure 5 Dissolution rate profile of Celebrex® and the test product in the pH 4.5+0.2% SLS medium of the dissolution test by maintaining the sink condition
  • Figure 6 Dissolution rate profile of Celebrex® and the test product in the pH 6.8+0.2% SLS medium of the dissolution test by maintaining the sink condition
  • Figure 7 Dissolution rate profile of Celebrex® and test product in the pH 1.2+0.2% SLS medium without maintaining sink condition.
  • Figure 8 Dissolution rate profile of Celebrex® and test product in the pH 4.5+0.2% SLS medium without maintaining sink condition.
  • Figure 9 Dissolution rate profile of Celebrex® and test product in the pH 6.8+0.2% SLS medium without maintaining sink condition.
  • Figure 10 X-ray diffraction patterns of the raw celecoxib, celecoxib milled alone with dry method, and the composition obtained as a result of co-milled celecoxib and povidone.
  • Figure 11 X-ray diffraction patterns of the compositions obtained as a result of co-milled celecoxib, povidone and mannitol in different weight ratios, and physical mixture of celecoxib, povidone, mannitol, and sodium lauryl sulfate.
  • Invention pharmaceutical composition prepared by dry milling method containing celecoxib or its pharmaceutically acceptable salt or hydrate, povidone, mannitol and at least one pharmaceutically acceptable excipient is characterized by that celecoxib :povidone:mannitol has a weight ratio of at least 1 :0.5:0.5 and it contains celecoxib with a particle size in the range of 200 nm-1500 nm, and it has a dissolution rate such that at least 85% of celecoxib is dissolved in 30 minutes.
  • the inventive pharmaceutical composition contains celecoxib in the range of 30-200 mg.
  • the inventive pharmaceutical composition contains povidone in the range of 15-1000 mg.
  • the inventive pharmaceutical composition contains mannitol in the range of 15-1000 mg.
  • At least one pharmaceutically acceptable excipient is selected from pharmaceutically acceptable surface-active agents, colorants, fillers, lubricants and glidants, dispersants, binding agents, or excipients consisting of combinations thereof.
  • At least one pharmaceutically acceptable excipient used in dry milling in the invention is preferred as sodium lauryl sulfate in surface active agent function.
  • At least one of the surface-active agents such as Brij700, Brij76, Cremophor EL, lecithin, poloxamer 188, poloxamer 407, polyethylene glycol 3000, polyethylene glycol 8000, polyoxyl 40 stearate, sodium dodecyl sulfate, sodium octadecyl sulfate, Soluplus HS15, Tween 80 can also be used as surface active agent.
  • croscarmellose sodium is preferred for dispersant function and magnesium stearate for lubricant function.
  • the average particle size of celecoxib used in the invention is 5-10 micrometers and its crystalline structure is form-III. Since celecoxib is a hydrophobic substance, its wettability is very weak. For this reason, sodium lauryl sulfate is used in Celebrex® product to increase its wettability and solubility. Similarly, Concensi®, a celecoxib-amlodipine combined product, contains sodium lauryl sulfate in its composition. ElyxybTM, the oral solution product of celecoxib, contains glyceryl monocaprylate, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil as emulsifier, and ethanol as co-solvent in its formulation.
  • Ball mills were also used in the invention to reduce the particle size of celecoxib.
  • Wet and dry milling can be done in planetary ball mills or high-energy ball mills. These mills can be rotated at different rotational speeds, and they can mill in the desired time. The milling speed and time vary according to the properties of the substances to be milled.
  • the ratio of the amount of substance placed in the milling chamber to the weight of the ball to be used affects the milling performance. For this reason, the ball: substance ratio by weight should be at an optimum level for effective milling.
  • celecoxib active ingredient was milled by using a planetary ball mill. Milling chamber of the ball mills and the balls; agate and zirconium oxide materials were chosen to minimize the interaction of celecoxib and other excipients with the milling chamber and balls.
  • the main milling components and surface-active agents used in the celecoxib milling composition are given in Table 2. It can be operated at a rotational speed of 50 rpm-650 rpm in the ball mill. Speeds of 250 rpm and 500 rpm were used in the experiments presented in the invention. The milling time varies depending on the substances to be milled, but the experiments presented in the invention were made using a milling time of 1 hour to 4 hours.
  • composition Components Weight Ratios of the Dissolved Amount at 120 th Substances in the Minute (mg) Composition
  • the dissolved amount is higher than at 1 :0.2: 1 ratio, but still low.
  • the highest dissolved amount was obtained at 1:1:2 and 1:2:1 ratio.
  • the milling parameters are changed; the highest dissolved amounts were obtained at 1:1:1, 1:1.5:1.5, 1:0.5:1.5 and 1:1.5:0.5 ratios.
  • the high ball: powder ratio makes it possible to obtain high solubility by using lower ratios of povidone and mannitol.
  • the raito of weight of celecoxib:povidone:mannitol in the milling composition should be at least 1 :0.5:0.5.
  • the solubility in water and physiological pH values increased.
  • the milling composition is celecoxib:povidone: sodium lauryl sulfate (1:1:0.2)
  • the dissolved amount at physiological pH is 5 mg/1000 mL (120. min) maximum
  • the milling composition is celecoxib:povidone: sodium lauryl sulfate: mannitol (1 : 1 :0.2: 1)
  • the dissolved amount is at least 45 mg/1000 mL (120 min).
  • celecoxib:povidone:mannitol in order to increase its solubility, celecoxib:povidone:mannitol must be used in a weight ratio of at least 1:0.5:0.5 in a pharmaceutical composition prepaid by dry milling containing celecoxib, povidone, mannitol and at least one pharmaceutically acceptable excipient. It may be possible to increase the solubility by increasing this ratio, but if the ratios used in the milling composition increase, the unit weight of the pharmaceutical composition to be given to the patient will also increase. This situation may create an undesirable situation in terms of patient compliance.
  • the maximum ratio determined from the experiments is 1:5:5, and in the case of using povidone and mannitol higher than this ratio, the solubility does not increase significantly and begins to decrease.
  • the production method applied to prepare a pharmaceutical composition after the dry milling experiments include the following process steps;

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
EP21803262.1A 2020-10-26 2021-06-17 Durch trockenmahlverfahren hergestellte pharmazeutische zusammensetzungen mit celecoxib mit erhöhter auflösungsgeschwindigkeit Pending EP4232046A4 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2020/17034A TR202017034A2 (tr) 2020-10-26 2020-10-26 Kuru öğütme yöntemi̇ i̇le hazirlanan ve çözünme hizi arttirilmiş selekoksi̇b i̇çeren farmasöti̇k kompozi̇syonlar
PCT/TR2021/050619 WO2021230849A1 (en) 2020-10-26 2021-06-17 Pharmaceutical compositions prepared by dry milling method and containing celecoxib with increased dissolution rate

Publications (2)

Publication Number Publication Date
EP4232046A1 true EP4232046A1 (de) 2023-08-30
EP4232046A4 EP4232046A4 (de) 2023-11-08

Family

ID=78524739

Family Applications (1)

Application Number Title Priority Date Filing Date
EP21803262.1A Pending EP4232046A4 (de) 2020-10-26 2021-06-17 Durch trockenmahlverfahren hergestellte pharmazeutische zusammensetzungen mit celecoxib mit erhöhter auflösungsgeschwindigkeit

Country Status (3)

Country Link
EP (1) EP4232046A4 (de)
TR (1) TR202017034A2 (de)
WO (1) WO2021230849A1 (de)

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010121328A1 (en) * 2009-04-24 2010-10-28 Iceutica Pty Ltd A novel formulation of indomethacin
WO2010121321A1 (en) * 2009-04-24 2010-10-28 Iceutica Pty Ltd Method for improving the dissolution profile of a biologically active material
CN102988296A (zh) * 2011-09-08 2013-03-27 江苏恒瑞医药股份有限公司 塞来昔布固体分散体及其制备方法
CN110840850B (zh) * 2018-07-24 2023-03-17 烟台药物研究所 一种高生物利用度的塞来昔布冻干口崩片及其制备方法

Also Published As

Publication number Publication date
EP4232046A4 (de) 2023-11-08
WO2021230849A1 (en) 2021-11-18
TR202017034A2 (tr) 2021-09-21

Similar Documents

Publication Publication Date Title
US11839689B2 (en) Formulations of enzalutamide
US20100233272A1 (en) Dosage forms comprising celecoxib providing both rapid and sustained pain relief
JP5439182B2 (ja) 化学物質のミセルのナノ粒子
EA028009B1 (ru) Фармацевтическая композиция с улучшенной биодоступностью
JP2011530532A (ja) 固体分子分散物中のｈｃｖプロテアーゼインヒビターの薬学的処方物
US20100168247A1 (en) Solid composites of a calcium receptor-active compound
KR20010054823A (ko) 생체내이용률 향상과 개인간 및 개인내 흡수 편차를감소시킨 이트라코나졸 함유 항진균성 제제
WO2006073154A1 (ja) 医薬組成物及びその製造方法
KR102290670B1 (ko) 자가나노유화 약물전달시스템을 이용한 리바록사반의 경구용 고형제 조성물 및 이의 제조방법
TWI392507B (zh) 包埋的膠束奈米顆粒
WO2021230849A1 (en) Pharmaceutical compositions prepared by dry milling method and containing celecoxib with increased dissolution rate
KR102601617B1 (ko) 비-뉴클레오시드 역전사 효소 억제제의 조성물
US20040185110A1 (en) Formulations of low solubility bioactive agents and processes for making the same
Lalani et al. LIQUISOLID COMPACT APPROACH TO ENHANCE DISSOLUTION RATE OF POORLY SOLUBLE DRUGS: A RECENT RESEARCH REVIEW.
CA3200729A1 (en) Pharmaceutical composition comprising meloxicam
Maincent Modified release formulations manufactured by hot-melt extrusion
KR20230061942A (ko) 알칼리화제를 포함하는 셀레콕시브 함유 고체분산체 및 이의 제조방법

Legal Events

Date Code Title Description
STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE INTERNATIONAL PUBLICATION HAS BEEN MADE

PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: REQUEST FOR EXAMINATION WAS MADE

17P Request for examination filed

Effective date: 20230427

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR

A4 Supplementary search report drawn up and despatched

Effective date: 20231010

RIC1 Information provided on ipc code assigned before grant

Ipc: A61K 9/14 20060101ALI20231004BHEP

Ipc: A61K 31/415 20060101ALI20231004BHEP

Ipc: A61K 31/635 20060101AFI20231004BHEP

DAV Request for validation of the european patent (deleted)
DAX Request for extension of the european patent (deleted)