WO2020214791A1 - Compositions de célécoxib et leurs méthodes d'utilisation - Google Patents

Compositions de célécoxib et leurs méthodes d'utilisation Download PDF

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Publication number
WO2020214791A1
WO2020214791A1 PCT/US2020/028478 US2020028478W WO2020214791A1 WO 2020214791 A1 WO2020214791 A1 WO 2020214791A1 US 2020028478 W US2020028478 W US 2020028478W WO 2020214791 A1 WO2020214791 A1 WO 2020214791A1
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Prior art keywords
powder
celecoxib
oral solution
patient
sodium
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PCT/US2020/028478
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English (en)
Inventor
Richárd Balázs Kárpáti
Nikoletta Erdősi
Betti SZABÓNÉ ORDASI
Ferenc TÓTH
Hristos Glavinas
Genovéva FILIPCSEI
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Nangenex Nanotechnology Incorporated
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Publication of WO2020214791A1 publication Critical patent/WO2020214791A1/fr

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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
    • A61K9/08—Solutions
    • 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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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

Definitions

  • compositions and methods for management of signs and symptoms of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, and ankylosing spondylitis; for the management of acute pain in adults and children and cancer related pain, and for the management of primary dysmenorrhea are provided. Furthermore, disclosed is a composition comprising celecoxib and methods of formulating and manufacturing the powder for oral solution.
  • Celecoxib (4-[5-(4-methylphenyl)- 3-(trifluoromethyl)-lH-pyrazol-l-yl] benzenesulfonamide) has a molecular formula is C 17 H 14 F 3 N 3 O 2 S, a molecular weight of 381.38, and the following structure:
  • Celecoxib is a white powder; insoluble in water; soluble in methanol and chloroform.
  • Celecoxib is available as oral capsules containing either 50 mg, 100 mg, 200 mg or 400 mg of Celecoxib, together with inactive ingredients including: croscarmellose sodium, edible inks, gelatin, lactose monohydrate, magnesium stearate, povidone and sodium lauryl sulfate.
  • Celecoxib is a nonsteroidal anti-inflammatory drug that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models.
  • the mechanism of action of celecoxib is believed to be due to inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2), and at therapeutic concentrations in humans, celecoxib does not inhibit the cyclooxygenase- 1 (COX-1) isoenzyme.
  • COX-2 cyclooxygenase-2
  • COX-1 cyclooxygenase- 1
  • Peak plasma levels of celecoxib occur approximately 3 hrs after an oral dose. Under fasting conditions, both peak plasma levels (C max ) and area under the curve (AUC) are roughly dose-proportional up to 200 mg BID; at higher doses there are less than proportional increases in C max and AUC, which are thought to be due to the low solubility of the drug in aqueous media. Absolute bioavailability studies have not been conducted. With multiple dosing, steady- state conditions are reached on or before day 5.
  • Celecoxib is indicated for the management of the signs and symptoms of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis in patients 2 years and older, and ankylosing spondylitis; for the management of acute pain in adults, and for the management of primary dysmenorrhea.
  • the main medical concerns surrounding celecoxib are related to slow absorption and variable first-pass metabolism that limit its utility for treatment of acute pain.
  • peak plasma levels occur 3 hours after an oral dose, however, onset of pain relief could be as early as 1 hour.
  • peak plasma levels are delayed for about 1 to 2 hours with an increase in total absorption (AUC) of 10% to 20%. Since it is a painkiller shortening this time and the elimination of the delay of peak plasma concentrations could be advantageous.
  • a method for the management of signs and symptoms of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, or ankylosing spondylitis in a patient in need thereof; for the management of acute pain or cancer related pain in a patient in need thereof, and for the management of primary dysmenorrhea in a patient in need thereof comprising: administering a powder for oral solution formulation of celocoxib.
  • the method comprises: administering a powder for oral solution formulation comprising a therapeutically effective amount of celecoxib to produce:
  • a celecoxib exposure (AUC) which is about 2500 h*ng/ml to 12500 h*ng/ml and a more uniform celecoxib exposure (AUC) than the celecoxib exposure (AUC) provided by the same dosage of a conventional celecoxib capsule formulation;
  • a peak celecoxib plasma concertation (c) which is about 300 ng/ml to 2850 ng/ml and a more uniform peak celecoxib plasma concertation (Cmax) than the peak celecoxib plasma concertation (Cmax) provided by the same dosage of a conventional celecoxib capsule formulation.
  • the powder for oral solution formulation comprises a therapeutically effective amount of celecoxib to produce:
  • a powder for oral solution comprising:
  • ADMINISTERING means to provide a compound or other therapy, remedy, or treatment such that an individual internalizes a compound.
  • CO-ADMINISTER As used herein,“co-administer“ and“co-administration” and variants thereof mean the administration of at least two drugs to a patient either subsequently, simultaneously, or consequently proximate in time to one another (e.g., within the same day, or week or period of 30 days, or sufficiently proximate that each of the at least two drugs can be simultaneously detected in the blood plasma).
  • two or more active agents can be co-formulated as part of the same composition or administered as separate formulations. This also may be referred to herein as“concomitant” administration or variants thereof.
  • PRESCRIBING means to order, authorize, or recommend the use of a drug or other therapy, remedy, or treatment.
  • a health care practitioner can orally advise, recommend, or authorize the use of a compound, dosage regimen or other treatment to an individual.
  • the health care practitioner may or may not provide a prescription for the compound, dosage regimen, or treatment.
  • the health care practitioner may or may not provide the recommended compound or treatment.
  • the health care practitioner can advise the individual where to obtain the compound without providing the compound.
  • a health care practitioner can provide a prescription for the compound, dosage regimen, or treatment to the individual.
  • a health care practitioner can give a written or oral prescription to an individual.
  • a prescription can be written on paper or on electronic media such as a computer file, for example, on a hand held computer device.
  • a health care practitioner can transform a piece of paper or electronic media with a prescription for a compound, dosage regimen, or treatment.
  • a prescription can be called in (oral), faxed in (written), or submitted electronically via the internet to a pharmacy or a dispensary.
  • a sample of the compound or treatment can be given to the individual.
  • giving a sample of a compound constitutes an implicit prescription for the compound.
  • Different health care systems around the world use different methods for prescribing and/or administering compounds or treatments and these methods are encompassed by the disclosure.
  • a prescription can include, for example, an individual’s name and/or identifying information such as date of birth.
  • a prescription can include: the medication name, medication strength, dose, frequency of administration, route of administration, number or amount to be dispensed, number of refills, physician name, physician signature, and the like.
  • a prescription can include a DEA number and/or state number.
  • a healthcare practitioner can include, for example, a physician, nurse, nurse practitioner, or other related health care professional who can prescribe or administer compounds (drugs) for the treatment of a condition described herein.
  • a healthcare practitioner can include anyone who can recommend, prescribe, administer, or prevent an individual from receiving a compound or drug including, for example, an insurance provider.
  • PREVENT, PREVENTING, OR PREVENTION As used herein, the term “prevent,”“preventing”, or“prevention,” such as prevention of a particular disorder or the occurrence or onset of one or more symptoms associated with the particular disorder and does not necessarily mean the complete prevention of the disorder.
  • the term“prevent,” “preventing” and “prevention” means the administration of therapy on a prophylactic or preventative basis to an individual who may ultimately manifest at least one symptom of a disease or condition but who has not yet done so. Such individuals can be identified on the basis of risk factors that are known to correlate with the subsequent occurrence of the disease. Alternatively, prevention therapy can be administered without prior identification of a risk factor, as a prophylactic measure. Delaying the onset of at least one symptom can also be considered prevention or prophylaxis.
  • TREAT, TREATING, OR TREATMENT means the administration of therapy to an individual who already manifests at least one symptom of a disease or condition or who has previously manifested at least one symptom of a disease or condition.
  • “treating” can include alleviating, abating or ameliorating a disease or condition symptoms, preventing additional symptoms, ameliorating the underlying metabolic causes of symptoms, inhibiting the disease or condition, e.g., arresting the development of the disease or condition, relieving the disease or condition, causing regression of the disease or condition, relieving a condition caused by the disease or condition, or stopping the symptoms of the disease or condition.
  • treating in reference to a disorder means a reduction in severity of one or more symptoms associated with that particular disorder. Therefore, treating a disorder does not necessarily mean a reduction in severity of all symptoms associated with a disorder and does not necessarily mean a complete reduction in the severity of one or more symptoms associated with a disorder.
  • TOLERATE As used herein, an individual is said to“tolerate” a dose of a compound if administration of that dose to that individual does not result in an unacceptable adverse event or an unacceptable combination of adverse events.
  • tolerance is a subjective measure and that what may be tolerable to one individual may not be tolerable to a different individual. For example, one individual may not be able to tolerate headache, whereas a second individual may find headache tolerable but is not able to tolerate vomiting, whereas for a third individual, either headache alone or vomiting alone is tolerable, but the individual is not able to tolerate the combination of headache and vomiting, even if the severity of each is less than when experienced alone.
  • INTOLERANCE As used herein,“intolerance” means significant toxicities and/or tolerability issues that led to a reduction in dose or discontinuation of the medication. “Intolerance” can be replaced herein with the term“unable to tolerate.”
  • an“adverse event” is an untoward medical occurrence that is associated with treatment with an active ingredient.
  • an adverse event is selected from: leukopenia, constipation, diarrhea, nausea, abdominal pain, neutropenia, vomiting, back pain, and menstrual disorder.
  • an adverse event is heart block, for example, a first-degree atrioventricular heart block.
  • an adverse event is an acute heart rate reduction.
  • an adverse event is an abnormal pulmonary function test finding, such as an FEV1 below 80%, FVC.
  • an adverse event is an abnormal liver function test, such as an elevated ALT & AST>2X ULN.
  • an adverse event is macular edema.
  • INDIVIDUAL As used herein,“individual” means any human. In some embodiments, a human individual is referred to a“subject” or“patient.”
  • therapeutically effective amount of an agent, compound, drug, composition or combination is an amount which is nontoxic and effective for producing some desired therapeutic effect upon administration to a subject or patient (e.g., a human subject or patient).
  • the precise therapeutically effective amount for a subject may depend upon, e.g., the subject’s size and health, the nature and extent of the condition, the therapeutics or combination of therapeutics selected for administration, and other variables known to those of skill in the art.
  • the effective amount for a given situation is determined by routine experimentation and is within the judgment of the clinician.
  • the therapeutically effective amount is the standard dose.
  • DOSE As used herein,“dose” means a quantity of an active ingredient given to the individual for treating or preventing the disease or disorder at one specific time.
  • “standard dose” means the dose of the active ingredient that is given to the individual for treating or preventing the disease or disorder. The target dose may vary depending on the nature and severity of the disease to be treated.
  • PHARMACEUTICAL COMPOSITION As used here,“pharmaceutical composition” or“composition” means a composition comprising at least one active ingredient, whereby the composition is amenable to investigation for a specified, efficacious outcome. Those of ordinary skill in the art will understand and appreciate the techniques appropriate for determining whether an active ingredient has a desired efficacious outcome based upon the needs of the artisan.
  • composition of matter, group of steps, or group of compositions of matter shall be taken to encompass one and a plurality (/. ⁇ ? . one or more) of those steps, compositions of matter, groups of steps, or groups of compositions of matter.
  • celecoxib powder for oral solution compositions and methods for its use.
  • a method for the management of signs and symptoms of osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, or ankylosing spondylitis in a patient in need thereof; for the management of acute pain or cancer related pain in a patient in need thereof, and for the management of primary dysmenorrhea in a patient in need thereof comprising: administering a powder for oral solution formulation comprising a therapeutically effective amount of celecoxib to produce:
  • a celecoxib exposure (AUC) which is about 2500 h*ng/ml to 12500 h*ng/ml and a more uniform celecoxib exposure (AUC) than the celecoxib exposure (AUC) provided by the same dosage of a conventional celecoxib capsule formulation;
  • a peak celecoxib plasma concertation (c) which is about 300 ng/ml to 2850 ng/ml and a more uniform peak celecoxib plasma concertation (Cmax) than the peak celecoxib plasma concertation (Cmax) provided by the same dosage of a conventional celecoxib capsule formulation.
  • the celecoxib powder for oral solution is used for the management of signs and symptoms of osteoarthritis in a patient in need thereof. In some embodiments, the celecoxib powder for oral solution is used for the management of signs and symptoms of rheumatoid arthritis in a patient in need thereof. In some embodiments, the celecoxib powder for oral solution is used for the management of signs and symptoms of juvenile rheumatoid arthritis in a patient in need thereof. In some embodiments, the celecoxib powder for oral solution is used for the management of signs and symptoms of juvenile rheumatoid arthritis, or ankylosing spondylitis in a patient in need thereof.
  • the celecoxib powder for oral solution is used for the management of acute pain or cancer related pain in a patient in need thereof. In some embodiments, the celecoxib powder for oral solution is used for the management of cancer related pain in a patient in need thereof. In some embodiments, the celecoxib powder for oral solution is used for the management of acute pain in a patient in need thereof. In some embodiments, the celecoxib powder for oral solution is used for the management of acute pain arising from a dental procedure, such as a tooth extraction, an oral surgery, or a root canal surgery, in a patient in need thereof. In some embodiments, the tooth extraction is a molar extraction, such as a third molar extraction or an impacted molar extraction.
  • the celecoxib powder for oral solution is administered to a patient in need of pain control or extension of pain control that has been administered a regional or local anesthetic.
  • the celecoxib powder for oral solution is administered during a dental procedure, near completion of a dental procedure or immediately following a dental procedure.
  • the patient is provided with or extended pain (chronic or acute) control during a dental procedure or following a dental procedure.
  • the celecoxib powder for oral solution is used for the management of primary dysmenorrhea in a patient in need thereof.
  • the patient is an adult. In some embodiments, for example, for the treatment of juvenile rheumatoid arthritis, the patient is age two or older. In some embodiments, the patient is between the age of 12 and 18 years.
  • the celecoxib powder for oral solution is characterized by one or more of the following physicochemical properties:
  • celecoxib spray-dried intermediate comprising celecoxib as active compound and pharmaceutical excipients chosen polyvinylcaprolactam-polyvinyl acetate- polyethylene-glycol graft copolymers, poloxamers; polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl-acetate, D-a-Tocopherol polyethylene glycol 1000 succinate crosslinked polyvinylpyrrolidone (crosspovidone), crosslinked cellulose and its sodium salt (crosscarmellose), crosslinked sodium carboxymethyl cellulose, sodium starch glycolate, crosslinked starch, sodium starch glycolate, colloidal silicon dioxide, sodium lauryl sulfate, and dioctyl sodium sulfosuccinate; or
  • (b) powder for oral solution composition comprising the mixture of celecoxib spray-dried intermediate and pharmaceutical excipients selected from lactose (anhydrous), lactose monohydrate, plant cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, starch, pregelatinized starch, anhydrous dibasic calcium phosphate, xylitol, dibasic calcium phosphate dihydrate, cellulose, methyl cellulose, cellulose ethers such as hydroxypropyl cellulose, magnesium stearate, talc, and sodium stearyl fumarate, sodium saccharine, saccharine, aspartame, Acesulfame-K, sodium cyclamate and strawberry aroma, raspberry aroma, mint aroma, and cherry aroma; wherein said celecoxib powder for oral solution characterized in that it possesses at least one of the following properties:
  • a) is instantaneously redispersible in physiological relevant media
  • b) has a disintegration time not more than 10 minutes, preferably not more than 5 minutes in a glass of water
  • the therapeutically effective amount of celecoxib is from about
  • the administration of said celecoxib powder for oral solution provides peak celecoxib plasma concertation (Cmax) which is about 800 to about 1300 ng/mL when 100 mg of celecoxib is administered orally in fasted state.
  • Cmax peak celecoxib plasma concertation
  • the administration of said celecoxib powder for oral solution provides peak celecoxib plasma concertation (Cmax) which is about 2600 to about 2850 ng/mL when 200 mg of celecoxib is administered orally in fasted state.
  • Cmax peak celecoxib plasma concertation
  • the administration of said celecoxib powder for oral solution provides peak celecoxib plasma concertation (Cmax) which is about 300 to about 600 ng/mL when 100 mg of celecoxib is administered orally in fed state.
  • Cmax peak celecoxib plasma concertation
  • the administration of said celecoxib powder for oral solution provides peak celecoxib plasma concertation (Cmax) which is about 800 to about 1500 ng/mL when 200 mg of celecoxib is administered orally in fed state.
  • Cmax peak celecoxib plasma concertation
  • the administration of said celecoxib powder for oral solution provides celecoxib exposure (AUC) which is about 2500 to about 4500 h*ng/mL when 100 mg of celecoxib is administered orally in fasted state.
  • AUC celecoxib exposure
  • the administration of said celecoxib powder for oral solution provides celecoxib exposure (AUC) which is about 4300 to about 11200 h*ng/mL when 200 mg of celecoxib is administered orally in fasted state.
  • AUC celecoxib exposure
  • the administration of said celecoxib powder for oral solution provides celecoxib exposure (AUC) which is about 2700 to about 600 h*ng/mL when 100 mg of celecoxib is administered orally in fed state.
  • AUC celecoxib exposure
  • the administration of said celecoxib powder for oral solution provides celecoxib exposure (AUC) which is about 5500 to about 12500 h*ng/mL when 200 mg of celecoxib is administered orally in fed state.
  • AUC celecoxib exposure
  • the administration of said celecoxib powder for oral solution provides celecoxib time to reach peak plasma concentration (tmax) which is about 30 to about 60 h*ng/mL when 100 mg of celecoxib is administered orally in fasted state.
  • the administration of said celecoxib powder for oral solution provides celecoxib time to reach peak plasma concentration (tmax) which is about 15 to about 240 h*ng/mL when 200 mg of celecoxib is administered orally in fasted state.
  • the administration of said celecoxib powder for oral solution provides celecoxib time to reach peak plasma concentration (tmax) which is about 30 to about 360 h*ng/mL when 100 mg of celecoxib is administered orally in fed state.
  • the administration of said celecoxib powder for oral solution provides celecoxib time to reach peak plasma concentration (tmax) which is about 120 to about 360 h*ng/mL when 200 mg of celecoxib is administered orally in fed state.
  • the therapeutically effective amount of the celecoxib is from about 25 mg/day to about 200 mg/day.
  • the therapeutically effective amount of the celecoxib is from about 50 mg/day to about 150 mg/day.
  • the therapeutically effective amount of the celecoxib is from about 75 mg/day to about 125 mg/day.
  • the therapeutically effective amount of the celecoxib in the form of powder for oral solution is administered orally 2 times a day (BID) or 3 times a day (TID) or 4 times a day (QID).
  • the therapeutically effective amount of the celecoxib is 1 mg/kg administered TID.
  • the therapeutically effective amount of the celecoxib is 3 mg/kg/day.
  • the therapeutically effective amount of the celecoxib is 2 mg/kg administered TID.
  • the therapeutically effective amount of the celecoxib is 6 mg/kg/day.
  • a powder for oral solution comprising:
  • the powder comprises from about 5 to about 40% celecoxib.
  • the powder comprises from about 7.5 to about 30 % celecoxib.
  • the powder comprises from about 10 to about 25 % celecoxib.
  • the powder comprises from about 10 to about 15 % celecoxib.
  • the water soluble polymer matrix is selected from polyvinylcaprolactam-poly vinyl acetate -poly ethylene-glycol graft copolymers, poloxamers; polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl-acetate and D-a-Tocopherol polyethylene glycol 1000 succinate.
  • the water soluble polymer matrix is polyvinylpyrrolidone or copolymers of vinylpyrrolidone and vinyl-acetate.
  • the water soluble polymer matrix is copolymer of vinylpyrrolidone and vinyl-acetate.
  • the powder comprises from about 35 to about 80 % of the water soluble polymer matrix.
  • the powder comprises from about 35 to about 75 % of the water soluble polymer matrix.
  • the powder comprises from about 45 to about 70 % of the water soluble polymer matrix.
  • the powder comprises from about 45 to about 65 % of the water soluble polymer matrix.
  • the powder comprises from about 45 to about 60 % of the water soluble polymer matrix.
  • the powder comprises from about 45 to about 55 % of the water soluble polymer matrix.
  • the one or more pharmaceutically acceptable excipients is chosen from one or more fillers and/or diluents.
  • the one or more fillers and/or diluents are chosen from lactose (anhydrous), lactose monohydrate, plant cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, starch, pregelatinized starch, anhydrous dibasic calcium phosphate, xylitol, and dibasic calcium phosphate dihydrate.
  • the one or more pharmaceutically acceptable excipients is chosen from one or more binders.
  • the one or more binders is selected from cellulose, methyl cellulose, microcrystalline cellulose, and cellulose ethers such as hydroxypropyl cellulose.
  • the one or more pharmaceutically acceptable excipients is chosen from one or more disintegrants and dispersing agents.
  • the one or more disintegrants and dispersing agents is selected from crosslinked polyvinylpyrrolidone (crosspovidone), crosslinked cellulose and its sodium salt (crosscarmellose), crosslinked sodium carboxymethyl cellulose, sodium starch glycolate, crosslinked starch, sodium starch glycolate, colloidal silicon dioxide, sodium lauryl sulfate, and dioctyl sodium sulfosuccinate.
  • the one or more disintegrant and dispersing agents is sodium lauryl sulfate.
  • the powder comprises from about 1 to about 15 % of one or more disintegrant and dispersing agents.
  • the powder comprises from about 2 to about 10 % of one or more disintegrant and dispersing agents.
  • the powder comprises from about 2 to about 8 % of one or more disintegrant and dispersing agents.
  • the powder comprises from about 2 to about 5 % of one or more disintegrant and dispersing agents.
  • the one or more pharmaceutically acceptable excipients is chosen from one or more lubricants.
  • the one or more lubricants is chosen from magnesium stearate, talc, and sodium stearyl fumarate.
  • the one or more pharmaceutically acceptable excipients is chosen from one or more flavoring agents and sweeteners.
  • the one or more flavoring agents and sweeteners is chosen from sodium saccharine, saccharine, aspartame, acesulfame-K, sodium cyclamate and strawberry aroma, raspberry aroma, mint aroma, and cherry aroma
  • the one or more flavoring agents and sweeteners is sodium saccharine.
  • the powder comprises from about 0.5 to about 10 % of one or more flavoring agents and sweeteners.
  • the powder for oral solution comprises:
  • fillers and/or diluents chosen from lactose (anhydrous), lactose monohydrate, xylitol and microcrystalline cellulose;
  • disintegrants and dispersing agents chosen from crosslinked polyvinylpyrrolidone (crosspovidone), crosslinked cellulose and its sodium salt (crosscarmellose), sodium starch glycolate, sodium lauryl sulfate;
  • one or more lubricants chosen from magnesium stearate, talc and sodium stearyl fumarate; and one or more sweetener chosen from sodium saccharine.
  • the powder for oral solution comprises
  • the powder for oral solution comprises
  • water soluble polymer matrix selected from polyvinylcaprolactam-polyvinyl acetate-polyethylene-glycol graft copolymers, poloxamers; polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinyl-acetate and D- a-Tocopherol polyethylene glycol 1000 succinate;
  • fillers and/or diluents chosen from lactose (anhydrous), lactose monohydrate, plant cellulose, microcrystalline cellulose, silicified microcrystalline cellulose, starch, pregelatinized starch, anhydrous dibasic calcium phosphate, xylitol, and dibasic calcium phosphate dihydrate;
  • binders selected from cellulose, methyl cellulose, microcrystalline cellulose, and cellulose ethers such as hydroxypropyl cellulose;
  • disintegrants and dispersing agents selected from crosslinked polyvinylpyrrolidone (crosspovidone), crosslinked cellulose and its sodium salt (crosscarmellose), crosslinked sodium carboxymethyl cellulose, sodium starch glycolate, crosslinked starch, sodium starch glycolate, colloidal silicon dioxide, sodium lauryl sulfate, and dioctyl sodium sulfosuccinate;
  • lubricants chosen from magnesium stearate, talc, and sodium stearyl fumarate;
  • flavoring agents and sweeteners chosen from sodium saccharine, saccharine, aspartame, acesulfame-K, sodium cyclamate and strawberry aroma, raspberry aroma, mint aroma, and cherry aroma.
  • the powder comprises
  • binders selected from cellulose, methyl cellulose, microcrystalline cellulose, and cellulose ethers such as hydroxypropyl cellulose;
  • disintegrants and dispersing agents selected from crosslinked polyvinylpyrrolidone (crosspovidone), crosslinked cellulose and its sodium salt (crosscarmellose), crosslinked sodium carboxymethyl cellulose, sodium starch glycolate, crosslinked starch, sodium starch glycolate, colloidal silicon dioxide, sodium lauryl sulfate, and dioctyl sodium sulfosuccinate;
  • flavoring agents and sweeteners chosen from sodium saccharine, saccharine, aspartame, Acesulfame-K, sodium cyclamate and strawberry aroma, raspberry aroma, mint aroma, and cherry aroma.
  • the powder for oral solution is suitable for oral administration.
  • the powder for oral solution disintegrates in liquids suitable for human consumption.
  • the liquids suitable for human use are selected from water, orange juice, apple juice, pineapple juice, and cranberry juice.
  • the powder for oral solution disintegrates in liquids suitable for human consumption in less than about 15 minutes.
  • the powder for oral solution disintegrates in liquids suitable for human consumption in less than about 10 minutes.
  • the powder for oral solution disintegrates in liquids suitable for human consumption in less than about 5 minutes.
  • compositions of powder for oral suspension are listed in Table 1 and Table 2.
  • Celecoxib Powder for Oral Solution manufacturing process consists of first spray drying the drug substance (Celecoxib) with the polymer matrix as Copolymer of vinylpyrrolidone and vinyl-acetate and the dispersing agent as Sodium Lauryl Sulfate to produce the Celecoxib spray dried powder.
  • the resultant Celecoxib spray dried powder is secondary dried for ⁇ 24 hours at a temperature of 80°C to produce the Celecoxib Spray Dried Dispersion Intermediate.
  • process controls include assay and residual solvent testing.
  • the Celecoxib Spray Dried Dispersion Intermediate screened and blended with pre- screened Saccharin Sodium and subjected to dry granulation prior to filling into a sachet to produce the final drug product.
  • the granules were packed into an aluminum pouch and heat sealed.
  • Subjects were dosed on the morning of Day 1 of each study period. Subjects received a single administration of investigational drug on 5 separate occasions. The sachet of investigational drug was emptied into a dosing cup/jar and reconstituted with 90 mL purified water. A rinsing step with 10 mL purified water was performed to ensure the total administered volume was 100 mL, and was then made up to 240 mL with water to drink.
  • Subjects were provided with a light snack on the evening of Day - 1 and then fasted from all food and drink (except water) for a minimum of 10 h on the day prior to dosing until approximately 4 h post-dose, at which time lunch was provided.
  • An evening meal was provided at approximately 10 h post-dose and an evening snack at approximately 14 h post-dose. On subsequent days, meals were provided at appropriate times.
  • Subjects were provided with a light snack on the evening of Day - 1 and then fasted from all food and drink (except water) until the following morning, when they were provided with an FDA specified high-fat high-calorie breakfast.
  • PK parameters are presented in Table 4 and 5 for the fasted state and fed state administration, respectively.
  • the primary outcome will be total pain relief 0 to 8 hours after dosing. Safety and tolerability may be evaluated with physical examination, vital signs, pulse oximetry, clinical laboratory tests, ECGs, and incidence of Adverse Events (AEs) and Serious Aes.
  • AEs Adverse Events
  • Secondary outcomes may include one or more of the following: ⁇ Total Pain Relief 0 - 4 hours after dosing (TOTPAR4) [ Time Frame: Hour 4 postdose ]
  • Time to first perceptible PR [ Time Frame: Up to 24 hours postdose ]
  • Time to meaningful PR [ Time Frame: Up to 24 hours postdose ]

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une méthode qui permet de gérer des signes et des symptômes de l'arthrose, de la polyarthrite rhumatoïde, de l'arthrite rhumatoïde juvénile, ou de la spondylarthrite ankylosante chez un patient en ayant besoin ; de gérer une douleur aiguë ou une douleur liée au cancer chez un patient en ayant besoin, et de gérer la dysménorrhée primaire chez un patient en ayant besoin, qui consiste à administrer une poudre pour une formulation de solution orale de célécoxib.
PCT/US2020/028478 2019-04-18 2020-04-16 Compositions de célécoxib et leurs méthodes d'utilisation WO2020214791A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7220867B2 (en) * 1999-12-08 2007-05-22 Pharmacia Corporation (Of Pfizer, Inc.) Solid-state form of celecoxib having enhanced bioavailability
US20150011514A1 (en) * 1998-11-30 2015-01-08 Pfizer Inc. Celecoxib Compositions
US20170340561A1 (en) * 2016-05-27 2017-11-30 Dr. Reddy's Laboratories Ltd. Oral composition of celecoxib for treatment of pain
US20180185393A1 (en) * 2016-12-14 2018-07-05 Druggability Technologies Ip Holdco Limited Pharmaceutical composition containing celecoxib

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20150011514A1 (en) * 1998-11-30 2015-01-08 Pfizer Inc. Celecoxib Compositions
US7220867B2 (en) * 1999-12-08 2007-05-22 Pharmacia Corporation (Of Pfizer, Inc.) Solid-state form of celecoxib having enhanced bioavailability
US20170340561A1 (en) * 2016-05-27 2017-11-30 Dr. Reddy's Laboratories Ltd. Oral composition of celecoxib for treatment of pain
US20180185393A1 (en) * 2016-12-14 2018-07-05 Druggability Technologies Ip Holdco Limited Pharmaceutical composition containing celecoxib

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