WO2016134200A1 - Gélules en gélatine molle contenant de la fexofénadine - Google Patents

Gélules en gélatine molle contenant de la fexofénadine Download PDF

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Publication number
WO2016134200A1
WO2016134200A1 PCT/US2016/018574 US2016018574W WO2016134200A1 WO 2016134200 A1 WO2016134200 A1 WO 2016134200A1 US 2016018574 W US2016018574 W US 2016018574W WO 2016134200 A1 WO2016134200 A1 WO 2016134200A1
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WO
WIPO (PCT)
Prior art keywords
weight
fexofenadine
composition
pharmaceutically acceptable
mixture
Prior art date
Application number
PCT/US2016/018574
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English (en)
Inventor
Abdul Rashid
Dahai Guo
Minh Tran
Zhang Julia ZHANG
Original Assignee
Enspire Group LLC
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
Priority claimed from US14/627,589 external-priority patent/US20160243044A1/en
Application filed by Enspire Group LLC filed Critical Enspire Group LLC
Priority to EP16753099.7A priority Critical patent/EP3258934A4/fr
Priority to CN201680011220.1A priority patent/CN107847496A/zh
Priority to US15/552,132 priority patent/US20180042857A1/en
Publication of WO2016134200A1 publication Critical patent/WO2016134200A1/fr

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Classifications

    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds

Definitions

  • the presently disclosed subject matter relates to bioavailable fill compositions containing fexofenadine or a fexofenadine salt, soft gelatin capsules filled with the bioavailable fexofenadine fill compositions, and methods of making same.
  • Fexofenadine is an antihistamine pharmaceutical drug used in the treatment of allergy symptoms, such as hay fever, nasal congestion, and urticaria or hives. It is known as a third-generation antihistamine, which means that its effect are limited to the periphery, that is, outside the brain and spinal cord, which is where most antihistamines mediate their sedating effects; therefore, fexofenadine has minimal sedation side effects. Fexofenadine is used for relief from physical symptoms associated with seasonal allergic rhinitis and for treatment of chronic urticaria.
  • Fexofenadine is a lipophilic solid which is frequently administered as the hydrochloride salt.
  • Both fexofenadine free base and fexofenadine salts have poor solubility in aqueous solution, and present difficult problems in formulating for effective administration with adequate bioavailability.
  • a well-designed formulation should, at a minimum, be capable of presenting a therapeutically effective amount of a hydrophobic compound to its desired absorption site, in an absorbable form. Even this minimal functionality is difficult to achieve when delivery of the hydrophobic therapeutic agent requires interaction with aqueous physiological environments, such as gastric and intestinal fluids.
  • drug absorption in various individuals might differ significantly due to differences in gastrointestinal function and food intake. Therefore, it is rather difficult to determine and control the dosage.
  • fexofenadine for oral administration is the low solubility of the compound, especially under the acidic aqueous gastric conditions (solubility of 0.2 mg of fexofenadine HCl per ml of pH 1.2 aqueous buffer solution).
  • a new formulation providing desirable protection and stabilization of the fexofenadine active ingredient is provided herein. This formulation also provides enhanced bioavailability.
  • an overall approach to formulating fexofenadine hydrochloride included isolating the active ingredient (AI) within a soft gelatin capsule (softgel) and specifically solubilizing the AI in a suitable fill composition matrix comprising a polymeric solubilizing agent in combination with an optional surfactant in an alkylene glycol and poly(alkylene glycol) vehicle.
  • the pH of the fill composition is maintained in the acid range with a pharmaceutically acceptable acidulant in a small weight percentage of water.
  • the solubilizing matrix comprises two parts.
  • Part A is a hydrophilic mixture of a pharmaceutically acceptable alkylene glycol, such as propylene glycol, a pharmaceutically acceptable poly(alkylene glycol), such as a polyethylene glycol (PEG), and a
  • solubilizing polymer such as a polyvinylpyrrolidone
  • Part B is a mixture of water, a pharmaceutically acceptable acidulant, such as citric acid, and optionally a pharmaceutically acceptable surfactant, such as sodium lauryl sulfate (SLS).
  • the optional surfactant can be ionic or non-ionic (e.g. a polysorbate).
  • Parts A and B are combined to form the solubilizing matrix, and fexofenadine hydrochloride is added to this solubilizing matrix to form the fill composition.
  • the fexofenadine fill composition of the invention can be encapsulated into soft gelatin capsules of the invention.
  • the fexofenadine AI is in the form of fexofenadine free base. In some embodiments the fexofenadine AI is a fexofenadine salt. In one embodiment the fexofenadine salt is fexofenadine hydrochloride. In some embodiments the fexofenadine free base or fexofenadine salt is the only active ingredient. In certain embodiments, one or more additional active ingredients are added to the fexofenadine-containing fill formulation.
  • One aspect of the invention is directed to a bioavailable liquid softgel fill composition
  • a bioavailable liquid softgel fill composition comprising: a) 4-40% by weight of fexofenadine or a fexofenadine salt; b) a matrix comprising: bi) 40-80% by weight of a pharmaceutically acceptable poly(alkylene glycol); bii) optionally, 0-30% by weight of a pharmaceutically acceptable alkylene glycol; biii) 0-10% by weight of a pharmaceutically acceptable polymeric solubilizing agent, preferably 1-10% by weight; and biv) optionally, 0-6% (e.g., 0.001-6%) by weight of a pharmaceutically acceptable surfactant; and c) 0.001-2%) by weight of a
  • compositions which have at least one of the following features: (a) the fexofenadine or fexofenadine salt and the matrix are present in a ratio of about 1 : 1.5 to about 1 :24 by weight; or (b) the fexofenadine or fexofenadine salt and the pharmaceutically acceptable polymer are present in a ratio of about 40: 1 to about 2:5 by weight; or (c) the fexofenadine or fexofenadine salt and the pharmaceutically acceptable surfactant (if present) are present in a ratio of about 40000: 1 to about 2:3 by weight.
  • One embodiment of the composition has all of the features (a), (b) and (c).
  • compositions contains on features (a) and (b).
  • the fexofenadine salt is fexofenadine hydrochloride.
  • the fexofenadine or fexofenadine salt is the only active ingredient.
  • Other embodiments of the composition further comprise one or more additional active ingredients.
  • the pharmaceutically acceptable poly(alkylene glycol) is selected from the group consisting of poly(ethylene glycol)s (PEGs); preferably the PEGs are selected from the group consisting of PEG 200, 300, 400, 600, mixtures thereof, and mixtures of these with PEG 800, 1000, 2000, 3000, 4000, 5000, 6000, 7000, or 8000.
  • the pharmaceutically acceptable alkylene glycol is propylene glycol.
  • the pharmaceutically acceptable polymeric solubilizing agent is a polyvinylpyrrolidone (PVP).
  • PVP polyvinylpyrrolidone
  • the PVP is selected from the group consisting of PVP K12, PVP K17, PVP K30, PVP K60, and PVP K90; preferably the polyvinylpyrrolidone is PVP K17.
  • the pharmaceutically acceptable alkylene glycol is propylene glycol.
  • the pharmaceutically acceptable polymeric solubilizing agent is a polyvinylpyrrolidone (PVP).
  • the PVP is selected from the group consisting of PVP K12, PVP K17, PVP K30, PVP K60, and PVP K90; preferably the polyvinylpyrrolidone is PVP K17.
  • composition is surfactant-free. In another embodiment the composition comprises 0 to about 0.5% by weight of a pharmaceutically acceptable surfactant.
  • acidulant is selected from the group consisting of pharmaceutically acceptable organic acids and mixtures of two or more thereof. In a preferred embodiment the acidulant is selected from the group consisting of lactic acid, malic acid, citric acid, fumaric acid, ascorbic acid, tartaric acid and mixtures of two or more thereof. In a particularly preferred embodiment the acidulant comprises citric acid.
  • Another aspect of the invention is directed to a method of preparing the above bioavailable liquid softgel fill composition, comprising the steps of: (a) combining the poly(alkylene glycol) and the alkylene glycol in a stainless steel container and heating the mixture to a temperature of 65 ⁇ 5°C with stirring for a first period of time to obtain a first mixture; (b) slowly adding the polymeric solubilizing agent in small quantities into the first suspension with stirring and continue stirring for a second period of time after powder addition is complete, at the same temperature to obtain a second mixture; (c) preparing a third mixture by combining the surfactant (if present) and acidulant with water in a separate stainless steel container and heating the mixture to a temperature of 65 ⁇ 5°C with stirring for a third period of time; (d) combining the second and third mixtures at the same temperature with mixing for a fourth period of time to provide a fourth mixture; (e) adding the fexofenadine or fexofenadine salt to the fourth mixture in small quantities
  • a softgel capsule comprising a soft gelatin capsule filled with the bioavailable liquid softgel fill composition disclosed above.
  • the gelatin of said soft gelatin (softgel) capsule comprises bovine-, avian-, porcine-, marine- or vegetable-based gelatin, or a mixture of two or more thereof.
  • the softgel capsule further comprises an enteric coating.
  • the enteric coating preferably comprises a controlled release polymer.
  • the controlled release polymer is an acid-resistant polymer.
  • bioavailable liquid softgel fill composition consisting essentially of: a) 4-40% by weight of fexofenadine hydrochloride; b) a matrix comprising: bi) 40-80% by weight of PEG 400; bii) optionally, 0-30% by weight of propylene glycol; biii) 0-10% by weight of polyvinylpyrrolidone, preferably 1- 10%) by weight; and biv) optionally 0.001-6%) by weight of sodium lauryl sulfate; c) 0.001-2%) by weight of citric acid; and d) 1-10%> of water, based on the total weight of the composition.
  • the pharmaceutically acceptable surfactant is present in 0 to about 0.5% by weight.
  • bioavailable liquid softgel fill composition consists essentially of: a) about 13.9% by weight of fexofenadine
  • hydrochloride b) a matrix comprising: bi) about 64.2%> by weight of PEG 400; bii) about 15.2%) by weight of propylene glycol; biii) about 3.4% by weight of polyvinylpyrrolidone; and biv) about 0.3%> by weight of sodium lauryl sulfate; c) about 0.5% by weight of citric acid; and d) about 2.5% of water, based on the total weight of the composition.
  • Still another aspect of the invention is directed to a bioavailable liquid softgel fill composition consisting of: a) 4-40% by weight of fexofenadine or a fexofenadine salt; b) a matrix consisting of: i) 40-80%> by weight of a pharmaceutically acceptable poly(alkylene glycol); ii) 0-30% by weight of a pharmaceutically acceptable alkylene glycol; and iii) 0- 10%) by weight of a pharmaceutically acceptable polymeric solubilizing agent, preferably 1-10%) by weight; c) 0.001-2%) by weight of a pharmaceutically acceptable acidulant; and d) 1-10%) of water; based on the total weight of the composition.
  • the bioavailable liquid softgel fill composition consists of: a) about 13.9% by weight of fexofenadine hydrochloride; b) a matrix consisting of: i) about 64.5% by weight of PEG 400; ii) about 15.2% by weight of propylene glycol; and iii) about 3.4% by weight of polyvinylpyrrolidone; c) about 0.5% by weight of citric acid; and d) about 2.5% of water; based on the total weight of the composition.
  • One embodiment of the above compositions is directed to a softgel capsule comprising a soft gelatin capsule filled with the above bioavailable liquid softgel fill composition.
  • the polyvinylpyrrolidone is PVP K17.
  • Figure 1 shows a picture of a fill solution without sodium lauryl sulfate after storage at ambient temperature for 4 months.
  • Fexofenadine free base has the structure of Formula (I):
  • a pharmaceutically acceptable salt, such as the hydrochloride salt, rather than the free base is frequently used as the active ingredient in pharmaceutical compositions.
  • One aspect of the invention is directed to a bioavailable liquid softgel fill composition
  • a bioavailable liquid softgel fill composition comprising: a) 4-40% (e.g. 5-35%, 5-20%, 10-30%, 15-25%, about 13% about 14%), about 15%> or about 20%>) by weight of fexofenadine or a fexofenadine salt; b) a matrix comprising: bi) 40-80% (e.g. 45-75%, 50-70%, 55-65%, about 60%, about 64%, 64-65%o or about 65%>) by weight of a pharmaceutically acceptable poly(alkylene glycol); bii) optionally, 0-30% (e.g.
  • a pharmaceutically acceptable alkylene glycol 5-30%, 5-25%, 10-25%, 15-16%, 15-20%, up to about 14%, up to about 15%) or up to about 16%>) by weight of a pharmaceutically acceptable alkylene glycol; biii) optionally 0-10% (e.g.
  • composition has all of the features (a), (b) and (c). In one embodiment the composition has all of the features (a), (b) and (c), and the surfactant is present in 0 to about 0.5% by weight. Other embodiments of the composition are surfactant-free and therefore contains only features (a) and (b).
  • the fexofenadine salt is fexofenadine hydrochloride. In a preferred embodiment the fexofenadine or fexofenadine salt is the only active ingredient. Other embodiments of the composition further comprise one or more additional active ingredients.
  • the pharmaceutically acceptable poly(alkylene glycol) is selected from the group consisting of poly(ethylene glycol)s (PEGs); preferably the PEGs are selected from the group consisting of PEG 200, 300, 400, 600, mixtures thereof, and mixtures of these with PEG 800, 1000, 2000, 3000, 4000, 5000, 6000, 7000, or 8000.
  • the pharmaceutically acceptable alkylene glycol is propylene glycol.
  • the pharmaceutically acceptable polymeric solubilizing agent is a polyvinylpyrrolidone (PVP).
  • the PVP is selected from the group consisting of PVP K12, PVP K17, PVP K30, PVP K60, and PVP K90, covering a molecular weight range of about 2,000 to about 1,500,000; preferably the polyvinylpyrrolidone is PVP K17.
  • the pharmaceutically acceptable surfactant is selected from the group consisting of sodium lauryl sulfate, polysorbates (e.g. TWEEN® 20, 40, 60, 80, etc.), and PEG-8 caprylic/capric glycerides (e.g LABRASOL®, also known as caprylocaproyl polyoxyl-8 glycerides).
  • the acidulant is selected from the group consisting of pharmaceutically acceptable organic acids and mixtures of two or more thereof.
  • the acidulant is selected from the group consisting of lactic acid, malic acid, citric acid, fumaric acid, ascorbic acid, tartaric acid and mixtures of two or more thereof.
  • the acidulant comprises citric acid.
  • Another aspect of the invention is directed to a method of preparing the above bioavailable liquid softgel fill composition, comprising the steps of: (a) combining the poly(alkylene glycol) and the alkylene glycol in a stainless steel container and heating the mixture to a temperature of 65 ⁇ 5°C with stirring (preferably with high shear mixing) for a first period of time (preferably 25-35 minutes, or until homogenized) to obtain a first mixture; (b) slowly adding the polymeric solubilizing agent in small quantities into the first suspension with stirring and continue stirring for a second period of time (preferably 25-35 minutes) after powder addition is complete, at the same temperature to obtain a second mixture; (c) preparing a third mixture by combining the optional surfactant and acidulant with water in a separate stainless steel container and heating the mixture to a temperature of 65 ⁇ 5°C with stirring for a third period of time (preferably 12-18 minutes, or until homogenized); (d) combining the second and third mixtures at the same temperature with mixing for a fourth period of time (
  • a softgel capsule comprising a soft gelatin capsule filled with the bioavailable liquid softgel fill composition disclosed above.
  • the gelatin of said soft gelatin (softgel) capsule comprises bovine-, avian-, porcine-, marine- or vegetable-based gelatin, or a mixture of two or more thereof.
  • the softgel capsule further comprises an enteric coating.
  • the enteric coating preferably comprises a controlled release polymer.
  • the controlled release polymer is an acid-resistant polymer.
  • Another aspect of the invention is directed to a bioavailable liquid softgel fill composition consisting essentially of: a) 4-40% (e.g. 5-35%, 5-20%, 10-30%, 15-25%, about 13%) about 14%, about 15%> or about 20%>) by weight of fexofenadine
  • hydrochloride b) a matrix comprising: bi) 40-80% (e.g. 45-75%, 50-70%, 55-65%, about 60%, about 64%, 64-65% or about 65%) by weight of PEG 400; bii) optionally, 0-30% (e.g. 5-30%, 5-25%, 10-25%, 15-16%, 15-20%, up to about 14%, up to about 15%, or up to about 16%)) by weight of propylene glycol; biii) optionally 0-10% (e.g.
  • composition contains 0 to about 0.5 wt% of surfactant.
  • surfactant concentration is 0%, providing a surfactant-free compostion.
  • One embodiment is directed to a bioavailable liquid softgel fill composition consisting essentially of: a) about 13.9% by weight of fexofenadine hydrochloride; b) a matrix comprising: bi) about 64.2% by weight of PEG 400; bii) about 15.2% by weight of propylene glycol; biii) about 3.4% by weight of polyvinylpyrrolidone; and biv) about 0.3%) by weight of sodium lauryl sulfate; c) about 0.5% by weight of citric acid; and d) about 2.5%) of water, based on the total weight of the composition.
  • Still another aspect of the invention is directed to a bioavailable liquid softgel fill composition consisting of: a) 4-40% by weight of fexofenadine or a fexofenadine salt; b) a matrix consisting of: i) 40-80%> by weight of a pharmaceutically acceptable poly(alkylene glycol); ii) 0-30% by weight of a pharmaceutically acceptable alkylene glycol; and iii) 0- 10%) by weight of a pharmaceutically acceptable polymeric solubilizing agent, preferably 1-10%) by weight; c) 0.001-2%) by weight of a pharmaceutically acceptable acidulant; and d) 1-10%) of water; based on the total weight of the composition.
  • the bioavailable liquid softgel fill composition consists of: a) about 13.9% by weight of fexofenadine hydrochloride; b) a matrix consisting of: i) about 64.5% by weight of PEG 400; ii) about 15.2% by weight of propylene glycol; and iii) about 3.4% by weight of polyvinylpyrrolidone; c) about 0.5% by weight of citric acid; and d) about 2.5% of water; based on the total weight of the composition.
  • One embodiment of the above compositions is directed to a softgel capsule comprising a soft gelatin capsule filled with the above bioavailable liquid softgel fill composition.
  • the polyvinylpyrrolidone is PVP K17.
  • the liquid softgel fill formulation can be encapsulated in soft gelatin shells to form softgel capsules using a conventional rotary die process.
  • Suitable soft gelatin shells may include (i) gelatin, 35-60% by weight; (ii) glycerin, 10-15% by weight; (iii) sorbitol, 11- 20% by weight; (iv) purified water, 20-40% by weight; and (v) artificial color, 0.0001- 0.002% by weight.
  • the softgel capsules of the invention can also be prepared by other methods well known in the art. See e.g., P. K. Wilkinson et a!., "Softgel s: Manufacturing
  • Example 2 Process for Preparation of Fill Composition of Examples 1 and 3. a) Add Propylene Glycol into PEG 400, PEG 600, or other liquid PEG or liquid PEG mixture in a suitable stainless steel container. Heat the solution to 65°C ⁇ 5°C. Use a Stainless Steel Propeller/High Shear Mixer to mix all ingredients for 30 ⁇ 5 minutes or until homogenized.
  • the softgel capsules are then provided with an enteric coating consisting of hydroxypropyl methyl cellulose stearate and castor oil as plasticizer, in the customary manner.
  • sample capsules were then examined for stability. More specifically, sample capsules were incubated at 40°C, 30°C, or 25°C under relative humidity (RH) of 75%, 65% or 60% for 1 month, 2, months, 3 months, or 9 months. It was found that during the periods of time, the sample capsules remained clear and the fill compositions also remained clear and odorless solution.
  • RH relative humidity
  • Example 5 Process for Preparation of Surfactant-Free Fill Composition of Example 4
  • ingredient such as impurities in the starting material and degradation products produced during processing.
  • the study consisted of two 3-day periods separated by at least a 14-day washout period between treatments.
  • Each of fourteen normal, healthy, non-smoking male 0 and female subjects received 1 unit of fexofenadine tablet or capsule at 0 hour on Day 1 of each study period.
  • a total of 21 PK blood sample were drawn for analysis of fexofenadine over the course of 36 hours.
  • fexofenadine mean plasma concentration reached a peak much faster in the subjects taking the soft gel capsules as compared to those taking the tablets. Also, the mean plasma concentration peaks were much higher in those taking the soft gel capsules as compared to those taking the tablets. The results indicate that the fexofenadine- containing soft gel capsules disclosed herein provide enhanced bioavailability.

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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)
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Abstract

La présente invention concerne des compositions de remplissage liquides biodisponibles à enveloppe molle comprenant a) de la fexofénadine ou un sel de fexofénadine ; b) une matrice comprenant un poly(alkylène glycol) pharmaceutiquement acceptable, éventuellement un alkylène glycol pharmaceutiquement acceptable, éventuellement un agent solubilisant polymère pharmaceutiquement acceptable, et éventuellement un agent tensioactif pharmaceutiquement acceptable ; et c) un agent acidifiant pharmaceutiquement acceptable. L'invention concerne également des procédés pour la préparation de telles compositions de remplissage, ainsi que des gélules à enveloppe molle contenant ladite composition de remplissage liquide biodisponible.
PCT/US2016/018574 2015-02-20 2016-02-19 Gélules en gélatine molle contenant de la fexofénadine WO2016134200A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP16753099.7A EP3258934A4 (fr) 2015-02-20 2016-02-19 Gélules en gélatine molle contenant de la fexofénadine
CN201680011220.1A CN107847496A (zh) 2015-02-20 2016-02-19 含有非索非那丁的软明胶胶囊
US15/552,132 US20180042857A1 (en) 2015-02-20 2016-02-19 Soft gelatin capsules containing fexofenadine

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US14/627,589 US20160243044A1 (en) 2015-02-20 2015-02-20 Soft gelatin capsules containing fexofenadine
US14/627,589 2015-02-20
US201562255615P 2015-11-16 2015-11-16
US62/255,615 2015-11-16

Publications (1)

Publication Number Publication Date
WO2016134200A1 true WO2016134200A1 (fr) 2016-08-25

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CN (1) CN107847496A (fr)
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WO (1) WO2016134200A1 (fr)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050266032A1 (en) * 2003-12-17 2005-12-01 Sovereign Pharmaceuticals, Ltd. Dosage form containing multiple drugs
US20120183608A1 (en) * 2011-01-14 2012-07-19 Enspire Group LLC Highly concentrated liquid acetaminophen solutions
US20140073670A1 (en) * 2011-05-20 2014-03-13 Aventis Pharmaceuticals Inc. Pharmaceutical composition comprising fexofenadine
US20140357586A1 (en) * 1999-11-23 2014-12-04 Lipocine Inc. Solid Carriers for Improved Delivery of Active Ingredients in Pharmaceutical Compositions

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5510389A (en) * 1994-03-02 1996-04-23 The Procter & Gamble Company Concentrated acetaminophen solution compositions
WO2015003109A1 (fr) * 2013-07-03 2015-01-08 R.P. Scherer Technologies, Llc Formulation de capsules comprenant de la fexofénadine
US9504656B2 (en) * 2013-10-21 2016-11-29 Banner Life Sciences, LLC Pharmaceutical compositions for poorly soluble active ingredients

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140357586A1 (en) * 1999-11-23 2014-12-04 Lipocine Inc. Solid Carriers for Improved Delivery of Active Ingredients in Pharmaceutical Compositions
US20050266032A1 (en) * 2003-12-17 2005-12-01 Sovereign Pharmaceuticals, Ltd. Dosage form containing multiple drugs
US20120183608A1 (en) * 2011-01-14 2012-07-19 Enspire Group LLC Highly concentrated liquid acetaminophen solutions
US20140073670A1 (en) * 2011-05-20 2014-03-13 Aventis Pharmaceuticals Inc. Pharmaceutical composition comprising fexofenadine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP3258934A4 *

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HK1253053A1 (zh) 2019-06-06
EP3258934A1 (fr) 2017-12-27
EP3258934A4 (fr) 2018-09-05

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