WO2013147452A1 - Composition pharmaceutique sous forme de liquide non-aqueux comprenant du révaprazan ou son sel - Google Patents

Composition pharmaceutique sous forme de liquide non-aqueux comprenant du révaprazan ou son sel Download PDF

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Publication number
WO2013147452A1
WO2013147452A1 PCT/KR2013/002316 KR2013002316W WO2013147452A1 WO 2013147452 A1 WO2013147452 A1 WO 2013147452A1 KR 2013002316 W KR2013002316 W KR 2013002316W WO 2013147452 A1 WO2013147452 A1 WO 2013147452A1
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WO
WIPO (PCT)
Prior art keywords
revaprazan
pharmaceutical composition
salt
polyoxylglyceride
surfactant
Prior art date
Application number
PCT/KR2013/002316
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English (en)
Inventor
Byoung-Moo Lee
Chang-Keun Hyun
Yoong-Sik Park
Original Assignee
Yuhan Corporation
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 Yuhan Corporation filed Critical Yuhan Corporation
Publication of WO2013147452A1 publication Critical patent/WO2013147452A1/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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K9/08—Solutions
    • 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
    • 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 present invention relates to a pharmaceutical composition for oral administration in a form of non-aqueous liquid (i.e., non-aqueous liquid formulation) comprising revaprazan or its salt.
  • Revaprazan whose chemical name is 5,6-dimethyl-2-(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine, is represented by the following Formula 1.
  • Revaprazan can be used in a form of an acid addition salt, including e.g., HCl salt (see International Publication No. WO1996/05177, WO1997/042186, and WO1998/018784).
  • Revaprazan or its salt is reversibly bound to a H + /K + exchange site of a proton pump (H + /K + ATPase) existing in a gastric parietal cell so that secretion of H + into the gastric lumen is competitively inhibited.
  • Revaprazan or its salt is also bound to a specific site of H + /K + ATPase, thereby inhibiting transport of H + and suppressing an acid secretion to the gastric lumen, which results in increasing the intragastric pH.
  • irreversible proton pump inhibitors e.g., omeprazole
  • revaprazan or its salt is not dependent upon acid activation of a drug in a stomach or secretion status of a proton pump. Therefore, based on the mechanism different from irreversible proton pump inhibitors, such as omeprazole, revaprazan or its salt is classified into an acid pump antagonist (APA).
  • APA acid pump antagonist
  • Revaprazan has very low water-solubility, i.e. less than 0.2 mg/mL, and even lower solubility in a buffer solution having pH 1 to 12. And also, revaprazan has very low intrinsic dissolution rate, i.e., about 0.0086 mg/min/cm 2 . Due to such a low solubility and intrinsic dissolution rate, its dissolution in the gastrointestinal tract is also very low. Therefore, when revaprazan is orally administered, its absorption rate is relatively low. Revaprazan also has strong adhesion and agglutination properties, and thus, when revaprazan is formulated into a capsule or a tablet, it may be stuck to a punch or a die, thereby showing low formulation processability.
  • WO 2008/078922 has disclosed a pharmaceutical composition for oral administration comprising a solid dispersion in which revaprazan particles are surface-modified with a water-soluble polymer, a water-soluble saccharide, a surfactant, or a mixture thereof.
  • a pharmaceutical composition for oral administration comprising a solid dispersion in which revaprazan particles are surface-modified with a water-soluble polymer, a water-soluble saccharide, a surfactant, or a mixture thereof.
  • the bioavailability thereof is still unsatisfactory.
  • the present inventors performed various researches for developing revaprazan or its salt-containing pharmaceutical formulations for oral administration, which has excellent bioavailability.
  • the present inventors designed various formulations that can provide efficient absorption of revaprazan in the gastrointestinal tract.
  • the present inventors designed a non-aqueous liquid formulation containing revaprazan or its salt along with a certain oil and a surfactant, the formulation being able to exist in a form of emulsion in the gastrointestinal tract through self-emulsifying.
  • a pharmaceutical composition for oral administration in a form of non-aqueous liquid comprising revaprazan or its salt; a certain oil; and a surfactant.
  • a pharmaceutical composition for oral administration in a form of non-aqueous liquid comprising revaprazan or its salt; an oil selected from the group consisting of glyceryl monolinoleate, glyceryl monooleate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, caprylocaproyl polyoxylglyceride, oleoyl polyoxylglyceride, linoleoyl polyoxylglyceride, and a mixture thereof; and a surfactant.
  • the surfactant may be selected from the group consisting of sorbitan ester, polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, polyethylene glycol-15-hydroxystearate, polyoxyethylene glycolated natural or hydrogenated castor oil, polyoxyethylene-polyoxypropylene copolymer, alpha-tocopheryl polyethylene glycol succinate, polyoxyethylene alkyl ester, fatty acid macrogol glyceride, polyglyceryl fatty acid ester, bile acid, sodium lauryl sulfate, lecithin, glyceryl fatty acid ester, polyethylene glycol stearate, and a mixture thereof.
  • the surfactant may be selected from the group consisting of sucrose fatty acid ester, alpha-tocopheryl polyethylene glycol succinate, polyethylene glycol-15-hydroxystearate, and a mixture thereof.
  • the oil may be present in an amount ranging from 4 to 20 parts by weight, based on 1 part by weight of revaprazan or its salt.
  • the surfactant may be present in an amount ranging from 0.2 to 10 parts by weight, based on 1 part by weight of revaprazan or its salt.
  • a process for preparing a pharmaceutical composition for oral administration in a form of non-aqueous liquid comprising (a) melting an oil selected from the group consisting of glyceryl monolinoleate, glyceryl monooleate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, caprylocaproyl polyoxylglyceride, oleoyl polyoxylglyceride, linoleoyl polyoxylglyceride, and a mixture thereof; and (b) dissolving or dispersing revaprazan or its salt and a surfactant in the melt obtained in the step (a).
  • a capsule comprising the pharmaceutical composition.
  • the pharmaceutical composition in a form of non-aqueous liquid according to the present invention contains a certain oil along with a surfactant, thereby not only increasing solubility and dissolution rate of revaprazan remarkably but also exhibiting excellent stability without phase separation. And also, through excellent solubilizing effects, the pharmaceutical composition according to the present invention can be suitably applied to production of capsules containing a therapeutically effective amount of revaprazan. That is, the pharmaceutical composition in a form of non-aqueous liquid according to the present invention can be easily filled into a capsule, thereby exhibiting excellent formulation processability.
  • the pharmaceutical composition in a form of non-aqueous liquid according to the present invention is maintained in a form of emulsion (where revaprazan is dissolved or dispersed through self-emulsifying) in the gastrointestinal tract, which leads to high gastrointestinal absorption rate, thereby being able to accomplish remarkably excellent bioavailability.
  • the process for preparing the pharmaceutical composition according to the present invention is simple and therefore can be easily applied to industrial mass production.
  • the present invention provides a pharmaceutical composition for oral administration in a form of non-aqueous liquid (i.e., non-aqueous liquid formulation), comprising revaprazan or its salt; an oil selected from the group consisting of glyceryl monolinoleate, glyceryl monooleate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, caprylocaproyl polyoxylglyceride, oleoyl polyoxylglyceride, linoleoyl polyoxylglyceride, and a mixture thereof; and a surfactant.
  • glyceryl monolinoleate glyceryl monooleate
  • propylene glycol monocaprylate diethylene glycol monoethyl ether
  • caprylocaproyl polyoxylglyceride oleoyl polyoxylglyceride
  • linoleoyl polyoxylglyceride linoleoyl polyoxyl
  • the present inventors designed a non-aqueous liquid formulation that can exist in a form of emulsion in the gastrointestinal tract through self-emulsifying.
  • the present inventors performed researches on various systems containing oil(s) and surfactant(s) that can dissolve or disperse revaprazan.
  • a certain oil e.g., glyceryl monolinoleate, glyceryl monooleate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, caprylocaproyl polyoxylglyceride, oleoyl polyoxylglyceride, and/or linoleoyl polyoxylglyceride
  • a certain oil e.g., glyceryl monolinoleate, glyceryl monooleate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, caprylocaproyl polyoxylglyceride, oleoyl polyoxylglyceride, and/or linoleoyl polyoxylglyceride
  • the pharmaceutical composition according to the present invention can be suitably applied to production of capsules containing a therapeutically effective amount (for example, about 10 to 500 mg) of revaprazan. That is, the pharmaceutical composition in a form of non-aqueous liquid according to the present invention can be easily filled into a capsule, thereby exhibiting excellent formulation processability.
  • the pharmaceutical composition in a form of non-aqueous liquid according to the present invention is maintained in a form of emulsion (where revaprazan is dissolved or dispersed through self-emulsifying) in the gastrointestinal tract, which leads to high gastrointestinal absorption rate, thereby being able to accomplish remarkably excellent bioavailability.
  • the process for preparing the pharmaceutical composition according to the present invention is simple and therefore can be easily applied to industrial mass production.
  • revaprazan or its salt may be used in a therapeutically effect amount, for example in range of 10 to 500 mg in a unit dosage form of capsule, but not limited thereto.
  • the pharmaceutically acceptable salt of revaprazan may be an acid addition salt, including revaprazan hydrochloride, revaprazan sulfate, revaprazan phosphate, revaprazan nitrate, revaprazan camphorsulfonate (i.e., revaprazan camsylate), revaprazan thiocyanate, and the like.
  • the salt of revaprazan is revaprazan hydrochloride.
  • the oil used as a medium in the pharmaceutical composition of the present invention includes glyceryl monolinoleate (for example, Maisine TM , etc.), glyceryl monooleate (for example, Peceol TM , etc.), propylene glycol monocaprylate (for example, Capryol TM 90, Capryol PGMC TM , etc.), diethylene glycol monoethyl ether (for example, Transcutol P TM , etc.), caprylocaproyl polyoxylglyceride (for example, Labrasol TM , etc.), oleoyl polyoxylglyceride (for example, Labrafil M 1944 TM , etc.), linoleoyl polyoxylglyceride (for example, Labrafil M 2125 TM , etc.), and a mixture thereof.
  • glyceryl monolinoleate for example, Maisine TM , etc.
  • glyceryl monooleate for
  • the oil may be present in an amount ranging from 4 to 20 parts by weight, preferably from 6 to 10 parts by weight, based on 1 part by weight of revaprazan or its salt. When the oil is present below 4 parts by weight, it may become difficult to form a composition capable of providing sufficient self-emulsification of revaprazan. When the oil is present above 20 parts by weight, it may become difficult to perform capsule-filling.
  • the surfactant includes any surfactants conventionally used in the field of pharmaceutics.
  • the surfactant include sorbitan ester (for example, Span TM , etc.), polyoxyethylene sorbitan fatty acid ester (for example, Tween TM , etc.), sucrose fatty acid ester (for example, Ryoto Ester L 1695 TM , etc.), polyethylene glycol-15-hydroxystearate (for example, Solutol HS15 TM , etc.), polyoxyethylene glycolated natural or hydrogenated castor oil (for example, Cremophor RH 40 TM , etc.), polyoxyethylene-polyoxypropylene copolymer (for example, Poloxamer TM , etc.), alpha-tocopheryl polyethylene glycol succinate, polyoxyethylene alkyl ester (for example, Brij 52 TM , etc.), fatty acid macrogol glyceride (for example, Gelucire 44/14 TM , etc.), polygly
  • a surfactant selected from the group consisting of sucrose fatty acid ester, alpha-tocopheryl polyethylene glycol succinate, polyethylene glycol-15-hydroxystearate, and a mixture thereof.
  • the surfactant may be present in an amount ranging from 0.2 to 10 parts by weight, preferably from 0.5 to 4 parts by weight, based on 1 part by weight of revaprazan or its salt. When the surfactant is present below 0.2 parts by weight, it may become difficult to obtain sufficient solubilizing effect of revaprazan. When the surfactant is present above 10 parts by weight, phase separation may occur.
  • the present invention also provides a process for preparing a pharmaceutical composition for oral administration in a form of non-aqueous liquid, the process comprising (a) melting an oil selected from the group consisting of glyceryl monolinoleate, glyceryl monooleate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, caprylocaproyl polyoxylglyceride, oleoyl polyoxylglyceride, linoleoyl polyoxylglyceride, and a mixture thereof; and (b) dissolving or dispersing revaprazan or its salt and a surfactant in the melt obtained in the step (a).
  • an oil selected from the group consisting of glyceryl monolinoleate, glyceryl monooleate, propylene glycol monocaprylate, diethylene glycol monoethyl ether, caprylocaproyl polyoxylglyceride, oleoyl polyoxylglycer
  • the melting in step (a) may be performed by heating the oil to about 40 to 80 °C, preferably about 50 to 60 °C, under stirring.
  • the dissolving or dispersing in step (b) may be performed by simultaneously or sequentially adding the surfactant and revaprazan or its salt to the melt obtained in the step (a), under stirring.
  • the present invention also provides a capsule comprising the pharmaceutical composition in a form of non-aqueous liquid.
  • the capsule may be prepared by filling a hard or soft capsule with the above-described non-aqueous liquid (i.e., non-aqueous liquid formulation), according to conventional methods.
  • the non-aqueous liquid formulations were prepared according to the components and amounts shown in Table 1.
  • the oil was melted by heating to about 50 to 60 °C under stirring. While stirring the resulting melt, the surfactant was dissolved therein; and then revaprazan was dissolved or dispersed therein to obtain each non-aqueous liquid formulation.
  • non-aqueous liquid formulations were prepared by using the same procedures of Examples 1 to 21, according to the components and amounts shown in Table 2.
  • non-aqueous liquid formulations were prepared by using the same procedures of Examples 1 to 21, according to the components and amounts shown in Table 3.
  • Glyceryl monolinoleate (Maisine TM , 346.2 g) was melted by heating to about 50 to 60 °C under stirring. While stirring the resulting melt, revaprazan (50 g) was added thereto. The resulting product was obtained in an inhomogeneous dispersion form, where revaprazan was not completely dispersed.
  • each aliquot i.e., non-aqueous liquid formulation
  • a hard capsule i.e., void capsule
  • the dissolution test of each resulting capsule was performed according to the 'Dissolution Test 2 (Paddle Method)' of the Korean Pharmacopeia.
  • 900 ml of a pH1.2 buffer was used as a dissolution medium and the dissolution test was performed at 37 ⁇ 0.5 °C and at the paddle rotation rate of 50 rpm.
  • Example Dissolution rate (60 min.) Example Dissolution rate (60 min.) 1 22 % 16 30 % 2 31 % 17 40 % 3 25 % 18 39 % 4 28 % 19 26 % 5 24 % 20 41 % 6 35 % 21 42 % 7 34 % 22 38 % 8 33 % 23 37 % 9 26 % 24 34 % 10 36 % 25 29 % 11 46 % 26 28 % 12 43 % 27 34 % 13 49 % 28 31 % 14 55 % Comparative Example 1 14 % 15 34 % Revanex TM 19 %
  • the capsules obtained from the non-aqueous liquid formulations according to the present invention exhibited remarkably increased dissolution rates, showing maximum 250% of high dissolution rate in comparison with the tablet of Revanex TM .
  • mice Male rats (body weight: about 200 g, 7 weeks old) fasted for 16 hours were subject to endotracheal intubation and then divided into 4 groups, each group having 3 rats.
  • the rats of each groups were orally administered with the non-aqueous liquid formulations obtained in Examples 17, 20, or 21 and the control (i.e., the 0.5 % MC suspension of revaprazan) in a dose of 20 mg/whole body, respectively.
  • the blood sample was collected at the time of 0, 0.5, 1, 1.5, 2, 3, 5, and 7 hours after the administration and then centrifuged to obtain the serum.
  • the concentration of revaprazan in the serum was analyzed with LC/MS/MS under the following conditions.
  • the standard material i.e., revaprazan (m/z 363.1 > 245.1)
  • the internal standard material i.e., oxybutynin (m/z 358.2 > 142.1)
  • Example 17 Example 20
  • Example 21 0.5% MC suspension Cmax(ng/mL) 3343 ⁇ 383.6 3033.3 ⁇ 269.3 2793.0 ⁇ 230.6 750.5 ⁇ 63.9
  • Tmax(hour) 5.0 ⁇ 1.2 3.0 ⁇ 0.0 3.7 ⁇ 0.7 1.8 ⁇ 0.2
  • the non-aqueous liquid formulations prepared according to the present invention exhibited remarkably increased AUC, thereby being able to accomplish high bioavailability. It is thought that these results are originated from the mechanism that, when orally administered, the formulations according to the present invention are maintained in a form of absorption-facilitated emulsion (where revaprazan is solubilzed through self-emulsifying) in the gastrointestinal tract, which leads to high gastrointestinal absorption rate.

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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)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
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Abstract

La présente invention concerne une composition pharmaceutique pour l'administration par voie orale sous forme de liquide non aqueux, comprenant du révaprazan ou son sel; une huile choisie dans le groupe constitué de mono-oléate de glycéryle, monolinoléate de glycéryle, monocaprylate de propylène glycol, éther monoéthylique de diéthylène glycol, polyoxylglycéride de caprylocaproyle, polyoxylglycéride d'oléoyle, linoléoyl polyoxylglyceride, et d'un mélange de ceux-ci; et un tensioactif. La présente invention concerne également un procédé de préparation de la composition pharmaceutique pour administration orale sous la forme de liquide non aqueux, et une capsule les comprenant.
PCT/KR2013/002316 2012-03-28 2013-03-21 Composition pharmaceutique sous forme de liquide non-aqueux comprenant du révaprazan ou son sel WO2013147452A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR1020120031411A KR101739820B1 (ko) 2012-03-28 2012-03-28 레바프라잔 또는 그의 염을 함유하는 비수성 액체 형태의 경구투여용 약학 조성물
KR10-2012-0031411 2012-03-28

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170319698A1 (en) * 2014-10-29 2017-11-09 Jagotec Ag Gastroretentive gel formulations
WO2020053662A3 (fr) * 2018-09-13 2020-07-30 Ftf Pharma Private Limited Solutions non aqueuses pour posologie orale
WO2022259205A1 (fr) * 2021-06-11 2022-12-15 Universidade Da Beira Interior Composition auto-émulsifiante, ses procédés de production et ses utilisations
US11767328B2 (en) 2018-03-14 2023-09-26 KaNDy Therapeutics Limited Method of treatment of symptoms of menopause

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102327750B1 (ko) * 2018-12-19 2021-11-18 대화제약 주식회사 Glp-1 유사체를 포함하는 경구투여용 약제학적 조성물

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US20060165797A1 (en) * 2005-01-12 2006-07-27 Pozen Inc. Dosage form for treating gastrointestinal disorders
US20080050428A1 (en) * 2004-10-05 2008-02-28 Altana Pharma Ag Oral Pharmaceutical Preparation Comprising a Proton Pump Antagonist and a Basic Excipient
US20080102133A1 (en) * 2004-10-05 2008-05-01 Antje Brueck-Scheffler Oral Pharmaceutical Preparation for Proton Pump Antagonists
US20100041688A1 (en) * 2006-12-22 2010-02-18 Yuhan Corporation Revaprazan-containing solid dispersion and process for the preparation thereof
WO2010122583A2 (fr) * 2009-04-24 2010-10-28 Rubicon Research Private Limited Compositions pharmaceutiques orales comprenant des substances labiles en milieu acide

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KR101739815B1 (ko) 2010-12-01 2017-05-26 주식회사유한양행 레바프라잔 또는 그의 염을 함유하는 주사용 액제 조성물

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US20080050428A1 (en) * 2004-10-05 2008-02-28 Altana Pharma Ag Oral Pharmaceutical Preparation Comprising a Proton Pump Antagonist and a Basic Excipient
US20080102133A1 (en) * 2004-10-05 2008-05-01 Antje Brueck-Scheffler Oral Pharmaceutical Preparation for Proton Pump Antagonists
US20060165797A1 (en) * 2005-01-12 2006-07-27 Pozen Inc. Dosage form for treating gastrointestinal disorders
US20100041688A1 (en) * 2006-12-22 2010-02-18 Yuhan Corporation Revaprazan-containing solid dispersion and process for the preparation thereof
WO2010122583A2 (fr) * 2009-04-24 2010-10-28 Rubicon Research Private Limited Compositions pharmaceutiques orales comprenant des substances labiles en milieu acide

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20170319698A1 (en) * 2014-10-29 2017-11-09 Jagotec Ag Gastroretentive gel formulations
US11767328B2 (en) 2018-03-14 2023-09-26 KaNDy Therapeutics Limited Method of treatment of symptoms of menopause
US11787820B2 (en) 2018-03-14 2023-10-17 KaNDy Therapeutics Limited Method of treating certain sex hormone-dependent diseases administering a soft gelatin capsule comprising NK1 and NK3 receptors antagonists
WO2020053662A3 (fr) * 2018-09-13 2020-07-30 Ftf Pharma Private Limited Solutions non aqueuses pour posologie orale
GB2596184A (en) * 2018-09-13 2021-12-22 Ftf Pharma Private Ltd Non-aqueous solutions for oral dosage
WO2022259205A1 (fr) * 2021-06-11 2022-12-15 Universidade Da Beira Interior Composition auto-émulsifiante, ses procédés de production et ses utilisations

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KR20130109570A (ko) 2013-10-08

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