WO1992004893A1 - Non-aqueous liquid oral suspensions - Google Patents
Non-aqueous liquid oral suspensions Download PDFInfo
- Publication number
- WO1992004893A1 WO1992004893A1 PCT/US1991/006493 US9106493W WO9204893A1 WO 1992004893 A1 WO1992004893 A1 WO 1992004893A1 US 9106493 W US9106493 W US 9106493W WO 9204893 A1 WO9204893 A1 WO 9204893A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- cimetidine
- oil
- antagonist
- oily vehicle
- Prior art date
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
- A61K9/0087—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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- This invention relates to pharmaceutical compositions suitable for oral administration which comprise histamine H 2 -antagonists and result in an improved taste.
- it relates to non-aqueous liquid oral suspensions which comprises cimetidine in an oily vehicle.
- Cimetidine is a histamine H 2 -antagonist which has been used for a number of years in the treatment of duodenal, gastric, stomal and recurrent ulceration. It has also been employed for reflux oesophagi tis and other conditions where reduction of gastric acid has been shown to be beneficial for example, persistent dyspeptic symptoms with or without ulceration. Cimetidine is absorbed almost exclusively in the small intestine where liquid compositions could be absorbed more quickly and efficiently than tablets.
- cimetidine has a very bitter taste and the majority of the oral compositions containing cimetidine are considered unpalatable.
- the unpleasant taste associated with cimetidine is much more noticeable in liquid oral compositions, particularly in aqueous vehicles. This has presented a major problem in the preparation of liquid oral compositions. There has been a long standing need for an elegant, palatable liquid oral composition which will mask the unpleasant taste of cimetidine.
- U.S. Patent 4,918,103 is representative of non-aqueous pharmaceutical vehicles employed to overcome stability problems associated with non steroidal anti-inflammatory drugs.
- U.S. Patents 4,639,367 and 4,752,465 disclose aerosol foams having the consistency of whipped cream employed as an alternative to liquid medicines having a bad taste.
- U.S. Patent 4,079,131 discloses anhydrous pharmaceutical vehicles employed to prepare permanent suspensions for water sensitive drugs.
- a palatable non-aqueous liquid oral pharmaceutical suspension which comprises a histamine H 2 -antagonist, preferably
- the oily vehicle employed in this invention may be, for example, an edible vegetable oil such as soybean oil, partially hydrogenated soybean oil, corn oil, sunflower oil, or peanut oil.
- an edible vegetable oil such as soybean oil, partially hydrogenated soybean oil, corn oil, sunflower oil, or peanut oil.
- the synthetic edible oils which are commercially
- the triglycerides of the C 8 -C 10 fatty acids of fractionated coconut oil which are available under the trade name of "Miglyol".
- Miglyol is a triglyceride of capric and caprylic acids with glycerol.
- the oils may also include sugar fatty acids known as "Olestras”.
- the partially hydrogenated soybean oils are particularly preferred.
- a species of this group of edible vegetable oils is commercially available under the trade name of "Durkex”. Most preferably, Durkex 25 is employed in the compositions of this invention.
- the above edible oils will be present in the non-aqueous pharmaceutical compositions of this invention in a range of from about 40% to about 90%, preferably from about 50 to about 80%.
- the histamine H 2 -antagonist employed in the non-aqueous liquid suspensions of this invention may be for example, cimetidine, ranitidine, famotidine, nizatidine, etintidine, lupitidine, nifentidine, niperotidine, roxatidine, sufotidine, tuvatidine and zaltidine.
- the H 2 -antagonist of this invention is cimetidine. It is well known that cimetidine can exist in at least five different polymorphic forms. Unless otherwise specified it is intended to include all polymorphs whether separated or mixtures thereof.
- the H 2 -antagonist of this invention will be present in the non-aqueous suspension in a nontoxic but effective amount to produce systemically effective histamine H 2 -antagonistic activity.
- the suspension will contain from about 1.0% to about 12.0% W/V of the antagonist, preferably from about 4.0% to about 8.0% W/V.
- the H 2 -antagonists are administered in conventional liquid dosage unit forms; preferab l y i n teaspoon quan t i t i e s . A teaspoon i s equ i va l en t to 5 ml . of the oral liquid composition.
- the active ingredient for example, cimetidine will normally be administered in an amount of from about 50 mg. to about 600 mg. per dosage unit, advantageously from about 200 mg. to about 400 mg. per dosage unit. Equal doses within the ranges given above will be administered preferably from about one to about four times a day.
- histamine H 2 -antagonists for example, those noted above, can also be present in the compositions of this
- compositions in a nontoxic but pharmaceutically effective amount.
- concentration will vary with the H 2 -antagonist employed and the unit dosage required.
- compositions will contain the H 2 -antagonist in an amount within dosage unit ranges which are well known to the medical art.
- additives well known to the art may be optionally added.
- these additives would be flavoring agents such as peppermint, vanilla, licorice, cinnamon, chocolate, spearmint or a combination of flavors; sweetening agents selected from aspartame, sodium cyclamate, calcium cyclamate or sodium saccharin; preservatives such as, for example, methylparaben, propyl paraben, butylparaben, benzoic acid and sorbic acid; emulsifying and surface active agents selected from nontoxic anionics such as sodium lauryl sulfate, cationics such as benzalkonium chloride or a non-ionic agent such as
- polyoxyethylene sorbitan monopalmi tate Teween 40
- sorbitan fatty acid esters such as, sorbitan monopalmi tate (Span 40) and natural emulsifiers selected from acacia, gelatin lecithin and cholesterol
- antioxidants selected from butylated
- butylhydroquinone and thickening agents such as silicon dioxide (Syloid) or colloidal silicon dioxide (Cab-O-Sil).
- These thickening agents may be present in an amount of from about 0.1% to about 5.0% of the composition.
- Sugars such as, for example, mannitol, sorbitol,
- confectioners sugar, lactose, fructose and glucose may be employed as both thickening and sweetening agents.
- the sugars may be present in the nonaqueous compositions of this invention in an amount of from about 10% to about 40%.
- compositions of this invention is within the skill of the pharmaceutical art except as specifically set forth herein.
- the compositions are prepared following the conventional techniques well known to those skilled in the art involving variously mixing, suspending and dispersing the ingredients as appropriate to give the desired composition.
- Soybean Oil (Durkex 25) q.s. 100. 0 ml .
- Durkex 25 50 ml. of Durkex 25 was placed in a propeller mixer and the propylparaben was dissolved in the oil. The flavors and butylhydroquinone were then added to the solution followed by the other ingredients with moderate mixing until the mixture was smooth and homogenous. The remaining Durkex was added with continued moderate mixing. The mixture was removed from the mixer and homogenized to a smooth consistency.
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US58186690A | 1990-09-13 | 1990-09-13 | |
US581,866 | 1990-09-13 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1992004893A1 true WO1992004893A1 (en) | 1992-04-02 |
Family
ID=24326890
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1991/006493 WO1992004893A1 (en) | 1990-09-13 | 1991-09-10 | Non-aqueous liquid oral suspensions |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP0548238A1 (en) |
JP (1) | JPH06501003A (en) |
AU (1) | AU8546591A (en) |
NZ (1) | NZ239784A (en) |
PT (1) | PT98975A (en) |
WO (1) | WO1992004893A1 (en) |
ZA (1) | ZA917310B (en) |
Cited By (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1210764A (en) * | 1968-03-28 | 1970-10-28 | Westinghouse Electric Corp | Self-aligning hydrostatic bearing |
WO1994008576A1 (en) * | 1992-10-16 | 1994-04-28 | Glaxo Group Limited | Taste-masking compositions of ranitidine |
WO1994012180A1 (en) * | 1992-11-27 | 1994-06-09 | Smithkline Beecham Plc | Cimetidine granules coated with a partially hydrogenated vegetable oil |
WO1996006599A1 (en) * | 1994-08-30 | 1996-03-07 | American Home Products Corporation | Taste-making lipid-based liquid medicinal composition |
WO1996008238A1 (en) * | 1994-09-14 | 1996-03-21 | Glaxo Group Limited | Use of paracellular absorption enhancers such as glucose for enhaincing the absorption of histamine h2-antagonists |
WO1997016159A1 (en) * | 1995-10-30 | 1997-05-09 | Warner-Lambert Company | Enhanced anti-inflammatory oral composition containing h2 receptor antagonist and antimicrobial oils |
WO2000076549A1 (en) * | 1999-06-10 | 2000-12-21 | Laboratorios S.A.L.V.A.T., S.A. | Liquid pharmaceutical composition for oral administration of bitter hydrolysis-susceptible active substances |
WO2004004682A2 (en) * | 2002-07-02 | 2004-01-15 | Laboratorios S.A.L.V.A.T., S.A. | Stable oily suspension of microgranules |
WO2004089337A1 (en) * | 2003-04-14 | 2004-10-21 | Cts Chemical Industries Ltd. | Oral administration form for veterinary use |
WO2006008640A1 (en) * | 2004-07-15 | 2006-01-26 | Pharmacia & Upjohn Company Llc | Non-aqueous suspension containing a drug having an unpleasant taste |
EP2319301A2 (en) | 2001-11-30 | 2011-05-11 | Amgen Fremont Inc. | Transgenic animals bearing human Ig lambda light chain genes |
US20120196800A1 (en) * | 2009-09-16 | 2012-08-02 | Novo Nordisk A/S | Stable non-aqueous liquid pharmaceutical compositions comprising an insulin |
US8309138B2 (en) | 2007-02-16 | 2012-11-13 | Aska Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising microparticle oily suspension |
EP2952207A1 (en) * | 2014-06-03 | 2015-12-09 | Essential Pharmaceuticals Ltd | Oil based pharmaceutical compositions for oral administration |
US9481721B2 (en) | 2012-04-11 | 2016-11-01 | Novo Nordisk A/S | Insulin formulations |
US9688737B2 (en) | 2008-03-18 | 2017-06-27 | Novo Nordisk A/S | Protease stabilized acylated insulin analogues |
US10265385B2 (en) | 2016-12-16 | 2019-04-23 | Novo Nordisk A/S | Insulin containing pharmaceutical compositions |
EP3784214A4 (en) * | 2018-04-27 | 2022-01-19 | Johnson & Johnson Consumer Inc. | Liquid oral pharmaceutical dosage form |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR102015024165A2 (en) * | 2015-09-18 | 2017-03-28 | Prati Donaduzzi & Cia Ltda | oral pharmaceutical composition comprising cannabinoid, process for its preparation and use |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0273390A2 (en) * | 1986-12-26 | 1988-07-06 | Mitsubishi Rayon Co., Ltd. | Radiation curable resin composition for use in magnetic recording media |
GB2218333A (en) * | 1988-05-11 | 1989-11-15 | Glaxo Group Ltd | Ranitidine adsorbates |
FR2643263A1 (en) * | 1989-02-23 | 1990-08-24 | Glaxo Canada | PHARMACEUTICAL COMPOSITION BASED ON RANITIDINE |
-
1991
- 1991-09-10 AU AU85465/91A patent/AU8546591A/en not_active Abandoned
- 1991-09-10 WO PCT/US1991/006493 patent/WO1992004893A1/en not_active Application Discontinuation
- 1991-09-10 JP JP3516163A patent/JPH06501003A/en active Pending
- 1991-09-10 EP EP91917176A patent/EP0548238A1/en not_active Withdrawn
- 1991-09-13 NZ NZ239784A patent/NZ239784A/en unknown
- 1991-09-13 ZA ZA917310A patent/ZA917310B/en unknown
- 1991-09-13 PT PT98975A patent/PT98975A/en not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0273390A2 (en) * | 1986-12-26 | 1988-07-06 | Mitsubishi Rayon Co., Ltd. | Radiation curable resin composition for use in magnetic recording media |
GB2218333A (en) * | 1988-05-11 | 1989-11-15 | Glaxo Group Ltd | Ranitidine adsorbates |
FR2643263A1 (en) * | 1989-02-23 | 1990-08-24 | Glaxo Canada | PHARMACEUTICAL COMPOSITION BASED ON RANITIDINE |
Cited By (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1210764A (en) * | 1968-03-28 | 1970-10-28 | Westinghouse Electric Corp | Self-aligning hydrostatic bearing |
WO1994008576A1 (en) * | 1992-10-16 | 1994-04-28 | Glaxo Group Limited | Taste-masking compositions of ranitidine |
US5635200A (en) * | 1992-10-16 | 1997-06-03 | Glaxo Group Limited | Taste-making compositions of ranitidine |
WO1994012180A1 (en) * | 1992-11-27 | 1994-06-09 | Smithkline Beecham Plc | Cimetidine granules coated with a partially hydrogenated vegetable oil |
US5597844A (en) * | 1992-11-27 | 1997-01-28 | Chauhan; Sushil | Cimetidine granules coated with a partially hydrogenated vegetable oil |
WO1996006599A1 (en) * | 1994-08-30 | 1996-03-07 | American Home Products Corporation | Taste-making lipid-based liquid medicinal composition |
WO1996008238A1 (en) * | 1994-09-14 | 1996-03-21 | Glaxo Group Limited | Use of paracellular absorption enhancers such as glucose for enhaincing the absorption of histamine h2-antagonists |
WO1997016159A1 (en) * | 1995-10-30 | 1997-05-09 | Warner-Lambert Company | Enhanced anti-inflammatory oral composition containing h2 receptor antagonist and antimicrobial oils |
WO2000076549A1 (en) * | 1999-06-10 | 2000-12-21 | Laboratorios S.A.L.V.A.T., S.A. | Liquid pharmaceutical composition for oral administration of bitter hydrolysis-susceptible active substances |
ES2153786A1 (en) * | 1999-06-10 | 2001-03-01 | S A L V A T Lab Sa | Liquid pharmaceutical composition for oral administration of bitter hydrolysis-susceptible active substances |
EP2319301A2 (en) | 2001-11-30 | 2011-05-11 | Amgen Fremont Inc. | Transgenic animals bearing human Ig lambda light chain genes |
WO2004004682A3 (en) * | 2002-07-02 | 2004-10-28 | S A L V A T Lab Sa | Stable oily suspension of microgranules |
WO2004004682A2 (en) * | 2002-07-02 | 2004-01-15 | Laboratorios S.A.L.V.A.T., S.A. | Stable oily suspension of microgranules |
WO2004089337A1 (en) * | 2003-04-14 | 2004-10-21 | Cts Chemical Industries Ltd. | Oral administration form for veterinary use |
WO2006008640A1 (en) * | 2004-07-15 | 2006-01-26 | Pharmacia & Upjohn Company Llc | Non-aqueous suspension containing a drug having an unpleasant taste |
US8309138B2 (en) | 2007-02-16 | 2012-11-13 | Aska Pharmaceutical Co., Ltd. | Pharmaceutical composition comprising microparticle oily suspension |
US9688737B2 (en) | 2008-03-18 | 2017-06-27 | Novo Nordisk A/S | Protease stabilized acylated insulin analogues |
US10259856B2 (en) | 2008-03-18 | 2019-04-16 | Novo Nordisk A/S | Protease stabilized acylated insulin analogues |
US20120196800A1 (en) * | 2009-09-16 | 2012-08-02 | Novo Nordisk A/S | Stable non-aqueous liquid pharmaceutical compositions comprising an insulin |
US9481721B2 (en) | 2012-04-11 | 2016-11-01 | Novo Nordisk A/S | Insulin formulations |
GB2529605A (en) * | 2014-06-03 | 2016-03-02 | Essential Pharmaceuticals Ltd | Pharmaceutical composition |
GB2529605B (en) * | 2014-06-03 | 2018-03-21 | Essential Pharmaceuticals Ltd | Pharmaceutical composition |
EP2952207A1 (en) * | 2014-06-03 | 2015-12-09 | Essential Pharmaceuticals Ltd | Oil based pharmaceutical compositions for oral administration |
US10265385B2 (en) | 2016-12-16 | 2019-04-23 | Novo Nordisk A/S | Insulin containing pharmaceutical compositions |
US10596231B2 (en) | 2016-12-16 | 2020-03-24 | Novo Nordisk A/S | Insulin containing pharmaceutical compositions |
EP3784214A4 (en) * | 2018-04-27 | 2022-01-19 | Johnson & Johnson Consumer Inc. | Liquid oral pharmaceutical dosage form |
US11433024B2 (en) | 2018-04-27 | 2022-09-06 | Johnson & Johnson Consumer Inc. | Liquid oral pharmaceutical dosage form |
Also Published As
Publication number | Publication date |
---|---|
PT98975A (en) | 1992-07-31 |
JPH06501003A (en) | 1994-01-27 |
EP0548238A1 (en) | 1993-06-30 |
AU8546591A (en) | 1992-04-15 |
NZ239784A (en) | 1994-05-26 |
ZA917310B (en) | 1992-10-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
WO1992004893A1 (en) | Non-aqueous liquid oral suspensions | |
EP0701434B1 (en) | Preparations containing silicon dioxide to improve the taste thereof | |
US4918103A (en) | Liquid oral pharmaceutical compositions of non-steroidal anti-inflammatory drugs | |
US5593685A (en) | Ranitidine compositions | |
JP2004535370A (en) | Liquid pharmaceutical composition with masked taste | |
FR2727016A1 (en) | ONDANSETRON-BASED PHARMACEUTICAL COMPOSITIONS | |
FR2727015A1 (en) | ONDANSETRON LIQUID PHARMACEUTICAL COMPOSITIONS | |
US4259323A (en) | Potassium chloride emulsion | |
JP4773619B2 (en) | Purcarapride oral solution | |
DD238920A5 (en) | PROCESS FOR PREPARING AN IMPROVED DAMAGING DEFLECTIVE COMPOSITION | |
IE913216A1 (en) | Non-aqueous liquid oral suspensions | |
US20060100271A1 (en) | Stabilized aqueous ranitidine compositions | |
EP0422290A1 (en) | Novel drug delivery system | |
US6235733B1 (en) | Oral liquid formulations of benzoxazinones HIV reverse transcriptase inhibitors | |
US6265449B1 (en) | Aqueous compositions comprising ranitidine and LCMT sucrose | |
US20050136116A1 (en) | Stabilized prednisolone sodium phosphate solutions | |
US20020061884A1 (en) | Oral liquid formulations of benzoxazinones HIV reverse transcriptase inhibitors | |
JPH0672897A (en) | Composition for reducing various unplesant symptoms before and during menstruation | |
US20060127472A1 (en) | Taste-masked prednisolone oral formulations | |
MXPA00007579A (en) | Oral liquid formulations of benzoxazinones hiv reverse transcriptase inhibitors | |
WO2007003020A1 (en) | Oral formulations comprising ondansetron and a highly dosed sweeten |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA JP KR US |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LU NL SE |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1991917176 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 1991917176 Country of ref document: EP |
|
NENP | Non-entry into the national phase |
Ref country code: CA |
|
WWW | Wipo information: withdrawn in national office |
Ref document number: 1991917176 Country of ref document: EP |