WO1992004893A1 - Non-aqueous liquid oral suspensions - Google Patents

Non-aqueous liquid oral suspensions Download PDF

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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
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WO
WIPO (PCT)
Prior art keywords
composition
cimetidine
oil
antagonist
oily vehicle
Prior art date
Application number
PCT/US1991/006493
Other languages
French (fr)
Inventor
Malcolm Foreman
Harvey Lee Zimmerman
Original Assignee
Smithkline Beecham 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 Smithkline Beecham Corporation filed Critical Smithkline Beecham Corporation
Publication of WO1992004893A1 publication Critical patent/WO1992004893A1/en

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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

Pharmaceutically elegant liquid oral compositions comprise a histamine H2-antagonist such as cimetidine in an edible oily vehicle. The compositions are extremely palatable and minimize the bitter taste associated with these compounds. Other pharmaceutical additives well known to the art may be optionally added.

Description

NON-AQUEOUS LIQUID ORAL SUSPENSIONS
This invention relates to pharmaceutical compositions suitable for oral administration which comprise histamine H2-antagonists and result in an improved taste. Preferably, it relates to non-aqueous liquid oral suspensions which comprises cimetidine in an oily vehicle.
BACKGROUND OF THE INVENTION
Cimetidine is a histamine H2-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.
It is known that 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 4,861,592 discloses aqueous buffered
cimetidine suspensions as an approach to overcome 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.
DESCRIPTION OF THE INVENTION
According to the present invention there is provided a palatable non-aqueous liquid oral pharmaceutical suspension which comprises a histamine H2-antagonist, preferably
cimetidine, in an edible oily vehicle. By employing a one phase oily vehicle, it was unexpectedly discovered that the unpleasant taste of cimetidine associated with aqueous liquid vehicles was significantly minimized.
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. The synthetic edible oils which are commercially
available and are equivalent to the vegetable oils may also be employed in this invention. For example, the triglycerides of the C8-C10 fatty acids of fractionated coconut oil which are available under the trade name of "Miglyol". Specifically, 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 H2-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. Preferably, the H2-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 H2-antagonist of this invention will be present in the non-aqueous suspension in a nontoxic but effective amount to produce systemically effective histamine H2-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 H2-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.
Other histamine H2-antagonists, for example, those noted above, can also be present in the compositions of this
invention in a nontoxic but pharmaceutically effective amount. The concentration will vary with the H2-antagonist employed and the unit dosage required. The compositions will contain the H2-antagonist in an amount within dosage unit ranges which are well known to the medical art.
To further enhance the basic compositions of this invention other pharmaceutically acceptable additives well known to the art may be optionally added. Exemplary of 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 (Tween 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
hydroxyanisole, butylated hydroxytoluene or tertiary
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%.
The selection and amounts of the above pharmaceutically acceptable additives and their use in the nonaqueous
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.
The invention is further illustrated by the following examples which are not intended to be limited in scope.
Example 1
Ingredient % W/V
Cimetidine 4 .0
Confectioners Sugar NF 12X 25 .0
Mannitol 10 .0
Cab-O-Sil 0. 2
Propyl paraben 0. 1
Tertiary Butyl hydroqui none 0 .02
Vanilla Flavor 0. 5
Peppermint Flavor 0. 5
Partially Hydrogenated
Soybean Oil (Durkex 25) q.s. 100. 0 ml .
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.
The formulations listed below were prepared following the procedure of Example 1.
Example 2
Ingredients % W/V
Cimetidine 8 .0
Mannitol 40 .0
Aspartame 0. 1
Cab-O-Sil 0 .2
Propylparaben 0. 1
Tertiary Butyl hydroqui none 0. 02
Vanilla 0. 5
Peppermint 0. 5
Durkex 25 q.s. 100. 0 m l .
Figure imgf000008_0001

Claims

What is claimed is:
1. A non-aqueous liquid pharmaceutical composition for oral administration comprising a nontoxic effective amount of a histamine H2-antagonist and an edible oily vehicle.
2. The composition according to Claim 1 wherein the H2-antagonist is cimetidine.
3. The composition of Claim 2 wherein the cimetidine is present in an amount of from about 1.0% to about 12.0% W/V of the composition.
4. The composition of Claim 2 wherein the edible oily vehicle comprises soybean oil, partially hydrogenated soybean oil, corn oil, sunflower oil, peanut oil, coconut oil, or fractionated coconut oil.
5. The composition of Claim 4 wherein the oily vehicle is partially hydrogenated soybean oil.
6. The composition of Claim 4 wherein the oily vehicle is present in an amount of from about 40% to about 90% W/V of the composition.
7. The composition of Claim 4 wherein the composition includes sugars selected from the group consisting of mannitol, sorbitol, lactose, fructose or confectioners sugar.
8. The composition of Claim 7 wherein the sugar is present in an amount of from about 10% to about 40% W/V.
9. The composition of Claim 8 which further includes a thickening agent.
10. The pharmaceutical composition of Claim 9 comprising from about 4.0% to about 8.0% of cimetidine, from about 10% to about 40% of mannitol from about 0.1% to about 5.0% of Cab-O-Sil and from about 40% to about 90% of partially hydrogenated soybean oil.
11. The pharmaceutical composition of Claim 1 wherein the histamine H2-antagonist is ranitidine.
PCT/US1991/006493 1990-09-13 1991-09-10 Non-aqueous liquid oral suspensions WO1992004893A1 (en)

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

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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)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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

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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

Patent Citations (3)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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

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