WO1994025006A1 - Compositions pharmaceutiques masquant le gout et leurs procedes de production - Google Patents

Compositions pharmaceutiques masquant le gout et leurs procedes de production Download PDF

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Publication number
WO1994025006A1
WO1994025006A1 PCT/US1994/004569 US9404569W WO9425006A1 WO 1994025006 A1 WO1994025006 A1 WO 1994025006A1 US 9404569 W US9404569 W US 9404569W WO 9425006 A1 WO9425006 A1 WO 9425006A1
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WIPO (PCT)
Prior art keywords
drug
lipid
aqueous solution
mixture
composition
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Application number
PCT/US1994/004569
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English (en)
Inventor
Seang H. Yiv
Alex K. Tustian
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Affinity Biotech, Inc.
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 Affinity Biotech, Inc. filed Critical Affinity Biotech, Inc.
Priority to AU67746/94A priority Critical patent/AU6774694A/en
Publication of WO1994025006A1 publication Critical patent/WO1994025006A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats

Definitions

  • This invention relates to techniques for taste- masking pharmaceutical drugs. More specifically, the invention relates to compositions comprising a drug having its taste masked by a lipid coating contained within an aqueous polymer system for oral administration thus providing an improved taste for the drug.
  • a more recent and convenient means of preparing these drugs is in a granule lipid format which avoids the storing of the drug in an aqueous solution which solution could destroy the lipid coating.
  • the granules are usually suspended in an aqueous solution immediately prior to oral administration and, in this manner, the drug is not dissolved in the mouth of the patient, but rather passes on to the gastro-intestinal tract where it is dissolved by stomach fluids.
  • the drug By storing the drug within an integral coating of a lipid in a granule format, the drug can be maintained in its flavor masked form for at least 14 days and maybe longer.
  • Lipid coatings for masking the bitter taste of certain drugs have been beneficially employed as is shown in U.S. Patent No.
  • a method of producing a stable drug composition which masks the flavor of a drug in need of flavor masking is provided which is broadly defined by the following steps.
  • a drug in particulate form is mixed with a lipid at a temperature below that where significant drug degradation occurs, preferably below about 50*C.
  • an emulsifier or surfactant to form the stable taste- masked drug composition.
  • a polymer solution to form the stable taste- masked drug composition.
  • the method proceeds as follows. A mixture of a lipid and an emulsifier are heated until that mixture is brought into a molten state. The lipid and emulsifier mixture temperature is then adjusted to a temperature below that where significant drug degradation occurs, preferably below about 50 ⁇ C. To this cooled mixture is then admixed the drug, in particulate form, which thereby forms a flavor masked drug/lipid dispersion. To this drug dispersion is supplied a polymer solution to form a concentrated drug composition. Finally, a dilution solution, preferably comprising a sweetening agent, is added to form the final drug composition.
  • a dilution solution preferably comprising a sweetening agent
  • the drug is selected from the group consisting of cimetidine, ranitidine, ibuprofen, acetaminophen, and erythromycin.
  • the method of the present invention provides a stable dispersion of the drug, in a flavor masked state, which dispersion has an extended shelf life of several months.
  • the drug to lipid weight ratio ranges from about 1:0.25 to about 1:2.
  • the drug is preferably added in amount up to about 800 milligrams per 10 milliliters (10 cc) of the drug composition.
  • the polymer is supplied as a polymer solution which contains the polymer in an aqueous solution and preferably contains carboxymethylcellulose and xanthan gum.
  • a further embodiment of the present invention is a method for preparing a taste-masked drug composition in which the tendency of the drug to aggregate is inhibited by the incorporation of a surfactant with the particulate drug.
  • the particulate drug is combined with the molten surfactant and the resultant mixture is then solidified and reduced to a powder form.
  • This powder is then admixed into a molten or semi-solid lipid, followed by the admixture of the polymer, suspension agent, and aqueous solution.
  • the lipid and drug mixture does not require resolidification or the formation of individual particles prior to being blended with the aqueous solution.
  • the invention also provides for the drug compositions produced by the inventive methods.
  • the present invention broadly relates to a novel and economical method of preparing a stable pharmaceutical composition, and the compositions produced therefrom, which compositions contain a drug, which is characterized by having an unpleasant taste, wherein the drug is provided in a flavor masked form in a dispersion system.
  • the invention provides for the effective flavor masked encapsulation of the drug in a lipid material and for the suspension of this drug/lipid component in an aqueous phase with the aid of emulsifiers and suspending agents.
  • the drug composition produced also contains an aqueous phase comprising a polymer system and additive agents such as sweeteners and flavor enhancers.
  • the stability of the drug composition has been demonstrated from as short as a day up to as long as 3 months in its flavor masked state.
  • the drug composition is generally stored at a temperature range of from about 4'C to about 40°C, preferably at about 15 ⁇ -25 ⁇ C, and most preferably at room temperature. Stability is dependent upon various factors such as the type and structure of the drug, and the sequence of addition of the constituents during the manufacturing process.
  • the drug which is in particulate form
  • the lipid is mixed by conventional methods with the lipid at a temperature below where degradation of the drug can significantly occur. This degradation is evidenced by a substantial inactivation of the drug and is readily determined.
  • the temperature is typically kept below about 90'C, more preferably 75*C, most preferably below about 50"C to avoid the degradation of the drug at higher temperatures for most drugs.
  • the lower temperature limit of the lipid is governed by the ability to thoroughly mix the drug in the lipid.
  • the lipid can be either a paste or a liquid and it is preferred that the lipid be in a liquid state to aid in the drug admixing.
  • An emulsifier, a polymer solution and a dilution solution are then mixed with the drug/lipid mixture to form the final stable taste-masked drug composition.
  • This final drug composition contains the drug, partially coated with the lipid and effectively taste-masked by the lipid, suspended in the polymer solution. It is preferred that the emulsifier be thoroughly admixed first, followed by the addition of the polymer solution, and the final drug volume achieved by addition of the dilution solution. However, these three components can be admixed together with the drug/lipid mixture.
  • the final drug composition is in a form which can be administered to a patient orally.
  • the inventive method can also be carried out by a different method.
  • a mixture of a lipid and an emulsifier is heated and mixed by conventional methods until a molten homogenous state is reached.
  • the temperature of the molten lipid will be at least about 20"C above the melting point of the lipid and typically will be in the range of from about 50 ⁇ C - 100 ⁇ C.
  • the temperature of this lipid and emulsifier mixture is then adjusted to a temperature below where significant drug degradation can occur, typically below about 50 ⁇ C, in order to accept the drug without degrading the integrity of the drug.
  • a drug in need of taste masking, in particulate form, is added to the lipid and emulsifier mixture which can be in the form of a semi-solid paste or a liquid. Then, a polymer is admixed to this dispersion. Finally, a dilution solution, preferably an aqueous solution containing, for example, sweetening agents and/or flavoring agents and/or coloring agents is added to the mixture to produce the final drug composition.
  • the melting point of the lipid should be sufficiently high to prevent melting of the substantially coated particles during the short period of time they are contacted with the mouth. Such melting would release the unpleasant taste. There potentially is no upper limit to the melting point of the lipid.
  • the lipids will conveniently have a melting point of from about 30°C to about 95 P C. It is preferred to select a lipid which allows for an effective amount of the drug to be released upon digestion, and most preferably to select a lipid which does not affect the bioavailability of the drug.
  • the lipids which can be employed in the practice of the present invention include triglycerides, for example a glycerol ester of a high molecular weight (C 10 . 30 ) aliphatic acid; fatty acids or monohydric alcohols thereof, fixed oils, fats, waxes, sterols, phospholipids and glycolipids.
  • the lipid may also, for example, be a high molecular weight straight chain (C 10 .
  • saturated or unsaturated aliphatic acid such as cotton seed oil, castrol oil, and coconut oil; waxes, for example, bees wax or carnauba wax; mixtures of high molecular weight fatty acids such as mixtures of stearic and palmitic acids, and mixtures of high molecular weight straight chain aliphatic alcohols.
  • a preferred lipid is a partially hydrogenated coconut oil sold by Karlshams Company under the trade name PURECO 92.
  • the emulsifiers, or surfactants, which are useful in the practice of the present invention maybe of the anionic or nonionic type.
  • the emulsifier of the present invention can be a mixture of several emulsifiers.
  • a mixture of an anionic and a nonionic emulsifier is preferred as the emulsifying agent.
  • emulsifiers include acids, for example, stearic acid, lauric acid, palmitic acid, etc.; glyceryl behenate, and monooleates, such as sorbitan monooleate and polyoxyethylene sorbitan monooleate.
  • Preferred emulsifiers include anionic surfactants such as a diacetyl tartaric acid monoglyceride, for example, those sold under the trade name PANODAN 205, FDP and SDK by the Grinsted Company.
  • a preferred nonionic surfactant is glycerol stearate, for example, LIPOGMS 470 manufactured by Lipo Chemical Company.
  • Drugs in need of taste masking are those drugs which have an unpleasant taste when orally administered and include cimetidine, ranitidine, ibuprofen, acetaminophen, erythromycin and the like. Cimetidine is conveniently preferred. Cimetidine can be obtained in various polymorphic forms such as polymorph A, B, C, D, and E.
  • the polymorphic form B in the formulation methods because some of the other forms, such as A, convert to form B over time and this conversion may adversely affect the viscosity of the composition.
  • the method of the invention provides a highly convenient and economical method of taste-masking certain unpleasant tasting drugs.
  • the drug is believed to be substantially coated but not entirely coated by the lipid.
  • certain drugs such as cifuroxime axetil which tend to gel upon contact with an aqueous medium are not suitable for use in the invention.
  • the drug is supplied in particulate form, and preferably has a weight average particle size below about 300 microns, most preferably below about 200 microns in order to avoid a gritty taste upon consumption.
  • the drug preferably has a low water solubility and the pH of the composition can be adjusted to enhance this aspect of the invention.
  • the polymers which are useful in the present invention are added to keep the lipid encapsulated drug in suspension and for thickening and include cellulose derivatives such as sodium carboxymethylcellulose as well as xanthan gum.
  • cellulose derivatives such as sodium carboxymethylcellulose as well as xanthan gum.
  • sodium carboxymethylcellulose for use in the present invention is a low molecular weight AQUALON 7LF PH manufactured by the Aqualon Company. It is preferred to provide the polymer in an aqueous solution. It is also preferred to add a substance to aid in the dissolution of the polymer in the aqueous solution, such as glycerin.
  • the dilution solution is preferably an aqueous solution and functions to dilute the concentrated drug emulsion to an acceptable level for oral administration.
  • Various sweeteners, flavoring agents, and coloring agents can also be added to the dilution solution.
  • the dilution solution is a sugar solution in a concentrated form, for example, above about 40% by weight, more preferably above about 50% by weight of sweetener.
  • the preferred amount of sweetener in the aqueous solution is from about 50 to about 85 w/v percent.
  • the various sweeteners include sucrose, sodium cyclamate, sodium saccharinate, aspartame and ammonium glycyrrhizinate.
  • Typical flavoring agents include peppermint oil flavor and artificial pineapple flavor.
  • coloring agents include titanium dioxide pigments, lake colors and iron oxide pigments.
  • Suitable additives are included within the scope of the invention, such as an antacid to a cimetidine preparation.
  • the pharmaceutical drug composition of the present invention can be formulated in any desired quantities.
  • a basis of 10 cc of the final stable taste-masked drug composition can be used to define weight and volume ratios.
  • Typical oral administration volumes range from about 5 cc to 15 cc.
  • the amount of the drug to be added to a 10 cc solution of the drug composition of the present invention is from about 100 to 800 milligrams of the drug.
  • the amount of lipid to be used can readily be determined.
  • the amount of lipid ranges from 25-200% by weight of the amount of drug employed.
  • the ratio of drug to lipid is 1:1.
  • the maximum amount of lipid to be added to a 10 cc solution of the drug composition is about 800 milligrams.
  • the amount of emulsifier to be used in the present invention varies depending upon the type of emulsifier utilized. An effective amount of emulsifier is needed however to provide a drug composition which exhibits extended shelf life. In a preferred embodiment, the amount of emulsifier is generally from about 0.3-3% by weight of the drug composition.
  • the amount of polymer to be added to a 10 cc solution of the drug composition of the present invention generally ranges from about 30 milligrams to about 120 milligrams.
  • the dilution sweetening agent solution (containing also the flavoring and coloring agents) generally is added in an amount to bring the volume of the drug composition to the 10 cc quantity.
  • the pharmaceutical drug composition of the present invention preferably contains from about 1.5 to about 8 wt. percent of the drug; from about 0.8 to about 8, more preferably about 1.5 to about 8 wt. percent of the lipid; from about 0.2 to about 4, more preferably from about 0.2 to about 3 wt. percent emulsifier or surfactant; from about 0.1 to about 2, preferably from about 0.2 to about 1.2 wt. percent of the polymer suspension agent; and about 80 to about 95 wt. percent of the aqueous dilution solution which itself contains from about 40 to about 65 wt. percent sweetener.
  • the method for producing the drug composition of the present invention comprises five broad steps.
  • the first step the weighed amount of lipid and emulsifier are mixed together and heated into a molten solution up to about 20°C above the melting point of the lipid. It is preferred that the temperature of the molten solution be from about 85-95 ⁇ C.
  • the lipid and emulsifier are mixed until a homogenous liquid phase is formed.
  • the second step requires for the molten solution to be cooled. It is preferred that the solution be cooled to at least 50 ⁇ C or below to avoid drug degradation, but such that the mixture remains a liquid or a semi-solid paste. - lo ⁇
  • the weighed amount of the drug to be used is added to this cooled lipid phase.
  • the drug and lipid phase are mixed thoroughly using any appropriate mixing device. In this way, the drug particles are substantially coated with the lipid material whereby a flavor masking effect is obtained as at least a portion of the drug is contained within the lipid phase and has its flavor masked by the lipid phase.
  • the polymer is preferably added as polymer solution.
  • This polymer solution is an aqueous solution in which the polymer is dissolved. If a non-aqueous solution is chosen it is to be compatible with the lipid.
  • the polymer is present in the polymer solution in an amount of from about 6% to about 10% by weight.
  • This solution may also contain glycerin in an amount of about 20% by weight to aid in the dissolution of the polymer.
  • the polymer solution is thoroughly mixed into the drug/lipid phase by the aid of mechanical mixing devices.
  • a sweetening dilution mixture is slowly added to the drug composition to enhance the flavor of that composition.
  • this sweetening solution is added in a concentrated form and contains sweetening agents, flavoring agents, and coloring agents.
  • the sweetening solution is an aqueous base solution and is added to the drug composition until the final drug composition attains its desired volume.
  • a taste masked drug composition is prepared having a less gritty feel upon oral administration. It has surprisingly been found that when a small amount of a surfactant, preferably an anionic surfactant, is incorporated into the drug particles prior to their formulation with the lipid material, the resulting composition has a less gritty feel in the mouth upon oral administration.
  • the resulting formulation also has an acceptable viscosity which does not increase adversely with time during storage. It is believed that the anionic surfactant acts to reduce any drug particle agglomeration during the formulation and storage of the composition.
  • a further preferred embodiment of the methods is to incorporate at least 70 wt. percent, preferably at least 90 wt. percent, and more preferably the entire amount of the surfactants and emulsifiers into the drug matrix prior to blending the drug with the lipid.
  • the incorporation of the anionic surfactant with the drug particles is accomplished by bringing the surfactant into the molten state.
  • the anionic surfactant is preferably selected to have a melting point below about 110"C, more preferably below about 95"C.
  • the particulate drug is then admixed to the molten surfactant and blended to obtain a homogeneous mixture.
  • This mixture is then solidified, preferably by cooling to below about 25 ⁇ C, more preferably to below about 10°C, and ground using conventional means to a desired particle size. This process of heating, mixing, cooling, and grinding can be repeated a plurality of times to increase the incorporation of the surfactant into the drug particle matrix.
  • the drug particles containing the surfactant are then admixed with the lipid or lipid mixture which is either in a molten or semi-solid state.
  • the polymer, suspension agent, and aqueous solution are admixed with the lipid and drug mixture while the lipid is either in a molten or semi-solid state.
  • the present inventive methods are advantageous over the prior processes in that the lipid and drug mixture does not require solidification prior to admixture with the aqueous solution or either the polymer and emulsifier.
  • the aqueous solution is blended with the lipid and drug mixture at a temperature above the melting point of the lipid.
  • the lipid or mixture of lipids may have a melting point range rather than a distinct melting point temperature.
  • the aqueous solution is preferably blended with the drug and lipid mixture at a temperature at which the entire lipid composition is molten, however the aqueous solution can also be blended while at least a portion of the lipid is in the molten state, and the lipid is generally referred to as a semi-solid at this state.
  • sucrose solution 65%w/w sucrose, 0.05%w/v methyl parabens; 10.560g
  • a spearmint oil flavor 8.mg
  • a peppermint oil flavor lmg
  • the product so obtained was a viscous syrup with a pH of 7.7 containing 400mg of cimetidine per approximately 10ml of liquid. This product has improved taste over the non-inventive formulation.
  • sucrose solution 65%w/w sucrose; 10.75g
  • Methyl parabens 5mg
  • artificial pineapple flavor 3mg
  • color 5%w/v FD&C yellow #5; 2.5mg
  • This composition has a pH of 7.4 and contains approximately 400mg cimetidine in 10ml of liquid.
  • EXAMPLE 3 Lipo GMS 470 (lOOmg) , stearic acid (lOOmg) and Pureco 92 (400mg) were mixed and heated to 90 degree centigrade until a homogeneous liquid was formed. The other ingredients were mixed in the same amount and in the same way described in inventive example 2.
  • This composition has a pH of 7.6 and contains about 400mg cimetidine in lOmg of liquid.
  • Lipo GMS 470 200mg
  • Pureco 92 400mg
  • This composition has a pH of 8.1 and contains about 400mg cimetidine in lO g of liquid.
  • Lipo GMS 470 150mg
  • Cottonseed oil (338mg)
  • glycerol behenate (112mg) were mixed and heated to about 90 degree centigrade until a homogeneous liquid was formed.
  • This lipid phase was allowed to cool to room temperature.
  • Cimetidine 400mg was added to this lipid phase. This mixture so obtained was mixed until homogeneous.
  • a CMC solution 8%w/v CMC 7LF PH, %w/v Glycerin; 788mg
  • sucrose solution 65%w/w sucrose; 10.75g
  • Methyl parabens 5mg
  • citric acid solution 10%w/v; 130mg
  • artificial pineapple flavor 4mg
  • This composition has a pH of 7.1 and contains approximately 400mg cimetidine in 10ml of liquid.
  • EXAMPLE 7 lOOul of Panodan SDK, 600ul of Nestle Choco-bake were mixed and heated to about 90 degree centigrade until a clear homogeneous liquid phase was formed. This lipid phase was allowed to cool to room temperature at which point it becomes a semisolid paste. To this lipid phase was added cimetidine (400mg) . This mixture was mixed until homogeneous. To this drug-lipid mixture was added a polymer solution (4%w/v 7LF PH, 10%w/v Glycerin; lOOOul) . The mixture so obtained was mixed until homogeneous.
  • sucrose solution 65%w/w sucrose, 0.05%w/v methyl parabens; 7.9ml
  • a peppermint oil flavor 0.7ul
  • sucrose solution 65%w/w sucrose
  • EXAMPLE 11 The following example was made in which an anionic surfactant was incorporated into the drug matrix prior to admixing the drug with the lipid.
  • Panodan FDP a modified monoglyceride anionic surfactant (Grinsted Co.), (2.33 g) , Lipo GMS-470 (1.67 g) , and cimetidine polymorph B (13.33 g) were mixed as dry powders, then heated to 90°C for 15-20 minutes with blending " and then cooled to about 25°C. The solidified mass was then ground into a powder. This blending process was repeated twice more by heating the ground powder to about 90°C, blending, cooling, solidifying the mass, and grounding it into a powder. The resulting powder was then admixed with Pureco 92, purified coconut oil (13.33 g, m.p. 34'C) at about 70°C.
  • Pureco 92 purified coconut oil
  • the mixture obtained was then cooled to about 45-50"C and blended with an aqueous sucrose solution (558 g; 65% w/w sucrose, preserved with methylparaben) , an aqueous xanthan gum solution (2.5 g; 7.5% w/v Keltrol xanthan gum from Kelco Co., 2% w/v glycerin) . After blending, this mixture was cooled to about 25 ⁇ C.
  • the drug composition obtained was a smooth suspension containing 267 mg of cimetidine per 10 ml of liquid and had a ncn-gritty feel upon oral administration.

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  • Pharmacology & Pharmacy (AREA)
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Abstract

L'invention concerne un procédé de masquage du goût d'un médicament se présentant sous forme particulaire, et la composition de médicament produite à partir dudit procédé. On mélange à un lipide un médicament sous forme particulaire d'un goût désagréable. On ajoute à ce mélange médicament/lipide un agent émulsifiant, une solution de polymère ainsi qu'une solution de dilution édulcorante afin de produire la composition de médicament finale stable.
PCT/US1994/004569 1993-04-26 1994-04-26 Compositions pharmaceutiques masquant le gout et leurs procedes de production WO1994025006A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU67746/94A AU6774694A (en) 1993-04-26 1994-04-26 Taste-masking pharmaceutical compositions and methods for making the same

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Application Number Priority Date Filing Date Title
US5277493A 1993-04-26 1993-04-26
US08/052,774 1993-04-26

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WO1994025006A1 true WO1994025006A1 (fr) 1994-11-10

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0750849A1 (fr) * 1995-06-06 1997-01-02 Kao Corporation Modificateur du goût
WO1997041839A1 (fr) * 1996-05-07 1997-11-13 F.H. Faulding & Co. Limited Suspensions liquides a gout masque
AU719137B2 (en) * 1996-05-07 2000-05-04 Mayne Pharma International Pty Ltd Taste masked liquid suspensions
WO2002049607A2 (fr) * 2000-12-20 2002-06-27 Firmenich Sa Systeme d'administration orale de medicament aromatise
US6515008B1 (en) * 2000-05-04 2003-02-04 Smithkline Beecham Corporation Formulation
GB2380936A (en) * 2001-10-18 2003-04-23 Reckitt Benckiser Healthcare Pharmaceutical composition in which the bitter taste of the active ingredient is masked
US6794411B1 (en) 1999-04-06 2004-09-21 Laboratoire Des Produits Ethiques Ethypharm Drinkable ibuprofen pharmaceutical suspension
WO2006013416A1 (fr) * 2004-07-29 2006-02-09 Firmenich Sa Compositions orales qui masquent l’amertume d’un agent amer
WO2013024373A1 (fr) 2011-08-12 2013-02-21 Dhanuka Laboratories Ltd. Composition pharmaceutique comprenant du céfuroxime

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3147187A (en) * 1962-09-10 1964-09-01 Don Hall Lab Sustained release pharmaceutical
US4861592A (en) * 1983-10-10 1989-08-29 Smith Kline Dauelsberg Gmbh Pharmaceutical compositions
US4865851A (en) * 1987-05-14 1989-09-12 Glaxo Group Limited Pharmaceutical composition comprising cefuroxime axetil
US4894233A (en) * 1984-10-05 1990-01-16 Sharma Shri C Novel drug delivery system for decongestants

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3147187A (en) * 1962-09-10 1964-09-01 Don Hall Lab Sustained release pharmaceutical
US4861592A (en) * 1983-10-10 1989-08-29 Smith Kline Dauelsberg Gmbh Pharmaceutical compositions
US4894233A (en) * 1984-10-05 1990-01-16 Sharma Shri C Novel drug delivery system for decongestants
US4865851A (en) * 1987-05-14 1989-09-12 Glaxo Group Limited Pharmaceutical composition comprising cefuroxime axetil

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0750849A1 (fr) * 1995-06-06 1997-01-02 Kao Corporation Modificateur du goût
WO1997041839A1 (fr) * 1996-05-07 1997-11-13 F.H. Faulding & Co. Limited Suspensions liquides a gout masque
AU719137B2 (en) * 1996-05-07 2000-05-04 Mayne Pharma International Pty Ltd Taste masked liquid suspensions
US6197348B1 (en) 1996-05-07 2001-03-06 F H Faulding & Co., Limited Taste masked liquid suspensions
US6794411B1 (en) 1999-04-06 2004-09-21 Laboratoire Des Produits Ethiques Ethypharm Drinkable ibuprofen pharmaceutical suspension
US6515008B1 (en) * 2000-05-04 2003-02-04 Smithkline Beecham Corporation Formulation
WO2002049607A3 (fr) * 2000-12-20 2003-03-20 Firmenich & Cie Systeme d'administration orale de medicament aromatise
WO2002049607A2 (fr) * 2000-12-20 2002-06-27 Firmenich Sa Systeme d'administration orale de medicament aromatise
GB2380936A (en) * 2001-10-18 2003-04-23 Reckitt Benckiser Healthcare Pharmaceutical composition in which the bitter taste of the active ingredient is masked
GB2380936B (en) * 2001-10-18 2003-07-09 Reckitt Benckiser Healthcare Improvements in or relating to compositions
AU2002330645B2 (en) * 2001-10-18 2008-12-18 Reckitt Benckiser Healthcare (Uk) Limited Composition comprising paracetamol and a bitterness masking component
WO2006013416A1 (fr) * 2004-07-29 2006-02-09 Firmenich Sa Compositions orales qui masquent l’amertume d’un agent amer
WO2013024373A1 (fr) 2011-08-12 2013-02-21 Dhanuka Laboratories Ltd. Composition pharmaceutique comprenant du céfuroxime

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