WO1992000725A1 - Liquid oral pharmaceutical compositions having anti-inflammatory activity - Google Patents

Liquid oral pharmaceutical compositions having anti-inflammatory activity Download PDF

Info

Publication number
WO1992000725A1
WO1992000725A1 PCT/EP1991/001245 EP9101245W WO9200725A1 WO 1992000725 A1 WO1992000725 A1 WO 1992000725A1 EP 9101245 W EP9101245 W EP 9101245W WO 9200725 A1 WO9200725 A1 WO 9200725A1
Authority
WO
WIPO (PCT)
Prior art keywords
compositions according
active ingredient
ketoprofen
cyclodextrins
pharmaceutical compositions
Prior art date
Application number
PCT/EP1991/001245
Other languages
French (fr)
Inventor
Ubaldo Conte
Original Assignee
Farcon Ag
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 Farcon Ag filed Critical Farcon Ag
Priority to DE1991911791 priority Critical patent/DE491897T1/en
Publication of WO1992000725A1 publication Critical patent/WO1992000725A1/en

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays

Definitions

  • the present invention relates to liquid pharmaceu ⁇ tical compositions for the oral topical treatment, containing non steroidal anti-inflammatory drugs as the active ingredients.
  • Therapeutical treatment of inflammations of the oral cavity such as aspecific odontostomatologic af ⁇ fections, gingivitis, glossitis, stomatitis and the like, is particularly complex and, until the specific pathogenic agent has precisely been determined, treat- ment can be restricted to the use of disinfectants of the general type.
  • Said drugs besides showing negative characteri ⁇ stics (remarkable side-effects) can cause severe and diffused allergy phenomena, so as to compel to immedia- tely interrupt treatment and to take suitable restora ⁇ tion measures.
  • compositions comprising non steroidal anti-inflammatory drugs (FANS) in form of solutions intended for the oral topical tre ⁇ atment (collutories) , allow to obtain very good thera ⁇ Promotionical results without causing sensitization pheno ⁇ mena.
  • FANS non steroidal anti-inflammatory drugs
  • the compositions of the invention are characteri ⁇ zed by the presence of a specific excipient, dimethyl isosorbide, giving them advantageous antiseptic proper ⁇ ties together with an antiplaque action which is parti- cularly desired in this kind of preparations.
  • Anti-in ⁇ flammatory properties of the active ingredients also turn out to be surprisingly enhanced through a synerge- tic interaction with dimethyl isosorbide.
  • compositions of the present invention can con- tain the active ingredient in amounts ranging from 0.001 to 20% by weight, whereas dimethyl isosorbide can be present in amounts ranging from 1 to 40% by weight.
  • compositions of the invention can also contain other excipients and/or coadjuvants, such as surfactants, flavouring and sweetening agents, in order to give the preparation suitable organoleptic characteristics.
  • excipients and/or co ⁇ adjuvants conventionally used for the preparation of collutories are described in "Remington's Pharm. Scien- ces Handbook", Mack Pub. Co., NY.
  • the compositions of the invention will preferably contain natural and/or synthetic sweetening agents such as saccharine, ammo ⁇ nium glycyrrhizinate, cycla ate or, more preferably, not cariogenic carbohydrates such as xylitol and sorbi- tol.
  • non steroidal anti- inflammatory drugs such as ketoprofen, ibuprofen, ibu- profen lysine salt, naproxen, suprofen, diclofenac, al- clofenac, indomethacin, acemethacin, benzidamine, flur- biprofen, piroxicam and the like, can be used as active ingredients, either in the free form or salified, in order to improve the solubility thereof.
  • the active ingredients are present in combination with cyclodextrins or derivatives thereof, for example in form of physical admixtures, inclusion products or co- precipitates.
  • Cyclodextrins or derivatives thereof such as hydroxypropyl beta-cyclodextrins, involve fa ⁇ vourable pharmacokinetic effects and, moreover, are useful to increase solubility and stability, or to im- prove the organoleptic characteristics of the medica ⁇ ment.
  • Cyclodextrin contents can range from 0.5 to 50% by weight of the finished composition, but equimolecular ratios of active ingredient to cyclodextrin are prefe- rably used.
  • cyclodex ⁇ trins (o , ⁇ , -) and the already cited hydroxypropyl ⁇ - cyclodextri ⁇ , dimethylcyclodextrins or other derivati ⁇ ves, possibly in a mixture thereof can also be used.
  • polymers having an adhesive power towards ucosae are used as excipients.
  • examples of said polymers are provided by carboxyvinyl polymers, ethyle e oxide - propylene oxide copolymers, cellulose derivatives such as carboxymethyl cellulose, calcium carboxymethyl cellulose, hydroxy- propylethyl cellulose, hydroxyethyl cellulose, hydroxy ⁇ propyl cellulose, carrageenan, dextrins, natural or synthetic gums and the like.
  • Said excipients, which can be def ned bioadhesive polymers can be present in per ⁇ centages ranging from 0.5 to 30%, preferably from 1 to 5%.
  • excipients allows to obtain sli ⁇ ghtly viscous solutions having adhesiveness towards mu- cosae, so as to achieve a better persistence of the preparation in contact with the area to be treated, thus obtaining a more effective and lasting action.
  • compositions can also contain no dimethyl isosor- bide : said compositions also fall within the scope of the present invention.
  • Each 15 ml ampoule contains: Active ingredient: ketoprofen Excipients:
  • Ketoprofen is dissolved in an ethanol solution containing dimethyl isosorbide and Tween 60, the solu ⁇ tion is heated to 35 C C under stirring, to obtain a clear solution which is added with the other components. After filtration, a clear homogeneous solution (collutory) is obtained.
  • Ketoprofen is added to a ⁇ -cyclodextrin aqueous solution (about 50 ml), which is heated to 30-40 e C for 30 hours. A solution is obtained which is added with dimethyl isosorbide and the other components, then fil ⁇ tered.
  • EXAMPLE 4 Collutory containing ketoprofen, dimethyl isosorbide and bioadhesive polymers (in form of solution) 100 ml of collutory contain (% composition): Active ingredient: ketoprofen 0.05 Excipients:
  • Each 15 ml ampoule contains : Active ingredient: Benzidamine 2 to 20 mg ExciDients: Tween 60 5 mg alpine herb flavor 52,503 T 15 mg dimethyl isosorbide 1500 mg
  • Collutory containing piroxicam (in form of solution) 100 ml of collutory contain (% composition) : Active ingredient:
  • Each 15 ml ampoule contains: Active ingredient: Piroxicam Excipients:

Abstract

Liquid pharmaceutical compositions for the oral topical treatment, containing as the active ingredients non steroidal anti-inflammatory drugs, characterized in that they contain dimethyl isosorbide as the carrier.

Description

LIQUID ORAL PHARMACEUTICAL COMPOSITIONS HAVING ANTI-IN¬ FLAMMATORY ACTIVITY
The present invention relates to liquid pharmaceu¬ tical compositions for the oral topical treatment, containing non steroidal anti-inflammatory drugs as the active ingredients. Therapeutical treatment of inflammations of the oral cavity, such as aspecific odontostomatologic af¬ fections, gingivitis, glossitis, stomatitis and the like, is particularly complex and, until the specific pathogenic agent has precisely been determined, treat- ment can be restricted to the use of disinfectants of the general type.
Moreover, even when the pathogenic agent has cer¬ tainly been determined, administration of antibiotics such as tetracyclines and the like, generally by the parenteral or systemic routes, must be carried out in most cases.
Said drugs, besides showing negative characteri¬ stics (remarkable side-effects) can cause severe and diffused allergy phenomena, so as to compel to immedia- tely interrupt treatment and to take suitable restora¬ tion measures.
Now it has been found, and it is the object of the present invention, that pharmaceutical compositions comprising non steroidal anti-inflammatory drugs (FANS) in form of solutions intended for the oral topical tre¬ atment (collutories) , allow to obtain very good thera¬ peutical results without causing sensitization pheno¬ mena. The compositions of the invention are characteri¬ zed by the presence of a specific excipient, dimethyl isosorbide, giving them advantageous antiseptic proper¬ ties together with an antiplaque action which is parti- cularly desired in this kind of preparations. Anti-in¬ flammatory properties of the active ingredients also turn out to be surprisingly enhanced through a synerge- tic interaction with dimethyl isosorbide.
The compositions of the present invention can con- tain the active ingredient in amounts ranging from 0.001 to 20% by weight, whereas dimethyl isosorbide can be present in amounts ranging from 1 to 40% by weight.
Of course, the compositions of the invention can also contain other excipients and/or coadjuvants, such as surfactants, flavouring and sweetening agents, in order to give the preparation suitable organoleptic characteristics. Examples of said excipients and/or co¬ adjuvants conventionally used for the preparation of collutories are described in "Remington's Pharm. Scien- ces Handbook", Mack Pub. Co., NY. The compositions of the invention will preferably contain natural and/or synthetic sweetening agents such as saccharine, ammo¬ nium glycyrrhizinate, cycla ate or, more preferably, not cariogenic carbohydrates such as xylitol and sorbi- tol.
All the up to now known non steroidal anti- inflammatory drugs such as ketoprofen, ibuprofen, ibu- profen lysine salt, naproxen, suprofen, diclofenac, al- clofenac, indomethacin, acemethacin, benzidamine, flur- biprofen, piroxicam and the like, can be used as active ingredients, either in the free form or salified, in order to improve the solubility thereof.
According to a particularly preferred embodiment, the active ingredients are present in combination with cyclodextrins or derivatives thereof, for example in form of physical admixtures, inclusion products or co- precipitates. Cyclodextrins or derivatives thereof, such as hydroxypropyl beta-cyclodextrins, involve fa¬ vourable pharmacokinetic effects and, moreover, are useful to increase solubility and stability, or to im- prove the organoleptic characteristics of the medica¬ ment.
Cyclodextrin contents can range from 0.5 to 50% by weight of the finished composition, but equimolecular ratios of active ingredient to cyclodextrin are prefe- rably used. Besides the commonly available cyclodex¬ trins (o , β, -) and the already cited hydroxypropyl β- cyclodextriπ, dimethylcyclodextrins or other derivati¬ ves, possibly in a mixture thereof, can also be used.
The techniques for the preparation of both inclu-* sion complexes with cyclodextrins and co-precipitates are well-known. In principle, the active ingredient is added to an aqueous solution of cyclodextrin or hy¬ droxypropyl β-cyclodextrin, keeping the mixture under stirring for 40-80 hours at a temperature from the room one to 80eC. The desired compound is obtained upon eva¬ poration of the solvent under vacuum.
Another particularly preferred embodiment of the invention is provided by formulations in which polymers having an adhesive power towards ucosae are used as excipients. Examples of said polymers are provided by carboxyvinyl polymers, ethyle e oxide - propylene oxide copolymers, cellulose derivatives such as carboxymethyl cellulose, calcium carboxymethyl cellulose, hydroxy- propylethyl cellulose, hydroxyethyl cellulose, hydroxy¬ propyl cellulose, carrageenan, dextrins, natural or synthetic gums and the like. Said excipients, which can be def ned bioadhesive polymers, can be present in per¬ centages ranging from 0.5 to 30%, preferably from 1 to 5%. The use of said excipients allows to obtain sli¬ ghtly viscous solutions having adhesiveness towards mu- cosae, so as to achieve a better persistence of the preparation in contact with the area to be treated, thus obtaining a more effective and lasting action.
Whenever said bioadhesive polymers are present, the compositions can also contain no dimethyl isosor- bide : said compositions also fall within the scope of the present invention.
The following examples further illustrate the in¬ vention.
EXAMPLE 1 Collutory containing ketoprofen (in form of solution) 100 ml of collutory contain i% composition) Active ingredient: ketoprofen 0.0133 to 0.133
Excipients: Tween 60 0.5 alpine herb flavor 52,503 T 0.100 dimethyl isosorbide 10
90% ethanol 15 sodium saccharinate 0.1 Sodium benzoate 0.2
? sorbitol solution 10 distilled water q.s. to ml 100
Each 15 ml ampoule contains: Active ingredient: ketoprofen Excipients:
Tween 60 alpine herb flavor 52,503 T dimethyl isosorbide
90% ethanol sodium saccharinate
Sodium benzoate
70% sorbitol solution distilled water q.s. to ml
Figure imgf000007_0001
Ketoprofen is dissolved in an ethanol solution containing dimethyl isosorbide and Tween 60, the solu¬ tion is heated to 35CC under stirring, to obtain a clear solution which is added with the other components. After filtration, a clear homogeneous solution (collutory) is obtained. EXAMPLE 2
Collutory containing ketoprofen - β-cyclodextrins (so¬ lution)
100 ml of collutory contain (% composition): Active ingredient: ketoprofen 0,25
Excipients: β-cyclodextrin 1.14 dimethyl isosorbie 10.00 ethanol 15.0 sodium saccharinate 0.1 sodium benzoate 0.2 70% sorbitol solution 10.0 distilled water q.s. to ml 100
Ketoprofen is added to a β-cyclodextrin aqueous solution (about 50 ml), which is heated to 30-40eC for 30 hours. A solution is obtained which is added with dimethyl isosorbide and the other components, then fil¬ tered.
EXAMPLE 3 Collutory containing ketoprofen and bioadhesive poly- mers (solution)
100 ml of collutory contain (% composition): Active ingredient: ketoprofen 0.05
Excipients: Ethylene oxide-propylene oxide copolymer
(Poloxamer 188) 1.2 ethanol 95e 5.0 sodium benzoate 0.1 sodium saccharinate 0.3 benzoic acid 0.05 natural flavor 0.05 depurated water q.s. to ml 100
EXAMPLE 4 Collutory containing ketoprofen, dimethyl isosorbide and bioadhesive polymers (in form of solution) 100 ml of collutory contain (% composition): Active ingredient: ketoprofen 0.05 Excipients:
Ethylene oxide-propylene oxide copolymer
(Poloxamer 188) 1.2 dimethyl isosorbide 5.0 ethanol 95 5.0 sodium benzoate 0.1 sodium saccharinate 0.3 benzoic acid 0.05 natural flavor 0.05 depurated water q.s. to ml 100 Ketoprofen is dissolved in ethanol, dimethyl iso¬ sorbide and Poloxamer 188 are added, then about 50 ml depurated water and the other components. The mixture is filtered to obtain a clear light solution.
EXAMPLE 5 Collutory containing benzidamine (in form of solution) 100 ml of collutory contain (% composition): Active inσredient:
Benzidamine 0.0133 to 0,133 Excipients: Tween 60 0.5 alpine herb flavor 52,503 T 0.100 dimethyl isosorbide 10
90% ethanol 15 sodium saccharinate 0.1 sodium benzoate 0.2 xylitol 10 distillated water q.s. to ml 100
Each 15 ml ampoule contains : Active ingredient: Benzidamine 2 to 20 mg ExciDients: Tween 60 5 mg alpine herb flavor 52,503 T 15 mg dimethyl isosorbide 1500 mg
90% ethanol 2250 mg sodium saccharinate 15 mg sodium benzoate 30 mg xyilitol 1500 mg distillated water q.s. to ml 100
EXAMPLE 6 Collutory containing ibuprofen lysinate (in form of so¬ lution)
100 ml of collutory contain (% composition) : Active ingredient:
Ibuprofen lisinate 0.0266 to 0,266 Excipients:
Tween 60 0.5 alpine herb flavor 52,503 T 0.100 dimethyl isosorbide 10
90% ethanol 15 sodium saccharinate 0.1 sodium benzoate 0.2
70% sorbitol solution 10 distillated water q.s. to ml 100 Each 15 ml ampoule contains : Active ingredient:
Ibuprofen lisinate 4 to 40 mg Excipients:
Tween 60 5 mg alpine herb flavor 52,503 T 15 mg dimethyl isosorbide 1500 mg
90% ethanol 2250 mg sodium saccharinate 15 mg sodium benzoate 30 mg
70% sorbitol solution 1500 mg distillated water q.s. to ml 100 EXAMPLE 7
Collutory containing piroxicam (in form of solution) 100 ml of collutory contain (% composition) : Active ingredient:
Piroxicam 0.001 to 0,01% Excipients:
Tween 60 0.5 alpine herb flavor 52,503 T 0.100 dimethyl isosorbide 10
90% ethanol 15 sodium saccharinate 0.1 sodium benzoate 0.2
70% sorbitol solution 10 distillated water q.s. to ml 100
Each 15 ml ampoule contains: Active ingredient: Piroxicam Excipients:
Tween 60 alpine herb flavor 52,503 T dimethyl isosorbide 90% ethanol sodium saccharinate sodium benzoate 70% sorbitol solution distillated water q.s. to ml
Figure imgf000011_0001

Claims

1. Liquid pharmaceutical compositions for the oral topical treatment, containing as the active ingredients non steroidal anti-inflammatory drugs, characterized in that they contain dimethyl isosorbide as the carrier.
2. Compositions according to claim 1, wherein di¬ methyl isosorbide is present in percentages from 1 to 40% by weight.
3. Compositions according to claim 1 or 2, wherein the active ingredient is present in percentages from 0.001 to 20% by weight.
4. Compositions according to any one of the preceding claims, wherein the active ingredient is selected from ketoprofen, ibuprofen, ibuprofen lysinate, suprofen, flurbiprofen, naproxen, diclofenac, alclofenac, benzi¬ damine, piroxicam, acemethacin, indomethacin.
5. Compositions according to claim 4, wherein the ac¬ tive ingredient is ketoprofen.
6. Compositions according to any one of the preceding claims, wherein the active ingredient is combined with cyclodextrins or derivatives thereof, in form of mixtu¬ res, inclusion complexes or co-precipitates.
7. Compositions according to claim 6, wherein combi- nations with &(. , β or g" cyclodextrins or hydroxypropyl β-cyclodextrins are used in almost equimolecular ratios to the active ingredient.
8. Compositions according to any one of the preceding claims, further containing bioadhesive polymers.
9. Liquid pharmaceutical compositions for the oral topical treatment, containing as the active ingredients non steroidal anti-inflammatory drugs, characterized in that they contain a bioadhesive polymer as an exci- pient.
10. Compositions according to claim 9, wherein the bioadhesive polymer is selected from carboxyvinyl poly¬ mers, ethylene oxide - propylene oxide copolymers, cel¬ lulose derivatives, carrageenan, dextrins, natural or synthetic gums.
PCT/EP1991/001245 1990-07-13 1991-07-04 Liquid oral pharmaceutical compositions having anti-inflammatory activity WO1992000725A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE1991911791 DE491897T1 (en) 1990-07-13 1991-07-04 LIQUID ANTI-FLAMMABLE MEDICINAL PRODUCTS.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT20944A/90 1990-07-13
IT02094490A IT1243342B (en) 1990-07-13 1990-07-13 ORAL PHARMACEUTICAL COMPOSITIONS FOR LIQUID ANTI-INFLAMMATORY ACTIVITIES

Publications (1)

Publication Number Publication Date
WO1992000725A1 true WO1992000725A1 (en) 1992-01-23

Family

ID=11174427

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1991/001245 WO1992000725A1 (en) 1990-07-13 1991-07-04 Liquid oral pharmaceutical compositions having anti-inflammatory activity

Country Status (7)

Country Link
EP (1) EP0491897A1 (en)
AU (1) AU8093591A (en)
CA (1) CA2066731A1 (en)
ES (1) ES2034926T1 (en)
GR (1) GR930300021T1 (en)
IT (1) IT1243342B (en)
WO (1) WO1992000725A1 (en)

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993025190A1 (en) * 1992-06-10 1993-12-23 Eastman Kodak Company Surface modified nsaid nanoparticles
EP0627915A1 (en) * 1992-12-04 1994-12-14 Mayor Pharmaceuticals Laboratories,Inc. Sprayable analgesic composition and method of use
WO1994028936A1 (en) * 1993-06-08 1994-12-22 Ciba-Geigy Ag Process for the preparation of an oral solid dosage form containing diclofenac
WO1995007104A1 (en) * 1993-09-11 1995-03-16 Smithkline Beecham Plc Inclusion complexes of beta-cyclodextrin with flurbiprofen, ketoprofen and naproxen
WO1995023591A1 (en) * 1994-03-03 1995-09-08 The Procter & Gamble Company Oral vehicle compositions
US5552160A (en) * 1991-01-25 1996-09-03 Nanosystems L.L.C. Surface modified NSAID nanoparticles
WO1997003655A1 (en) * 1995-07-20 1997-02-06 Pharmacia & Upjohn Company Stable clear solutions of non-steroidal anti-inflammatory drugs for incorporation into gelatin capsules
US5626837A (en) * 1993-08-12 1997-05-06 Lion Corporation Oral composition
WO1997018802A1 (en) * 1995-11-22 1997-05-29 The Boots Company Plc Pharmaceutical compositions comprising flurbiprofen
US5674854A (en) * 1993-10-08 1997-10-07 Farmarc Nederland Bv Inclusion complex of beta-cyclodextrin and diclofenac, its preparation and use
US5679660A (en) * 1993-12-02 1997-10-21 Farmarc Nederland Bv Pharmaceutical composition comprising diclofenac and cyclodextrin
DE19651055A1 (en) * 1996-12-09 1998-06-10 Beiersdorf Ag Stabilised light-protection combination, e.g. for cosmetic use
WO1998052539A1 (en) * 1997-05-22 1998-11-26 The Boots Company Plc Process for making flurbiprofen lozenges
US6071964A (en) * 1996-03-27 2000-06-06 Hexal Ag Diclofenac/gamma-cyclodextrin inclusion compounds
ES2171110A1 (en) * 2000-03-03 2002-08-16 Aplicaciones Farmacodinamicas Pharmaceutical composition based on ibuprofen and a procedure for the preparation thereof
WO2003094905A1 (en) * 2002-05-10 2003-11-20 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Diclofenac-based composition for the topical treatment of oropharyngeal cavity disorders
WO2005074885A1 (en) * 2004-02-03 2005-08-18 Philippe Perovitch Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method
GB2416123B (en) * 2003-04-07 2007-06-06 Jurox Pty Ltd Stable carprofen composition
ES2347754A1 (en) * 2009-04-27 2010-11-03 Laboratorios De Aplicaciones Farmacodinamicas, S.A Oral suspension of ibuprophene lisinate (Machine-translation by Google Translate, not legally binding)
GB2486567A (en) * 2010-12-15 2012-06-20 Reckitt Benckiser Healthcare Int Ltd Solutions of an NSAID and one or more cyclodextrins
JP2012525359A (en) * 2009-04-27 2012-10-22 ラボラトリオ デ アプリカシオネス ファルマコディナミカス，エセ．アー． Suspension for oral administration of ibuprofen ricinate
US8580954B2 (en) 2006-03-28 2013-11-12 Hospira, Inc. Formulations of low dose diclofenac and beta-cyclodextrin
WO2019105957A1 (en) * 2017-11-30 2019-06-06 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Stable liquid composition of ketoprofen, salts and enantiomers thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0215423A2 (en) * 1985-09-12 1987-03-25 Dolorgiet GmbH & Co. KG Transdermally resorbable aqueous compositions of arylpropionic-acid derivatives and process for their preparation
EP0284588A1 (en) * 1987-03-13 1988-09-28 "PHARLYSE", Société Anonyme Pharmaceutical preparation containing indomethacin
WO1989004179A1 (en) * 1987-11-03 1989-05-18 Also Laboratori S.A.S. Pharmaceutical formulations for transdermal administration

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0215423A2 (en) * 1985-09-12 1987-03-25 Dolorgiet GmbH & Co. KG Transdermally resorbable aqueous compositions of arylpropionic-acid derivatives and process for their preparation
EP0284588A1 (en) * 1987-03-13 1988-09-28 "PHARLYSE", Société Anonyme Pharmaceutical preparation containing indomethacin
WO1989004179A1 (en) * 1987-11-03 1989-05-18 Also Laboratori S.A.S. Pharmaceutical formulations for transdermal administration

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5552160A (en) * 1991-01-25 1996-09-03 Nanosystems L.L.C. Surface modified NSAID nanoparticles
WO1993025190A1 (en) * 1992-06-10 1993-12-23 Eastman Kodak Company Surface modified nsaid nanoparticles
EP0627915A1 (en) * 1992-12-04 1994-12-14 Mayor Pharmaceuticals Laboratories,Inc. Sprayable analgesic composition and method of use
EP0627915A4 (en) * 1992-12-04 1996-02-07 Mayor Pharma Lab Inc Sprayable analgesic composition and method of use.
WO1994028936A1 (en) * 1993-06-08 1994-12-22 Ciba-Geigy Ag Process for the preparation of an oral solid dosage form containing diclofenac
US5702724A (en) * 1993-06-08 1997-12-30 Ciba-Geigy Corporation Process for the preparation of an oral solid dosage form containing diclofenac
US5626837A (en) * 1993-08-12 1997-05-06 Lion Corporation Oral composition
WO1995007104A1 (en) * 1993-09-11 1995-03-16 Smithkline Beecham Plc Inclusion complexes of beta-cyclodextrin with flurbiprofen, ketoprofen and naproxen
US5674854A (en) * 1993-10-08 1997-10-07 Farmarc Nederland Bv Inclusion complex of beta-cyclodextrin and diclofenac, its preparation and use
US5679660A (en) * 1993-12-02 1997-10-21 Farmarc Nederland Bv Pharmaceutical composition comprising diclofenac and cyclodextrin
WO1995023591A1 (en) * 1994-03-03 1995-09-08 The Procter & Gamble Company Oral vehicle compositions
AU702889B2 (en) * 1994-03-03 1999-03-11 Procter & Gamble Company, The Oral vehicle compositions
WO1997003655A1 (en) * 1995-07-20 1997-02-06 Pharmacia & Upjohn Company Stable clear solutions of non-steroidal anti-inflammatory drugs for incorporation into gelatin capsules
WO1997018802A1 (en) * 1995-11-22 1997-05-29 The Boots Company Plc Pharmaceutical compositions comprising flurbiprofen
US5889057A (en) * 1995-11-22 1999-03-30 The Boots Company Plc Flurbiprofen lozenge for the treatment of sore throat
AU707749B2 (en) * 1995-11-22 1999-07-22 Reckitt Benckiser Healthcare (Uk) Limited Medical Treatment
US6166083A (en) * 1995-11-22 2000-12-26 The Boots Company, Plc Suckable flurbiprofen lozenges for treatment of sore throat
US6071964A (en) * 1996-03-27 2000-06-06 Hexal Ag Diclofenac/gamma-cyclodextrin inclusion compounds
DE19651055A1 (en) * 1996-12-09 1998-06-10 Beiersdorf Ag Stabilised light-protection combination, e.g. for cosmetic use
DE19651055B4 (en) * 1996-12-09 2006-03-16 Beiersdorf Ag Cosmetic and dermatological sunscreen formulations containing triazine derivatives and dimethyl isosorbide and their use
US6194003B1 (en) 1997-05-22 2001-02-27 The Boots Company Plc Process for making flurbiprofen lozenges
WO1998052539A1 (en) * 1997-05-22 1998-11-26 The Boots Company Plc Process for making flurbiprofen lozenges
ES2171110A1 (en) * 2000-03-03 2002-08-16 Aplicaciones Farmacodinamicas Pharmaceutical composition based on ibuprofen and a procedure for the preparation thereof
WO2003094905A1 (en) * 2002-05-10 2003-11-20 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Diclofenac-based composition for the topical treatment of oropharyngeal cavity disorders
CN1303992C (en) * 2002-05-10 2007-03-14 方济各安吉利克化学联合股份有限公司 Diclofenac-based composition for the topical treatment of oropharyngeal cavity disorders
GB2416123B (en) * 2003-04-07 2007-06-06 Jurox Pty Ltd Stable carprofen composition
US8846083B2 (en) 2004-02-03 2014-09-30 Philippe Perovitch Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method
EP1711162B1 (en) 2004-02-03 2017-11-01 Philippe Perovitch Composition for use in the local treatment of oropharyngeal conditions comprising ibuprofen or ketoprofen
WO2005074885A1 (en) * 2004-02-03 2005-08-18 Philippe Perovitch Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method
US8580954B2 (en) 2006-03-28 2013-11-12 Hospira, Inc. Formulations of low dose diclofenac and beta-cyclodextrin
US8946292B2 (en) 2006-03-28 2015-02-03 Javelin Pharmaceuticals, Inc. Formulations of low dose diclofenac and beta-cyclodextrin
JP2012525359A (en) * 2009-04-27 2012-10-22 ラボラトリオ デ アプリカシオネス ファルマコディナミカス，エセ．アー． Suspension for oral administration of ibuprofen ricinate
ES2347754A1 (en) * 2009-04-27 2010-11-03 Laboratorios De Aplicaciones Farmacodinamicas, S.A Oral suspension of ibuprophene lisinate (Machine-translation by Google Translate, not legally binding)
GB2486567B (en) * 2010-12-15 2014-09-10 Reckitt Benckiser Healthcare Int Ltd Pharmaceutical formulation
WO2012080718A1 (en) * 2010-12-15 2012-06-21 Reckitt Benckiser Healthcare International Limited Novel pharmaceutical formulation comprising nsaid and cyclodextrin
US9138482B2 (en) 2010-12-15 2015-09-22 Reckitt Benckiser Healthcare International Limited Pharmaceutical formulation comprising NSAID and cyclodextrin
RU2607592C2 (en) * 2010-12-15 2017-01-10 Рекитт Бенкизер Хелскэа Интернэшнл Лимитед New pharmaceutical composition containing nsaid and cyclodextrin
GB2486567A (en) * 2010-12-15 2012-06-20 Reckitt Benckiser Healthcare Int Ltd Solutions of an NSAID and one or more cyclodextrins
US10363316B2 (en) 2010-12-15 2019-07-30 Reckitt Benckiser Healthcare (Uk) Limited Pharmaceutical formulation comprising NSAID and cyclodextrin
WO2019105957A1 (en) * 2017-11-30 2019-06-06 Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. Stable liquid composition of ketoprofen, salts and enantiomers thereof

Also Published As

Publication number Publication date
IT1243342B (en) 1994-06-10
EP0491897A1 (en) 1992-07-01
IT9020944A1 (en) 1992-01-13
ES2034926T1 (en) 1993-04-16
AU8093591A (en) 1992-02-04
CA2066731A1 (en) 1992-01-14
GR930300021T1 (en) 1993-04-28
IT9020944A0 (en) 1990-07-13

Similar Documents

Publication Publication Date Title
WO1992000725A1 (en) Liquid oral pharmaceutical compositions having anti-inflammatory activity
KR100439090B1 (en) Taste-masking liquid
CA1234050A (en) Injectable solution for the treatment of inflammations
EP0444492B1 (en) Topically administered compositions based on high molecular weight hyaluronic acid for treating inflammations of the oral cavity, and for oral cavity hygiene and cosmetic treatment
JPH05504783A (en) Highly water-soluble cyclodextrin derivative composition and its uses
EP0441307A1 (en) Syrup composition
PT1609481E (en) Injectable pharmaceutical compositions comprising sodium diclofenac, beta-cyclodextrin and a polysorbate
PT1998762E (en) Solid dosage form containing a taste masked active agent
KR20030069979A (en) Pharmaceutical compositions for the treatment of mucositis, stomatitis and Behcet's syndrome
JP2002510652A5 (en)
JPH0257049B2 (en)
AU2002306329B2 (en) Aqueous cilostazol preparation for injection
KR20040084891A (en) Taste masking spill-resistant formulation
EP1974751A1 (en) Formulations for non-steroidal anti-inflammatory drugs
EP0633787B1 (en) Use of ibuprofen-beta-cyclodextrin complex for oral consumption
AU2003232480B2 (en) Diclofenac-based composition for the topical treatment of oropharyngeal cavity disorders
WO2005065674A1 (en) Pharmaceutical composition of 2-(4-isobutylphenyl) propionic acid
JPH0616547A (en) Antiphlogistic ophthalmic solution
JPH035438A (en) Flurbiprofen clathrate compound and anti-inflammatory and analgesic agent using the same clathrate compound
EP0867181A1 (en) Nasal melatonin composition
CA2259270C (en) Pharmaceutical preparation containing nimesulide for oral administration
JPS6393718A (en) Injection
KR20040079012A (en) Acetylcysteine oral dosage forms
EP1242062B1 (en) Anhydrous gel comprising nsaid for topical administration to the oral cavity
KR100567131B1 (en) Taste masking of oral ibuprofen and arginine solution

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU BB BG BR CA CS FI HU JP KP KR LK MC MG MN MW NO PL RO SD SU US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE BF BJ CF CG CH CI CM DE DK ES FR GA GB GN GR IT LU ML MR NL SE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 1991911791

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2066731

Country of ref document: CA

WWP Wipo information: published in national office

Ref document number: 1991911791

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1991911791

Country of ref document: EP