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WO1991008734A1 - Suspension liquide et anhydre a base d'huile servant a liberer un medicament - Google Patents

Suspension liquide et anhydre a base d'huile servant a liberer un medicament Download PDF

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Publication number
WO1991008734A1
WO1991008734A1 PCT/US1990/003250 US9003250W WO9108734A1 WO 1991008734 A1 WO1991008734 A1 WO 1991008734A1 US 9003250 W US9003250 W US 9003250W WO 9108734 A1 WO9108734 A1 WO 9108734A1
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WO
WIPO (PCT)
Prior art keywords
liquid suspension
delivery system
medicament
oil
aqueous liquid
Prior art date
Application number
PCT/US1990/003250
Other languages
English (en)
Inventor
Akwete L. Adjei
Saul Borodkin
Richard B. Doyle
Original Assignee
Abbott Laboratories
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 Abbott Laboratories filed Critical Abbott Laboratories
Priority to KR1019910701847A priority Critical patent/KR920702616A/ko
Publication of WO1991008734A1 publication Critical patent/WO1991008734A1/fr

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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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions

Definitions

  • This invention relates to liquid drug vehicles. More particularly, this invention concerns liquid oil-based drug vehicles having improved shelf life and stability.
  • clorazepate dipotassium is one such drug that is not available in liquid form.
  • Clorazepate dipotassium is a minor tranquilizer used for the management of anxiety disorders and for short-term relief of symptoms of anxiety. It is also used as adjunctive therapy in the management of partial seizures and in the symptomatic relief of acute alcohol withdrawal.
  • a particular drug may be chemically stable in water
  • liquid formulations such as aqueous solutions and suspensions for oral administration are not used because of the unpalatatability of the particular drug.
  • Unpalatable drugs which are carried in aqueous media are tasted almost immediately upon ingestion and produce an unpleasant taste or after-taste.
  • the antibiotics clarithromycin and erythromycin are valuable therapeutic agents for treating infections and are somewhat unpalatable.
  • United States Patent No.4,080,445 discloses non-aqueous suspensions for oral administration comprising a therapeutically effective amount of a water sensitive drug in an anhydrous vehicle comprising a sugar and a vegetable oil.
  • FIGURE 1 represents a graph of the particle size distribution of an unmilled prior art drug formulation immediately after formulation and after two weeks of standing at 25°C .
  • FIGURE 2 represents a graph of the particle size distribution of a milled prior art drug formulation immediately after formulation and after two weeks of standing at 25°c .
  • FIGURE 3 represents a graph of the particle size distribution of an unmilled prior art drug formulation immediately after formulation and after two weeks of standing at 40°c and 80% relative humidity.
  • FIGURE 4 represents a graph of the particle size distribution of a milled prior art drug formulation immediately after formulation and after two weeks of standing at 40° C and 80% relative humidity.
  • FIGURE 5 represents a graph of the particle size distribution of a milled drug formulation in accordance with the present invention immediately after formulation and after standing at 25°C for periods of one, two and four weeks .
  • FIGURE 6 represents a graph of the particle size distribution of a milled drug formulation in accordance with the present invention immediately after formulation and after standing at 40°C and 80% relative humidity, for periods of one, two and four weeks .
  • FIGURE 7 represents the stratification rates of prior art milled and unmilled drag formulations and milled and unmilled drug formulations in accordance with the present invention after eight weeks' storage at room temperature. Summary of the Invention
  • the present invention relates to a pharmaceutical formulation
  • a pharmaceutical formulation comprising an essentially anhydrous liquid vehicle containing a therapeutically effective amount of a water-sensitive or unpalatable drug.
  • the essentially anhydrous liquid vehicle comprises an oil, a sugar, and a suspending agent.
  • the average particle size of all solid components of the formulation is 30 ⁇ or less.
  • the formulation also contains a drying agent to help bind any residual water that would otherwise degrade the active therapeutic agent. It is also preferred that buffer be present to stabilize the suspension at a pH favorable to the drug being delivered. In another preferred embodiment the suspension also contains one or more ingredients such as sa and flavor to aid the palatability of the formulation.
  • the suspension of the present invention provides an environment for water-sensitive or unpalatable drugs which is both chemically and physically stable. Furthermore, there is no oily taste or mouthfeel or bitter after-taste of the suspension made according to the embodiments containing sugar, salt and flavorings.
  • the suspension of the present invention is an anhydrous oil-based liquid suspension for delivering a medicament
  • anhydrous means having les than about 0.8% w/v moisture.
  • the suspension contains less than about 0.3% w/v moisture.
  • the suspension contains a suspending agent which forms a protective colloid around the drug to protect the drug from moisture and assure that the medicament is uniformly dispersed within the suspension.
  • the oil is preferably one that is considered safe for oral consumption, and is relatively stable. Furthermore, the oil should not be incompatible with the drug being delivered.
  • Preferred oils are selected from mixed triglycerides derived from capric, caproic, and caprylic acids. Furthermore, the vegetable oils containing glycerides of saturated or unsaturated aliphatic acids, such as stearic, palmitic, lauric, margaric, linoleic, linolenic, and myristic acids are suitable for u in the present invention. The most preferred embodiments presently use a winterized safflower o available from California Oils, Richmond, California.
  • suspending agents function to suspend the drug uniformly in the oil-based vehicle so that dosages of the drug are uniform.
  • Suitable suspending agents for use in the fomulations of the present invention include bentonite (a finely powdered montmorillonite aluminum silicate which is available under the tradename Bentone® from American Colloid Corporation); finely powdered sodium calcium alginate (available under the trade name Kelset® from Kelco, a division of Merck & Company); trihydroxystearin and hydrogenated castor oil (available under the tradename Thixcin® from NL Chemicals, Highstown, New Jersey); cellulose derivatives; silicates; bentonites; stearates; silicon dioxide; and acacia.
  • bentonite a finely powdered montmorillonite aluminum silicate which is available under the tradename Bentone® from American Colloid Corporation
  • finely powdered sodium calcium alginate available under the trade name Kelset® from Kelco, a division of Merck & Company
  • the suspending agent is finely powdered sodium calcium alginate.
  • Suspending agents act to slow down stratification and sedimentation of suspended particles by increasing the viscosity of the liquid and thereby improving the bouyancy of the solids suspended in the liquid. It is theorized that the powdered sugar and finely powdered sodium calcium alginate react with the drug to form a protective colloid around the drug particles in the oil-based vehicle resulting in a dispersed system that is highly stabilized. Further, the complex formed by the drug, suspending agent, and sugar provides a complex pathway for moisture to diffuse through.
  • the active drug component of the formulation is moisture sentsitive
  • the drug is shielded by the protective colloid and any moisture that is present in the oil-based vehicle is kept away from the drug.
  • the protective colloidal shield formed around the drug diminishes the undesirable taste effect while the liquid formulation is in the mouth cavity.
  • a drying agent is also included in the suspension.
  • the drying agent is a hygroscopic compound that absorbs or adsorbs water found in the suspension and which may degrade the drug.
  • the drying agent may, in some circumstances, also function as the suspending agent
  • silica gel has been found to have good suspending properties as well as good water absorbing properties.
  • a preferred drying agent in formulations of the present invention is silica gel.
  • any sweetener or sugar that is physically and chemically compatible with the drug being delivered is suitable for use in the formulations of this invention.
  • the preferred sweetener used is sucrose, and is most advantageously micronized and superfine so as to disperse easily in the suspension.
  • Other sugars, however, such as maltose, fructose, sorbitol and xylitol may also be used.
  • flavor and salt also contain flavor and salt. These ingredients help to make the otherwise unpalatable oil-based suspension palatable, in cases where the oil employed has an unpleasant taste or the active drug component of the formulation is bitter or has an unpalatable taste.
  • a preferred flavoring agent is a mixture of vanilla and peppermint extracts, but may also include other oil compatible flavoring agents, such as cherry, chocolate, cinnamon, coconut, coffee, orange, lemon, lime, strawberry, banana and peanut In preferred embodiments the flavoring agents are free of glycol and alcohol, both of which degrade some drugs such as clorazepate dipotassium.
  • the salt is believed to function primarily as a flavor enhancer to avoid a bland tasting product. The salt also masks the oiliness of the vehicle. It should be present in an amount sufficien to mask the oiliness of the oil based suspension without producing a noticeable salty taste.
  • Sodium chloride is the preferred flavor masking agent
  • Another suitable masking agent is potassium chloride.
  • the formulations of the present invention contain an alkaline buffer and a preservative.
  • the alkaline buffer maintains the pH at a level at which the drug is stable.
  • Clorazepate dipotassium for example, is most stable at a pH greater than about 9.0.
  • potassium carbonate is the preferred buffer; however, other carbonates, hydroxides, oxides and organic amines may be used.
  • Suitable preservative agents include the paraben class of compounds. Most preferred is a combination of parabens, such as those marketed under the tradename Aseptoform-M® (methylparaben) and Aseptoform-P® (propylparaben) available from Mallinckrodt, Inc. of St. Louis, Missouri. Any biologically acceptable benzoate or other preservative system that does not complex with or solubilize the drug to be delivered is also suitable.
  • surfactants has also been found to be advantageous to the physical stability of the suspension. Most surfactants that are compatible with the drug to be delivered as well as the oil vehicle are deemed suitable for use in the present invention.
  • the preferred surfactant is marketed under the tradename Emulphor EL 719P® by GAF Corp., Wayne, N.J., a polyoxyethylated vegetable oil having low dioxin levels.
  • the ingredients of the suspension of the preferred embodiments of the present invention are present in the following amounts: a therapeutically effective amount of a medicament, about 30% w/v to about 75% w/v sugar, about 30% w/v to about 75% w/v oil, about 0.05% w/v to about 5% w/v suspending agent, about 0.05 w/v to about 2% w/v salt, about 0.01% w/v to about 2% w/v alkaline buffer, about 0.01% w/v to about 3% w/v preservative, less than about 5% w/v surfactant, and about 0.01% w/v to about 5% w/v flavor.
  • Formulations having less than about 30% w/v sugar are generally unpalatable, while those having more than about 75% w/v generally have a consistency that is too thick.
  • the ingredients are present in the following ranges: a therapeutically effective amount of a medicament about 40% w/v to about 65% w/v sugar, about 45% w/v to about 65% w/v oil, about 0.1% w/v to about 2% w/v suspending agent about 0.2% w/v to about 1% w/v salt, about 0.05% w/v to about 1% w/v alkaline buffer, about 0.1% w/v to about 1% w/v preservative, less than about 2% w/v surfactant, about 0.01% w/v to about 3% w/v flavoring.
  • the formulations in accordance with the present invention are subjected to milling to reduce the average particle size of all solid contained in the mixture to less than about 30 ⁇ , preferably to less than 10 ⁇ -20 ⁇ .
  • the milling step may be performed by any conventional technique known to those skilled in the pharmaceutical formulations arts as, for example, liquid milling.
  • the preformulations were passed through either a Fryma MZM- Vk7 Delmix mixer or a Manton-Gaulin homogenizer. In most cases a single pass is sufficient to reduce the average particle size of the solids contained in the formulations to a value below the desired level of 30 ⁇ , often below about 20 ⁇ . If needed, the material can be subjected to two or more passes through the mill to obtain the desired average particle size.
  • Neobee® oil (320 g) was combined with 5 g of Bentone 34 and 290 g sugar. Sodium chloride powder (1.84 g) was then added. To 100 ml of the above mixture was added 180 mg of clorazepate dipotassium. The ingredients were mixed well. The resulting formulation tasted slightly saline, moderately sweet, with an oily and slightly bitter aftertaste.
  • Example 2 To 244 g of the mixture of Example 1 was added 4 g surfactant PVP K30 (polyvinyl pyrolidone having an average molecular weight of about 30,000). The resulting mixture was smooth, thin, and free flowing. To this mixture was then added 0.59 g of vanilla flavor. The taste was good, but the mixture turned very thick. An additional 244 g of the mixture of Example 1 was added to thin out the suspension. The resulting mixture was thick but pourable and had excellent taste.
  • PVP K30 polyvinyl pyrolidone having an average molecular weight of about 30,000
  • Clorazepate dipotassium (375 mg ) was mixed with 250 ml of a vehicle produced in accordance with the method of Example 2. The taste of the resulting formulation was excellent, but some bitterness of the drug was noted.
  • Neobee oil M5 (300 g), 300 g powdered sugar 12X and 8.85 g of Bentone 34 were combined. Some evidence of thixotropy was noted at final volume. Vanilla flavor (1.0 g) was added, causing the suspension to thicken significantly. The ingredients were mixed well at high speed for 15 minutes. An additional 70.38 g of Neobee oil M5 was added to 2.0 g sodium chloride which had been reduced to a fine powder in a mortar/pestle before addition to the suspension. In order to formulate a suspension containing 7.5 mg drug per 5ml of suspension, 300mg of clorazepate dipotassium was added to 200 ml of a vehicle produced as above and then mixed well. The resulting mixture was heavy, thixotropic and tasted good.
  • Neobee oil M5 600 g and 8.85 g of Bentone 34 were mixed together well. Powdered sodium chloride (3.60 g) was added with good mixing. Powdered sugar 12X (517 g) was added and mixed until smooth. The resulting mixture was allowed to deaerate. An additional 34 g of Neobee M5 oil was then added to bring the volume of the mixture to 1.0 liter, and then mixed until uniform. A small amount of vehicle was removed and mixed with 1.50 g of clorazepate dipotassium until smooth, and then added back into the main batch and mixed well. Vanilla flavor (1.80 g) was added. The mixture became thixotropic after the addition of vanilla. The taste of the suspension was good.
  • Example 6 To 6.30 kg Neobee M5 oil was mixed 86.0 g of Bentone-34® . Powdered potassium carbonate (10.0 g) and 35.0g of powdered sodium chloride were mixed with above oil mixture to make a smooth paste. The paste was diluted with additional oil and mixed until uniform consistency was attained. The diluted paste was then added to the main batch. Clorazepate dipotassium was mixed with a small amount of oil until smooth, and then diluted further and added to the main batch. 5.20kg powdered sugar 12X was slowly added to the main batch and mixed for approximately 1 hour. Immediately after all the sugar was added the suspension showed thixotropic character. After 1 hour of mixing the mixture became smooth and uniform, and lost its thixotropic character.
  • Flavor (15 ml) was then added.
  • Emulphor El 719P surfactant was added to thicken the mixture.
  • the mixture was passed through a Manton-Gaulin homogenizer at 1500 psi to yield a smooth and uniform product.
  • the product was placed in a vacuum for 1 hour to deaerate. The taste of the suspension was good.
  • Example 7 From an initial amount of 1833 g Neobee oil, 1 liter Neobee oil was taken and mixed with 39 g Emulphor EL 719P. Bentone 34 (25 g) was blended with Neobee oil and added to the main batch. Powdered sodium chloride (10 g) was blended with a small amount of Neobee oil and then added to the main batch. A preservative agent having 6.8 g Aseptoform M and 3.4 g Aseptoform P was mixed in 40 g of oil and heated until completely in solution, and then added to the main batch. The balance of the oil was then added and blended with a small amount of oil and added to the main batch.
  • Clorazepate dipotassium (4.46 g) was blended with a small amount of oil and added to the main batch. The balance of the oil was added and blended. Powdered sugar (1513.0 g) was mixed in and deaerated. Natural and artificial vanilla/peppermint extract (4.5 ml, obtained from Florasynth, Des Plaines, Illinois) was also mixed in. The entire mixture was passed through a Manton & Gaulin homogenizer to obtain a mixture with an average particle size below about
  • Example 8 A placebo vehicle was prepared by mixing a small amount of Neobee M5 oil with 85.5 g of Bentone 34. The Bentone 34/Neobee oil mixture was then added to approximately 6.0 kg of Neobee oil. Powdered sugar 12X (6.17kg ) and 36.00 g powdered sodium chloride were mixed in. The resulting mixture was thick after the first hour of mixing with a turbine blade, but thinned out after 3 hours mixing. The taste of the suspension was good.
  • Example 9 A prototype stability batch was prepared by mixing 2.95 kg safflower oil with 5.0 g Aseptoform-M® and 1.0 g Aseptoform-P®. The mixture was heated to approximately 80°C and 45.0 g and 12.5 g Thixcin-R were added. After dissolving the ingredients, the mixture was cooled to room temperature, and vacuum placed on the vehicle. Clorazepate dipotassium (7.5 g) and 10 g potassium carbonate were then added while the vehicle was being mixed under vacuum. Sodium chloride (17.5 g) and 3.0 kg of powdered sugar were added and homogenized using a Fryma MZM-Vk7 Delmix mixer while still under vacuum.
  • Flavor (7.5 g) was then added and the resulting mixture mixed for approximately 15 minutes.
  • the resulting mixture was milled using a Fryma M5-18 Coball mill (obtained from Fryma, Inc., 40 Ethel Road, Edison, N.J.) to obtain a smooth, uniform formulation having the desired average particle size and acceptable taste and stability requirements.
  • Neobee M5 oil 400 ml was heated to approximately 90°C and then allowed to stand for approx. 1 hour to equilibrate. Aseptoform M and P powders were mixed in until dissolved. Kelset,® Thixcin®, and Tween 80 were mixed to form an uniform dispersion. Estazolam was added and homogenized in a beadmill or a high energy mill. Flavors were then added until the resulting product was uniform. The volume of the resulting product was adjusted to 1 liter with Neobee Oil as required.
  • N-2-[benzo[b]thien-2-yl]ethyl-N-hydroxyurea is an inhibitor of the lipoxygenase enzymes and is useful in the treatment of inflammatory and allergic disease states. Its preparation and use is disclosed in United States Patent No. 4,873,159.
  • Valproic acid 5.00 Methylparaben 0.20 Propylparaben 0.10 Sodium chloride 0.35 Kelset® 0.90 Powdered sugar, 12X 45.00 Flavor enhancer, Prosweet® 0.25 Safflower oil, q.s. 100.00
  • ⁇ -Methyl-4-(2-methylpropyl)benzeneacetic acid 4 5.00 Methylparaben 0.20 Propylparaben 0.10 Sodium chloride 0.35 Kelset® 0.90 Powdered sugar, 12X 45.00 Flavor enhancer, Prosweet® 0.25 Safflower oil, q.s. 100.00
  • Example 17 An oil-based aspirin suspension was prepared in accordance with the teachings of United States Patent 4,080,445 to Lin, et al.
  • the composition of the formulation was as follows:
  • the sample was not milled following thorough mixing.
  • the composition was tested for particle size distrinbution just after formulation and two weeks later at two different temperatures (25°C and 40°C ) .
  • the particle size distribution graphs for this formula at 25°C and 40°C and 80% relative humidity appear in Figures 1 and 3, respectively. As can be seen from those graphs, considerable separation was noted after two weeks standing. Particle agglomeration and caking was noted since thorough shaking of the bottle and its contents after two weeks standing did not yield a uniform suspension. Gross separation and caking was noted in the formulation after standing for four weeks.
  • a formulation having the same composition as Example 17 was prepared with the exception that, following thorough mixing of the ingredients, the formulation was subjected to milling to reduce the average particle size to a value below 30 ⁇ in accordance with the teachings of this invention.
  • the formulation was subjected to particle size analysis immediately after formulation and again after two weeks standing at 25°C and at 40°C and 80% relative humidity . The results of these particle size analyses appear in Figures 2 and 4, respectively.
  • Example 19 A formulation containing clorazepate dipotassium was made having the same composition as that given in Example 11 above, but omitting the milling step. The formulation was subjected to particle size analysis immediately after formulation and again after two weeks and four weeks standing at 25°C and at 40°Cand 80% relative humidity. The results of these analyses appear in

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Supports de libération de médicaments sous forme de suspension liquide et non aqueuse à base d'huile, aptes à libérer des médicaments sensibles à l'eau ou ayant un goût désagréable, et comprenant une huile comestible, un sucre et un agent de suspension. La taille moyenne des particules de tous les constituants solides de la formulation est égale ou inférieure à 30 ν, ce qui permet d'obtenir des formulations qui présentent une stabilité physique excellente, c'est-à-dire par exemple une résistance à l'agglomération particulaire, à la sédimentation et à l'agglutination.
PCT/US1990/003250 1989-06-13 1990-06-08 Suspension liquide et anhydre a base d'huile servant a liberer un medicament WO1991008734A1 (fr)

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KR1019910701847A KR920702616A (ko) 1989-06-13 1990-06-08 약제를 전달하기 위한 무수 오일-기제된 액체 현탁액

Applications Claiming Priority (2)

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US36540989A 1989-06-13 1989-06-13
US365,409 1989-06-13

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WO1991008734A1 true WO1991008734A1 (fr) 1991-06-27

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EP (1) EP0477289A4 (fr)
JP (1) JPH04506216A (fr)
KR (1) KR920702616A (fr)
AU (1) AU639004B2 (fr)
CA (1) CA2060501A1 (fr)
GR (1) GR1001028B (fr)
IE (1) IE902109A1 (fr)
IL (1) IL94710A (fr)
PT (1) PT94372A (fr)
WO (1) WO1991008734A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998025621A1 (fr) * 1996-12-09 1998-06-18 Pharmacia & Upjohn Company Compositions pharmaceutiques ameliorees
WO2003013473A1 (fr) * 2001-08-06 2003-02-20 Pharmacia Corporation Preparation de suspension orale stabilisee
WO2004089337A1 (fr) * 2003-04-14 2004-10-21 Cts Chemical Industries Ltd. Composition a administration per os a usage veterinaire
WO2006008640A1 (fr) * 2004-07-15 2006-01-26 Pharmacia & Upjohn Company Llc Suspension non aqueuse contenant un medicament a gout desagreable

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001240534A (ja) * 2000-02-29 2001-09-04 Bio Kagaku Kk 液状組成物

Citations (5)

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US2238973A (en) * 1940-07-26 1941-04-22 American Cyanamid Co Sulphonamide compound in oil
US2867565A (en) * 1957-08-12 1959-01-06 Feinstone Wolffe Harry Sulfonamide composition comprising a lipid-aqueous emulsion carrier
US4080445A (en) * 1975-01-02 1978-03-21 American Home Products Corporation Permanent suspension pharmaceutical dosage forms
EP0295941A2 (fr) * 1987-06-19 1988-12-21 ELAN CORPORATION, Plc Dispersion liquide administrable oralement
EP0310801A1 (fr) * 1987-09-14 1989-04-12 Abbott Laboratories Suspension liquide anhydre à base d'huile pour délivrer un médicament

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US2951014A (en) * 1957-01-03 1960-08-30 Upjohn Co Process for a stable oil suspension
US4684666A (en) * 1986-08-19 1987-08-04 Haas Pharmaceuticals, Inc. Stabilized liquid analgesic compositions
IL87219A0 (en) * 1987-08-07 1988-12-30 Abbott Lab Erythromycin formulations for oral administration

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2238973A (en) * 1940-07-26 1941-04-22 American Cyanamid Co Sulphonamide compound in oil
US2867565A (en) * 1957-08-12 1959-01-06 Feinstone Wolffe Harry Sulfonamide composition comprising a lipid-aqueous emulsion carrier
US4080445A (en) * 1975-01-02 1978-03-21 American Home Products Corporation Permanent suspension pharmaceutical dosage forms
EP0295941A2 (fr) * 1987-06-19 1988-12-21 ELAN CORPORATION, Plc Dispersion liquide administrable oralement
EP0310801A1 (fr) * 1987-09-14 1989-04-12 Abbott Laboratories Suspension liquide anhydre à base d'huile pour délivrer un médicament

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0477289A4 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998025621A1 (fr) * 1996-12-09 1998-06-18 Pharmacia & Upjohn Company Compositions pharmaceutiques ameliorees
CZ297632B6 (cs) * 1996-12-09 2007-02-14 Pharmacia & Upjohn Company Zlepsené farmaceutické kompozice
WO2003013473A1 (fr) * 2001-08-06 2003-02-20 Pharmacia Corporation Preparation de suspension orale stabilisee
EA007901B1 (ru) * 2001-08-06 2007-02-27 Фармация Корпорейшн Стабилизированная суспензионная лекарственная форма для перорального применения
AP1817A (en) * 2001-08-06 2008-01-07 Pharmacia Corp Stabilized oral suspension formulation.
WO2004089337A1 (fr) * 2003-04-14 2004-10-21 Cts Chemical Industries Ltd. Composition a administration per os a usage veterinaire
WO2006008640A1 (fr) * 2004-07-15 2006-01-26 Pharmacia & Upjohn Company Llc Suspension non aqueuse contenant un medicament a gout desagreable

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IL94710A (en) 1995-05-26
AU5934290A (en) 1991-07-18
GR1001028B (el) 1993-03-31
JPH04506216A (ja) 1992-10-29
GR900100441A (en) 1991-11-15
IE902109A1 (en) 1991-01-02
IL94710A0 (en) 1991-04-15
AU639004B2 (en) 1993-07-15
KR920702616A (ko) 1992-10-06
CA2060501A1 (fr) 1990-12-14
PT94372A (pt) 1991-02-08
EP0477289A4 (en) 1992-07-22
EP0477289A1 (fr) 1992-04-01
IE902109L (en) 1990-12-13

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