WO2012035378A1 - Crème dermaceutique fabriquée en utilisant du fusidate de sodium et du propionate de fluticasone, processus de fabrication de celle-ci et procédé de traitement l'utilisant - Google Patents

Crème dermaceutique fabriquée en utilisant du fusidate de sodium et du propionate de fluticasone, processus de fabrication de celle-ci et procédé de traitement l'utilisant Download PDF

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Publication number
WO2012035378A1
WO2012035378A1 PCT/IB2010/056124 IB2010056124W WO2012035378A1 WO 2012035378 A1 WO2012035378 A1 WO 2012035378A1 IB 2010056124 W IB2010056124 W IB 2010056124W WO 2012035378 A1 WO2012035378 A1 WO 2012035378A1
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Prior art keywords
amount
vessel
mixture
cream
fusidic acid
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PCT/IB2010/056124
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English (en)
Inventor
Sulur Subramaniam Vanangamudi
Madhavan Srinivasan
Neelakandan Narayanan Chulliel
Kausik Ghosh
Original Assignee
Sulur Subramaniam Vanangamudi
Madhavan Srinivasan
Neelakandan Narayanan Chulliel
Kausik Ghosh
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Application filed by Sulur Subramaniam Vanangamudi, Madhavan Srinivasan, Neelakandan Narayanan Chulliel, Kausik Ghosh filed Critical Sulur Subramaniam Vanangamudi
Publication of WO2012035378A1 publication Critical patent/WO2012035378A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • 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
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles

Definitions

  • the present invention relates to primary & secondary bacterial skin infections and inflammations and in particular it relates to the single dose treatment using a cream containing a steroid which is in the form of Fluticasone Propionate, and an antibacterial agent in the form of Fusidic acid wherein the Fusidic acid has been 10 made using Sodium Fusidate as the starting Active Pharmaceutical Ingredient
  • Topical and systemic inflammatory treatment compositions typically employ a combination of corticosteroids in a base component.
  • the active ingredients typically comprise Corticosteroids such as Betamethasone Valerate, Fluticasone Propionate, Mometasone Furoate, Dexamethasone Acetate, Hydrocortisone Acetate, Clobetasol Propionate, Beclomethasone Dipropionate, Betamethasone Dipropionate and the like.
  • Topical and systemic bacterial infection treatment compositions typically employ at least one active pharmaceutical ingredient (API) in combination with a base component.
  • APIs typically comprise an antibiotic/antibacterial such as Fusidic acid and the like.
  • Fusidic acid in fine powder form is used as source API.
  • the small particle size enhances its dermal contact by providing a large specific surface area and penetration, and provides a smooth feel on application to skin.
  • a serious shortcoming of the fine size of Fusidic acid particles is that it presents an enormous surface area for contact and reaction with molecular Oxygen during manufacture, handling, and processing of the cream. This has serious implications to its chemical stability and results in rapid reduction in potency of the API (Fusidic acid) in the final cream formulation.
  • Sodium Fusidate is known to have been used to make dermaceutical medicaments for topical application.
  • these are in the form of ointment rather than cream.
  • Drawbacks of ointments over creams are well known and it's generally preferable to use creams rather than ointments for topical application.
  • Fusidic acid cream in which Fusidic acid will be of greater stability at the time of the manufacture of the cream, and which will sustain its stability at an acceptable level throughout its shelf life.
  • the invention discloses a dermaceutical cream containing Fluticasone Propionate as a steroid, and an antibacterial agent in the form of Fusidic acid, which Fusidic acid is formed in situ from Sodium Fusidate as the starting raw material, wherein Sodium Fusidate is converted into Fusidic acid under oxygen-free environment.
  • the cream of the present invention has greater shelf-life stability and the finer particle size of the API than the conventional creams containing Fusidic acid.
  • the cream of the present invention contains Fusidic acid as the API that has been formed in situ from Sodium Fusidate, and Fluticasone Propionate as a steroid, in a cream base comprising a preservative, an acid, a co-solvent, emulsifiers and a waxy material along with water, preferably purified water.
  • Creams containing Fusidic acid that are made using Sodium Fusidate as starting API are not available.
  • Creams containing Fusidic acid that are made using Sodium Fusidate as starting API along with Fluticasone Propionate as a steroid are not available.
  • fusidic acid has very labile trans, sys, trans arrangement of these rings which forces ring B into a boat conformation.
  • fusidic acid readily undergoes acid mediated dehydration of C-l l hydroxy group to generate a C9-C11 double bond which on further isomerization followed by oxidization in the presence of oxygen leads to a mixture of biologically inactive fusidic acid derivatives.
  • carboxylic acid functional group present in the fusidic acid facilitates the above process more readily upon storage.
  • carboxylic acid promoted decomposition is not feasible.
  • sodium fusidate has superior solid state stability when compared to fusidic acid. This discovery of the inventor has also been corroborated through stability assessment of sodium fusidate and fusidic acid.
  • Tables 1 and 2 also show the comparison between the stability of the Fusidic acid and Sodium Fusidate as raw APIs.
  • the study was carried out using an in-house UPLC method developed by the applicant, which the applicant believes is a true stability-indicating method as opposed to the titration method suggested in British Pharmacopoeia (BP). This is because the BP method does not differentiate between the intact API and the degraded form.
  • BP British Pharmacopoeia
  • a dermaceutical cream that uses Sodium Fusidate and Fluticasone Propionate as a steroid would exploit the benefit of the fact that Sodium Fusidate is more stable than Fusidic acid and it would also provide a cream formulation which is far superior in its application qualities than an ointment. It would thus fill an existing need for a cream that has better stability than currently available creams containing Fusidic acid and steroids.
  • the applicant has also discovered that the Fusidic acid, cream prepared using Sodium Fusidate as the starting API and Fluticasone Propionate as a steroid, showed good chemical stability, and efficacy.
  • the application discloses a cream containing Fluticasone Propionate as a steroid, and Fusidic acid that has been prepared using Sodium Fusidate as the starting API, in which Fusidic acid forms in-situ under totally oxygen free environment by slow addition of an acid, into a molecular dispersion form (due to the presence of a co-solvent) at the intermediate stage, and which Fusidic acid regenerates as an extremely fine dispersion when added to a final cream base, thereby resulting in a finely and homogeneously dispersed Fusidic acid in the final cream.
  • the cream of the present invention contains Fusidic acid as the API that has been formed in situ from Sodium Fusidate as the starting API, Fluticasone Propionate as a steroid in a cream base comprising a preservative, an acid, a co-solvent, a preservative, emulsifiers and a waxy material along with water, preferably purified water.
  • the cream base of the present invention optionally further comprises an ingredient selected from a group comprising a buffering agent, an anti oxidant, a chelating agent, and a humectant, or any combination thereof.
  • the present invention provides a novel cream that has been produced using Sodium Fusidate as the starting raw material, and which cream contains Fusidic acid of high therapeutic efficacy and of chemical stability that is generally superior to the commercially available creams containing Fusidic acid.
  • the cream of the present invention containing Fusidic acid has been manufactured in a totally oxygen free environment under purging with inert gas and applying vacuum. Under these conditions, the Sodium Fusidate is converted in situ into Fusidic acid and to which Fluticasone Propionate as a steroid is added.
  • the cream of the present invention is used in the treatment of bacterial skin infections and inflammations.
  • the H of the product of the present invention is from about 3 to 6.
  • Sodium Fusidate ointments that are commercially available are greasy and cosmetically non elegant. It is essential that the active drug penetrates the skin for the optimum bio-dermal efficacy.
  • the particle size of the active drug plays an important role here. It is necessary that the active drug is available in a finely dispersed form for the product to be being efficacious. Also this is to be achieved in the safe pH compatible environment of skin (4.0 to 6.0). To achieve all these, it is essential to choose proper vehicles or co-solvents for the dissolution or dispersion of the drug.
  • the product of the present invention is efficacious due to the pronounced antiinflammatory, antibacterial activity of the steroids and regenerated Fusidic acid which is available in reduced particle size than the conventional products, and in a finely dispersed form.
  • the average size of the fusidic acid particles in the present invention has been found to be approximately 1 ⁇ whereas that for the existing creams varies between 14 ⁇ to 22 ⁇ . Euqlly importantly, the minimum particle size observed was approx. 0.4 ⁇ whereas the minimum particle size observed for existing creams ranged between 4 ⁇ and 10 ⁇ . The cream of the present invention is therefore physically distinct from any of the existing creams and easily distinguishable.
  • the reduced particle size of the fusidic acid of the present invention is of particular significance as it has been achieved without compromising the stability of fusidic acid.
  • WO2007087806 by Leo Pharma have employed mechanical means such as mortar and pestle to mechanically grind fusidic acid for adding to a cream base.
  • mechanical means such as mortar and pestle to mechanically grind fusidic acid for adding to a cream base.
  • WO2007087806 is silent on the particle size achieved, it will be known to a person skilled in the art that its particle size of fusidic acid cannot be finer than that of the present invention.
  • the stability of the fusidic acid in creams produced by the teachings of WO2007087806 or indeed any fusidic acid creams that employ grinding of fusidic acid in presence of oxygen cannot be as good as that of the present invention as evidenced by the data included in Table 2A.
  • the inventor has screened different co-solvents such as Propylene Glycol, Hexylene Glycol, PolyEthyleneGlycol-400 & the like and dissolved the Sodium Fusidate in one of above co-solvents varying from about 5% (w/w) to 40% (w/w) under inert gas purging and under vacuum and converted to Fusidic acid in- situ by adding an acid such as HC1, H 2 SO 4 , HNO 3 , Lactic acid and the like from about 0.005% (w/w) to about 0.5% (w/w) under stirring and obtained Fusidic acid in more stabilized and solution form, which makes our final product in a cream base which easily penetrates the skin and highly efficacious, and also highly derma compatible by having a pH of about 3.0 to about 6.0.
  • co-solvents such as Propylene Glycol, Hexylene Glycol, PolyEthyleneGlycol-400 & the like and dissolved the Sodium Fusidate in one
  • the stability of the product is confirmed by the stability studies performed for 3 months as per ICH guidelines.
  • said corticosteroid is added from about 0.005% to about 2.5% by weight, preferably from about 0.005% to about 1.00% by weight, and most preferably about 0.05% by weight, and further wherein said corticosteroid is Fluticasone Propionate, and said Fusidic acid is present in an amount between 0.1% (w/w) and about 25% (w/w), preferably between 0.5% (w/w) and about 5%(w/w), and more preferably about 2.00 % (w/w), and in which the amount of said Sodium Fusidate used to form in situ said Fusidic acid is in the range between about
  • said preservatives is selected from a group comprising Methylparaben, Propylparaben, Chlorocresol, Potassium sorbate, Benzoic acid and the like, either singly or any combination thereof, and added in an amount between 0.05% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), more preferably 0.2% (w/w), said primary and secondary emulsifier is selected from a group comprising Cetostearyl alcohol, Cetomacrogol-1000, Polysorbate-80, Span-80 and the like, either singly or any combination thereof, and added in an amount between 1% (w/w) to 25% (w/w), preferably 20% (w/w), more preferably
  • said waxy material is selected from a group comprising White soft paraffin, Liquid Paraffin, Hard paraffin and the like, either singly or any combination thereof, and added in an amount between 5% (w/w) to 20% (w/w), preferably
  • said co-solvent is selected from a group comprising Propylene Glycol, Hexylene Glycol, PolyEthylene Glycol-400 and the like, either singly or any combination thereof, and added in an amount between 5% (w/w) to 40%
  • said acid is selected from a group comprising acids such as HC1, H 2 SO 4 , HNO 3 , Lactic acid and the like, either singly or any combination thereof, and added in an amount between 0.005% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), more preferably 0.25% (w/w), and water in an amount in the range between 5% (w/w) and 70% (w/w), preferably 10% (w/w) to 50% (w/w), more preferably 35% (w/w) to 45% (w/w), preferably purified water.
  • a buffering agent is selected from a group comprising Di Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phosphate and the like, either singly or any combination thereof, to form a proportion between 0.01 % (w/w) to 2.00% (w/w), preferably 1.0% (w/w), more preferably 0.5% (w/w).
  • Hydroxy Toluene and the like either singly or any combination thereof, to form a proportion between 0.001 % (w/w) to 5% (w/w), preferably 0.1 % (w/w), more preferably 0.01% (w/w).
  • a novel dermaceutical cream as described in the preferred embodiment 1 and embodiments nos. 1 to 4 which further comprises a chelating agent, wherein said chelating agent is selected from a group comprising Disodium EDTA and the like, either singly or any combination thereof, to form a proportion between 0.01 % (w/w) to 1% (w/w), preferably 0.5% (w/w), more preferably 0.1 % (w/w).
  • a novel dermaceutical cream as described in the preferred embodiment 1 and embodiments nos. 1 to 5 which further comprises a humectant, wherein said humectant is selected from a group comprising Glycerin, Sorbitol, Propylene glycol and the like, either singly or any combination thereof, to form a proportion between 5% (w/w) to 40% (w/w), preferably 30% (w/w), more preferably 25% (w/w).
  • a process to make a cream containing Fluticasone Propionate and_fusidic acid said cream being as disclosed in preferred embodiment 1 and embodiment 1 , said process comprising the step of using sodium fusidate as the raw active pharmaceutical ingredient and converting said sodium fusidate in situ into fusidic acid under oxygen-free environment in a cream base, to which Fluticasone Propionate is added.
  • a preservative selected from a group comprising Methylparaben, Propylparaben, Chlorocresol, Potassium sorbate, Benzoic acid and the like, either singly or any combination thereof, in an amount between 0.05% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), more preferably 0.2% (w/w),
  • waxy materials selected from a group comprising white soft paraffin, liquid paraffin, hard paraffin and the like, either singly or any combination thereof, in an amount between 5% (w/w) to 20% (w/w), preferably 15% (w/w), more preferably 12.5% (w/w), to an oil-phase vessel and melting said wax by heating to 70 ° C to 80 ° C,
  • a primary emulsifier preferably in the form of a non ionic Surfactant, selected from a group comprising Cetostearyl alcohol, Cetomacrogol-1000, either singly or any combination thereof, preferably Cetostearyl alcohol in an amount between 1% (w/w) to 15% (w/w), preferably 15% (w/w), more preferably 12.5% (w/w), and optionally a secondary emulsifier selected from a group comprising Polysorbate-80, Span-80 and the like, preferably Polysorbate-80, in an amount between 1 to 5% w/w, more preferably 2% w/w and mixing the mixture thoroughly, preferably using an agitator, at 10 to 50 RPM while maintaining the temperature of the mixture at 70 °C to 80 0 C,
  • a primary emulsifier preferably in the form of a non ionic Surfactant, selected from a group comprising Cetostearyl alcohol, Cetomacrogol-1000, either singly or any combination
  • a co-solvent selected from a group comprising
  • an acid selected from a group comprising acids such as HC1
  • H 2 SO 4 , HNO 3 , Lactic acid and the like either singly or any combination thereof, preferably Nitric acid in an amount between about 0.005% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), more preferably 0.25% (w/w), adding in a second API- vessel propylene glycol in an amount between 1%
  • Surfactant preferably Cetomacrogol-1000 in an amount between 0.1 %
  • step j 1. transferring the contents of said second API-vessel of step j to the mixing vessel of step g with continuous stirring at 10 to 50 RPM and homogenizing the mixture at 1000 to 3000 RPM under inert gas flushing and under vacuum of minus 1000 to minus 300 mm of mercury, said inert gas being preferably nitrogen,
  • the process described in embodiment no. 10 further incorporates after the step of adding a preservative, a step of adding a chelating agent, selected from a group comprising Disodium EDTA and the like, either singly or any combination thereof, in an amount between about 0.01% (w/w) to 1% (w/w), preferably 0.5% (w/w), more preferably 0.1 % (w/w).
  • a chelating agent selected from a group comprising Disodium EDTA and the like, either singly or any combination thereof, in an amount between about 0.01% (w/w) to 1% (w/w), preferably 0.5% (w/w), more preferably 0.1 % (w/w).
  • the process described in embodiments no. 10 and 11 further incorporates after the step of adding chelating agent, a buffering agent selected from a group comprising Di Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phosphate and the like from about 0.01% (w/w) to 2.00% (w/w), preferably 1 % (w/w), more preferably 0.5% (w/w).
  • a buffering agent selected from a group comprising Di Sodium Hydrogen Ortho Phosphate, Sodium Hydrogen Ortho Phosphate and the like from about 0.01% (w/w) to 2.00% (w/w), preferably 1 % (w/w), more preferably 0.5% (w/w).
  • the process described in embodiments no. 10, 11 , and 12 further incorporate in the step h of embodiment 10, an anti oxidant selected from a group comprising Butylated Hydroxy Anisole, Butylated Hydroxy Toluene and the like from about 0.001% (w/w) to 5% (w/w), preferably 0.1 % (w/w), more preferably 0.01 % (w/w).
  • an anti oxidant selected from a group comprising Butylated Hydroxy Anisole, Butylated Hydroxy Toluene and the like from about 0.001% (w/w) to 5% (w/w), preferably 0.1 % (w/w), more preferably 0.01 % (w/w).
  • the process described in embodiments no. 10, 11 ,12 and 13 further incorporate a humectant in the step a of embodiment 10, wherein said humectant is selected from a group comprising Glycerin, Sorbitol, Propylene glycol and the like, either singly or any combination thereof, to form a proportion between 5% (w/w) to 40% (w/w), preferably 30% (w/w), more preferably 25% (w/w).
  • a humectant is selected from a group comprising Glycerin, Sorbitol, Propylene glycol and the like, either singly or any combination thereof, to form a proportion between 5% (w/w) to 40% (w/w), preferably 30% (w/w), more preferably 25% (w/w).
  • a process to make a cream containing Fluticasone Propionate and fusidic acid as described in embodiment numbers 1 and 9 comprising the steps of: a. heating purified water in the range from 5% (w/w) to 60% (w/w), preferably 10% (w/w) to 50% (w/w), more preferably 30% (w/w) to 45% (w/w), in a water-phase vessel to 70 0 C to 80 0 C,
  • a preservative selected from a group comprising Methylparaben, Propylparaben, Chlorocresol, Potassium sorbate, Benzoic acid and the like, either singly or any combination thereof, in an amount between 0.05% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), more preferably 0.2% (w/w), preferably Benzoic acid, c.
  • a chelating agent preferably being Disodium edetate added in an amount preferably between 0.01 and 1 %, more preferably 0.1%
  • said buffering agent preferably being Di Sodium Hydrogen Ortho Phosphate added in an amount preferably between 0.01% (w/w) and 2.00% (w/w), preferably 1%
  • step b mixing the mixture of water phase vessel in step b using an agitator at 10 to 50 RPM while maintaining the temperature of said mixture at 70 0 C to
  • an emulsifying wax preferably Cetostearyl alcohol, in an amount preferably between 1 and 15 %, more preferably
  • waxy material white soft paraffin in an amount preferably between 5 and 20 %, more preferably 12.5 %, and melting them by heating to 70 ° C to 80 ° C,
  • Polysorbate 80 and mixing the mixture thoroughly using an agitator at 10 to 50 RPM while maintaining the temperature of the mixture at 70 0 C to 80 ° C,
  • said inert gas preferably being nitrogen and adding Sodium Fusidate to the mixture and dissolving it in the mixture, said sodium fusidate being added in an amount between 0.1% (w/w) and about 25% (w/w), preferably between 0.5% (w/w) and about 5% (w/w) and more preferably about 2.08 % (w/w),
  • H 2 SO 4 , HNO 3 , Lactic acid and the like either singly or any combination thereof, preferably Nitric acid in an amount between about 0.005% (w/w) to 0.5% (w/w), preferably 0.3% (w/w), more preferably 0.25% (w/w),
  • step h mixing vessel of step h with continuous stirring at 10 to 50 RPM and homogenizing the mixture at 1000 to 3000 RPM under inert gas flushing and under vacuum of minus 1000 to minus 300 mm of mercury, said inert gas being preferably nitrogen,
  • step h cooling the contents of the mixing vessel of step h to 30 °C to 37 °C using circulation of cooled water from a cooling tower at 8 °C to 15 °C into the jacket of mixing vessel,
  • a method of treating primary & secondary bacterial skin infections and inflammations comprising applying of a cream containing at least one corticosteroid and Fusidic acid which is made in situ under oxygen-free environment using Sodium Fusidate, wherein said cream comprises Fusidic acid made using Sodium Fusidate, a cream base containing a preservative, primary and secondary emulsifiers, waxy materials, co-solvents, acids, and water.
  • a method of treating primary & secondary bacterial skin infections and inflammations comprising applying of a cream as described in the preferred embodiment 1 and any of embodiments 1 to 9.
  • APIs-stability experiments were carried out (see tables 4 - 6) using the product of the present invention. Tests were carried out to observe (or measure as appropriate) the physical appearance of the product, the pH value and assay of the APIs over a period of time. Each gram of product of the present invention used for the tests contained Sodium Fusidate in the amount required to produce 2% (w/w) Fusidic acid in the finished product and appropriate amount of steroids as mentioned below.
  • composition Sodium Fusidate + Fluticasone Propionate Cream
  • Each gm contains:
  • the product used for the Stability Studies tests contained approximately 10% extra APIs (overages). It was packaged in an aluminium collapsible tube and each gram of the product contained 20.8 mg of Sodium Fusidate (in conformance with BP), which is equivalent to 20 mg of Fusidic acid (BP conformant). The % of sodium fusidate and the corticosteroid used in all examples are measured w/w with respect to the final product.
  • the Fusidic acid in the present invention degrades more slowly than the conventional products.
  • the stability level of the Fusidic acid in the present invention remains within the acceptable limits throughout the shelf life of the product.
  • the particle size of the Fusidic acid is finer and overall particle distribution in the cream is better, thereby providing better dermaceutical efficacy.

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Abstract

L'invention concerne une crème dermaceutique contenant du propionate de fluticasone en tant que corticostéroïde, et un agent antibactérien sous forme d'acide fusidique, cet acide fusidique étant formé in situ à partir de fusidate de sodium en tant que matière première de départ, le fusidate de sodium étant converti en acide fusidique dans un environnement exempt d'oxygène. La crème de la présente invention a une stabilité de durée de conservation supérieure et une dimension de particules plus fine de l'ingrédient pharmaceutique actif (API) que les crèmes classiques contenant de l'acide fusidique. La crème de la présente invention contient de l'acide fusidique en tant qu'API qui a été fabriqué in situ à partir de fusidate de sodium, et de propionate de fluticasone, dans une base de crème comprenant un conservateur, un acide, un cosolvant, des émulsifiants et un matériau cireux en association avec de l'eau, de préférence de l'eau purifiée.
PCT/IB2010/056124 2010-09-14 2010-12-30 Crème dermaceutique fabriquée en utilisant du fusidate de sodium et du propionate de fluticasone, processus de fabrication de celle-ci et procédé de traitement l'utilisant WO2012035378A1 (fr)

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IN2531/MUM/2010 2010-09-14
IN2531MU2010 2010-09-14

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007087806A1 (fr) 2006-02-02 2007-08-09 Leo Pharma A/S Composition topique comprenant une substance antibactérienne
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