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US 8,282,909 B2Granted
Pharmaceutical composition for topical application of poorly soluble compounds
AssigneeIntendis GmbH
InventorsHartwig Steckel, Karin Hoffmann
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AssigneeIntendis GmbH
InventorsHartwig Steckel, Karin Hoffmann
Estimating the term…
The present invention provides a formulation which contains a poorly water soluble pharmaceutically active compound at a concentration of 50 mg per 100 g formulation or above. The solubility is achieved by a mixture of solvents as described herein. Moreover the formulation as described herein may be used as a base formulation to generate a cream, an ointment, a spray, a foam or an oleogel.
A pharmaceutical formulation containing at least one pharmaceutically active compound, which is
A pharmaceutical formulation containing at least one pharmaceutically active compound, which is
Dependencies are inferred from the claim text.
From the US filing history. Foreign family members aren’t listed.
Galenical forms characterised by the site of application: skin, i.e. galenical aspects of topical compositions
Medicinal preparations characterised by special physical form: ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
Having six-membered rings with one nitrogen as the only ring hetero atom: quinolines; Isoquinolines
Containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides: alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene…
About 3 years 3 months of term left · ends 12 Jan 2030 (estimated)
Topically administered active substances are mainly used to treat the redness, swelling, itching and discomfort of psoriasis, atopic dermatitis and other pathologies of the skin. The majority of such active drug substances exhibit poor solubility in standard solvents, such as water. Poor solubility in the context of this application means that the solubility of the compound in water is 20 mg/l or less at 20° C. Glucocorticosteroids, steroids, calcineurin inhibitors, vitamin D analoques, retinoids, immunosuppressants, antimycotics, antiinfectives, estrogens, androgens, fumaric acid esters are typical drug classes for topical administration with such low water solubility. Other examples for such poorly soluble compounds are provided e.g. in WO 03/082827 or WO 2006/050998. One example is the non-steroidal active substance having the chemical name (R)-1,1,1-Trifluoro-4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-4-methyl-2-{[(2-methyl-5-quinolyl)amino]methyl}pentan-2-ol, the empirical formula of which is C25H26F4N2O2, having a molecular weight of 462.5. This is the compound according to example 1 of WO 2006/050998 (hereinafter Ex1/998). Said compound is a crystalline, non-polymorphic yellowish-to-green powder that is insoluble in water, only slightly soluble in hexane and moderately soluble in ethyl alcohol. It has very poor solubility in standard cream and ointment vehicles being in use for the topical administration, such as petrolatum and mineral oils.
Commercially, topically administered drug products are available as solutions, suspensions, creams and ointments. U.S. Pat. No. 3,892,856 describes the use of corticosteroids dissolved in polyethylene glycol and emulsified into an oleaginous base. Another option to present poorly water-soluble compounds for patient use is the formulation of an oil-in-water type formulation containing the active compound in suspended form.
Other examples can be found in the scientific and patent literature.
The present invention is further described in the following examples, which shall not be interpreted as limiting in any way.
Examples (cream) 1 2 3 4 5 Ranges active compound 0.10 0.10 0.10 0.10 0.10 0.001-0.50 Oleyl alcohol 10.00 10.00 10.00 5.00 10.00 3.00-15.00 Medium-chained triglycerides — — — 5.00 — 2.00-10.00 Mineral oil 8.00 4.00 4.00 4.00 4.00 2.00-10.00 Cetearyl octanoate 3.00 10.00 10.00 10.00 10.00 2.00-15.00 Soybean Oil (vegetable oils) 6.00 4.00 4.00 4.00 4.00 3.00-15.00 Cyclomethicone 3.50 2.50 2.50 2.50 2.50 1.00-5.00 Stearyl alcohol 2.00 2.00 2.00 2.00 2.00 1.00-5.00 Butylated hydroxytoluene 0.05 0.05 0.05 0.05 0.05 0.01-0.20 Glycerol (85%) 8.00 8.00 8.00 8.00 8.00 4.00-10.00 Macrogolglycerolhydroxystearate 1.50 1.50 1.50 1.50 1.50 0.50-5.00 Povidone 90 4.00 4.00 4.00 4.00 4.00 2.00-8.00 Propylene Glycol 8.00 8.00 8.00 8.00 8.00 4.00-10.00 Acrylic acid copolymer 0.30 — 0.30 0.30 — 0.10-1.00 Hydroxyethylcellulose — 1.50 — — — 0.10-1.00 Acrylic acid — — — — 1.00 0.50-2.00 Trometamol solution 10% to pH 7 to pH 7 to pH 7 to pH 7 to pH 7 to pH 7.0 Purified water [ad 100.0] [ad 100.0] [ad 100.0] [ad 100.0] [ad 100.0] [ad 100.0]
Examples (liquid spray) 1 2 3 4 5 Ranges active compound 0.10 0.10 0.10 0.10 0.10 0.001-0.5 Oleyl alcohol 40.00 30.00 20.00 35.00 10.00 10.00-50.00 Medium-chained — 10.00 — 5.00 10.00 2.00-15.00 triglycerides Mineral oil — 4.00 10.00 4.00 15.00 2.00-15.00 Cetearyl 40.00 30.00 40.00 35.00 20.00 10.00-50.00 octanoate Soybean Oil 19.90 20.00 20.00 16.00 30.00 10.00-50.00 (vegetable oils) Cyclomethicone — 5.90 9.90 4.90 14.90 1.00-15.00