Self-emulsifying formulation for lipophilic compounds
AssigneePharmacia & Upjohn Company
InventorsPing Gao, Walter Morozowich
Life of this patent
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Abstract
The present invention provides a novel pharmaceutical composition based on the use of a particular oil phase which comprises a lipophilic, pharmaceutically active agent, a mixture of diglyceride and monoglyceride in a ratio of from about 9:1 to about 6:4 by weight (diglyceride:monoglyceride) wherein the diglyceride and monoglyceride are mono- or di- unsaturated fatty acid esters of glycerol having sixteen to twenty-two carbon chain length, one or more pharmaceutically acceptable solvents, and one or more pharmaceutically acceptable surfactants. The composition is in a form of self-emulsifying formulation which provides high concentration and high oral bioavailability for lipophilic compounds.
Claims39
A pharmaceutical composition comprising;
- (a) a lipophilic, pharmaceutically active agent,
- (b) a mixture consisting essentially of diglyceride and monoglyceride in a ratio of from about 9:1 to about 6:4 by weight (diglyceride:monoglyceride) wherein the diglyceride and monoglyceride are mono- or di-unsaturated tatty acid esters of glycerol having sixteen to twenty-two carbon chain length,
- (c) one or more pharmaceutically acceptable solvents, and
- (d) one or more pharmaceutically acceptable surfactants;
- wherein the solvent is propylene glycol, polypropylene glycol, polyethylene glycol, glycerol, ethanol, dimethyl isosorbide, glycofurol, propylene carbonate, dimethyl acetamide, or a mixture thereof;
- wherein said surfactant is Polyoxyl 40 hydrogenated castor oil, Polyoxyl 35 castor oil, polyethylene glycol 12-hydroxy stearate, polyoxyethylene glyceryl trioleate, Peglicol 6-oleate, Polyoxyethylene stearates, Poloxamers, Polysorbates, or Saturated Polyglycolyzed Glycerides;
- with the proviso that said lipophilic, pharmaceutically active agent has a LOG P value ≧2, an intrinsic aqueous solubility ≦0.1 in the pH range of 1 to 8 and a solubility greater than 1 mg/ml in the mixture of b, c and d as defined herein.
A self-emulsifying formulation vehicle comprising a mixture consisting essentially of diglyceride and monoglyceride in a ratio of from about 9:1 to about 6:4 by weight (diglyceride:monoglyceride) wherein the diglyceride and monoglyceride are mono- or di- unsaturated fatty acid esters of glycerol having sixteen to twenty-two carbon chain length, one or more pharmaceutically acceptable solvents, and one or more pharmaceutically acceptable surfactants;
- wherein the solvent is propylene glycol, polypropylene glycol, polyethylene glycol, glycerol, ethanol, dimethyl isosorbide, glycofurol, propylene carbonate, dimethyl acetamide, or a mixture thereof;
- wherein said surfactant is Polyoxyl 40 hydrogenated castor oil, Polyoxyl 35 castor oil, polyethylene glycol 12-hydroxy stearate, polyoxyethylene glyceryl trioleate, Peglicol 6-oleate, Polyoxyethylene stearates, Poloxamers, Polysorbates, or Saturated Polyglycolyzed Glycerides.
A pharmaceutical composition comprising:
- (a) a lipophilic, pharmaceutically active agent;
- (b) a mixture consisting of diolein and monoolein in a ratio of about 9:1 to about 8:2 by weight;
- (c) a solvent comprising propylene glycol or a mixture of propylene glycol and ethanol in an amount of from about 15% to about 25% by weight of the total composition;
- (d) a surfactant comprising glycerol polyethylene glycol oxystearate or glycerol polyethylene glycol ricinoleate in an amount of from about 30% to about 45% by weight of the total composition;
- and
- optionally a basic amine in an amount of about 0.1% to about 7% of the total composition;
- and
- wherein the lipophilic active agent has a LOG P value ≧2, an intrinsic aqueous solubility ≦0.1 mg/ml in the pH range of 1 to 8, and a solubility greater than 1 mg/ml in the mixture of b, c and d as defined herein.
Dependencies are inferred from the claim text.