Pharmaceutical compositions of fenretinide having increased bioavailability and methods of using the same
View Patent ↗A pharmaceutical composition for parenteral delivery, comprising a retinide such as fenretinide in combination with a solvent capable of dispersing or solubilizing the retinide. The solvent comprises an alcohol, such as ethanol, in combination with an alkoxylated castor oil, such as CREMOPHOR® EL, or comprising a retinide, such as fenretinide, in an emulsion composed of a lipoid dispersed in an aqueous phase, a stabilizing amount of a non-ionic surfactant, optionally a solvent, and optionally an isotonic agent. In addition, a method of use in the treatment of hyperproliferative disorders, such as cancers is described.
1. A pharmaceutical emulsion composition for parenteral delivery, said composition consisting essentially of, in combination:
(a) a hydrophilic phase;
(b) from about 2 to 40 percent volume per volume of a pharmacologically acceptable lipoid as a hydrophobic phase dispersed as particles in said hydrophilic phase, wherein said lipoid is soybean oil, and wherein said particles are from 5 to 1000 nanometers in diameter;
(c) from about 0.01 to 2 percent weight per volume of fenretinide;
(d) from about 0.01 to 10 percent volume per volume of ethanol;
(e) from about 0.01 to 10 percent weight per volume of a surfactant to stabilize said emulsion composition, wherein said surfactant is selected from egg phospholipids; and
(f) from about 1 to 10 percent weight per volume of glycerin;
said emulsion composition having a pH of about 5 to 10.
2. The composition of claim 1 wherein fenretinide is present at about 0.1 to 0.5 percent weight per volume.
3. The composition of claim 1 wherein ethanol is present at about 0.01 to 5.0 percent volume per volume.
4. The composition of claim 1 wherein the egg phospholipid is present at about 2 percent weight per volume.
5. The composition of claim 1 wherein the glycerin is present in an amount of about 1 to 3 percent weight per volume.
6. The composition of claim 1 wherein said particles are from 50 to 400 nanometers in diameter.
7. The composition of claim 1 wherein:
fenretinide is present at about 0.1 to 0.5 percent weight per volume;
ethanol is present at about 0.01 to 5.0 percent volume per volume;
egg phospholipid is present at about 2 percent weight per volume;
glycerin is present in an amount of about 1 to 3 percent weight per volume; and
said particles are from 50 to 400 nanometers in diameter.