Pharmaceutical formulation
Soft gelatin capsules comprising a suspension composition of nintedanib or a pharmaceutically acceptable salt thereof in medium chain triglycerides and carrier system, wherein the carrier system comprises solubilizers, phospholipids, thickeners and mixtures thereof.
1 . A pharmaceutical dosage form which comprises a soft gelatin capsule for oral administration, wherein the soft gelatin capsule comprises a pharmaceutical formulation comprising a suspension of the following components:
a carrier system comprising phospholipids and medium chain triglycerides or mixtures thereof, wherein the phospholipids are lecithins and are present in an amount of 11% to 20% by weight of the total formulation, and wherein the medium chain triglyceride is present in an amount of 25% to 40% w/w of the total formulation;
a therapeutically effective amount of nintedanib or its pharmaceutically acceptable salt, wherein the nintedanib or pharmaceutically acceptable salt thereof is present in an amount of about 30% to about 50% w/w of the total formulation, and wherein the nintedanib or its pharmaceutically acceptable salt is present partially in the form of finely divided particles suspended in the carrier system and partially in the form of a solution; and
optionally including additional pharmaceutically acceptable excipients.
2 . The dosage form of claim 1 , wherein the nintedanib or pharmaceutically acceptable salt thereof comprises nintedanib esylate salt.
3 . The dosage form of claim 1 , wherein the carrier system further comprises a surfactant, a solubilizing agent, an emulsifying agent, a thickener, or mixtures thereof.
4 . The dosage form of claim 3 , wherein the surfactants are selected from the group consisting of: polyoxyethylene castor oil derivatives, polyoxyethylene polyoxypropylene block copolymers, polyoxyethylene polypropylene glycol, a mono fatty acid ester of polyoxyethylene sorbitan, polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan monolaurate, propylene glycol monolaurate, propylene glycol dicaprylate, sorbitan laurate, sorbitan monostearate, caprylocaproyl macrogolglyceride, octadecanoic acid, sorbitan oleate, sorbitan palmitate, sorbitan stearate, propylene glycol monocaprylate, soyabean oil, vegetable oil, triacetin, triethyl citrate, macrogolglycerol-hydroxystearate, macrogolglycerol-ricinoleate, and mixtures thereof.
5 . The dosage form of claim 4 , wherein the surfactants are selected from polyoxyl castor oil, caprylocaproyl macrogolglyceride, or octadecanoic acid and are present in an amount of 10% to 30% w/w of the total formulation.
6 . The dosage form of claim 3 , wherein the thickener is selected from the group consisting of: polyethylene glycols, colloidal silica, bees wax, glycerol monostearate, hydrogenated vegetable oil, partially hydrogenated vegetable oil, and a hard fat.
7 . The dosage form of claim 6 , wherein the thickener is hard fat present in an amount of 10% to 30% w/w of the total formulation.
8 . The dosage form of claim 1 , further comprising a solubilizing agent selected from the group consisting of: lineleoyl polyoxyl-6-glycerides, corn oil mono glycerides, corn oil di glycerides, corn oil triglycerides, and mixtures thereof.
9 . The dosage form of claim 8 , wherein the solubilizing agent is present in an amount of less than 10% w/w of the total formulation.
10 . The dosage form of claim 1 , further comprising phosphatidylcholine and a solvent in an amount of about 1% to 50% w/w of the total formulation.
11 . The dosage form of claim 1 , wherein the carrier system further comprises a pharmaceutically acceptable nonphospholipid surfactant, wherein the pharmaceutically acceptable nonphospholipid surfactant comprises polysorbate 80, polysorbate 20, Vitamin E TPGS, or d-a-tocopheryl polyethylene glycol 1000 succinate in an amount of 1% to about 25% w/w of the total formulation.
12 . A lipid suspension comprising:
a carrier system comprising:
25% to 40% medium chain triglycerides by weight of the suspension;
10% to 30% of hard fat by weight of the suspension; and
11% to 20% of lecithin by weight of the suspension; and
nintedanib esylate in an amount of 30% to 50% by weight of the suspension, wherein the nintedanib esylate is present partially in the form of finely divided particles and suspended in the carrier system and partially in the form of a solution.
13 . A lipid suspension of claim 12 , wherein the lecithin is present in an amount of 11% by weight of the suspension.