Formulations for hydrophobic pharmaceutical agents
AssigneeSugen, Inc.
InventorsNarmada Shenoy, Gregory S. Wagner
Life of this patent
Estimating the term…
Abstract
The present invention features formulations, including liquid, semi-solid or solid pharmaceutical formulations, that improve the oral bioavailability of hydrophobic pharmaceutical agents, such as quinazoline-, nitrothiazole-, and indolinone-based compounds. Also featured are formulations for parenteral delivery of such hydrophobic pharmaceutical agents, as well as methods of making and using both types of formulations.
Claims61
A formulation comprising:
- (a) one or more hydrophobic pharmaceutical agents, wherein said agents are independently selected from the group consisting of quinazoline-, nitrothiazole-, and indolinone-based compounds;
- (b) one or more polyoxyhydrocarbyl compounds;
- and
- (c) one or more pharmaceutically acceptable surfactants.
The formulation of claim 11 wherein said hydrophobic pharmaceutical agent is a nitrothiazole-based compound of formula V, 24
- wherein R1 and R2 are independently selected from the group consisting of:
- (i) hydrogen;
- (ii) saturated or unsaturated alkyl;
- (iii) an aryl optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, nitro, and ester moieties;
- (iv) an amine of formula —NX2X3, wherein X2 and X3 are independently selected from the group consisting of hydrogen, saturated or unsaturated alkyl, and homocyclic or heterocyclic ring moieties;
- (v) halogen or trihalomethyl;
- (vi) a ketone of formula —CO—X4, wherein X4 is selected from the group consisting of alkyl and homocyclic or heterocyclic ring moieties;
- (vii) a carboxylic acid of formula —(X5)n—COOH or ester of formula —(X6)n—COO—X7, wherein X51 X6, and X7 and are independently selected from the group consisting of alkyl and homocyclic or heterocyclic ring moieties and wherein n is 0 or 1;
- (viii) an alcohol of formula (X8)n—OH or an alkoxy moiety of formula —(X8)n—O—X9, wherein X8 and X9 are independently selected from the group consisting of saturated or unsaturated alkyl and homocyclic or heterocyclic ring moieties, wherein said ring is optionally substituted with one or more substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, nitro, and ester and wherein n is 0 or 1;
- (ix) an amide of formula —NHCOX10, wherein X10 is selected from the group consisting of alkyl, hydroxyl, and homocyclic or heterocyclic ring moieties, wherein said ring is optionally substituted with one or more substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, nitro, and ester;
- (x) —SO2NX11X12, wherein X11 and X12 are selected from the group consisting of hydrogen, alkyl, and homocyclic or heterocyclic ring moieties;
- (xi) a homocyclic or heterocyclic ring moiety optionally substituted with one, two, or three substituents independently selected from the group consisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate, nitro, and ester moieties;
- (xii) an aldehyde of formula —CO—(xiii) a sulfone of formula —SO2—X13, wherein X13 is selected from the group consisting of saturated or unsaturated alkyl and homocyclic or heterocyclic ring moieties;
- and
- (xiv) a nitro of formula —NO2.
A formulation comprising:
- (a) one or more hydrophobic pharmaceutical agents, wherein said agents are independently selected from the group consisting of quinazoline-, nitrothiazole-, and indolinone-based compounds;
- (b) one or more polyoxyhydrocarbyl compounds;
- (c) one or more polyglycolized lipids;
- and
- (d) one or more pharmaceutically acceptable surfactants.
A method of testing the solubility of a hydrophobic pharmaceutical agent in a parenteral formulation comprising one or more hydrophobic pharmaceutical agents, wherein said agents are independently selected from the group consisting of a quinazoline-, a nitrothiazole-, and an indolinone-based compound;
- one or more polyoxyhydrocarbyl compounds;
- and one or more pharmaceutically acceptable surfactants, wherein said method comprises the following steps:
- (a) interacting said formulation with a hydrophobic support in a first solvent;
- (b) eluting said hydrophobic pharmaceutical agent from said support with a second solvent;
- and
- (c) comparing the amount of said hydrophobic pharmaceutical agent that elutes from said support to the amount that was added to said formulation.
A method of testing the solubility of hydrophobic pharmaceutical agents in an oral formulation comprising one or more hydrophobic pharmaceutical agents, wherein said agents are independently selected from the group consisting of a quinazoline-, a nitrothiazole-, and an indolinone-based compound;
- one or more polyoxyhydrocarbyl compounds;
- one or more polyglycolized lipids;
- and one or more pharmaceutically acceptable surfactants, wherein said method comprises the following steps:
- (a) interacting said formulation with a hydrophobic support in a first solvent;
- (b) eluting said hydrophobic pharmaceutical agent from said support with a second solvent;
- and
- (c) comparing the amount of said hydrophobic pharmaceutical agent that elutes from said support to the amount that was added to said formulation.
A method of preparing a parenteral formulation comprising the following steps:
- (a) dissolving one or more hydrophobic pharmaceutical agents into one or more polyoxyhydrocarbyl compounds to form a solution, wherein said agents are independently selected from the group consisting of a quinazoline-, a nitrothiazole-, and an indolinone-based compound;
- and
- (b) dissolving one or more surfactants into said solution.
A method of preparing an oral formulation comprising the following steps:
- (a) melting one or more polyglycolyzed lipids;
- (b) dissolving one or more polyoxyhydrocarbyl compounds and one or more surfactants, into said melted polyglycolyzed lipid;
- and
- (c) dissolving one or more hydrophobic pharmaceutical agents, wherein said agents are independently selected from the group consisting of:
- a quinazoline-, a nitrothiazole-, and an indolinone-based compound;
- into the solution.
A method of preventing or treating an abnormal condition in a patient in need of treatment comprising the following steps:
- (a) diluting a parenteral formulation into a pharmaceutically acceptable solution, said parenteral formulation comprising one or more hydrophobic pharmaceutical agents, wherein said agents are independently selected from the group consisting of a quinazoline-, a nitrothiazole-, and an indolinone-based compound;
- one or more polyoxyhydrocarbyl compounds;
- and one or more pharmaceutically acceptable surfactants;
- and
- (b) parenterally administering the diluted formulation to the patient.
A method of preventing or treating an abnormal condition in a patient in need of treatment comprising the following steps:
- (a) preparing a pharmaceutically acceptable oral formulation comprising:
- one or more hydrophobic pharmaceutical agents, wherein said agents are independently selected from the group consisting of a quinazoline-, a nitrothiazole-, and an indolinone-based compound;
- one or more polyoxyhydrocarbyl compounds;
- one or more polyglycolized lipids;
- and one or more pharmaceutically acceptable surfactants;
- and
- (b) orally administering said formulation to said patient.
Dependencies are inferred from the claim text.