Solid Compositions Comprising a Glucokinase Activator and Methods of Making and Using the Same
The invention relates to solid compositions comprising {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid, and methods of making and using such solid compositions.
1 . A solid composition comprising wet granulated particles which comprise {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid, a binder, and a water-soluble surfactant,
wherein the binder comprises polyvinylpyrrolidone.
2 . The solid composition of claim 1 , wherein at least 80% by weight of the wet granulated particles have a particle size that is between 1 μm and 1 mm.
3 . The solid composition of claim 1 , wherein at least 80% by weight of the wet granulated particles have a particle size that is between 1 μm and 500 μm.
4 . The solid composition of claim 1 , wherein at least 90% of the particles of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid used in the wet granulation process have a particle size between 0.1 μm and 10 μm.
5 . The solid composition of claim 4 , wherein at least 85% of the particles of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid used in the wet granulation process have a particle size between 0.4 μm and 6 μm.
6 . The solid composition of claim 1 , wherein the water-soluble surfactant is a sulfuric acid alkyl ester salt, a bile acid salt, a propylene glycol fatty acid mono- or diester, a polyethylene glycol fatty acid ester, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene-polyoxypropylene copolymer or block copolymer surfactant, a polyoxyethylene derivative of a tocopherol or a tocotrienol, a polyoxyethylene derivative of a natural oil or wax, a sorbitan fatty acid ester, or a mixture thereof.
7 . The solid composition of claim 1 , wherein the water-soluble surfactant is a sulfuric acid alkyl ester salt, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene derivative of a tocopherol or a tocotrienol, or a mixture thereof.
8 . The solid composition of claim 1 , wherein the water-soluble surfactant comprises sodium lauryl sulfate, polysorbate 80, d-alpha-tocopheryl polyethylene glycol succinate, or a mixture thereof.
9 . The solid composition of claim 1 , wherein the weight/weight ratio of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid to the water-soluble surfactant in the solid composition ranges from 10:1 to 100:1.
10 . The solid composition of claim 9 , wherein the weight/weight ratio of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid to the water-soluble surfactant in the solid composition ranges from 15:1 to 60:1.
11 . The solid composition of claim 10 , wherein the weight/weight ratio of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid to the water-soluble surfactant in the solid composition ranges from 22:1 to 40:1.
12 . The solid composition of claim 1 , wherein the weight/weight ratio of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid to the binder ranges from 25:1 to 400:1.
13 . The solid composition of claim 12 , wherein the weight/weight ratio of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid to the binder ranges from 50:1 to 250:1.
14 . The solid composition of claim 13 , wherein the weight/weight ratio of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid to the binder ranges from 75:1 to 150:1.
15 . The solid composition of claim 1 , wherein the solid composition is in the form of a powder, a capsule, or a tablet.
16 . A method of making wet granulated particles comprising:
a) mixing {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid, a binder, and a water-soluble surfactant in the presence of a solvent to form a solution or suspension,
wherein the binder comprises polyvinylpyrrolidone,
and
b) removing the solvent from the solution or suspension to form a powder.
17 . The method of claim 16 , wherein at least 90% of the particles of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid used in the wet granulation process have a particle size between 0.1 μm and 10 μm.
18 . The method of claim 16 , wherein at least 85% of the particles of {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid used in the wet granulation process have a particle size between 0.4 μm and 6 μm.
19 . The method of claim 16 , wherein the removing step comprises either air drying the solution or comprises fluid-bed drying the solution.
20 . The method of claim 16 , further comprising the step of sizing the powder such that at least 80% by weight of the powder has a particle size that is between 1 μm and 1 mm.
21 . The method of claim 16 , further comprising the step of sizing the powder such that at least 80% by weight of the powder has a particle size that is between 1 μm and 500 μm.
22 . The method of claim 16 , further comprising the step of:
c) forming the powder into a tablet, encapsulating the powder, or packaging the powder into a sachet.
23 . A method of treating type 2 diabetes in a human, of treating of type 1 diabetes in a human, of lowering blood glucose concentrations in a human, of activating glucokinase in a human, or of increasing hepatic glucose use in a human, wherein the method comprises administering a solid composition of claim 1 to a human in need thereof.