A process for the production of glycolic acid or a derivative thereof comprises: reacting formaldehyde with carbon monoxide and water in a carbonylation reactor in the presence of a sulfur catalyst, said reactor operating under suitable conditions, such that glycolic acid is formed; recovering a first product stream comprising glycolic acid, impurities and a sulfur species in the carbonylation reactor; passing the first product stream to an esterification reactor where it is subjected to esterification to form an alkylglycolate and wherein the esterification is catalysed by the sulfur species recovered in the first product stream; recovering a second product stream comprising the alkylglycolate, sulfur species and impurities from the esterification reactor; separating the sulfur species from the second product stream and recycling it to the carbonylation reactor in step (a) to form a sulphur depleted second product stream; separating the alkylglycolate from the sulphur depleted second product stream in a distillation zone; and recovering the alkylglycolate and converting the alkylglycolate to glycolic acid.

Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

Core-shell particles and methods of making and using thereof are described herein. The core is formed of or contains one or more hydrophobic materials or more hydrophobic materials. The shell is formed of or contains hyperbranched polyglycerol (HPG). The HPG coating can be modified to adjust the properties of the particles. Unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption and increase circulation in the blood. The hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups and adhere the particles to tissue, cells, or extracellular materials, such as proteins.

A process for the production of glycolic acid or a derivative thereof comprises: reacting formaldehyde with carbon monoxide and water in a carbonylation reactor in the presence of a sulfurcatalyst, said reactor operating under suitable conditions, such that glycolic acid is formed; recovering a first product stream comprising glycolic acid, impurities and a sulfur species in the carbonylation reactor; passing the first product stream to an esterification reactor where it is subjected to esterification to form an alkylglycolate and wherein the esterification is catalysed by the sulfur species recovered in the first product stream; recovering a second product stream comprising the alkylglycolate, sulfur species and impurities from the esterification reactor; separating the sulfur species from the second product stream and recycling it to the carbonylation reactor in step (a) to form a sulphur depleted second product stream; separating the alkylglycolate from the sulphur depleted second product stream in a distillation zone; and recovering the alkylglycolate and converting the alkylglycolate to glycolic acid.

A process for the production of glycolic acid or a derivative thereof comprises: reacting formaldehyde with carbon monoxide and water in a carbonylation reactor in the presence of a sulfurcatalyst, said reactor operating under suitable conditions, such that glycolic acid is formed; recovering a first product stream comprising glycolic acid, impurities and a sulfur species in the carbonylation reactor; passing the first product stream to an esterification reactor where it is subjected to esterification to form an alkylglycolate and wherein the esterification is catalysed by the sulfur species recovered in the first product stream; recovering a second product stream comprising the alkylglycolate, sulfur species and impurities from the esterification reactor; separating the sulfur species from the second product stream and recycling it to the carbonylation reactor in step (a) to form a sulphur depleted second product stream; separating the alkylglycolate from the sulphur depleted second product stream in a distillation zone; and recovering the alkylglycolate and converting the alkylglycolate to glycolic acid.

A process for the production of glycolic acid or a derivative thereof comprises: reacting formaldehyde with carbon monoxide and water in a carbonylation reactor in the presence of a sulfurcatalyst, said reactor operating under suitable conditions, such that glycolic acid is formed; recovering a first product stream comprising glycolic acid, impurities and a sulfur species in the carbonylation reactor; passing the first product stream to an esterification reactor where it is subjected to esterification to form an alkylglycolate and wherein the esterification is catalysed by the sulfur species recovered in the first product stream; recovering a second product stream comprising the alkylglycolate, sulfur species and impurities from the esterification reactor; separating the sulfur species from the second product stream and recycling it to the carbonylation reactor in step (a) to form a sulphur depleted second product stream; separating the alkylglycolate from the sulphur depleted second product stream in a distillation zone; and recovering the alkylglycolate and converting the alkylglycolate to glycolic acid.

Crystalline forms of 5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide (Compound I) were prepared and characterized in the solid state:

##STR00001##

Also provided are processes of manufacture and methods of using the crystalline forms.

Crystalline forms of 5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide (Compound I) were prepared and characterized in the solid state:

##STR00001##

Also provided are processes of manufacture and methods of using the crystalline forms.

Core-shell particles have a hydrophobic core and a shell formed of or containing hyperbranched polyglycerol (HPG). The HPG can be covalently bound to the one or more materials that form the core or coated thereon. The HPG coating can be modified to adjust the properties of the particles. For example, unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption. Alternatively, the hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups on tissue or otherwise interact with tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins. Such functional groups include, but not limited to, aldehydes, amines, and O-substituted oximes. Topical formulation for application to the skin contain these HPG coated nanoparticles. In some embodiments, the particles include therapeutic, diagnostic, nutraceutical, and/or prophylactic agents such as those used as sunblock compositions.

Core-shell particles have a hydrophobic core and a shell formed of or containing hyperbranched polyglycerol (HPG). The HPG can be covalently bound to the one or more materials that form the core or coated thereon. The HPG coating can be modified to adjust the properties of the particles. For example, unmodified HPG coatings impart stealth properties to the particles which resist non-specific protein absorption. Alternatively, the hydroxyl groups on the HPG coating can be chemically modified to form functional groups that react with functional groups on tissue or otherwise interact with tissue to adhere the particles to the tissue, cells, or extracellular materials, such as proteins. Such functional groups include, but not limited to, aldehydes, amines, and O-substituted oximes. Topical formulation for application to the skin contain these HPG coated nanoparticles. In some embodiments, the particles include therapeutic, diagnostic, nutraceutical, and/or prophylactic agents such as those used as sunblock compositions.