Nanodispersions

Abstract

The invention provides process for making contra-soluble nano-dispersions of at most sparingly-soluble materials in a soluble carrier material comprising the steps of: (i) providing a single phase mixture of: (a) a solvent or a mixture of miscible solvents wherein at least one of the solvents is an aqueous solvent and at least another solvent is a non-aqueous solvent, (b) at least one carrier material soluble in solvent (a), said carrier material being also contra-soluble to payload material (c) and solid at ambient temperature, (c) at least one a payload material which is soluble in solvent (a), and, (ii) freeze-drying the mixture to remove solvent (a) and thereby obtain the carrier material (b) in solid form with payload (c) dispersed therein as nanoparticles.

1 . A process for making contra-soluble nano-dispersions of at most sparingly-soluble materials in a soluble carrier material comprising the steps of:
 (i) providing a single phase mixture of:
 a) a solvent or a mixture of miscible solvents wherein at least one of the solvents is an aqueous solvent and at least another solvent is a non-aqueous solvent, 
 b) at least one carrier material soluble in solvent (a), said carrier material being also contra-soluble to payload material (c) and solid at ambient temperature, 
 c) at least one payload material which is soluble in solvent (a), and, 
   (ii) freeze-drying the mixture to remove solvent (a) and thereby obtain the carrier material (b) in solid form with payload (c) dispersed therein as nanoparticles.   
     
     
         2 . A process according to  claim 1  wherein the solvent (a) comprises one or more of dichloromethane, chloroform, methanol, ethanol, isopropanol, isobutanol, formic acid, acetic acid, formamide, N,N-dimethylformamide, aceto-nitrile, ethyl acetate, methyl ethyl ketone, acetone, tetrahydrofuran, and dialkylsulphoxide. 
     
     
         3 . A process according to  claim 1  wherein the carrier (b) comprises one or more of Polyethylene glycol (PEG), Polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), hydroxypropyl cellulose, hydroxypropyl methyl-cellulose (HPMC), alginate PEG/PPG alkoxylated non-ionic surfactant, PEG/alcohol non-ionic surfactant, aromatic non-ionic surfactant, alkyl sulphonate surfactant, ether-sulphate surfactants, ester surfactant and cationic surfactant. 
     
     
         4 . A process according to  claim 1  wherein the carrier (b) comprises:
 a) at least one of: polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), poly(2-ethyl-2-oxazaline), polyvinyl alcohol (PVA) hydroxypropyl cellulose and hydroxypropyl-methyl cellulose (HPMC), alginate, and, 
 b) at least one of: alkoxylated nonionic's, phenol-ethoxylates, alkyl sulphonates (preferably SDS), ether-sulphates (preferably SLES), ester surfactants, cationics (preferably cetyltrimethylammonium bromide—CTAB). 
 
     
     
         5 . A process according to  claim 1 , for making a nano-dispersion of a water insoluble material in a water-soluble carrier material comprising the steps of:
 (i) providing a mixture of:
 a) an aqueous solvent for a carrier material; 
 b) at least one water-soluble carrier material soluble in the mixture of aqueous solvent (a) and second solvent (c), said carrier material being solid at ambient temperature, 
 c) at least one non-aqueous second solvent said second solvent being miscible with aqueous solvent (a) to form a mixed solvent capable of dissolving carrier material (b) and payload (d), and; 
 d) a payload material which is dispersible or soluble in the mixture of aqueous solvent (a) and non-aqueous solvent (c) but not in aqueous solvent (a) alone, and; 
   (ii) freeze-drying the mixture to remove solvents (a) and (c) and thereby obtain the carrier material (b) in a solid form with payload (d) dispersed therein in a nanoparticulate form, wherein the product of the drying step is water dispersible to give an aqueous solution of (b) and an aqueous nano dispersion of (d).   
     
     
         6 . A process according to  claim 1 , for making water-soluble nano-dispersions of water insoluble materials in a water-soluble carrier material comprising the steps of:
 (i) providing a mixture of:
 a) water and a non-aqueous solvent or a mixture of miscible non-aqueous solvents, 
 b) at least one carrier material soluble in non-aqueous solvent (a), said carrier material being also soluble in water and solid at ambient temperature, 
 c) at least one water-insoluble payload material which is soluble in non-aqueous solvent (a), and, 
   (ii) freeze-drying the mixture to remove solvent (a) and thereby obtain the carrier material (b) in solid form with payload material (c) dispersed therein in a nanoparticulate form, wherein the product of the drying step is water dispersible to give an aqueous solution of (b) and an aqueous nano dispersion of (c).   
     
     
         7 . A process according to  claim 1  wherein the redispersed product of the drying step has a particle size of 2-500 nm (expressed as a diameter) when measured using a Malvern™ ‘Nano-S’ apparatus. 
     
     
         8 . A process according to  claim 1  wherein the payload material has a water solubility of below 5 g/L. 
     
     
         9 . A process according to  claim 1  wherein the feedstock to the drying step has a solids content of less than 5% wt.