Dried Formulations of Nanoparticle-Coated Capsules

Abstract

A method of producing a dried formulation for an active substance such as a drug compound is described. The method involves dispersing a discontinuous phase (e.g. an oil-based or lipidic medium) comprising the active substance into a continuous phase (e.g. water) so as to form a two-phase liquid system comprising droplets of said discontinuous phase, allowing nanoparticles to congregate at the phase interface at the surface of the droplets such that at least one layer of nanoparticles coat the droplets and thereby provide sufficient structural integrity to the droplets to enable the subsequent removal of the continuous phase, and thereafter removing the continuous phase from the nanoparticle-coated droplets to produce a dried formulation.

1 . A method of producing a dried formulation for an active substance, said method comprising the steps of:
 (i) dispersing a discontinuous phase comprising an active substance into a continuous phase so as to form a two-phase liquid system comprising droplets of said discontinuous phase, each of said droplets having, at its surface, a phase interface;   (ii) allowing nanoparticles provided to said two-phase liquid system to congregate at the phase interface to coat said surface of the droplets in at least one layer of said nanoparticles, wherein said at least one layer of nanoparticles provides sufficient structural integrity to the droplets to enable the subsequent removal of the continuous phase; and   (iii) removing the continuous phase from the nanoparticle-coated droplets to produce a dried formulation.   
     
     
         2 . A method of producing a dried formulation for an active substance, said method comprising the steps of:
 (i) dispersing a discontinuous phase comprising an active substance into a continuous phase so as to form a two-phase liquid system comprising droplets of said discontinuous phase, each of said droplets having, at its surface, a phase interface; and   (ii) removing the continuous phase to produce a dried formulation, during which nanoparticles provided to said two-phase liquid system congregate at the phase interface to coat said surface of the droplets in at least one layer of said nanoparticles, wherein said at least one layer of nanoparticles provides sufficient structural integrity to the droplets to withstand the removal of the continuous phase.   
     
     
         3 . The method of  claim 1 , wherein the discontinuous phase is an oil-based or lipidic medium and the continuous phase is aqueous. 
     
     
         4 . The method of  claim 1 , wherein the discontinuous phase is aqueous and each droplet is surrounded by a single or multiple lipid bilayer, and the continuous phase is also aqueous. 
     
     
         5 . The method of  claim 3 , wherein either or both of the discontinuous and continuous phases comprises an emulsifier to stabilise the emulsion prior to the congregation of the nanoparticles. 
     
     
         6 . The method of  claim 5 , wherein the emulsifier is lecithin or oleylamine. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the active substance is selected from nutriceutical substances, cosmetic substances and drug compounds. 
     
     
         9 . The method of  claim 8 , wherein the active substance is selected from lipophilic drug compounds and the discontinuous phase is an oil-based or lipidic medium. 
     
     
         10 . The method of  claim 3 , wherein the nanoparticles are provided by dispersing the nanoparticles in the discontinuous phase prior to the formation of the two-phase liquid system in step (i). 
     
     
         11 . The method of  claim 3 , wherein the nanoparticles are provided by dispersing the nanoparticles in both the discontinuous phase and the continuous phase prior to the formation of the two-phase liquid system in step (i). 
     
     
         12 . The method of  claim 3 , wherein the nanoparticles are provided in an amount such that the mass ratio of the discontinuous phase to nanoparticles is at least 1:0.05. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The method of  claim 1 , wherein the nanoparticles have hydrophilic surfaces. 
     
     
         16 . The method of  claim 1 , wherein the droplets are coated with an inner and outer layer of nanoparticles, the nanoparticles of the inner layer having hydrophobic surfaces and the nanoparticles of the outer layer having hydrophilic surfaces. 
     
     
         17 . The method of  claim 15 , wherein the nanoparticles having hydrophilic surfaces are silica nanoparticles. 
     
     
         18 . The method of  claim 1 , wherein said nanoparticles have an average diameter in the range of 20-80 nm. 
     
     
         19 . The method of  claim 18 , wherein said nanoparticles have an average diameter of about 50 nm. 
     
     
         20 . The method of  claim 1 , wherein the size of said nanoparticles is such that the ratio of nanoparticle size to the size of the nanoparticle-coated droplets is about 1:10. 
     
     
         21 . The method of  claim 1 , wherein step (ii) is conducted in the presence of an amount of electrolyte in the range of 0.5×10 −4  to 1×10 −1  M. 
     
     
         22 . The method of  claim 21 , wherein the electrolyte is NaCl. 
     
     
         23 . The method of  claim 1 , wherein step (iii) is performed by spray drying. 
     
     
         24 . The method of  claim 1 , wherein the nanoparticle-coated droplets of the dried formulation can be readily re-dispersed to form a two-phase liquid system which is substantially identical or similar in composition to that from which the dried formulation was prepared after storage at room temperature for 24 hours. 
     
     
         25 - 26 . (canceled) 
     
     
         27 . A method of producing a dried formulation for an active substance, said method comprising the steps of:
 (i) dispersing an oil-based medium comprising an active substance into an aqueous phase so as to form a two-phase liquid system comprising droplets of said oil-based medium, each of said droplets having, at its surface, a phase interface;   (ii) allowing nanoparticles provided to said two-phase liquid system to congregate at the phase interface to coat said surface of the droplets in at least one layer of said nanoparticles, wherein said at least one layer of nanoparticles provides sufficient structural integrity to the droplets to enable the subsequent removal of the continuous phase, and wherein the average diameter of the nanoparticles is in the range of 20-80 nm, and the nanoparticles are provided at a mass ratio of the discontinuous phase to nanoparticles of at least 1:0.05; and   (iii) removing the continuous phase from the nanoparticle-coated droplets to produce a dried formulation.   
     
     
         28 . The method of  claim 27 , wherein either or both of the discontinuous and continuous phases comprises an emulsifier to stabilise the emulsion prior to the congregation of the nanoparticles. 
     
     
         29 . The method of  claim 27 , wherein the emulsifier is lecithin or oleylamine. 
     
     
         30 . (canceled) 
     
     
         31 . The method of  claim 27 , wherein the active substance is selected from nutriceutical substances, cosmetic substances and drug compounds. 
     
     
         32 . The method of  claim 31 , wherein the active substance is selected from lipophilic drug compounds. 
     
     
         33 . The method of  claim 27 , wherein the nanoparticles are provided by dispersing the nanoparticles in the discontinuous phase prior to the formation of the two-phase liquid system in step (i). 
     
     
         34 . The method of  claim 27 , wherein the nanoparticles are provided by dispersing the nanoparticles in both the discontinuous phase and the continuous phase prior to the formation of the two-phase liquid system in step (i). 
     
     
         35 - 36 . (canceled) 
     
     
         37 . The method of  claim 27 , wherein the nanoparticles have hydrophilic surfaces. 
     
     
         38 . The method of  claim 27 , wherein the droplets are coated with an inner and outer layer of nanoparticles, the nanoparticles of the inner layer having hydrophobic surfaces and the nanoparticles of the outer layer having hydrophilic surfaces. 
     
     
         39 . The method of  37 , wherein the nanoparticles having hydrophilic surfaces are silica nanoparticles. 
     
     
         40 . The method of  claim 27 , wherein said nanoparticles have an average diameter of about 50 nm. 
     
     
         41 . The method of  claim 27 , wherein the size of said nanoparticles is such that the ratio of nanoparticle size to the size of the nanoparticle-coated droplets is about 1:10. 
     
     
         42 . The method of  claim 27 , wherein step (ii) is conducted in the presence of an amount of electrolyte in the range of 0.5×10 −4  to 1×10 −1  M. 
     
     
         43 . The method of  claim 42 , wherein the electrolyte is NaCl. 
     
     
         44 . The method of  claim 43 , wherein step (ii) is conducted in the presence of about 1×10 −4  NaCl. 
     
     
         45 . The method of  claim 27 , wherein step (iii) is performed by spray drying. 
     
     
         46 . The method of  claim 27 , wherein the nanoparticle-coated droplets of the dried formulation can be readily re-dispersed to form a two-phase liquid system which is substantially identical or similar in composition to that from which the dried formulation was prepared, after storage at room temperature for 24 hours. 
     
     
         47 - 48 . (canceled) 
     
     
         49 . A dried formulation produced in accordance with  claim 1 . 
     
     
         50 . (canceled) 
     
     
         51 . The formulation of  claim 49 , wherein the discontinuous phase is an oil-based or lipidic medium and the continuous phase is aqueous. 
     
     
         52 . The formulation of  claim 49 , wherein the discontinuous phase is aqueous and each droplet is surrounded by a single or multiple lipid bilayer underlying the at least one layer of nanoparticles, and the continuous phase is also aqueous. 
     
     
         53 . The formulation of  claim 51 , wherein either or both of the discontinuous and continuous phases comprises an emulsifier. 
     
     
         54 . The formulation of  claim 53 , wherein the emulsifier is lecithin or oleylamine. 
     
     
         55 . (canceled) 
     
     
         56 . The formulation of  claim 49  wherein the active substance is selected from nutriceutical substances, cosmetic substances and drug compounds. 
     
     
         57 . The formulation of  claim 56 , wherein the active substance is selected from lipophilic drug compounds and the discontinuous phase is an oil-based or lipidic medium. 
     
     
         58 . The formulation of  claim 49 , wherein the nanoparticles have hydrophilic surfaces. 
     
     
         59 . The formulation of  claim 49 , wherein the droplets are coated with an inner and outer layer of nanoparticles, the nanoparticles of the inner layer having hydrophobic surfaces and the nanoparticles of the outer layer having hydrophilic surfaces. 
     
     
         60 . The formulation of  claim 58 , wherein the nanoparticles having hydrophilic surfaces are silica nanoparticles. 
     
     
         61 . The formulation of  claim 49 , wherein said nanoparticles have an average diameter in the range of 20-80 nm. 
     
     
         62 . The formulation of  claim 61 , wherein said nanoparticles have an average diameter of about 50 nm. 
     
     
         63 . The formulation of  claim 49 , wherein the size of said nanoparticles is such that the ratio of nanoparticle size to the size of the nanoparticle-coated droplets is about 1:1. 
     
     
         64 . The formulation of  claim 49 , wherein the nanoparticle-coated droplets can be readily re-dispersed to form a two-phase liquid system which is substantially identical or similar in composition to that from which the formulation was prepared, after storage at room temperature for 24 hours. 
     
     
         65 - 84 . (canceled)