Particulate composition

Abstract

Nanoparticles are prepared from a colloidal system comprising a continuous phase and micelles, the micelles comprising surfactant material. A microemulsion is formed by admixing the colloidal system with a solution of an active material, such as a medicament, dissolved in a solvent wherein the solution forms a disperse phase with the micelles of surfactant material. At least the dispersed phase is quenched to a solid state and the continuous phase and solvent are removed to produce the nanoparticles. The nanoparticles can be incorporated in an aerosol composition suitable for deep lung delivery by means of a metered dose inhaler.

1 . A particulate composition comprising particles wherein the particles: 
 (a) include a medicament and, with respect to the total weight of the particles, from about 2 to about 90 wt % of a surfactant material;    (b) have an average diameter of more than about 1 nm and less than about 1000 nm;    (c) are spheroidal or spherical in shape; and    (d) contain no cross-linked polymer formed from a monomer or preformed polymer with a cross-linking agent and initiator.    
   
   
       2 . The particulate composition according to  claim 1  wherein the particles comprise a core material including the medicament and a coating on the core material comprising the surfactant material.  
   
   
       3 . The particulate composition according to  claim 2  wherein the core material is hydrophilic.  
   
   
       4 . The particulate composition according to  claim 2  wherein the core material is hydrophobic.  
   
   
       5 . The particulate composition according to  claim 1  wherein the particles have an average diameter from about 10 nm to about 800 nm.  
   
   
       6 . The particulate composition according to  claim 1  wherein the particles comprise, with respect to the total weight of the particles, up to about 60 wt % surfactant material.  
   
   
       7 . The particulate composition according to  claim 1  wherein the surfactant material is selected from the group consisting of emulsifiers, ionic surfactants, nonionic surfactants, zwitterionic surfactants, amphoteric surfactants and mixtures thereof.  
   
   
       8 . The particulate composition according to  claim 1  wherein the surfactant material is selected from the group consisting of phospholipids, sorbitan esters, poloxamers, polyoxyethylene sorbitan esters, polyoxyethylene esters, bile salts, sodium bis (2-ethylhexyl) sulphosuccinate and mixtures thereof.  
   
   
       9 . The particulate composition according to  claim 1  wherein the medicament is selected from the group consisting of salbutanol, salbutanol sulphate, terbutaline, terbutaline sulphate, ipratropium bromide or any physiologically acceptable salts or solvates thereof; beclomethasone dipropionate, budesonide, triamcinolone acetonide or any physiologically acceptable solvates thereof; corticosteroid, bronchodilator; peptides, proteins, nucleic acids or derivatives thereof; insulin, calcitonin growth hormone, lutenising hormone releasing hormone, leuprolide, oxytocin or any physiologically acceptable salts or solvates thereof; or any mixture thereof.  
   
   
       10 . The particulate composition according to  claim 1  wherein the particles further comprise a polymeric material having a molecular weight between 250 and 10×10 6  daltons, wherein said polymeric material contains no cross-linked polymer formed from a monomer or preformed polymer with a cross-linking agent and initiator.  
   
   
       11 . The particulate composition according to  claim 10  wherein the weight ratio of medicament to polymeric material is from about 99:1 to about 1:99.  
   
   
       12 . The particulate composition according to  claim 1  wherein the particles further comprise a sugar.  
   
   
       13 . The particulate composition according to  claim 12  wherein the weight ratio of active material to sugar is from about 99:1 to 1:99.  
   
   
       14 . The particulate composition according to  claim 1  wherein the particles further comprise a cationic lipid.  
   
   
       15 . The particulate composition according to  claim 1  wherein the particles further comprise a nucleic acid precondensed with a polycationic peptide.  
   
   
       16 . An aerosol composition comprising the particulate composition of  claim 1  and a liquid aerosol propellant.  
   
   
       17 . The aerosol composition according to  claim 16  wherein the liquid propellant is selected from the group consisting of hydrocarbons, hydrochlorocarbons, chlorocarbons, hydrochlorofluorocarbons, chlorofluorocarbons, hydrofluorocarbons, fluorocarbons and mixtures thereof.  
   
   
       18 . The aerosol composition according to  claim 17  wherein the liquid propellant is a hydrofluorocarbon selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane and mixtures thereof.  
   
   
       19 . The aerosol composition according to  claim 16  wherein the weight ratio of propellant to particulate composition is from about 10,000:1 to about 25:1.  
   
   
       20 . The aerosol composition according to  claim 16  in the form of a metered dose inhaler.  
   
   
       21 . The aerosol composition according to  claim 16  in a form suitable for oral inhalation, nasal administration or ocular administration.  
   
   
       22 . The aerosol composition according to  claim 16  for use in the administration of a medicament to the lung of a patient in need thereof.  
   
   
       23 . The aerosol composition according to  claim 22  for use in the treatment of respiratory disease.  
   
   
       24 . The aerosol composition according to  claim 22  wherein the medicament is absorbed systemically by the patient.  
   
   
       25 . A metered dose inhaler comprising an aerosol composition according to claim  36 .  
   
   
       26 . A method for treating a respiratory disorder in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of the particulate composition of  claim 1 .  
   
   
       27 . A method of administering a particulate composition to a patient in need thereof comprising spraying the aerosol composition of  claim 16  on to or towards the area intended to receive the particulate composition.  
   
   
       28 . A method according to  claim 27  further comprising the patient inhaling the aerosol.