Preparation of drug particles using evaporation precipitation into aqueous solutions
A method for preparing poorly water soluble drug particles is disclosed. The method comprises dissolving a drug in at least one organic solvent to form a drug/organic mixture, spraying the drug/organic mixture into an aqueous solution and concurrently evaporating the organic solvent in the presence of the aqueous solution to form an aqueous dispersion of the drug particles. The resulting drug particles are in the nanometer to micrometer size range and show enhanced dissolution rates and reduced crystallinity when compared to the unprocessed drug. The present invention additionally contemplates products and processes for new drug formulations of insoluble drug particles having high dissolution rates and extremely high drug-to-excipient ratios.
1. A method of producing poorly water soluble drug particles for release comprising the steps of:
providing a drug;
providing a container comprising aqueous solution;
spraying the drug and one or more excipients below the surface level of the aqueous solution wherein the one or more excipients selected from polyoxyethylene sorbitan monolaurate, phosphatidyl choline, a poly(ethylene)-poly(propylene) copolymer, sodium lauryl sulfate (SLS), Poly(vinyl pyrrolidone) (PVP), Poloxamer, polyoxyethylene monostearate, gelation agent, deoxycholic acid, poly(vinyl alcohol) (PVA), cetostearyl alcohol, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate, noncrystalline cellulose, magnesium aluminum silicate, and triethanolamine;
forming one or more stabilized drug particles by solution precipitation, anti-solvent precipitation, spray freezing, evaporative precipitation or lyophilization;
separating said one or more stabilized drug particles from a suspension solution;
removing said solution from the one or more stabilized drug particles; and
producing one or more stabilized drug particles having a drug-to-excipient ratio of greater than about 4:1 and an average particle diameter from 50 nanometers to about 20 microns; and
a dissolution rate greater than about 65% drug in about 60 minutes;
wherein the drug-to-excipient ratio is about 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1 or greater;
wherein the drug particles have a surface area greater than about 2.5 m 2 /g, 5 m 2 /g, 10 m 2 /g, 20 m 2 /g or 30 m 2 /g; and wherein the drug potency is about 80% or 100%.
2. The method of claim 1 , wherein the drug particles are separated by centrifugation, settling, or filtering.
3. The method of claim 1 , wherein the step of removing the solution from the resulting drug particles comprises lyophilization, vacuum dried, or spray drying, or spray drying.
4. The method of claim 1 , wherein the amount of drug dissolved is about 80%, 85%, 90%, 95% or 100%.
5. The method of claim 4 , wherein the dissolution occurs about 5, 7, 10, 15, 20, 25 or 30 times faster than the bulk drug.