Process for enhancing the solubility of poorly soluble drugs

A continuous process for enhancing the dissolution rate/solubility of a poorly soluble drug comprising the steps of:

• (a) providing a twin-screw grinder/mixer containing temperature control means and the following zones in sequential communication with one another:
• (i) a feed zone containing a first liquid and powder feed stations;
• (ii) a grinding/mixing zone containing a second liquid feed port located at an upstream portion of such zone;
• or a second continuous granulator placed in series;
• (iii) a granulation zone containing a second powder feed station located at an upstream portion of such zone and a third liquid feed port located at a downstream portion of such zone;
• and (iv) a wet milling zone;
• (b) feeding into the first powder feed station a powder comprising the drug and 0 to about 1000 parts, per 100 parts of the drug, of one or more first excipients selected from the group consisting of solubilizing agents, complexing agents, buffers, polymers, plasticizers, surfactants, self-emulsifiers, hydrophilic waxes, fatty acids, fatty alcohols and mixtures thereof;
• (c) injecting into the first and second liquid ports 0 to about 1000 parts, per 100 parts of the powder fed into the first powder station in step (b), of a pharmaceutically acceptable liquid containing 0 to about 1000 parts, per 100 parts of the drug of one or more second excipients selected from the group consisting of solubilizing agents, complexing agents, buffers, polymers, plasticizers, surfactants, self-emulsifiers and mixtures thereof;
• (d) grinding/mixing in the grinding/mixing zone the drug and any first excipients employed in step (b) and any liquid employed in step (c) at a temperature of about 20° to less than about 100° C.;
• (e) conveying the material resulting from step (d) to the granulation zone;
• (f) feeding into the second powder station one or more third excipients selected from the group consisting of fillers, glidants, lubricants, absorbents, enteric coating agents, anti-caking agents, anti-oxidants, anti-adherents, disintegrants, flavorants, stabilizers, colorants, preservatives, carrier materials, and mixtures thereof;
• (g) injecting into the third liquid port a binder solution in the amount of 0 to about 1000 parts per 100 parts of the material conveyed into the granulation zone;
• (h) granulating the material and any binder solution present in the granulation zone;
• (i) conveying the granulated material resulting from step (h) into the wet milling zone and wet milling the granulated material in such zone;
• (j) discharging the granulated material resulting from step (h);
• and
• (k) drying the discharged granulated material.