Method for preparing suspensions of low-solubility materials

1. A process for producing a pharmaceutical suspension that comprises an active pharmaceutical ingredient (“API”) having low solubility, the process comprising:

(a) preparing a first solution comprising a carboxy-containing vinyl polymer and water, said first solution having an acidic pH;

(b) adjusting said pH of said first solution to, and maintaining said pH at, 6.5-6.7;

(c) adjusting a temperature of said first solution to, and maintaining said temperature at, 20-30° C.;

(d) adding a compound of the API to said first solution under conditions of high-shear mixing for a time from about 5 minutes to about 5 hours, said compound of the API being soluble in water, thereby producing a suspension of particles of said API in a composition comprising said carboxy-containing vinyl polymer;

(e) adjusting a pH of said suspension to, and maintaining said pH at, 6.5-6.7; and

(f) adjusting a temperature of said suspension to, and maintaining said temperature at, 20-30° C. to produce said pharmaceutical suspension;

wherein said API is a quinolone, said compound is added in amount sufficient to yield a concentration of said API in said suspension that is higher than a solubility of said API in water; said compound is a salt, a hydrate, or a solvate of said API; and said compound is added in step (d) as a neat, solid material.

2. The process of claim 1 , wherein the carboxy-containing vinyl polymer comprises a crosslinked polyacrylic add polymer.

3. The process of claim 1 , wherein the crosslinked polyacrylic add polymer comprises polycarbophil.

4. The process of claim 1 , wherein the carboxy-containing polymer is present at an amount of 0.01 to about 10 percent by weight of the final suspension.

5. The process of claim 1 , wherein the particles of said API in said suspension have a mean particle diameter in the range from about 1 to about 4 μm, and a D 90 in the range from about 3 to about 7 μm.

6. The process of claim 5 , wherein the suspension has a viscosity in the range from about 500 to about 3000 cp (or mPa·s).

7. The process of claim 1 , wherein the conditions of high-shear mixing are effected by a mixing implement at a rotational speed in the range from about 500 to about 2000 rpm.

8. The process of claim 7 , wherein the rotational speed is in the range from about 1000 to about 1600 rpm.

9. The process of claim 1 ; wherein the carboxy-containing polymer comprises a crosslinked polyacrylic acid polymer, the high-shear mixing conditions are effected by a mixing implement operating at about 500-2000 rpm, and the particles have a mean diameter in the range from about 1 to about 4 μm, and a D 90 in the range from about 3 to about 7 μm.