Process of forming and modifying particles and compositions produced thereby - Patents

Process of forming and modifying particles and compositions produced thereby

Agent: Finnegan, Henderson, Farabow, Garrett & Dunner LLP - Washington, DC, US
Inventors: James D Talton, Christopher McConville
Class: 424489000 (USPTO), A61K009/14 (Intl Class)
#20050175707
08/11/05

The present invention relates to processes for forming particles including drugs in a solution, changing the bulk or surface properties of a drug particle, and/or microencapsulation drug particles, and compositions produced thereby. In some embodiments, the process described utilized mechanical agitation, more specifically low-frequency sonication, under controlled conditions, which provides mild shear forces during forming and/or precipitation to control the particle growth and mixing properties. Particle size can range from less than about 200 nanometers to greater than about one millimeter, depending on the processing conditions and application. The process described can be used to form a drug particle suspension, dry a wet powder slurry or suspension, as well as to improve the surface properties of the particle through conditioning the structure of the particle or particle surface and/or annealing the particle or particle surface. Annealing or conditioning drug particles may be used to force an amorphous to crystalline transition, creating a more stable powder, or smooth a particle surface. In addition, the process can be used to microencapsulate particles by suspending the microparticles in a non-solvent including a coating material (such as a biodegradable polymer) under controlled process conditions. The powder compositions produced thereby possess improved properties including, but not limited to, improved flow and dispersibility, controlled bioadhesion, stability, resistance to moisture, dissolution/release profiles, and/or bioavailabilities. This process, and the compositions produced, provide significant advantages in the manufacture of pharmaceutical particulate formulations, as well as biomedical, diagnostic, and chromatography particulate compositions, where sensitive macromolecules, such as proteins or DNA, are involved that would be degraded using more rigorous processing conditions or temperatures.
SUMMARY OF THE INVENTION
[0015] A. Features and Advantages of the Invention
[0016] The present invention overcomes these and other inherent deficiencies in existing methods by providing novel particle forming methods for use in preparing improved pharmaceutical products. The described processes involve forming particles, which may include drugs, in a solution, changing the bulk or surface properties of a particle, and/or microencapsulating particles, and compositions produced thereby. The process utilizes mechanical agitation, more specifically low-frequency sonication, under controlled conditions, which provide mild shear forces during precipitation to control the particle growth and mixing properties. Particle size control from <200 nanometers to greater than one millimeter is shown, which has not been described using other known systems. Drug particles may be (1) formed in a solution to obtain a particle suspension and then collected, (2) dried a wet powder slurry or suspension, and/or (3) sonicated dry to anneal/condition the structure of the particle or particle surface. In addition, the process can be used to microencapsulate particles by suspending the drug particles in a solution including a coating material (such as a biodegradable polymer) and evaporating the solution under controlled process conditions. The drug particle compositions produced thereby possess improved properties including, but not limited to, improved flow and dispersibility, controlled bioadhesion, stability, resistance to moisture, dissolution/release profiles, and/or bioavailabilities. This process, and the compositions produced, provide significant advantages in the manufacture of pharmaceutical particulate formulations, as well as biomedical, diagnostic, and chromatography particulate compositions, where sensitive macromolecules, such as proteins or DNA, are involved that would be degraded using more rigorous processing conditions or temperatures. The processes are not limited to those for making drug particles, and they may be extended to processes for making particles that do not include drugs.
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