Manufacturing Articles

Abstract: The feasibility of using dense gas techniques such as rapid expansion of supercritical solutions (RESS) and aerosol solvent extraction system (ASES) for micronization of pharmaceutical compounds is demonstrated. The chiral nonsteroidal anti-inflammatory racemic ibuprofen is soluble in carbon dioxide at 35°C and pressures above 90 bar. The particle size decreased to less than 2 µm while the degree of crystallinity was slightly decreased when processed by RESS. The dissolution rate of the ibuprofen (a poorly water-soluble compound) was significantly enhanced after processing by RESS. The nonsteroidal anti-inflammatory drug Cu2(indomethacin)4L2(Cu-Indo); (L = dimethylformamide [DMF]), which possessed very low solubility in supercritical CO2, was successfully micronized by ASES at 25°C and 68.9 bar using DMF as the solvent and CO2 as the antisolvent. The concentration of solute dramatically influenced the precipitate characteristics.

In the manufacture of many pharmaceutical products, dry-particle blending is a critical step that directly affects content uniformity. Tumbling blenders—a common way to mix granular constituents—are hollow containers attached to a rotating shaft; the vessel is partially loaded with materials and rotated. Their main advantages are large capacities, low-shear stresses, flexibility, containment, and easy cleaning. The blenders come in a variety of geometries and sizes (ranging from a minimum of ,16 qt to a maximum .500 ft3). The convective blender is another common mixer, in which flow is created by impellers rotating within a fixed shell. The blender can impart high shear, reduce ingredient segregation, and be used for wet granulation.

Process scale-up is an increase in batch size or production capacity, usually in response to increased product demand, concerns about high production costs, or an increased need for clinical research supplies. Conversely, scale-down is a decrease in batch size or productivity.

These problems include but are not limited to dissimilar processing equipment between one scale and another; various requirements for process control at different production scales; insufficient data about equipment performance at different production scales; the complexity of pharmaceutical processing, which may involve several very different unit operations and equipment; and variations in macroscopic and microscopic properties of formulation components and products at different production scales. Additional usually in response to decreased product demand. Pharmaceutical manufacturing scales range from the laboratory to the pilot plant to full production.