Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids

• Published in: Pharmaceutical research Vol. 25; no. 9; pp. 1967 - 1990
• Main Authors: Cape, Stephen P., Villa, Joseph A., Huang, Edward T. S., Yang, Tzung-Horng, Carpenter, John F., Sievers, Robert E.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2008; Springer; Springer Nature B.V
• Subjects: Aerosols; alpha 1-Antitrypsin - chemistry; Animals; Antibodies - chemistry; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Carbon Dioxide - chemistry; CD4 Antigens - immunology; Chemistry, Pharmaceutical; Chromatography, Supercritical Fluid - instrumentation; Drug Stability; Enzyme Stability; Expert Review; General pharmacology; Humans; Medical Law; Medical sciences; Nebulizers and Vaporizers; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Powders; Protein Denaturation; Proteins; Proteins - chemistry; Scientific method; Solvents - chemistry; Technology, Pharmaceutical - instrumentation; Technology, Pharmaceutical - methods; Trypsinogen - chemistry; Vaccines - chemistry; α; CAN-BD; assisted nebulization with a bubble dryer; anti-CD4 antibody; trypsinogen; antitrypsin; CO; Pharmaceutical technology; α1-antitrypsin; Antibody; Carbon dioxide; Nebulization; Vaccine; Protein; Preparation; T-Lymphocyte; CO2-assisted nebulization with a bubble dryer; Fine powder
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-008-9575-6

Supercritical or near-critical fluid processes for generating microparticles have enjoyed considerable attention in the past decade or so, with good success for substances soluble in supercritical fluids or organic solvents. In this review, we survey their application to the production of protein particles. A recently developed process known as CO 2 -assisted nebulization with a Bubble Dryer® (CAN-BD) has been demonstrated to have broad applicability to small-molecule as well as macromolecule substances (including therapeutic proteins). The principles of CAN-BD are discussed as well as the stabilization, micronization and drying of a wide variety of materials. More detailed case studies are presented for three proteins, two of which are of therapeutic interest: anti-CD4 antibody (rheumatoid arthritis), α 1 -antitrypsin (cystic fibrosis and emphysema), and trypsinogen (a model enzyme). Dry powders were formed in which stability and activity are maintained and which are fine enough to be inhaled and reach the deep lung. Enhancement of apparent activity after CAN-BD processing was also observed in some formulation and processing conditions.