Super Critical Carbon Dioxide in the Large Scale Drug Manufacturing

There is an urgent need for the development of novel large-scale manufacture engineering methods, which enhance sustainability and renewability while minimizing or eliminating the use of hazardous chemicals, biologicals and solvents that are harmful to the earth. In this regard, use of supercritical carbon dioxide (scCO2) solvent is very attractive as scCO2 is easily available, non-toxic, non-flammable, and amenable for large-scale reactions. Furthermore, its properties can easily be tuned through changing temperature and pressure. We propose to exploit the advantages of scCO2 in the development of novel manufacturing processes for the production of biotechnological heparin anticoagulants. Currently heparin anticoagulants are derived from over 700 million pigs and used in over 100 million surgical procedures annually worldwide and listed as one of the most critical essential medicines by World Health Organization. In addition, continuous availability of heparin blood thinner is at risk due to recent spread of African Swine Fever in China and elsewhere. Finally, we also explore the use of scCO2 in the continuous manufacturing of advanced pharmaceutical ingredients that have limited water solubility.

The team has faculty members from Medicinal Chemistry, Hunstman Cancer Institute [University of Utah Therapeutics Accelerator Hub (U2-TAH)] and Chemical Engineering with expertise in the chemistry of drugs being manufactured and in supercritical extraction.

Current Status

2021-09-14
Abstract:
There is an urgent need for the development of novel large-scale manufacture engineering methods, which enhance sustainability and renewability while minimizing or eliminating the use of hazardous chemicals, biologicals and solvents that are harmful to the earth. In this regard, use of supercritical carbon dioxide (scCO2) solvent is very attractive as scCO2 is easily available, non-toxic, non-flammable, and amenable for large-scale reactions. Furthermore, its properties can easily be tuned through changing temperature and pressure. We propose to exploit the advantages of scCO2 in the development of novel manufacturing processes for the production of biotechnological heparin anticoagulants and isolation of heparin from animal tissues. Currently heparin anticoagulants are derived from over 700 million pigs and used in over 100 million surgical procedures annually worldwide and listed as one of the most critical essential medicines by World Health Organization. Toward this goal, we have designed a miniature scCO2 reactor system to promote epimerization, one of the critical steps in the heparin manufacturing. This miniature system is capable of handling very small volumes of samples (1-5 ml) and can perform batch or flow through extractions at pressures of up to 35 MPa and up to temperatures of 800C. Our preliminary results suggest that scCO2 treatment may generate infrequent conversion. Efforts are currently underway to further explore whether we can improve frequency of conversion. In addition, with this new designed reactor system, we plan to study extraction efficiency of heparin like molecules from animal tissues.