António Ferreira

Effect of operating conditions on batch and continuous paracetamol crystallization in an oscillatory flow mesoreactor

The batch and continuous crystallization of paracetamol from aqueous solutions is studied in a novel oscillatory flow mesoreactor equipped with smooth periodic constrictions. The aim of this study is to evaluate the influence of the operating and thermodynamic variables on the size of the crystals for enhanced direct crystallization of micronized powders. It was found that mixing intensity, supersaturation and temperature determine the crystal size properties. Evaluating the results according to the classical nucleation theory, it was observed that the kinetic and the thermodynamic parameters are mainly influenced by the mixing intensity and by the crystallization temperature, respectively. The continuous-flow operation mode was revealed to be more suitable in the production of inhalable size particles because it provides smaller residence times and reduced friction, breakage and aggregation phenomena. Growth kinetic data were also obtained. This new reactor showed great potential to be used for direct crystallization of this drug for pulmonary drug delivery.

Determination of the critical mixing intensity for secondary nucleation of paracetamol in an oscillatory flow crystallizer

A simple approach was employed to determine the critical mixing intensity for secondary nucleation of paracetamol, Reco, in an oscillatory flow crystallizer, i.e., the mixing intensity at which the transition from crystal growth to secondary nucleation control of crystal size occurs. Reco was determined for different initial supersaturations as a break in the trend of increasing crystal size with mixing intensity by performing several seeded batch experiments at different oscillation frequencies. It was found that Reco is high and virtually constant at low initial supersaturations and decreases when supersaturation increases. This parameter has a great influence on crystal growth rate and, consequently, on crystal size. Since larger particles offer greater collision success for attrition than small ones and contact nucleation is favored by high supersaturations, a lower mixing intensity level is required to reach the limit for secondary nucleation control under higher levels of supersaturation. The placement of the limit for secondary nucleation control in a real crystallization environment makes it possible to predict the system behavior under certain operating conditions.

Nonmechanically Agitated Bioreactors

Bubble column and airlift reactors are normally the first choice in many applications, especially ones involving biomaterials. Their popularity is essentially related to the simple design, nonmechanical agitation, and satisfactory heat and mass transfer properties. However, problems related to poor mixing, scale-up, product quality, and process reproducibility are typically reported. To overcome some of these limitations, oscillatory flow reactors (OFR) have been studied. These reactors, located on the frontier of mechanically and nonmechanically agitator reactors, will be explored in this chapter. The following sections present the two most common reactors (bubble column and airlift) used in bioprocesses as well as OFRs, highlighting the advantages and limitations of these reactors and their possible contribution to future developments in biotechnology and bioengineering.

Characterization of Industrial Bioreactors (Mixing, Heat, and Mass Transfer)

Abstract Multiphase contactors are intensively used in chemical, biochemical, pharmaceutical, petrochemical, and others industries. The complexity and diversity of industrial processes implies that different types of gas–liquid contactors have been developed and constructed, such as bubble columns, airlifts, oscillatory flow reactors, pipes and tubes, mechanical agitated tanks, packed columns, plate and tray columns, spray towers, jet (loop) reactors, tubular Venturi ejectors, and motionless mixers. Mixing, heat, and mass transfer performance characterize the different reactors, and choosing the best reactor for a certain application is not an easy task. System characteristics such as viscosity, surface tension, density, and the presence or absence of solids, among others, have a high influence on the mixing process as well as heat and mass transfer. This chapter provides a general introduction to mixing, heat, and mass transfer in bioreactors. An analogy is also explored between these properties and reactor design, in particular for bubble column, airlift, and stirred-tank reactors.