2.1.7. Examples of Successful Applications Confined impinging jet systems have been used in our laboratory to consistently produce submicron API suspensions via a continuous process that involves crystallization via the solvent/antisolvent technique to generate supersaturation conditions. Microfliudics Reaction Technology (MRT) was selected for this bottom-up processing since it is based on novel multiple stream inlet capabilities coupled with the impinging jet concept [11–14, 26]. It is designed to produce jet velocities and energy dissipation orders of Inhibitors,research,lifescience,medical magnitude higher than those of conventional impinging
jet reactors. The technology provides precise control of the feed rates, and the subsequent location and intensity of mixing of the reactants. It may provide significant technical and economical advantages due to its process intensification character that minimizes energy requirements, and the proven scalability of the reactor. In our first proof of concept studies performed, nanosuspensions Inhibitors,research,lifescience,medical of several APIs were produced varying the key parameters of the technology . Five different model APIs were used for testing and were selected to belong to different chemical families that exhibit different pharmacological activities. There were two antibiotics (azithromycin and API-2), an antihistamine (loratadine), an anticonvulsant
(oxycarbazepine) Inhibitors,research,lifescience,medical and a non-steroidal anti-inflammatory (NSAIS, API-1). The particle size depended Inhibitors,research,lifescience,medical on the supersaturation ratio and energy dissipation expressed as process pressure. The nanosuspensions were stable with narrow particle size Regorafenib distributions and median particle sizes in the range of 50–760nm. This “bottom up” process was compared to a
“top down” process in which drug nanosuspensions were created as a result of particle size reduction. It was found that the “bottom up” process was substantially more efficient and resulted in smaller particles. This first study did not attempt to identify crystalline structure and therefore no polymorph Inhibitors,research,lifescience,medical selectivity capabilities were evaluated. To accomplish this, two additional, more in depth studies were conducted on single APIs: Carbamazepine (CBZ), an anticonvulsant, out and Norfloxacin (NFN), an antibacterial agent. The details of the experimental protocols and results are reported in separate papers, CBZ  and NFN . A few brief comments are given here to help validate the benefits of bottom up processing with respect to the stated objectives of creating carefully engineered particles with “tunable” characteristics. The NFN nanosuspensions had narrow particle size distributions and median particle sizes in the range of 170–350nm depending on the supersaturation ratio and energy dissipation expressed as process pressure. However, the particle size was found to be insensitive to the presence of the surfactant used.