Preventing Crystal Agglomeration of Pharmaceutical Crystals Using Temperature Cycling and a Novel Membrane Crystallization Procedure for Seed Crystal Generation
In this work, a novel membrane crystallization system was used to crystallize micro-sized seeds of piroxicam monohydrate by reverse antisolvent addition. Membrane crystallization seeds were compared with seeds produced by conventional antisolvent addition and polymorphic transformation of a fine powdered sample of piroxicam form I in water. The membrane crystallization process allowed for a consistent production of pure monohydrate crystals with narrow size distribution and without significant agglomeration. The seeds were grown in 350 g of 20:80 w/w acetone-water mixture. Different seeding loads were tested and temperature cycling was applied in order to avoid agglomeration of the growing crystals during the process. Focused beam reflectance measurement (FBRM); and particle vision and measurement (PVM) were used to monitor crystal growth; nucleation and agglomeration during the seeded experiments. Furthermore; Raman spectroscopy was used to monitor solute concentration and estimate the overall yield of the process. Membrane crystallization was proved to be the most convenient and consistent method to produce seeds of highly agglomerating compounds; which can be grown via cooling crystallization and temperature cycling.
Microwave Assisted Direct Nucleation Control for Batch Crystallization: Crystal Size Control with Reduced Batch Time
Direct nucleation control (DNC) is a feedback control strategy, based on an in situ measurement of the number of particles. In batch cooling crystallization processes, the DNC approach utilizes temperature cycling to control the supersaturation profile during the batch. As a result of this cycling, product crystals with a large mean size and a narrow size distribution can be achieved due to the dissolution of undesired fines. However, implementing the temperature cycles may come at the expense of significantly prolonged batch times due to conventional heat transfer limitations and practical limitations for implementing actuation for both conventional heating and cooling. In this work, microwave heating in combination with DNC is presented to eliminate limitations of conventional heating and further improve the effectiveness of DNC. The results show a very rapid response when using microwave heating, which allowed for improved effectiveness of DNC. In particular, batch times under DNC could be reduced by 5...
Persius and the Programmatic Satire: A Study in Form and Imagery
Introduction 1. Style and expression in Persius' fifth satire 2. The programmatic satire and the method of Persius I 3. The nature and sources of Persius' imagery 4. Persius' first satire: analysis 5. Grandeur and humility: Juvenal and the high style Appendixes Text Translation Index of modern authors Index locorum potiorum Index of images, topics and words.