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Nitrofurantoin can form two monohydrates, which have the same chemical composition and molar ratio of water, but differ in the crystal arrangements. The two monohydrates (hydrates I and II) could be produced independently via evaporative crystallization, where supersaturation and solvent composition were both found to have an effect. Hydrate I showed much slower crystallization than hydrate II. During cooling crystallization, the nucleation and growth of hydrate II was again dominant, consuming all supersaturation and leading to no hydrate I formation. Seeding of hydrate I during cooling crystallization was also applied, but the hydrate I seeds were not able to initiate its nucleation rather than dissolving into crystallizing solution. Although solubility tests revealed that hydrate II is more stable than hydrate I due to its lower solubility (110 +/- 4 and 131 +/- 12 microg/mL for hydrates II and I, respectively), this difference is rather small. Therefore, the small free energy difference between the two hydrates, together with the slow crystallization of hydrate I, both lead to a hindrance of hydrate I formation. Furthermore, the crystal structure of hydrate II demonstrated a higher H-bonding extent than hydrate I, suggesting its more favorable crystallization. This is in good agreement with experimental results., ((c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.)

Sonocrystallization has proved to be an efficient tool to influence the external appearance and structure of a crystalline product obtained by various crystallization methods. The present work focuses on high intensity sonocrystallization of glycine by varying amplitude of ultrasound with an ultrasound frequency of 20kHz at two temperature ranges 40-50 and 20-30 degrees C in a jacketed 250-ml cooling crystallizer equipped with a stirrer. The polymorph composition of the obtained crystals was analyzed with a temperature variable X-ray powder diffractometer (XRPD). XRPD results showed that, besides the operating temperature, the glycine polymorphism was affected also by insonation. This was especially the case at the lower temperature range. Furthermore, based on the heat balance within the crystallizer, an increase in required cooling capacity was presented as a function of increasing ultrasound power. This study also showed, the higher the ultrasound amplitude the smaller the crystals obtained.

Currently there is a great interest in new process analytical approaches to increase the process understanding of pharmaceutical unit operations. In the present study, the influence of the solvent composition on the material properties and, further, on the filtration characteristics, of different crystal suspensions obtained through an unseeded batch-cooling-crystallization process was studied. Sulphathiazole, which is an antibiotic agent with multiple polymorphic forms, was produced by performing laboratory-scale cooling crystallization experiments from five different mixtures of water and propan-1-ol (n-propanol). The size, shape and polymorphic composition of the crystals produced were characterized with a scanning electron microscope, with a novel automated image analyser and with an X-ray powder diffractometer. All of the monitored crystal properties were found to clearly differ between the samples obtained from different solvents. The crystals produced in the batch-cooling-crystallization experiments were separated from the crystallizing solvents using a batch-type pressure Nutsche filter, and the filtration characteristics of the suspensions were evaluated on the basis of average filter-cake porosities and average specific cake resistances, which were determined from the experimentally obtained filtration data. Comparison between the calculated filtration characteristics revealed that considerable differences existed between the different suspensions, and it could therefore be concluded that the pressure-filtration process was influenced by the composition of the crystallizing solvent. The filterability of all the studied sulphathiazole suspensions was considered to be rather good on the basis of the relatively low cake porosities (0.51-0.63), which were accompanied with low average specific cake resistances [(8.7 x 10(7))-(1.2 x 10(9)) m/kg].

Natural freezing has the possible use to be used as a purification technique to treat wastewater. Natural freezing was simulated experimentally for ice crystallization from unsaturated Na 2 SO 4 (aq) solutions to assess the feasibility of such a technique for being used to purify wastewater. The influence of solution concentration and different growth conditions, such as ambient temperature, freezing time and freezing rate, on the efficiency of the purification process was investigated by analysis of the effective distribution coefficient ( K ) of the solute between the ice and the solution. A calculation method is introduced to estimate the concentration of solution at the advancing ice–solution interface in terms of the limiting distribution coefficient ( K ⁎ ) from experimental K values at different growth conditions. The heat transfer controlled growth rate of the ice limited by the free convective heat transfer coefficient of air ( h air ) rather than the thermal conductivity of the ice ( k ice ) and the heat transfer coefficient of the solution ( h sol ) found to prevail over the mass transfer of rejected solute molecules from the ice–solution interface to the bulk solution. Advancement of the thermal ( δ T ) and concentration boundary layer ( δ C ) at the ice–solution interface was proportional to the square root of freezing time. A simplified model is developed to estimate the thickness of the ice layer formed from solutions at different freezing conditions and the model is validated with experimental results. [ABSTRACT FROM AUTHOR]

Evaporation rates play a key role in evaporation crystallization and the drying of crystal products. Raman analysis was used to study the effect of the evaporation rate on the polymorphs of indomethacin at room temperature. The studied solvents were highly volatile ethanol, acetone, and ethyl acetate. The approach was based on a mass transfer model of evaporation, and experimental flux measurements were used for model evaluation. Evaporation rates from porous carriers were also investigated. The studied mesoporous silicon microparticles can be used in oral dosage forms of poorly soluble active pharmaceutical ingredients. Evaporation rates of dimethyl sulfoxide from a pure solvent, from indomethacin solutions, and from solutions containing microparticles were measured at 100 °C. An evaporation rate model of porous particles was used and the predicted results were compared with the experimental results obtained. [ABSTRACT FROM AUTHOR]

Abstract: Crystallization conditions in the crystallization unit and composition of the solution determine the crystal size distribution and shape. The objective of this study was to chart those physical properties and operating conditions that could explain the crystal size distribution for a compound in the industrial crystallizer using artificial intelligence based on the already existing data obtained for various compounds. The authors applied case-based reasoning (CBR) which is based on the reuse of the past experience in finding the solutions to new, similar problems. The proposed approach may save the time-consuming experimental work when the crystal size distribution of a new compound should be predicted. The example of continuous suspension crystallization is used to prove the usefulness of the proposed approach using rough and fuzzy sets in adaptation phase of case-based reasoning. [Copyright &y& Elsevier]

Abstract: This study was conducted to gain a deeper understanding of the crystallization behavior of both known nitrofurantoin (NF) monohydrates (monohydrates I and II). NF monohydrate crystals were obtained by evaporative crystallization from a series of acetone–water mixtures. The water activity of each solution together with the solubility of NF was used for calculation of the NF supersaturation profiles during evaporative crystallization. The crystallization process for each solution was monitored in situ by optical and Raman microscopy. It was found that the fraction of the metastable monohydrate I in the final product increased with decreasing water fraction, suggesting that the nucleation rate of monohydrate I increases with decreasing water activity. In addition, the morphology of both monohydrate forms was affected by the water fraction in the solvent. The in situ images and Raman spectra taken during the evaporative crystallization from water–acetone mixture (0.67mole fraction of water) demonstrated that the crystallization of the stable monohydrate II was encountered first, and the nucleation of the metastable monohydrate I happened afterwards at a reduced supersaturation level. This indicates that the crystal packing of the NF monohydrate from acetone–water solutions was affected by both supersaturation and water activity. [Copyright &y& Elsevier]

Due to stringent legislation, wastewater needs to be treated before dispersing in the environment. Wastewater can be purified through the formation of less contaminated ice layer by freezing. Freezing of the wastewater leaves the remaining wastewater more concentrated. Attainment of eutectic point (both ice and soluble salt crystallize simultaneously) by freeze crystallization can add extra financial value in terms of salt recovery. Separation of ice from salt becomes very easy because of significant density difference. Na 2 SO 4 is one of the key components present in wastewater emanating from different industrial sources, considered as a model compound in this study. Recovery of Na 2 SO 4 from the aqueous solution by eutectic freeze crystallization air-cooled through the ice layer and solution surface is an energy-efficient and cost effective method. This method was investigated experimentally to recover Na 2 SO 4 from its solution. Furthermore, the influence of different factors and operating conditions was studied on the efficiency of the purification and recovery process. [ABSTRACT FROM AUTHOR]