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Crystallization experiments performed with highly supercooled solutions produced highly pure (>99 wt %) and highly crystalline mesocrystals of curcumin from impure solutions (∼22% of two structurally similar impurities) in one step. These mesocrystals exhibited a crystallographic hierarchy and were composed of perfectly or imperfectly aligned nanometer-thick crystallites. X-ray diffraction and spectroscopic analysis confirmed that the spherulites are a new solid form of curcumin. A theoretical hypothesis based on particle aggregation, double nucleation, and repeated secondary nucleation is proposed to explain the spherulite formation mechanism. The experimental results provide, for the first time, evidence for an organic molecule to naturally form spherulites without the presence of any stabilizing agents. Control experiments performed with highly supercooled pure solutions produced spherulites, confirming that the formation of spherulites is attributed to the high degree of supercooling and not due to the presence of impurities. Likewise, control experiments performed with a lower degree of supercooling produced impure crystals of curcumin via classical molecular addition mechanisms. Collectively, these experimental observations provide, for the first time, evidence for particle-mediated crystallization as an alternate and efficient method to purify organic compounds.

Two sulfa drugs, sulfamethazine and sulfamerazine, have been used as model compounds in the evaluation of microwave assisted slurry conversion crystallization for manufacturing of co-crystals. It is shown that the formation of the co-crystals is much faster using microwaves than simple conductive/convective heating to the same temperature. The favourable effect of using microwaves goes beyond the simple heating effect, likely due to an influence of the microwaves on solution structuring. It is also shown that the process of microwave assisted slurry conversion crystallization for efficient manufacturing of co-crystals can be scaled up from 0.2 to at least 20 g with the same outcome. In the work, three new co-crystals, sulfamethazine–nicotinamide, sulfamerazine–anthranilic acid and sulfamerazine–salicylamide have been found. Their crystal structures were solved successfully using single crystal X-ray diffraction (SC-XRD). A further thorough characterization has been carried out by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and Raman and FT-IR spectroscopy. It is shown that these co-crystals increase the equilibrium concentration of the drug compared to that of the respective pure solid forms. By Hirshfeld analysis and interaction energy calculations, the difference in stability, reactivity and rate of formation of co-crystals for sulfamethazine and sulfamerazine can be explained.

peer-reviewed This work investigated the technical feasibility of preparing, stabilizing and isolating poorly water-soluble drug nanoparticles via a small-scale antisolvent precipitation process operating in semi-continuous mode. Specifically, a novel semi-continuous process was demonstrated for the carrier particle mediated production, stabilization and isolation of valsartan nanoparticles into a solid form using montmorillonite clay particles as the carrier. The semi continuous process operated robustly for the full duration of the experiment (~16 min) and steady-state conditions were reached after ~5 min. Nanoparticles of valsartan (51 ± 1 nm) were successfully prepared, stabilized and isolated with the help of montmorillonite (MMT) or protamine functionalized montmorillonite (PA-MMT) into the dried form by this semi-continuous route. The dissolution profile of the isolated valsartan nanocomposite solids was similar to that of valsartan nanocomposite solids produced via the corresponding laboratory scale batch mode process, indicating that the product quality (principally the nanoscale particle size and solid-state form) is retained during the semi-continuous processing of the nanoparticles. Furthermore, tablets produced via direct compression of the isolated valsartan nanocomposite solids displayed a dissolution profile comparable with that of the powdered nanocomposite material. PXRD, DSC, SSNMR and dissolution studies indicate that the valsartan nanoparticles produced via this semi-continuous process were amorphous and exhibited shelf-life stability equivalent to > 10 months.

Crystallization experiments performed with highly supercooled solutions produced highly pure (> 99 wt%) and highly crystalline mesocrystals of curcumin from impure solution (~22% of two structurally similar impurities) in one step. These mesocrystals exhibited a crystallographic hierarchy and were composed of perfectly or imperfectly aligned nanometer thick crystallites. X-ray diffraction and spectroscopic analysis confirmed that the spherulites are a new solid form of curcumin. A theoretical hypothesis based on particle aggregation, double nucleation and a repeated secondary nucleation is proposed to explain the spherulite formation mechanism. The experimental results provide for the first time evidence for an organic molecule to naturally form spherulites without the presence of any stabilizing agent. Control experiments performed with highly supercooled pure solutions produced spherulites confirming the formation of spherulites is attributed to the high degree of supercooling and not due to the presence of impurities. Likewise control experiments performed with a lower degree of supercooling produced impure crystals of curcumin via the classical molecular addition mechanisms. These experimental observations all together provide first time evidence for particle mediated crystallization as an alternate and efficient method to purify organic compounds.

The present work investigates the application of different sonochemical reactor designs for the preparation of stable nanoemulsions considering the emulsion of coconut oil in water as the model system. The effect of different operating parameters as well as chemical compositions on the stability and droplet size of emulsion has also been investigated. Different processing capacities over the range of 50mL–2 L have been used with different power ratings for the sonochemical reactors. Two emulsifying agents viz. Tween 80 and Span 80 were used to prepare stable emulsions and the effect of emulsifying agent volume fraction on the emulsion droplet size has been illustrated. Zeta sizer has been used to measure the droplet size and distribution of internal phase of emulsion. Intensity mean diameter has been used to compare the droplet size distribution of the nanoemulsion formed using different sonochemical reactors. Power dissipated per unit volume of emulsion has been considered as the unified criteria for understanding the dependency of the prepared emulsions on the type of sonochemical reactor designs.

The present work reports the use of venturi-based hydrodynamic cavitation reactor for the preparation of stable submicron emulsions. Different types of cavitating devices such as circular venturi and slit venturi have been used in this study. Effect of different operating parameters such as inlet pressure and number of passes of the emulsion through the cavitating zone on the droplet size and the stability of emulsion has been investigated. Emulsion of coconut oil in water has been chosen as the model system. Two types of emulsifying agents, namely, Tween 80 and Span 80, were used for the preparation of the emulsions, and the effect of emulsifying agent volume fraction on the emulsion droplet size has been illustrated. Zetasizer has been used to measure the droplet size and distribution of internal phase of emulsion. It has been established that the inlet pressure affects the droplet size of emulsion favorably due to the enhanced cavitational intensity with increasing inlet pressures. Among the two types ...

This work investigates the application of ultrasound for improving the antisolvent crystallization of benzoic acid. The main objective of applying ultrasound is to enhance the crystal productivity ...