Spherical Crystallization Based on Liquid-Liquid Phase Separation in a Reverse Antisolvent Crystallization Process.

Vanillin crystals undergo needle-like morphology that results in poor flowability, crystal breakage, and low packing density. The spherical crystallization technology can produce particles with improved flowability and stability. A reverse antisolvent crystallization based on liquid-liquid phase separation is proposed in this work to produce vanillin spherical agglomerates. Hansen Solubility Parameters are applied to explain the liquid-liquid phase separation (LLPS) phenomenon. The Pixact Crystallization Monitoring system is applied to in-situ monitor the whole process. A six-step spherical crystallization mechanism is revealed based on the recorded photos, including the generation of oil droplets, nucleation inside oil droplets, the coalescence and split of oil droplets, crystal growth and agglomeration, breakage of oil droplets, and attrition of agglomerates. Different working conditions are tested to explore the best operation parameters and a frequency-conversion stirring strategy is proposed to improve the production of spherical crystals.

Production of cocrystals in an excipient matrix by spray drying.

Spray drying is a well-established scale-up technique for the production of cocrystals. However, to the best of our knowledge, the effect of introducing a third component into the feed solution during the spray drying process has never been investigated. Cocrystal formation in the presence of a third component by a one-step spray drying process has the potential to reduce the number of unit operations which are required to produce a final pharmaceutical product (e.g. by eliminating blending with excipient). Sulfadimidine (SDM), a poorly water soluble active pharmaceutical ingredient (API), and 4-aminosalicylic acid (4ASA), a hydrophilic molecule, were used as model drug and coformer respectively to form cocrystals by spray drying in the presence of a third component (excipient). The solubility of the cocrystal in the excipient was measured using a thermal analysis approach. Trends in measured solubility were in agreement with those determined by calculated Hansen Solubility Parameter (HSP) values. The ratio of cocrystal components to excipient was altered and cocrystal formation at different weight ratios was assessed. Cocrystal integrity was preserved when the cocrystal components were immiscible with the excipient, based on the difference in Hansen Solubility Parameters (HSP). For immiscible systems (difference in HSP > 9.6 MPa0.5), cocrystal formation occurred even when the proportion of excipient was high (90% w/w). When the excipient was partly miscible with the cocrystal components, cocrystal formation was observed post spray drying, but crystalline API and coformer were also recovered in the processed powder. An amorphous dispersion was formed when the excipient was miscible with the cocrystal components even when the proportion of excipient used as low (10% w/w excipient). For selected spray dried cocrystal-excipient systems an improvement in tableting characteristics was observed, relative to equivalent physical mixtures.

Application of the Hansen solubility Parameters theory to carbon nanotubes.

Carbon nanotubes (CNT) are very promising nano-objects due to their exceptional properties. However, their tendency to form bundles as well as their insolubility in common solvents makes them difficult to handle. The main way to solve the problem is chemical or physical CNTs functionalisations, with all the problems inherent to the methods. In this contribution, we present a new approach that allows predicting the solubility of carbon nanotubes in many solvents but also predicting the most appropriate solvents to use for given samples of CNTs. Solubilisation and dispersion being directly connected, the present approach of solubilisation proves also to be efficient in dispersing the CNTs bundles. This contribution is a first step toward the control of carbon nanotube's dispersion in polymers and their homogenous functionalisation. Moreover, we also report here a new method, based on solvents, to separate carbon nanotubes by size, the use of mixture of non-solvents in order to obtain good solvents and the use of mixture of good solvents to obtain higher solubility. The use of mixture of good solvents allowed us to obtain high solubility, up to three times higher then that reported in literature. We have also measured and analysed the solubility of some functionalised carbon nanotubes.