Influence mechanism of excipients on drug crystallization: experimental investigation and model analysis and prediction

The influence of temperature, stirring speed, and excipients on crystal growth kinetics of mesalazine and allopurinol was investigated through experiment and chemical potential gradient model. The results indicated that the Diffusion-Surface Reaction model (DSR (1,2)) showed good performance in modeling API crystal growth kinetics within the ARDs of 4%. Excipients played a crucial role in inhibiting crystal growth in all the systems. It can not only improve the API solubility, but also reduce the crystal growth rate. By comparing diffusion rate and surface-reaction rate constant within the DSR (1,2) model, it was found that the controlling step of mesalazine crystallization was surface-reaction. Allopurinol crystallization was dominated by both surface-reaction and diffusion. Meanwhile, the crystal growth kinetics of mesalazine and allopurinol were predicted successfully with the ARDs of 2.53% and 4.78%. This work provided a mechanistic understanding of polymer influence on the inhibition of API crystal growth.

Patterned crystal growth and heat wave generation in hydrogels

The crystallization of metastable liquid phase change materials releases stored energy as latent heat upon nucleation and may therefore provide a triggerable means of activating downstream processes that respond to changes in temperature. In this work, we describe a strategy for controlling the fast, exothermic crystallization of sodium acetate from a metastable aqueous solution into trihydrate crystals within a polyacrylamide hydrogel whose polymerization state has been patterned using photomasks. A comprehensive experimental study of crystal shapes, crystal growth front velocities and evolving thermal profiles showed that rapid growth of long needle-like crystals through unpolymerized solutions produced peak temperatures of up to 45˚C, while slower-crystallizing polymerized solutions produced polycrystalline composites and peaked at 30˚C due to lower rates of heat release relative to dissipation in these regions. This temperature difference in the propagating heat waves, which we describe using a proposed analytical model, enables the use of this strategy to selectively activate thermoresponsive processes in predefined areas.

Synthesis of zeolitic imidazolate framework-8 and gold nanoparticles in a sustained out-of-equilibrium state

The design and synthesis of crystalline materials are challenging due to the proper control over the size and polydispersity of the samples, which determine their physical and chemical properties and thus applicability. Metal − organic frameworks (MOFs) are promising materials in many applications due to their unique structure. MOFs have been predominantly synthesized by bulk methods, where the concentration of the reagents gradually decreased, which affected the further nucleation and crystal growth. Here we show an out-of-equilibrium method for the generation of zeolitic imidazolate framework-8 (ZIF-8) crystals, where the non-equilibrium crystal growth is maintained by a continuous two-side feed of the reagents in a hydrogel matrix. The size and the polydispersity of the crystals are controlled by the fixed and antagonistic constant mass fluxes of the reagents and by the reaction time. We also present that our approach can be extended to synthesize gold nanoparticles in a redox process.