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.

Effect of Different Catalysts and Growth Temperature on the Photoluminescence Properties of Zinc Silicate Nanostructures Grown via VLS Method

Herein, we explore the photoluminescence properties of zinc silicate (Zn2SiO4) nanostructures synthesized by vapor-liquid-solid (VLS) mode of growth using three different catalysts (Sn, Ag and Mn). Different catalysts significantly influence the growth rate which in turn has an impact on the structure and hence the photoluminescence of the prepared zinc silicate nanostructures. Zn2SiO4 has a wide bandgap of about 5.5 eV and in its pure form, it does not emit in visible region due to its inner shell electronic transitions between the 3d5 energy levels. However, the incorporation of different catalysts (Sn, Ag and Mn) at different growth temperatures into the Zn2SiO4 crystal growth kinetics provides wide visible spectral range of photoluminescence (PL) emissions. PL analysis shows broad multi-band spectrum in the visible region and distinct colours (red, yellow, green, blue, cyan and violet) are obtained depending on the crystalline structure of the prepared nanostructures. The allowed transitions due to the effect of different catalysts on zinc silicate lattice offer a huge cross-section of absorption that generates strong photoluminescence. The correlation between the structural and optical properties of the synthesized nanostructures is discussed in detail. The synthesized photoluminescent nanostructures have potential applications in solid-state lighting and display devices.

Studies on nucleation and crystal growth kinetics of plutonium(IV) oxalatex

A new method is developed to calculate the dilution ratio N of the two reactant solutions during nucleation rate determination. When the initial apparent supersaturation ratio S N = f(N) in the dilution tank is controlled between 1.66 and 1.67, the counted nuclei is the most, both nuclei dissolving and secondary nucleation avoided satisfactorily. Based on this methoed, Plutonium(IV) oxalate is precipitated by mixing equal volumes of tetravalent plutonium nitrate and oxalic acid solutions. Experiments are carried out by varying the supersaturation ratio from 8.37 to 22.47 and temperature from 25 to 50 °C. The experimental results show that the nucleation rate of plutonium(IV) oxalate in the supersaturation range cited above can be expressed by the equation R N = A N exp(−E a /RT)exp[−B/(ln S)2], where A N = 4.8 × 1023 m−3 s−1 , and E a = 36.2 kJ mol−1, and B = 20.2. The crystal growth rate of plutonium(IV) oxalate is determined by adding seed crystals into a batch crystallizer. The crystal growth rate can be expressed by equation G(t) = k g exp(−E’ a /RT) (c − c eq) g , where k g = 7.3 × 10−7 (mol/L)−1.1(m/s), E’ a = 25.7 kJ mol−1, and g = 1.1.

Determination of chlorzoxazone crystal growth kinetics and size distribution under controlled supersaturation at 293.15 K

Background: Chlorzoxazone (CHZ) is a water-insoluble drug having bioavailability problems. The absorption rate of such drugs can be improved by reducing their particle size. In this work, the crystal growth kinetics of CHZ–ethanol for different degrees of supersaturation (SS) has been studied. Method: The equilibrium solubility data of CHZ in ethanol is determined by the shake-flask method within the 283.15–313.15 K temperature range. The mole fraction solubility of CHZ is calculated and correlated with the modified Apelblat equation, λh equation, van’t Hoff equation, Wilson, and non-random two liquid (NRTL) equation. Batch crystallization experiments are performed on three different degrees of SS-1.16, 1.18, and 1.20 at 293.15 K as a function of time. Results: The maximum root mean square difference (RMSD) and relative average deviation (RAD) values of 169.24 x10-6 and 0.699 x10-2, respectively, are observed in the NRTL equation model. The dissolution properties such as standard enthalpy, standard entropy, and Gibbs free energy are predicted using van’t Hoff equation. Using a simple integral technique, the average crystal growth rate constant KG is calculated as 1.58 (μm/min) (mg/ml)-1 and the order n=1 for CHZ–ethanol at 293.15 K. Conclusion: The obtained result concludes that the crystals growth size is found to be varied at different SS ratio in batch crystallization. The particle size control in batch crystallization can be achieved by optimizing the operating conditions to get the desired size crystals.