Biochar (BC) and hydrochar (HC) have attracted considerable attention owing to their versatile characteristics and proven effectiveness in diverse technical fields. Solid BC is generated as a result of the dry carbonisation process of pyrolysis, in contrast to the slurry HC, which is produced during the hydrothermal carbonisation process. In this study, we evaluated the adsorption potential of two hydrochar samples (HCs) and three biochar samples (BCs) produced from sugar cane bagasse. The adsorption capacity of these samples was tested for ammonium, nitrate, and phosphate ions under various conditions. The BCs and HCs were subjected to characterisation using a CHNS/O analyser, the zeta potential, and Fourier transform infrared (FTIR). Elevating the pyrolysis temperature of the biochar resulted in changes in the fixed carbon and ash contents, while the volatile matter and H/C and O/C atomic ratios decreased. As the residence time increased, the H/C ratio and volatile matter content of the hydrochars (HCs) decreased. However, the fixed carbon content, ash content, and O/C and C/N ratios exhibited an increase. Thermodynamics, adsorption isotherms, and pH were also taken into consideration. The FTIR spectra analysis indicated that the carboxyl and ester functional groups present in both the BCs and HCs displayed reduced peak intensities subsequent to the adsorption of the three ions. While the adsorption was exothermic, we noticed that the adsorption capacity increased with temperature. The results indicate that sorption was homogenous across all binding sites, as evidenced by the optimal fit to the Langmuir isotherm. The research findings indicate that the adsorption capacity of various BC and HC adsorbents is significantly influenced by the surface area of the adsorbents in the case of nitrate and phosphate, but in the case of ammonia, adsorption is dictated by the functional polar groups present on the adsorbent surface.

Background: Metastable zone width (MSZW) and solubility are crucial for developing crystallization procedures in the purification of active pharmaceutical ingredients (APIs). Traditionally, determining these properties involves labor-intensive methods that can take weeks or even months. With advancements in process analytical technologies (PAT) and the increasing focus on quality by design (QbD) in pharmaceutical manufacturing, more efficient and reliable protocols are needed. In this study, we employ in situ Fourier Transform Infrared (FTIR) spectroscopy and Focused Beam Reflectance Measurement (FBRM) to establish protocols for measuring solubility at different temperatures and MSZW at varying cooling rates. Methods: We experimentally determined MSZW and solubility using FTIR spectroscopy and FBRM. IR spectra were analyzed to obtain solubility concentrations, while FBRM counts were used to extract MSZW and supersolubility concentrations. The collected data were assessed using four theoretical models, including a newly developed model based on classical nucleation theory. By fitting experimental MSZW data to these models, we determined nucleation kinetics and thermodynamic parameters. Results: Our novel model exhibited excellent agreement with experimental MSZW data across different cooling rates, demonstrating its robustness. The nucleation rate constant and nucleation rate ranged between 10²¹ and 10²² molecules/m³·s. The Gibbs free energy of nucleation was calculated as 3.6 kJ/mol, with surface energy values between 2.6 and 8.8 mJ/m². The estimated critical nucleus radius was in the order of 10⁻³ m. Conclusions: The protocols we developed for predicting MSZW and solubility of paracetamol using PAT can serve as a guideline for other APIs. Our theoretical model enhances the predictive accuracy of nucleation kinetics and thermodynamics, contributing to optimized crystallization processes.

Cooling crystallization experiments of curcumin in isopropanol confirmed that curcumin can crystallize via classical or nonclassical pathways, depending on the levels of supersaturation and supercooling. Light microscopy analysis revealed that classical crystallization produces needle-shaped single crystals with an equilibrium habit, while nonclassical crystallization results in spherulitic mesocrystals. Through a series of experiments under various conditions, we developed a crystal habit phase diagram for curcumin in pure isopropanol. Presented here for the first time, this diagram illustrates the relationship between supersaturation, supercooling, and crystal habit, offering a valuable guide for controlling curcumin crystallization pathways.

Developing theory-informed standard operating procedures (SOPs) for the continuous crystallisation of pharmaceuticals still remains a bottleneck. For the continuous manufacturing of pharmaceuticals, the current methods rely on the laborious trial-and-error approach to identify process conditions such as the dilution rate (flow per unit volume of reactor) and initial supersaturation, where the productivity will be at maximum at steady-state conditions. This approach, while proven and considered to be useful, lacks or ignores the information obtained from batch kinetics. Herein for the first time, we propose a theoretical method to develop batch kinetics-informed theoretical procedures for the continuous manufacturing of a model compound curcumin in isopropanol. The theoretical approach uses batch kinetic constants to theoretically identify the optimum dilution rate and the corresponding mass of the model compound curcumin when crystallised, as well as its productivity at steady-state conditions as a function of initial supersaturation. The theory-informed procedures will serve as a valuable guideline to develop operating procedures for the continuous production of the target compound and thus eliminate the trial-and-error approach used to develop the protocols for the continuous manufacturing of pharmaceuticals. We also showed that our methods allow for the estimation of the dilution rate that corresponds to washout conditions (i.e., where all the crystals in the crystalliser will be washed out due to the high flow rate of the input stream) during the continuous manufacturing of crystals.

A new mathematical model that relies on the classical nucleation theory is proposed to predict the nucleation rate, nucleation rate kinetic constant and the Gibbs free energy of nucleation from the MSZW measured as a function of solubility temperatures. The model allows to calculate the nucleation rate at different cooling rates. The model seems to be universal as it well predicts the experimental data of 16 different combination of APIs and solvents that involves 10 APIs. According to the proposed model, the nucleation rate was found to be in the range of 1020 to 1024 molecules/m3s and the Gibbs free energy of nucleation was found to be in the range of 8 – 62 kJ/mol. The proposed model is also used to obtain the induction time based on MSZW obtained at different cooling rate. The proposed model is further exploited to obtain the thermodynamic parameters that includes the surface free energy, size of the critical nucleus and the number of unit cells that constitute the critical nucleus.