Development of a Semi-Mechanistic Modeling Framework for Wet Bead Milling of Pharmaceutical Nanosuspensions.

This study aimed to develop a practical semi-mechanistic modeling framework to predict particle size evolution during wet bead milling of pharmaceutical nanosuspensions over a wide range of process conditions and milling scales. The model incorporates process parameters, formulation parameters, and equipment-specific parameters such as rotor speed, bead type, bead size, bead loading, active pharmaceutical ingredient (API) mass, temperature, API loading, maximum bead volume, blade diameter, distance between blade and wall, and an efficiency parameter. The characteristic particle size quantiles, i.e., x10, x50, and x90, were transformed to obtain a linear relationship with time, while the general functional form of the apparent breakage rate constant of this relationship was derived based on three models with different complexity levels. Model A, the most complex and general model, was derived directly from microhydrodynamics. Model B is a simpler model based on a power-law function of process parameters. Model C is the simplest model, which is the pre-calibrated version of Model B based on data collected from different mills across scales, formulations, and drug products. Being simple and computationally convenient, Model C is expected to reduce the amount of experimentation needed to develop and optimize the wet bead milling process and streamline scale-up and/or scale-out.

Detection of Atrazine and Its Metabolites in Natural Water Samples Using Photonic Molecularly Imprinted Sensors.

In a previous study, photonic-based molecularly imprinted polymers (MIPs) were fabricated using atrazine (ATZ) and its metabolites, desethylatrazine (DEA) and desisopropylatrazine (DIA), as templates in separate matrices. For the purposes of monitoring the abovementioned molecules in natural waters, the effect of natural waters-featuring ionic strength and natural organic matter (NOM) on atrazine MIP-were studied in this work, and the photonic MIP was implemented for monitoring the target molecules in natural water samples collected from land in nearby farms in northeast of Columbia MO. Non-imprinted polymers (NIP) were also fabricated and applied in the experiments as a control test. In presence of NaCl, CaCl2, and NOM, MIPs presented lower responses by 26%, higher responses by 23%, and higher responses by 35%, respectively. NIPs response in terms of an increase or decrease was consistent with those of MIPs, but only for a lower percentage. MIPs response in natural waters-which were characterized for their physicochemical characteristics such as conductivity, total organic carbon content, etc.-provided a good approximation of the real concentrations obtained from the LCMS instrument; in general, they showed a good concordance, although large discrepancies occurred for some samples, which can be related to reproducibility issues in the manufacturing process or the presence of unknown interfering compounds in the real samples.

Detection of progesterone in aqueous samples by molecularly imprinted photonic polymers.

A label-free molecular imprinted polymer (MIP) sensor was fabricated for the detection of progesterone in aqueous solutions, by polymerization inside the void spaces of colloidal crystals, which gave them photonic properties. The prepolymerization mixture was prepared from acrylic acid as the functional monomer, ethylene glycol as the cross-linker agent, ethanol as solvent, and progesterone as the imprinted template. After polymerization, the colloidal crystal was removed by acid etching and the target eluted with a solvent. Material characterization included as follows: attenuated total reflectance-Fourier-transform infrared spectroscopy, dynamic light scattering, swelling experiments, and environmental scanning electron microscopy. MIPs were investigated by equilibrium binding, kinetics experiments, and UV-visible spectra to investigate Bragg diffraction peak shift that occurs with the rebinding at different progesterone concentrations in deionized water and 150-mM NaCl solutions. The MIP response was investigated with progesterone concentration in the 1-100 µg L-1 range, with LOD of 0.5 µg L-1, reaching the detected range of hormone in natural waters. Furthermore, hydrogel MIP films were successfully tested in various real water matrices with satisfactory results. Moreover, the MIP film exhibited good selectivity toward the progesterone hormone evidenced by a larger response than when exposed to structurally similar molecules. Computational studies suggested that size along with surface potential influenced the binding of analog compounds. Due to their ease of use and low cost, the sensors are promising as screening tools for the presence of progesterone in aqueous samples.

Detection of chlorantraniliprole residues in tomato using field-deployable MIP photonic sensors.

A photonic sensor based on inversed opal molecular imprinted polymer (MIP) film to detect the presence of chlorantraniliprole (CHL) residue in tomatoes was developed. Acrylic acid was polymerized in the presence of CHL inside the structure of a colloidal crystal, followed by etching of the colloids and CHL elution. Colloidal crystals and MIP films were characterized by scanning electron microscopy and FT-IR, confirming the inner structure and chemical structure of the material. MIP films supported on polymethylmethacrylate (PMMA) slides were incubated in aqueous solutions of the pesticide and in blended tomato samples. The MIP sensor displayed shifts of the peak wavelength of the reflection spectra in the visible range when incubated in CHL concentrations between 0.5 and 10 µg L-1, while almost no peak displacement was observed for non-imprinted (NIP) films. Whole tomatoes were blended into a liquid and spiked with CHL; the sensor was able to detect CHL residues down to 0.5 µg kg-1, significantly below the tolerance level established by the US Environmental Protection Agency of 1.4 mg kg-1. Stable values were reached after about 30-min incubation in test samples. Control samples (unspiked processed tomatoes) produced peak shifts both in MIP and NIP films; however, this matrix effect did not affect the detection of CHL in the spiked samples. These promising results support the application of photonic MIP sensors as an economical and field-deployable screening tool for the detection of CHL in crops.