Elucidating the Splitting Behavior of Tablets to Optimize the Pharmacotherapy in Veterinary Medicine.

It is well known that the splitting of tablets can bring serious risks to the health of the treated animals, e.g., the possible adverse reactions caused by overdoses of fenbendazole or aspirin. In this regard, this work aimed to evaluate, for the first time, the splitting behavior of commercial veterinary tablets and identifying the technological aspects that interfere in this process. Tablets were cut in halves using a tablet splitter and were analyzed regarding mass variation, mass loss, friability, and hardness. Microstructural and morphological evaluations were also performed. For most of the tablets, organic flavor additives provided more uniformity and cohesive matrix, which preserved its hardness after the cut and led to subdivision results within acceptable limits for mass measurements and friability. Apart from the microstructure, the most critical technological aspect for a correct splitting performance in such tablets was the presence of a score. Thus, the results presented here allow us to guide the manufacturing of veterinary drug products in order to produce tablets more adapted to the splitting process.

Deciphering the Dynamics of Organic Nanoaggregates with AIEE Effect and Excited States: Lipophilic Benzothiadiazole Derivatives as Selective Cell Imaging Probes.

An aggregation-induced emission enhancement (AIEE) effect in fluorescent lipophilic 2,1,3-benzothiadiazole (BTD) derivatives and their organic nanoaggregates were studied. A set of techniques such as single-crystal X-ray, dynamic light scattering (DLS), electron paramagnetic resonance (EPR), UV-vis, fluorescence, and density functional theory (DFT) calculations have been used to decipher the formation/break (kinetics), properties, and dynamics of the organic nanoaggregates of three BTD small organic molecules. An in-depth study of the excited-state also revealed the preferential relaxation emissive pathways for the BTD derivatives and the dynamics associated with it. The results described herein, for the first time, explain the formation of fluorescent BTD nanoaggregate derivatives and allow for the understanding of their dynamics in solution as well as the ruling forces of both aggregation and break processes along with the involved equilibrium. One of the developed dyes could be used at a nanomolar concentration to selectively stain lipid droplets emitting an intense and bright fluorescence at the red channel. The other two BTDs could also stain lipid droplets at very low concentrations and were visualized preferentially at the blue channel.

Hot-Melt Extrusion as an Advantageous Technology to Obtain Effervescent Drug Products.

Here, we assessed the feasibility of hot-melt extrusion (HME) to obtain effervescent drug products for the first time. For this, a combined mixture design was employed using paracetamol as a model drug. Extrudates were obtained under reduced torque (up to 0.3 Nm) at 100 °C to preserve the stability of the effervescent salts. Formulations showed vigorous and rapid effervescent disintegration (<3 min), adequate flow characteristics, and complete solubilization of paracetamol instantly after the effervescent reaction. Formulations containing PVPVA in the concentration range of 15-20% m/m were demonstrated to be sensitive to accelerated aging conditions, undergoing marked microstructural changes, since the capture of water led to the agglomeration and loss of their functional characteristics. HPMC matrices, in contrast, proved to be resistant to storage conditions in high relative humidity, showing superior performance to controls, including the commercial product. Moreover, the combined mixture design allowed us to identify significant interactions between the polymeric materials and the disintegrating agents, showing the formulation regions in which the responses are kept within the required levels. In conclusion, this study demonstrates that HME can bring important benefits to the elaboration of effervescent drug products, simplifying the production process and obtaining formulations with improved characteristics, such as faster disintegration, higher drug solubilization, and better stability.

Predictive models of FDM 3D printing using experimental design based on pharmaceutical requirements for tablet production.

The present study aimed to analyze how the printing process affects the final state of a printed pharmaceutical product and to establish prediction models for post-printing characteristics according to basic printing settings. To do this, a database was constructed through analysis of products elaborated with a distinct printing framework. The polymers acrylonitrile butadiene styrene (ABS), polylactic acid (PLA), and high-impact polystyrene (HIPS) were tested in a statistically-based experiment to define the most critical printing factors for mass, mass variation, printing time, and porosity. Then, a predictive model equation was established and challenged to determine two different medical prescriptions. The factors of size scale, printlet format, and print temperature influenced printlet mass, while the printing time was impacted by size scale, printing speed, and layer height. Finally, increased printing speed leads to more porous printlets. The prescript-printed tablets showed average mass, mass variations, and porosity close to theoretical values for all filaments, which supports the adequacy of the optimized design of experiments for tablet production. Hence, printing settings can be preselected according to the desired product's characteristics, resulting in tablets produced with higher precision than usually achieved by compounding pharmacies.

Highly Magnetizable Crosslinked Chloromethylated Polystyrene-Based Nanocomposite Beads for Selective Molecular Separation of 4-Aminobenzoic Acid.

In this work, we describe the preparation and characterization of highly magnetizable chloromethylated polystyrene-based nanocomposite beads. For synthesis optimization, acid-resistant core-shelled maghemite (γ-Fe2O3) nanoparticles are coated with sodium oleate and directly incorporated into the organic medium during a suspension polymerization process. A crosslinking agent, ethylene glycol dimethacrylate, is used for copolymerization with 4-vinylbenzyl chloride to increase the resistance of the microbeads against leaching. X-ray diffraction, inductively coupled plasma atomic emission spectroscopy, thermogravimetric analysis, scanning electron microscopy, transmission electron microscopy, and optical microscopy are used for bead characterization. The beads form a magnetic composite consisting of ∼500 nm-sized crosslinked polymeric microspheres, embedding ∼8 nm γ-Fe2O3 nanoparticles. This nanocomposite shows large room temperature magnetization (∼24 emu/g) due to the high content of maghemite (∼45 wt %) and resistance against leaching even in acidic media. Moreover, the presence of superficial chloromethyl groups is probed by Fourier transform infrared and X-ray photoelectron spectroscopy. The nanocomposite beads displaying chloromethyl groups can be used to selectively remove aminated compounds that are adsorbed on the beads, as is shown here for the molecular separation of 4-aminobenzoic acid from a mixture with benzoic acid. The high magnetization of the composite beads makes them suitable for in situ molecular separations in environmental and biological applications.

Hot Melt Extrudates Formulated Using Design Space: One Simple Process for Both Palatability and Dissolution Rate Improvement.

This work aimed at obtaining an optimized itraconazole (ITZ) solid oral formulation in terms of palatability and dissolution rate by combining different polymers using hot melt extrusion (HME), according to a simplex centroid mixture design. For this, the polymers Plasdone® (poly(1-vinylpyrrolidone-co-vinyl acetate) [PVP/VA]), Klucel® ELF (2-hydroxypropyl ether cellulose [HPC]), and Soluplus® (SOL, polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol) were processed using a laboratory HME equipment operating without recirculation at constant temperature. Samples were characterized by physicochemical assays, as well as dissolution rate and palatability using an e-tongue. All materials became homogeneous and dense after HME processing. Thermal and structural analyses demonstrated drug amorphization, whereas IR spectroscopy evidenced drug stability and drug-excipient interactions in HME systems. Extrudates presented a significant increase in dissolution rate compared to ITZ raw material, mainly with formulations containing PVP/VA and HPC. A pronounced improvement in taste masking was also identified for HME systems, especially in those containing higher amounts of SOL and HPC. Data showed polymers act synergistically favoring formulation functional properties. Predicted best formulation should contain ITZ 25.0%, SOL 33.2%, HPC 28.9%, and PVP/VA 12.9% (w/w). Optimized response considering dissolution rate and palatability reinforces the benefit of polymer combinations.

Fabrication of glycine-functionalized maghemite nanoparticles for magnetic removal of copper from wastewater.

Maghemite nanoparticles (MNPs) were functionalized with glycine, by a cost-effective and environmentally friendly procedure, as an alternative route to typical amine-functionalized polymeric coatings, for highly efficient removal of copper ions from water. MNPs were synthesized by co-precipitation method and adsorption of glycine was investigated as a function of ligand concentration and pH. The efficiency of these functionalized nanoparticles for removal of Cu(2+) from water has been explored and showed that adsorption is highly dependent of pH and that it occurs either by forming chelate complexes and/or by electrostatic interaction. The adsorption process, which reaches equilibrium in few minutes and fits a pseudo second-order model, follows the Langmuir adsorption model with a very high maximum adsorption capacity for Cu(2+) of 625mg/g. Furthermore, these nanoadsorbents can be used as highly efficient separable and reusable materials for removal of toxic metal ions.