Solid-state vibrational circular dichroism for pharmaceutical applications: Polymorphs and cocrystal of sofosbuvir.

X-ray diffraction is a commonly used technique in the pharmaceutical industry for the determination of the atomic and molecular structure of crystals. However, it is costly, sometimes time-consuming, and it requires a considerable degree of expertise. Vibrational circular dichroism (VCD) spectroscopy resolves these limitations, while also exhibiting substantial sensitivity to subtle modifications in the conformation and molecular packaging in the solid state.

The impact of polymer mixture composition on the properties of electrospun membranes for drug delivery applications.

Orally dispersible films (ODFs) prepared by an electrospinning are a novel type of pharmaceutical formulation. This dosage form has the potential to be beneficial for small children and the elderly, who can have problems with administration of classical tablets due to the increased risk of choking and difficulty with swallowing. Due to the highly porous nanofiber morphology, the ODFs examined in this study achieve rapid disintegration into drug microparticles when in contact with saliva.

Herbal concoction Unveiled: A computational analysis of phytochemicals' pharmacokinetic and toxicological profiles using novel approach methodologies (NAMs).

Herbal medications have an extensive history of use in treating various diseases, attributed to their perceived efficacy and safety. Traditional medicine practitioners and contemporary healthcare providers have shown particular interest in herbal syrups, especially for respiratory illnesses associated with the SARS-CoV-2 virus. However, the current understanding of the pharmacokinetic and toxicological properties of phytochemicals in these herbal mixtures is limited.

Efficient full solar spectrum-driven photocatalytic hydrogen production on low bandgap TiO/conjugated polymer nanostructures.

The development of photocatalysts that can utilize the entire solar spectrum is crucial to achieving efficient solar energy conversion. The utility of the benchmark photocatalyst, TiO, is limited only to the UV region due to its large bandgap. Extending the light harvesting properties across the entire spectrum is paramount to enhancing solar photocatalytic performance.

3D Raman mapping as an analytical tool for investigating the coatings of coated drug particles.

The properties of dry-coated paracetamol particles (fast-dissolving model drug) with carnauba wax particles as the coating agent (dissolution retardant) were investigated. Raman mapping technique was used to non-destructively examine the thickness and homogeneity of coated particles. The results showed that the wax existed in two forms on the surface of the paracetamol particles, forming a porous coating layer: i) whole wax particles on the surface of paracetamol and glued together with other wax surface particles, and ii) deformed wax particles spread on the surface.

Formation of ibrutinib solvates: so similar, yet so different.

The transformation processes of non-solvated ibrutinib into a series of halogenated benzene solvates are explored in detail here. The transformation was studied in real time by X-ray powder diffraction in a glass capillary. Crystal structures of chlorobenzene, bromobenzene and iodobenzene solvates are isostructural, whereas the structure of fluorobenzene solvate is different.

Computational fluid dynamics simulation improves the design and characterization of a plug-flow-type scale-down reactor for microbial cultivation processes.

The scale-up of bioprocesses remains one of the major obstacles in the biotechnology industry. Scale-down bioreactors have been identified as valuable tools to investigate the heterogeneities observed in large-scale tanks at the laboratory scale. Additionally, computational fluid dynamics (CFD) simulations can be used to gain information about fluid flow in tanks used for production.

Quality assessment of niosomal suspensions.

Niosomes are vesicular carriers formed by a bilayer shell, which is composed of non-ionic surfactants with the addition of a structural supporting agent. Cholesterol is typically used as an additive to increase the stability or drug entrapment efficiency of niosomes. Although increasing the amount of cholesterol is reported to improve niosomal properties, an excessive amount of cholesterol may not be accommodated in the bilayer shell, and thus remain in the crystalline form in the niosomal solution.

Application of Oil-in-Water Cannabidiol Emulsion for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with unknown cause. It mainly affects joints and, without proper treatment, negatively impacts their movement, causes painful deformities, and reduces the patients' quality of life. Current treatment options consist of various types of disease-modifying antirheumatic drugs (DMARDs), however 20-30% of patients are partially resistant to them.

Pharmaceutical Product Characterization and Manufacturability of Surfactant-Enriched Oil Marbles with Abiraterone Acetate.

The present study investigates the physicochemical properties and stability of a novel lipid-based formulation-surfactant-enriched oil marbles containing abiraterone acetate. While the biopharmaceutical performance of this formulation has been reported recently, this study aims to fill the gap between a promising in vivo performance and industrial applicability. A series of techniques were employed to assess the solid-state characteristics of oil marble cores along with their physicochemical properties upon stability testing.

Structure-property relations of a unique and systematic dataset of 19 isostructural multicomponent apremilast forms.

The structure-property relations are examined for apremilast cocrystals and solvates in this work. A unique and large dataset of multicomponent crystal forms is presented including 7 cocrystals and 12 solvates. In total, 15 of the presented multicomponent forms and their crystal structures are published here for the first time.

The impact of the lamination pressure on the properties of electrospinned nanofibrous films.

The purpose of this work is to explore the preparation of nanofibrous orally dispersible films (ODFs) by needleless electrospinning from the active pharmaceutical ingredient (API) Tadalafil using particles suspended in a solution of polymers and other excipients. The prepared films were characterized by a combination of scanning electron microscopy, mechanical tests, measurements of the disintegration time and dissolution characteristic, X-ray diffraction, and differential scanning calorimetry. Furthermore, we investigated the impact of lamination pressures in the range of 0 to 5 bars combined with films at various relative humidity values on the mechanical properties of the ODF.

Impact of Solvent-Drug Interactions on the Desolvation of a Pharmaceutical Solvate.

In drug manufacturing, solvent-based methods are used for the crystallization of active pharmaceutical ingredients (APIs). Often, the solvent interacts with the API resulting in the formation of a new solid compound, the solvate. When desolvation occurs upon heating, it might result in the formation of new solid forms with significantly different physicochemical properties.

Monitoring of particle sizes distribution during Valsartan precipitation in the presence of nonionic surfactant.

Particle size is a key parameter when dealing with drug particle formation, delivery or dissolution. The correct measurement of particle size depends on various factors, such as sample preparation or dilution, but also on the choice of method for its characterization. In this work, we study the process of precipitation of poorly water-soluble drug Valsartan from supersaturated solution in the presence of nonionic surfactant Tween 20.

Morphology of Shear-Induced Colloidal Aggregates in Porous Media: Consequences for Transport, Deposition, and Re-entrainment.

Colloid deposition in granular media is relevant to numerous environmental problems. Classic filtration models assume a homogeneous pore space and largely ignore colloid aggregation. However, substantial evidence exists on the ubiquity of aggregation within porous media, suggesting that deposition is enhanced by it.

Numerical Modeling of Viscoelasticity in Particle Suspensions Using the Discrete Element Method.

The rheological behavior of particle suspensions is a challenging problem because its description depends on the interaction of two phases with different material properties. This interaction can lead to complex behavior because of acting forces at the solid-liquid interface such as lubrication. The goal of this work is to propose a method for the modeling of fluids viscoelasticity in the presence of spherical particles including fluid-particle interactions.

Complex methodology for rational design of Apremilast-benzoic acid co-crystallization process.

A new co-crystal of pharmaceutical active ingredient Apremilast was successfully designed in this work. The discovered co-crystal with benzoic acid significantly improves key properties like the dissolution and stability of an otherwise poorly soluble Apremilast. A crystallization process was developed, which includes efficient solvent selection and ternary phase diagram construction to minimize risks during scale up.

Transcriptome and proteome analysis of steady-state in a perfusion CHO cell culture process.

Long-term continuous protein production can be reached by perfusion operation. Through the continuous removal of waste metabolites and supply of nutrients, steady-state (SS) conditions are achieved after a certain transient period, where the conditions inside the reactor are not only uniform in space but also constant in time. Such stable conditions may have beneficial influences on the reduction of product heterogeneities.

Numerical Study of Soft Colloidal Nanoparticles Interaction in Shear Flow.

The mechanical behavior of nanoparticle assemblies depends on complex particle interactions that are difficult to study experimentally. Depending on the nanoparticle morphology, these interactions could lead to adhesive and elastic-plastic behavior during contact deformation. The aim of this research is to study the effect of contact interactions between polymer nanoparticles and their impact on the macroscopic properties of formed aggregates.

Proteomic analysis of micro-scale bioreactors as scale-down model for a mAb producing CHO industrial fed-batch platform.

The pharmaceutical production of recombinant proteins, such as monoclonal antibodies, is rather complex and requires proper development work. Accordingly, it is essential to develop appropriate scale-down models, which can mimic the corresponding production scale. In this work, we investigated the impact of the bioreactor scale on intracellular micro-heterogeneities of a CHO cell line producing monoclonal antibodies in fed-batch mode, using a 10 mL micro-bioreactor (ambr™) scale-down model and the corresponding 300 L pilot-scale bioreactor.

Isotope labeling to determine the dynamics of metabolic response in CHO cell perfusion bioreactors using MALDI-TOF-MS.

The steady-state operation of Chinese hamster ovary (CHO) cells in perfusion bioreactors requires the equilibration of reactor dynamics and cell metabolism. Accordingly, in this work we investigate the transient cellular response to changes in its environment and their interactions with the bioreactor hydrodynamics. This is done in a benchtop perfusion bioreactor using MALDI-TOF MS through isotope labeling of complex intracellular nucleotides (ATP, UTP) and nucleotide sugars (UDP-Hex, UDP-HexNAc).

Glycosylation flux analysis reveals dynamic changes of intracellular glycosylation flux distribution in Chinese hamster ovary fed-batch cultures.

N-linked glycosylation of proteins has both functional and structural significance. Importantly, the glycan structure of a therapeutic protein influences its efficacy, pharmacokinetics, pharmacodynamics and immunogenicity. In this work, we developed glycosylation flux analysis (GFA) for predicting intracellular production and consumption rates (fluxes) of glycoforms, and applied this analysis to CHO fed-batch immunoglobulin G (IgG) production using two different media compositions, with and without additional manganese feeding.

Modulation and modeling of monoclonal antibody N-linked glycosylation in mammalian cell perfusion reactors.

Mammalian cell perfusion cultures are gaining renewed interest as an alternative to traditional fed-batch processes for the production of therapeutic proteins, such as monoclonal antibodies (mAb). The steady state operation at high viable cell density allows the continuous delivery of antibody product with increased space-time yield and reduced in-process variability of critical product quality attributes (CQA). In particular, the production of a confined mAb N-linked glycosylation pattern has the potential to increase therapeutic efficacy and bioactivity.

Slip on a particle surface as the possible origin of shear thinning in non-Brownian suspensions.

Concentrated suspensions of non-Brownian particles exhibit a decrease in their viscosity with the increasing shear rate, a phenomenon called shear thinning. We present a possible explanation for this long-standing problem based on recent advances in the connection between the slip on the surface of the particles and the suspension viscosity. By expressing the energy dissipation between a pair of particles as a function of the local shear rate, it is possible to directly link the decrease of the viscosity with the shear rate to the slip of solvent molecules on the particle surface.