The influence of solute concentration and filtration on mesoscale clusters of flufenamic acid, a typical pharmaceutical compound, in ethanol.

Hypothesis: It is hypothesised in this work that mesoscale clusters will be present in both undersaturated and supersaturated solutions of organic pharmaceutical molecules. These clusters, being loose aggregates, could be sensitive to shear forces experienced during filtration. Thus, comparing the behaviour of these clusters alongside nanoparticles during filtration-an important sample treatment parameter during crystallization-will elucidate qualitative differences from solid, crystalline nanoparticles of similar size.

Guest Diffusion Versus Recrystallization in A Single Crystal: Two Growing Mechanisms for Griseofulvin Clathrates.

Griseofulvin represents a rare case of a close-packed organic apohost that can clathrate selected volatile guests in a solid-gas fashion. Inclusion mechanisms and solvent exchange were investigated by a combination of single crystal and powder X-ray diffraction, coupled to optical microscopy and thermal analyses. In particular, gas diffusion and dissolution/recrystallization are alternatively observed, depending on the host polymorph, as well as the chemical nature of the guest and its physical state.

System analysis with life cycle assessment for NiMH battery recycling.

The nickel metal hydride (NiMH) battery technology has been designed for use in electric vehicles, solar-powered applications and power tools. These batteries contain the critical and strategic raw materials cobalt, nickel and several rare earth elements (REE). When designing a battery recycling process, there are several choices to be made regarding end-products and process chemicals.

Tracking Prenucleation Molecular Clustering of Salicylamide in Organic Solvents.

Crystal nucleation shapes the structure and product size distribution of solid-state pharmaceuticals and is seeded by early-stage molecular self-assemblies formed in host solution. Here, molecular clustering of salicylamide in ethyl acetate, methanol, and acetonitrile was investigated using photon correlation spectroscopy. Cluster size steadily increased over 3 days and with concentration across the range from undersaturated to supersaturated solutions.

Impact of carrier particle surface properties on drug nanoparticle attachment.

Hypothesis: The stabilization and isolation to dryness of drug nanoparticles has always been a challenge for nano-medicine production. In the past, the use of montmorillonite (MMT) clay carrier particles to adsorb drug nanoparticles and maintain their high surface area to volume ratio after isolation to dryness has proven to be effective. We hypothesise that the distribution of hydrophilic and hydrophobic patches on the clay's surface as well as its porosity/roughness, hinder the agglomeration of the drug nanoparticles to the extent that they retain their high surface area to volume ratio and display fast dissolution profiles.

New Solid Forms of Griseofulvin: A Solvate and a Relict Polymorph Related to Reported Solvates.

This work presents two new solid forms, a polymorph and a solvate, of the antifungal active pharmaceutical ingredient griseofulvin (GSF). The novel forms were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis, and their crystal structures were determined by single-crystal X-ray diffraction. The new polymorphic form (GSF Form VI) was obtained upon drying at room temperature the GSF-acetonitrile solvate.

Impact of Additives on Drug Particles during Liquid Antisolvent Crystallization and Subsequent Freeze-Drying.

The impact of single or combinations of additives on the generation of nanosuspensions of two poorly water-soluble active pharmaceutical ingredients (APIs), fenofibrate (FF) and dalcetrapib (DCP), and their isolation to the dry state via antisolvent (AS) crystallization followed by freeze-drying was explored in this work. Combinations of polymeric and surfactant additives such as poly(vinyl alcohol) or hydroxypropyl methyl cellulose and sodium docusate were required to stabilize nanoparticles (∼200-300 nm) of both APIs in suspension before isolation to dryness. For both FF and DCP, multiple additives generated the narrowest, most-stable particle size distribution, with the smallest particles in suspension, compared with using a single additive.

Nucleation of the Theophylline:Salicylic Acid 1:1 Cocrystal.

The nucleation behavior of the theophylline-salicylic acid 1:1 (THP:SA) cocrystal in chloroform has been investigated and compared with the corresponding behavior of the pure compounds. Induction times have been determined at different supersaturations at 10 °C under each condition in approximately 40-80 repetition experiments in 20 mL vials. Nucleation times, extracted from the median induction times by accounting for a nucleus growth time, have been used to determine the interfacial energy and the pre-exponential factor within the classical nucleation theory.

Pure Curcumin Spherulites from Impure Solutions Nonclassical Crystallization.

Crystallization experiments performed with highly supercooled solutions produced highly pure (>99 wt %) and highly crystalline mesocrystals of curcumin from impure solutions (∼22% of two structurally similar impurities) in one step. These mesocrystals exhibited a crystallographic hierarchy and were composed of perfectly or imperfectly aligned nanometer-thick crystallites. X-ray diffraction and spectroscopic analysis confirmed that the spherulites are a new solid form of curcumin.

Thermodynamics of the Enantiotropic Pharmaceutical Compound Benzocaine and Solubility in Pure Organic Solvents.

The thermodynamic relationship between FI and FII of ethyl 4-aminobenzoate (benzocaine) has been investigated. Slurry conversion experiments show that the transition temperature below which FI is stable is located between 302 K-303 K (29 °C-30 °C). The polymorphs FI and FII have been characterised by infrared spectroscopy (IR), Raman spectroscopy, transmission powder X-ray diffraction (XRPD) and differential scanning calorimetry (DSC).

Solubility and thermodynamic analysis of ketoprofen in organic solvents.

The solubility of the racemic solid phase of ketoprofen (KTP) in methanol, ethanol, isopropanol, butanol, acetonitrile, ethyl acetate, 1,4-dioxane and toluene has been determined between 273 and 303 K by a gravimetric method. FTIR and Raman spectroscopy, SEM and PXRD, have been used to characterise the solid phase. The melting data and heat capacity of solid and melt have been determined by DSC, and used to estimate fusion thermodynamics and the activity of the solid phase as functions of temperature.

Anionic nanoparticle and microplastic non-exponential distributions from source scale with grain size in environmental granular media.

Nanoparticle and microplastic (colloid) transport behaviors impact strategies for groundwater protection and remediation. Complex colloid transport behaviors of anionic nano- and micro-sized colloids have been previously elucidated via independent experiments in chemically-cleaned and amended granular media with grain sizes in the range of fine to coarse sand (e.g.

Pathogen Prevalence in Fractured versus Granular Aquifers and the Role of Forward Flow Stagnation Zones on Pore-Scale Delivery to Surfaces.

Lesser pathogen prevalence is well recognized in granular versus fractured aquifers; however, the impact of residence time (inactivation/death) versus removal (pore-scale delivery to surfaces) on pathogen prevalence remains unaddressed. The objective of this study was to examine the specific role of pore-scale delivery to surfaces (removal) as an explanation of contrasting pathogen prevalence in granular versus fractured media from Wisconsin. Inactivation/death was obviated by the use of nonbiological colloids in column transport experiments conducted in representative media from the two Wisconsin sites.

A Unified Force and Torque Balance for Colloid Transport: Predicting Attachment and Mobilization under Favorable and Unfavorable Conditions.

Colloid attachment and detachment behaviors concern a wide range of environmental contexts but have typically been mechanistically predicted exclusive of one another despite their obvious coupling. Furthermore, previous mechanistic prediction often addressed packed column contexts, wherein specific forces and torques on the colloid could not be well-constrained, preventing robust predictions. These weaknesses were addressed through direct observation experiments under conditions where perfect sink assumptions fail and allow calibration of the contact between the colloid and collector.

Solid and Solution State Thermodynamics of Polymorphs of Butamben (Butyl 4-Aminobenzoate) in Pure Organic Solvents.

The solubility of butamben has been measured gravimetrically in pure methanol, 1-propanol, 2-propanol, 1-butanol, and toluene over the temperature range 268-298 K. Polymorph transition and melting temperatures, associated enthalpy changes, and the heat capacity of the solid forms and the supercooled melt have been measured by differential scanning calorimetry. Based on extrapolated calorimetric data, the Gibbs energy, enthalpy and entropy of fusion, and the activity of solid butamben (the ideal solubility) have been calculated from below ambient temperature up to the melting point.

Hydrodynamic versus Surface Interaction Impacts of Roughness in Closing the Gap between Favorable and Unfavorable Colloid Transport Conditions.

Recent experiments revealed that roughness decreases the gap in colloid attachment between favorable (repulsion absent) and unfavorable (repulsion present) conditions through a combination of hydrodynamic slip and surface interactions with asperities. Hydrodynamic slip was calibrated to experimentally observed tangential colloid velocities, demonstrating that slip length was equal to maximum asperity relief, thereby providing a functional relationship between slip and roughness metrics. Incorporation of the slip length in mechanistic particle trajectory simulations yielded the observed modest decrease in attachment over rough surfaces under favorable conditions, with the observed decreased attachment being due to reduced colloid delivery rather than decreased attraction.

Why Variant Colloid Transport Behaviors Emerge among Identical Individuals in Porous Media When Colloid-Surface Repulsion Exists.

We herein demonstrate the cause of well-observed variant transport behaviors for apparently identical colloids in porous media under conditions of colloid-collector repulsion (unfavorable attachment conditions). We demonstrate that variant colloid transport behavior under unfavorable conditions can be explained by inherently variable colloid residence times prior to arrest on grains (collectors). We demonstrate that the residence time distributions derived from particle trajectory simulations incorporating representative nanoscale heterogeneity provide quantitative prediction of colloid transport under unfavorable conditions.

Crystal Nucleation of Tolbutamide in Solution: Relationship to Solvent, Solute Conformation, and Solution Structure.

The influence of the solvent in nucleation of tolbutamide, a medium-sized, flexible and polymorphic organic molecule, has been explored by measuring nucleation induction times, estimating solvent-solute interaction enthalpies using molecular modelling and calorimetric data, probing interactions and clustering with spectroscopy, and modelling solvent-dependence of molecular conformation in solution. The nucleation driving force required to reach the same induction time is strongly solvent-dependent, increasing in the order: acetonitrile View Article and Find Full Text PDF

Modelling and understanding powder flow properties and compactability of selected active pharmaceutical ingredients, excipients and physical mixtures from critical material properties.

The development of solid dosage forms and manufacturing processes are governed by complex physical properties of the powder and the type of pharmaceutical unit operation the manufacturing processes employs. Suitable powder flow properties and compactability are crucial bulk level properties for tablet manufacturing by direct compression. It is also generally agreed that small scale powder flow measurements can be useful to predict large scale production failure.

Effects of direct oral anticoagulants on lupus anticoagulant assays in a real-life setting.

Laboratory diagnosis of lupus anticoagulant (LA) is based on prolongation in at least one coagulation assay (diluted Russell's viper venom time - dRVVT or activated partial thromboplastin time - aPTT), which normalises after addition of phospholipids. Both assays may be influenced by anticoagulants and therefore LA should not be tested during warfarin or heparin treatment. It has been shown (primarily in vitro) that direct oral anticoagulants (DOACs - dabigatran [DAB], rivaroxaban [RIV] and apixaban [API]) may also influence LA testing.