Development of a dry powder insufflation device with application in in vitro cell-based assays in the context of respiratory delivery.

Research on pharmaceutical dry powders has been increasing worldwide, along with increased therapeutic strategies for an application through the pulmonary or the nasal routes. In vitro methodologies and tests that mimic the respiratory environment and the process of inhalation itself are, thus, essential. The literature frequently reports cell-based in vitro assays that involve testing the dry powders in suspension.

Coamorphous Systems of Valsartan: Thermal Analysis Contribution to Evaluate Intermolecular Interactions Effects on the Structural Relaxation.

Coamorphous formation in binary systems of valsartan (Val) with 4,4'-bipyridine (Bipy) and trimethoprim (Tri) was investigated for mixtures with a mole fraction of 0.16~0.86 of valsartan and evaluated in terms of the glass transition temperature.

Understanding Fenofibrate Release from Bare and Modified Mesoporous Silica Nanoparticles.

To investigate the impact of the surface functionalization of mesoporous silica nanoparticle (MSN) carriers in the physical state, molecular mobility and the release of Fenofibrate (FNB) MSNs with ordered cylindrical pores were prepared. The surface of the MSNs was modified with either (3-aminopropyl) triethoxysilane (APTES) or trimethoxy(phenyl)silane (TMPS), and the density of the grafted functional groups was quantified via H-NMR. The incorporation in the ~3 nm pores of the MSNs promoted FNB amorphization, as evidenced via FTIR, DSC and dielectric analysis, showing no tendency to undergo recrystallization in opposition to the neat drug.

TSDC and DSC Investigation on the Molecular Mobility in the Amorphous Solid State and in the Glass Transformation Region of Two Benzodiazepine Derivatives: Diazepam and Nordazepam.

In this work we study the molecular mobility in the amorphous solid state and in the glass transformation region of two compounds, diazepam and nordazepam; these are two benzodiazepines, a family of psychotropic drugs with sedative, anxiolytic and muscle-relaxing properties. The experimental techniques used are thermostimulated currents (TSC) and differential scanning calorimetry (DSC). TSC is a time-dependent technique recognized for its high resolving power; the use of this technique in the depolarization and polarization modes (TSDC and TSPC respectively), provides results that confirm and complement results of dielectric relaxation spectroscopy (DRS) published recently.

Thermal behavior and molecular mobility studies in the supercooled liquid and glassy states of carvedilol and loratadine.

The thermal behavior of carvedilol and loratadine was studied by differential scanning calorimetry (DSC). The glass-forming ability, as well as the the tendency for crystallization from the glass (glass stability) and from the metastable and equilibrium melt were also investigated by DSC. In addition this technique was also used to characterize the glass transition of carvedilol and loratadine by determining the activation energy of the structural relaxation, the dynamic fragility, and the heat capacity jump associated with the glass transformation.

Synthesis and Characterization of Isosorbide-Based Polyurethanes Exhibiting Low Cytotoxicity Towards HaCaT Human Skin Cells.

The synthesis of four samples of new polyurethanes was evaluated by changing the ratio of the diol monomers used, poly(propylene glycol) (PPG) and D-isosorbide, in the presence of aliphatic isocyanates such as the isophorone diisocyanate (IPDI) and 4,4'-methylenebis(cyclohexyl isocyanate) (HMDI). The thermal properties of the four polymers obtained were determined by DSC, exhibiting values in the range 55⁻70 °C, and their molecular structure characterized by FTIR, ¹H, and C NMR spectroscopies. The diffusion coefficients of these polymers in solution were measured by the Pulse Gradient Spin Echo (PGSE) NMR method, enabling the calculation of the corresponding hydrodynamic radii in diluted solution (1.

Thermal Behavior and Slow Relaxation Dynamics in Amorphous Efavirenz: A Study by DSC, XRPD, TSDC, and DRS.

The analysis of the thermal behavior of efavirenz showed a high glass-forming ability and good glass stability of this glass-forming liquid at room temperature. No polymorphic forms were formed either by cold crystallization or by recrystallization from solvent acetone. The determination of the dynamic fragility by the differential scanning calorimetry, thermally stimulated depolarization currents (TSDC), and dielectric relaxation spectroscopy (DRS) techniques is unanimous in suggesting efavirenz as a moderately fragile liquid.

Structural Elucidation of Poloxamer 237 and Poloxamer 237/Praziquantel Solid Dispersions: Impact of Poly(Vinylpyrrolidone) over Drug Recrystallization and Dissolution.

Praziquantel (PZQ) is the recommended, effective, and safe treatment against all forms of schistosomiasis. Solid dispersions (SDs) in water-soluble polymers have been reported to increase solubility and bioavailability of poorly water-soluble drugs like PZQ, generally due to the amorphous form stabilization. In this work, poloxamer (PLX) 237 and poly(vinylpyrrolidone) (PVP) K30 were evaluated as potential carriers to revert PZQ crystallization.

MechanoAPI-ILs: Pharmaceutical Ionic Liquids Obtained through Mechanochemical Synthesis.

An alternative, efficient, and green synthetic strategy for the preparation of pharmaceutical ionic liquids using mechanochemistry (MechanoAPI-ILs) is reported. Six new API-ILs based on gabapentin and l-glutamic acid were successfully synthesized and characterized, demonstrating that mechanochemistry is a very promising synthetic strategy. Results compare both the new and the classical approach and clearly show the advantages of the new method.

The Slow Relaxation Dynamics in the Amorphous Pharmaceutical Drugs Cimetidine, Nizatidine, and Famotidine.

The slow molecular mobility in the amorphous solid state of 3 active pharmaceutical drugs (cimetidine, nizatidine, and famotidine) has been studied using differential scanning calorimetry and the 2 dielectric-related techniques of dielectric relaxation spectroscopy and thermally stimulated depolarization currents. The glass-forming ability, the glass stability, and the tendency for crystallization from the equilibrium melt were investigated by differential scanning calorimetry, which also provided the characterization of the main relaxation of the 3 glass formers. The chemical instability of famotidine at the melting temperature and above it prevented the preparation of the amorphous for dielectric studies.

Unexpected solvent impact in the crystallinity of praziquantel/poly(vinylpyrrolidone) formulations. A solubility, DSC and solid-state NMR study.

The saturation solubility of PVP:PZQ physical mixtures (PMs) and solid dispersions (SDs) prepared from ethanol (E/E) or ethanol/water (E/W) by the solvent evaporation method at 1:1, 2:1 and 3:1 ratio (w/w) was determined. The presence of PVP improves the solubility of PZQ (0.31±0.

Dynamic spin interchange in a tridentate Fe(iii) Schiff-base compound.

The thermosalient effect is still a rare and poorly understood phenomenon, where crystals suddenly jump, bend, twist or explode upon undergoing a thermally activated phase transition. The synthesis and characterisation of the new spin transition Fe(iii) compound [Fe(5-Br-salEen)][ClO] (salEen = -ethyl--(2-aminoethyl)salicylaldiminate) is described and its thermosalient behaviour reported. It is the first example of a thermosalient effect with a spin transition and magnetic, calorimetric, diffraction, microscopy and computational studies are used to characterise these effects.

Dipolar Reorientations in Amorphous Nimesulide: A TSDC and DSC Study.

Background: The preparation of APIs in the amorphous solid form can be a means of circumventing problems arising from poor solubility and low dissolution rate of the crystalline drugs. However, molecular mobility can be responsible for the glass instability, so that the kinetic characterization of the different relaxations that subsist in the amorphous solid is useful to allow define the conditions for greater stability of the glassy pharmaceutical. Our purpose is to use the experimental techniques of differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC) to study the thermal behavior of the pharmaceutical drug nimesulide and its slow molecular mobility in the amorphous solid state.

The slow relaxation dynamics in active pharmaceutical ingredients studied by DSC and TSDC: Voriconazole, miconazole and itraconazole.

The slow molecular mobility of three active pharmaceutical drugs (voriconazole, miconazole and itraconazole) has been studied by differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC). This study yielded the main kinetic features of the secondary relaxations and of the main (glass transition) relaxation, in particular their distribution of relaxation times. The dynamic fragility of the three glass formers was determined from DSC data (using two different procedures) and from TSDC data.

The Slow Molecular Mobility in Amorphous Ketoprofen and Ibuprofen.

The slow molecular dynamics in two active pharmaceutical drugs, ketoprofen and ibuprofen, have been studied by differential scanning calorimetry (DSC) and thermally stimulated depolarization currents (TSDC). This study allowed finding the main kinetic features of the fast secondary (γ) relaxation, of the Johari-Goldstein relaxation, and of the main (glass transition) relaxation, in particular their distribution of relaxation times. The fragility index of the two glass formers was determined based on data from DSC and from TSDC.

The segmental and chain relaxation modes in high-cis-polyisoprene as studied by thermally stimulated currents.

The technique of Thermally Stimulated Currents is used to study the slow molecular mobility in a series of poly (1,4-cis-isoprene) samples with different molecular weights, Mw, and low polydispersity. The technique revealed a high resolution power, particularly useful in the study of the lower molecular weight samples where the chain and the segmental relaxations strongly overlap. The dynamic crossover that is reported for the normal mode by varying the molecular weight is clearly revealed by the thermally stimulated depolarization currents results through the temperature location, TMn, of the normal mode peak, the values of the relaxation time at TMn, τ(TMn), and the value of the fragility index of the normal mode, mn.

Enthalpy of formation of anisole: implications for the controversy on the O-H bond dissociation enthalpy in phenol.

Significant discrepancies in the literature data for the enthalpy of formation of gaseous anisole, ΔfHmo(PhOCH3, g), have fueled an ongoing controversy regarding the most reliable enthalpy of formation of the phenoxy radical and of the gas phase O-H bond dissociation enthalpy, DHo(PhO-H), in phenol. In the present work ΔfHmo(PhOCH3, g) was reassessed using a combination of calorimetric determinations and high-level (W2-F12) ab initio calculations. Static-bomb combustion calorimetry led to the standard molar enthalpy of formation of liquid anisole at 298.

A stable amorphous statin: solid-state NMR and dielectric studies on dynamic heterogeneity of simvastatin.

Statins have been widely used as cholesterol-lowering agents. However, low aqueous solubility of crystalline statins and, consequently, reduced biovailability require seeking for alternative forms and formulations to ensure an accurate therapeutic window. The objective of the present study was to evaluate the stability of amorphous simvastatin by probing molecular dynamics using two nondestructive techniques: solid-state NMR and dielectric relaxation spectroscopy.

Thermal stability of simvastatin under different atmospheres.

Simvastatin (SV) is a widely used drug for the treatment of hypercholesterolemia in humans. Nevertheless, serious efforts are still being made to develop new SV formulations with, for example, improved tabletability or bioavailability properties. These efforts frequently involve heating the compound well above ambient temperature or even fusion.

On the heterogeneous composition of bacterial polyhydroxyalkanoate terpolymers.

Poly(3-hydroxybutyrate-4-hydroxybutyrate-3-hydroxyvalerate) (P(3HB-4HB-3HV)) terpolymers of low 3-hydroxyvalerate (3HV) content (1.7-6.4%) with 4-hydroxybutyrate (4HB) molar fractions from 1.

Energetics and structure of simvastatin.

The study of structure-energetics relationships for active pharmaceutical ingredients has received considerable attention in recent years, due to its importance for the effective production and safe use of drugs. In this work the widely prescribed cholesterol-lowering drug simvastatin was investigated by combining experimental (combustion calorimetry and differential scanning calorimetry, DSC) and computational chemistry (quantum chemistry and molecular dynamics calculations) results. The studies addressed the crystalline form stable at ambient temperature (form I) and the liquid and gaseous phases.

Molecular dynamics of amorphous gentiobiose studied by solid-state NMR.

A solid-state NMR (SSNMR) study is reported on the effect of temperature on the molecular mobility of amorphous gentiobiose, which is complemented with data obtained from crystalline samples. (13)C cross-polarization/magic-angle-spinning (CPMAS) spectra and (1)H MAS spectra were obtained for gentiobiose at natural abundance, in the amorphous state, from 293 K up to the glass transformation region (T(g) = 359 K). Two well-defined molecular mobility regimes were observed, corresponding to different motional modes.

Thermodynamic characterization of three polymorphic forms of piracetam.

Combustion calorimetry, solution calorimetry, and differential scanning calorimetry (DSC) were used to determine the standard (p° = 0.1 MPa) molar enthalpies of formation of Forms I, II, and III piracetam at 298.15 K, namely, Δ(f) H(m)° (C(6)H(10)O(2)N(2), cr I) = -520.

Molecular mobility studies on the amorphous state of disaccharides. I-thermally stimulated currents and differential scanning calorimetry.

The relaxational processes in amorphous solid gentiobiose and cellobiose are studied by thermally stimulated depolarization currents (TSDC) in the temperature region from 108K up to 423K. The slow molecular mobility was characterized in the crystal and in the glassy state. The features of different motional components of the secondary relaxation have been monitored as a function of time as the glass structurally relaxes on aging.

Slow molecular mobility in the amorphous solid state of fructose: fragility and aging.

The molecular mobility of beta-D-fructose was studied by thermally stimulated depolarization currents (TSDC) in the amorphous solid state. The amorphous solid samples were prepared in such a way that the tautomeric mixture was near the equilibrium composition. A broad secondary relaxation was observed, that merges, at high temperatures, with the alpha relaxation.