Inhibition of naproxen crystallization by polymers: The role of topology and chain length of polyvinylpyrrolidone macromolecules.

This paper presents an innovative approach that utilizes self-synthesized homopolymers of polyvinylpyrrolidone (PVP) with different architectures as effective matrices for inhibiting the crystallization of naproxen (NAP). We have thoroughly investigated amorphous solid dispersions containing NAP and (i) self-synthesized linear PVP, (ii) self-synthesized three-armed star-shaped PVP, and (iii) self-synthesized linear PVP with a mass (M) corresponding to the length of one arm of the star polymer, as well as (iv) commercial linear PVP K30 as a reference. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and infrared spectroscopy (FTIR) studies, as well as molecular dynamics simulations were conducted to gain comprehensive insights into the thermal and structural properties, as well as intermolecular interactions in the NAP-PVP systems.

The existence of a strongly bonded layer in associating liquids within silica pores - a spectral and molecular dynamics study.

The properties of confined materials are assumed to be governed by the phenomena occurring at the interface, especially the formation of an irreversible adsorption layer (IAL), which has been widely discussed and detected in the case of thin polymer films and silica nanoparticles. In this paper, we present a novel experimental approach allowing us to reveal the formation of an IAL in two phenyl alcohols infiltrated into various mesoporous silica templates. The proposed methodology (based on evaporation) allowed us to detect the alterations in the OH and aromatic CH stretching vibration bands in infrared spectra, which were considered as evidence of the existence of IAL in constrained systems.

The Impact of Various Poly(vinylpyrrolidone) Polymers on the Crystallization Process of Metronidazole.

In this paper, we propose one-step synthetic strategies for obtaining well-defined linear and star-shaped polyvinylpyrrolidone (PVP and PVP). The produced macromolecules and a commercial PVP K30 with linear topology were investigated as potential matrices for suppressing metronidazole (MTZ) crystallization. Interestingly, during the formation of binary mixtures (BMs) containing different polymers and MTZ, we found that linear PVPs exhibit maximum miscibility with the drug at a 50:50 weight ratio (/), while the star-shaped polymer mixes with MTZ even at a 30:70 /.

Pressure-Induced Aggregation of Associating Liquids as a Driving Force Enhancing Hydrogen Bond Cooperativity.

The behavior of hydrogen bonds under extreme pressure is still not well understood. Until now, the shift of the stretching vibration band of the X-H group (X = the donor atom) in infrared spectra has been attributed to the variation in the length of the covalent X-H bond. Herein, we combined infrared spectroscopy and X-ray diffraction experimental studies of two H-bonded liquid hexane derivatives, i.

Experimental and Computational Approach to Studying Supramolecular Structures in Propanol and Its Halogen Derivatives.

A series of four alcohols, -propanol and its halogen (Cl, Br, and I) derivatives, were selected to study the effects of variation in polarity and halogen-driven interactions on the hydrogen bonding pattern and supramolecular structure by means of experimental and theoretical methods. It was demonstrated on both grounds that the average strength of H-bonds remains the same but dissociation enthalpy, the size of molecular nanoassemblies, as well as long-range correlations between dipoles vary with the molecular weight of halogen atom. Further molecular dynamics simulations indicated that it is connected to the variation in the molecular order introduced by specific halogen-based hydrogen bonds and halogen-halogen interactions.

Preconcentration of phosphate ions on graphene oxide decorated with lanthanum oxide from waters followed by energy dispersive X-ray fluorescence spectrometric determination.

A method for energy dispersive X-ray fluorescence spectrometric (EDXRF) determination of phosphate ions via the PKα line in diverse types of water samples is described. The method is based on ultrasonically assisted dispersive micro-solid phase extraction (USA-DMSPE) using lanthanum oxide supported on graphene oxide (LaO-GO) as a solid adsorbent. Under optimal preconcentration conditions, i.

High-pressure studies in the supercooled and glassy state of the strongly associated active pharmaceutical ingredient-ticagrelor.

In this paper, the molecular dynamics at different thermodynamic conditions of hydrogen-bonded (H-bonded) active pharmaceutical ingredient-ticagrelor (TICA) have been investigated. Extensive high-pressure (HP) dielectric studies revealed surprising high sensitivity of the structural (α)-relaxation to compression. They also showed that unexpectedly the shape of the α-peak remains invariable at various temperature (T) and pressure (p) conditions at constant α-relaxation time.

On the relationship between the Debye process in dielectric response and a dissociation-association phenomenon in phenyl alcohols.

In this paper, we have examined a series of phenyl-substituted primary monohydroxy alcohols (phenyl alcohols, PhAs), from ethanol to hexanol by means of dielectric and Fourier transform infrared (FTIR) spectroscopies supported by the mechanical investigations. The combination of both dielectric and mechanical data allows calculation of the energy barrier, , for dissociation by the Rubinstein approach developed to describe the dynamical properties of self-assembling macromolecules. It was observed that the determined activation energy remains constant, || ∼ 12.

Studies on the nature and pressure evolution of phase transitions in 1-adamantylamine and 1-adamantanol.

In this paper, several experimental techniques, i.e., differential scanning calorimetry, X-ray diffraction, Fourier transform infrared, Raman, and broadband dielectric spectroscopy were applied to study the nature of the phase transitions in 1-adamantylamine (1-NH-ADM, CHN) and 1-adamantanol (1-OH-ADM, CHO).

Studying the Intermolecular Interactions, Structural Dynamics, and Non-Equilibrium Kinetics of Cilnidipine Infiltrated into Alumina and Silica Pores.

In the present study, the behavior of the calcium channel blocker cilnidipine (CLN) infiltrated into silica (SiO) and anodic aluminum oxide (AAO) porous membranes characterized by a similar pore size ( = 8 nm and = 10 nm, respectively) as well as the bulk sample has been investigated using differential scanning calorimetry, broadband dielectric spectroscopy (BDS), and Fourier-transform infrared spectroscopy (FTIR) techniques. The obtained data suggested the existence of two sets of CLN molecules in both confined systems (core and interfacial). They also revealed the lack of substantial differences in inter- and intramolecular dynamics of nanospatially restricted samples independently of the applied porous membranes.

The unique role of pore wall nanostructurization in the intrachannel photo-ATRP for fine-tuning PMMA tacticity.

In this paper, efficient MMA photo -ATRP protocols conducted inside nanoreactors varying in nanostructured interfaces are reported for the first time. We showed that the microstructure of recovered polymers could be easily tuned just by implementing a given type of nanochannel ( = 10, 19-28, 35, 160 nm).

The Effect of Various Poly (-vinylpyrrolidone) (PVP) Polymers on the Crystallization of Flutamide.

In this study, several experimental techniques were applied to probe thermal properties, molecular dynamics, crystallization kinetics and intermolecular interactions in binary mixtures (BMs) composed of flutamide (FL) and various poly(-vinylpyrrolidone) (PVP) polymers, including a commercial product and, importantly, samples obtained from high-pressure syntheses, which differ in microstructure (defined by the tacticity of the macromolecule) from the commercial PVP. Differential Scanning Calorimetry (DSC) studies revealed a particularly large difference between the glass transition temperature () of FL+PVPsynth. mixtures with 10 and 30 wt% of the excipient.

The impact of H/D exchange on the thermal and structural properties as well as high-pressure relaxation dynamics of melatonin.

In this paper, thermal properties, atomic-scale structure, and molecular dynamics (at ambient and high pressure) of native melatonin (MLT) and its partially-deuterated derivative (MLT-d) have been investigated. Based on infrared spectroscopy, it was shown that treating MLT with DO causes the replacement of hydrogen atoms attached to the nitrogen by deuterium. The degree of such substitution was very high (> 99%) and the deuterated sample remained stable after exposure to the air as well as during the melting and vitrification processes.

A study of OH···O hydrogen bonds along various isolines in 2-ethyl-1-hexanol. Temperature or pressure - which parameter controls their behavior?

The nature of H-bonding interactions is still far from being understood despite intense experimental and theoretical studies on this subject carried out by the leading research centers. In this paper, by a combination of unique high-pressure infrared, dielectric and volumetric data, the intramolecular dynamics of hydroxyl moieties (which provides direct information about H-bonds) was studied along various isolines, i.e.

The impact of the size of acetylated cyclodextrin on the stability of amorphous metronidazole.

Modified oligosaccharides with cyclic topology seem to be promising excipients for the preparation of Amorphous Solid Dispersions (ASDs), especially with those Active Pharmaceutical Ingredients (APIs), which have a strong crystallization tendency from the amorphous/glassy state. Herein, the usefulness of two acetylated cyclodextrins (ac-α-CD and ac-β-CD) with various molecular weights (M) as stabilizers for the supercooled metronidazole (Met) has been discussed. X-ray diffraction (XRD) studies carried out on Met-acCDs mixtures (prepared in molar ratios from 1:2 to 5:1) showed that the system with ac-α-CD containing the highest amount of API (5:1 m/m) crystallizes immediately after preparation, whereas all Met-ac-β-CD ASDs remain stable.

Aromaticity effect on supramolecular aggregation. Aromatic vs. cyclic monohydroxy alcohols.

In this paper, the steric hindrance effect related to the presence of either a cyclic or aromatic ring on the self-association process in the series of monohydroxy alcohols (MAs), from cyclohexanemethanol to 4-cyclohexyl-1-butanol and from benzyl alcohol to 4-phenyl-1-butanol, was studied using X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, Broadband Dielectric Spectroscopy (BDS) and the Pendant Drop (PD) methods. Based on FTIR results, it was shown that phenyl alcohol (PhA) and cyclohexyl alcohol (CA) derivatives reveal substantial differences in the association degree, the activation energy of dissociation, and the homogeneity of supramolecular nanoassociates suggesting that the phenyl ring exerts a stronger steric impact on the self-assembling of molecules than cyclohexyl one. Additionally, XRD data revealed that phenyl moiety introduces more heterogeneity in the organization of molecules compared to the cyclic one.

Studies on the Vitrified and Cryomilled Bosentan.

In this paper, several experimental techniques [X-ray diffraction, differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy, and broad-band dielectric spectroscopy] have been applied to characterize the structural and thermal properties, H-bonding pattern, and molecular dynamics of amorphous bosentan (BOS) obtained by vitrification and cryomilling of the monohydrate crystalline form of this drug. Samples prepared by these two methods were found to be similar with regard to their internal structure, H-bonding scheme, and structural (α) dynamics in the supercooled liquid state. However, based on the analysis of α-relaxation times (dielectric measurements) predicted for temperatures below the glass-transition temperature (), as well as DSC thermograms, it was concluded that the cryoground sample is more aged (and probably more physically stable) compared to the vitrified one.

Broadband-dielectric-spectroscopy study of molecular dynamics in a mixture of itraconazole and glycerol in glassy, smectic-A, and isotropic phases.

Itraconazole (ITZ) is a thermotropic liquid crystal that exhibits isotropic, nematic, and smectic phases on cooling towards the glass transition upon melting. Over the years, new aspects regarding the liquid-crystalline ordering of this antifungal drug were systematically revealed. It has been shown recently that the temperature range of individual mesophases in ITZ can be modified by adding a small amount of glycerol (GLY).

The impact of the length of alkyl chain on the behavior of benzyl alcohol homologues - the interplay between dispersive and hydrogen bond interactions.

In this work, we examined the effect of the length of alkyl chain attached to the benzene ring on the self-assembling phenomena for a series of phenyl alcohol (PhA) derivatives, from phenylmethanol (benzyl alcohol) to 7-phenyl-1-heptanol, by means of X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, and Broadband Dielectric Spectroscopy (BDS) methods. XRD data in the reciprocal and real spaces showed a gradual increase in the local order with the elongation of the alkyl chain. However, the position and full width at half maximum of the main diffraction peak exhibited a non-systematic behavior.

How does pressure affect the molecular dynamics, intramolecular interactions, and the relationship between structural (α) and secondary (JG-β) relaxation above and below the glass transition temperature in binary mixtures of H-bonded API - probucol and acetylated saccharides?

In this paper, the molecular dynamics as well as inter- and intramolecular interactions in the homogenous solid dispersions (SDs) of active pharmaceutical ingredient - probucol (PRO) with acetylated glucose (acGLU), acetylated sucrose (acSUC), and sucrose acetoisobutyrate (aibSUC), prepared in 5:1 molar ratio, have been investigated using broadband dielectric (BD) and Fourier transform infrared (FTIR) spectroscopy. Importantly, high pressure dielectric measurements revealed that as for neat PRO, a breakdown of the isochronal structural (α) and JG-β exact superpositioning, due to increasing separation between both processes under compression, can also be detected in its mixtures with acetylated saccharides (acSACCHs). Furthermore, the analysis of temperature dependences of JG-β-relaxation times for PRO and PRO-acSACCH SDs at selected isobaric conditions indicated the increase in the cooperativity of the secondary process (reflected in the value of the activation entropy, ΔS) at elevated pressure in all systems.

Is a Dissociation Process Underlying the Molecular Origin of the Debye Process in Monohydroxy Alcohols?

Herein, we investigated the molecular dynamics as well as intramolecular interactions in two primary monohydroxy alcohols (MA), 2-ethyl-1-hexanol (2EHOH) and -butanol (BOH), by means of broad-band dielectric (BDS) and Fourier transform infrared (FTIR) spectroscopy. The modeling data obtained from dielectric studies within the Rubinstein approach [ 2013, 46, 7525-7541] originally developed to describe the dynamical properties of self-assembling macromolecules allowed us to calculate the energy barrier () of dissociation from the temperature dependences of relaxation times of Debye and structural processes. We found ∼ 19.

Impact of the Chain Length and Topology of the Acetylated Oligosaccharide on the Crystallization Tendency of Naproxen from Amorphous Binary Mixtures.

The impact of the chain length or dispersity of polymers in controlling the crystallization of amorphous active pharmaceutical ingredients (APIs) has been discussed for a long time. However, because of the weak control of these parameters in the majority of macromolecules used in pharmaceutical formulations, the abovementioned topic is poorly understood. Herein, four acetylated oligosaccharides, maltose (acMAL), raffinose (acRAF), stachyose (acSTA), and α-cyclodextrin (ac-α-CD) of growing chain lengths and different topologies (linear cyclic), mimicking the growing backbone of the polymer, were selected to probe the influence of these structural factors on the crystallization of naproxen (NAP)-an API that does not vitrify regardless of the cooling rate applied in our experiment.

Correlation between Locally Ordered (Hydrogen-Bonded) Nanodomains and Puzzling Dynamics of Polymethysiloxane Derivative.

We examined the behavior of poly(mercaptopropyl)methylsiloxane (PMMS), characterized by a polymer chain backbone of alternate silicon and oxygen atoms substituted by a polar pendant group able to form hydrogen bonds (-SH moiety), by means of infrared (FTIR) and dielectric (BDS) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rheology. We observed that the examined PMMS forms relatively efficient hydrogen bonds leading to the association of chains in the form of ordered lamellar-like hydrogen-bonded nanodomains. Moreover, the recorded mechanical and dielectric spectra revealed the presence of two relaxation processes.

Unique Behavior of Poly(propylene glycols) Confined within Alumina Templates Having a Nanostructured Interface.

Herein we show that the nanostructured interface obtained via modulation of the pore size has a strong impact on the segmental and chain dynamics of two poly(propylene glycol) (PPG) derivatives with various molecular weights ( = 4000 g/mol and = 2000 g/mol). In fact, a significant acceleration of the dynamics was observed for PPG infiltrated into ordinary alumina templates ( = 36 nm), while bulklike behavior was found for samples incorporated into membranes of modulated diameter (19 nm < < 28 nm). We demostrated that the modulation-induced roughness reduces surface interactions of polymer chains near the interface with respect to the ones adsorbed to the ordinary nanochannels.