Characterisation and processing of amorphous binary mixtures with low glass transition temperature

The number of drug substances in formulation development in the pharmaceutical industry is increasing. Some of these are amorphous drugs and have glass transition below ambient temperature, and thus they are usually difficult to formulate and handle. One reason for this is the reduced viscosity, related to the stickiness of the drug, that makes them complicated to handle in unit operations. Thus, the aim in this thesis was to develop a new processing method for a sticky amorphous model material. Furthermore, model materials were characterised before and after formulation, using several characterisation methods, to understand more precisely the prerequisites for physical stability of amorphous state against crystallisation. The model materials used were monoclinic paracetamol and citric acid anhydrate. Amorphous materials were prepared by melt quenching or by ethanol evaporation methods. The melt blends were found to have slightly higher viscosity than the ethanol evaporated materials. However, melt produced materials crystallised more easily upon consecutive shearing than ethanol evaporated materials. The only material that did not crystallise during shearing was a 50/50 (w/w, %) blend regardless of the preparation method and it was physically stable at least two years in dry conditions. Shearing at varying temperatures was established to measure the physical stability of amorphous materials in processing and storage conditions. The actual physical stability of the blends was better than the pure amorphous materials at ambient temperature. Molecular mobility was not related to the physical stability of the amorphous blends, observed as crystallisation. Molecular mobility of the 50/50 blend derived from a spectral linewidth as a function of temperature using solid state NMR correlated better with the molecular mobility derived from a rheometer than that of differential scanning calorimetry data. Based on the results obtained, the effect of molecular interactions, thermodynamic driving force and miscibility of the blends are discussed as the key factors to stabilise the blends. The stickiness was found to be affected glass transition and viscosity. Ultrasound extrusion and cutting were successfully tested to increase the processability of sticky material. Furthermore, it was found to be possible to process the physically stable 50/50 blend in a supercooled liquid state instead of a glassy state. The method was not found to accelerate the crystallisation. This may open up new possibilities to process amorphous materials that are otherwise impossible to manufacture into solid dosage forms.

Electron Mean Energy, Secondary Ionization Coefficients And (E/P)Crit In Binary-Mixtures Of Sf6-N2 And Ccl2f2-N2

Measurements of the ratio of diffusion coefficient to mobility (D/ mu ) of electrons in SF6-N2 and CCl2F2-N2 mixtures over the range 80mixtures and 5.12 for CCl2F2 mixtures. In the present study, it has been possible to show that beta is indeed to a factor of synergism. Estimated gamma values (secondary ionisation coefficients) did not show any significant variation with F for F<50.

Ionisation and attachment in binary mixtures of SF6-N2 and CCl2F2-N2

Experimental results are presented of ionisation (a)a nd electron attachment ( v ) coefficients evaluated from the steady-state Townsend curregnrto wth curves for SFsN2 and CC12FrN2 mixtures over the range 60 S E/P 6 240 (where E is the electric field in V cm" and P is the pressure in Torr reduced to 20'C). In both the mixtures the attachment coefficients (vmu) evaluated were found to follow the relationship; where 7 is the attachment coefficient of pure electronegative gas, F is the fraction of the electronegative gas in the mixture and /3 is a constant. The ionisation coefficients (amlx) generally obeyed the relationship where w2a nd aAa re thei onisation coefficients of nitrogen and the attachinggraess pectively. However, in case of CC12FrN2 mixtures, there were maxima in the a,,,v,a,l ues for CCI2F2 concentrations varying between 10% and 30% at all values of E/P investigated. Effective ionisation coefficients (a - p)/P obtained in these binary mixtures show that the critical E/P (corresponding to (a - q)/P = 0) increases with increase in the concentration of the electronegative gas up to 40%. Further increase in the electronegative gas content does not seem to alter the critical E/P.

Electron attachment in binary mixtures of electronegative and buffer gases

The ratio of the electron attachment coefficient eta to the gas pressure p (reduced to 0 degrees C) evaluated from the Townsend current growth curves in binary mixtures of electronegative gases (SF6, CCl2F2, CO2) and buffer gases (N2, Ar, air) clearly indicate that the eta /p ratios do not scale as the partial pressure of electronegative gas in the mixture. Extensive calculations carried out using data experimentally obtained have shown that the attachment coefficient of the mixture eta mix can be expressed as eta mix= eta (1-exp- beta F/(100-F)) where eta is the attachment coefficient of the 100% electronegative gas, F is the percentage of the electronegative gas in the mixture and beta is a constant. The results of this analysis explain to a high degree of accuracy the data obtained in various mixtures and are in very good agreement with the data deduced by Itoh and co-workers (1980) using the Boltzmann equation method.

Ultrasonic propagation through binary mixtures containing acetic acid

Ultrasonic absorption has been studied by the pulse technique in the binary mixtures of acetic acid in water, methyl and ethyl alcohols and covers a range of 2 to 26 Mc/s. The mixtures are studied from 0 to 100% by weight of the acid. In all the three mixtures, two relaxation processes are observed, the first occurring below the frequency range of the study. The second one occurs near 20 Mc/s in the acid-water mixtures and at much higher frequencies in the other cases. It is qualitatively explained that the monomer-dimer reaction of the acetic acid giving a relaxation near 1 Mc/s has shifted to a higher frequency when mixed in a solvent thus giving rise to a second relaxation in the mixtures.

Communication: Unusual dynamics of hybrid nanoparticles and their binary mixtures

We present the results on the evolution of microscopic dynamics of hybrid nanoparticles and their binary mixtures as a function of temperature and wave vector. We find unexpectedly a nonmonotonic dependence of the structural relaxation time of the nanoparticles as a function of the morphology. In binary mixtures of two of the largest nanoparticles studied, we observe re-entrant vitrification as a function of the volume fraction of the smaller nanoparticle, which is unusual for such high diameter ratio. Possible explanation for the observed behavior is provided. (C) 2010 American Institute of Physics. doi:10.1063/1.3495480]

Inherent structures of phase-separating binary mixtures: Nucleation, spinodal decomposition, and pattern formation

An energy landscape view of phase separation and nonideality in binary mixtures is developed by exploring their potential energy landscape (PEL) as functions of temperature and composition. We employ molecular dynamics simulations to study a model that promotes structure breaking in the solute-solvent parent binary liquid, at low temperatures. The PEL of the system captures the potential energy distribution of the inherent structures (IS) of the system and is obtained by removing the kinetic energy (including that of intermolecular vibrations). The broader distribution of the inherent structure energy for structure breaking liquid than that of the structure making liquid demonstrates the larger role of entropy in stabilizing the parent liquid of the structure breaking type of binary mixtures. At high temperature, although the parent structure of the structure breaking binary mixture is homogenous, the corresponding inherent structure is found to be always phase separated, with a density pattern that exhibits marked correlation with the energy of its inherent structure. Over a broad range of intermediate inherent structure energy, bicontinuous phase separation prevails with interpenetrating stripes as signatures of spinodal decomposition. At low inherent structure energy, the structure is largely phase separated with one interface where as at high inherent structure energy we find nucleation type growth. Interestingly, at low temperature, the average inherent structure energy (< EIS >) exhibits a drop with temperature which signals the onset of crystallization in one of the phases while the other remains in the liquid state. The nonideal composition dependence of viscosity is anticorrelated with average inherent structure energy.

Three-dimensional double-diffusive convection and macrosegregation during non-equilibrium solidification of binary mixtures

A three-dimensional transient mathematical model (following a fixed-grid enthalpy-based continuum formulation) is used to study the interaction of double-diffusive natural convection and non-equilibrium solidification of a binary mixture in a cubic enclosure cooled from a side. Investigations are carried out for two separate test systems, one corresponding to a typical model "metal-alloy analogue" system and other corresponding to a real metal-alloy system. Due to stronger effects of solutal buoyancy in actual metal-alloy systems than in corresponding analogues, the convective transport mechanisms for the two cases are quite different. However, in both cases, similar elements of three-dimensionality are observed in the curvature and spacing of the projected streamlines. As a result of three-dimensional convective flow patterns, a significant solute macrosegregation is observed across the transverse sections of the cavity, which cannot be captured by two-dimensional simulations. (C) 2003 Elsevier Science Ltd. All rights reserved.

Re-entrant behavior in dynamics of binary mixtures of soft hybrid nanocolloids and homopolymers

We present results of measurements of temperature and wavevector dependent dynamics in binary mixtures of soft polymer grafted nanoparticles and linear homopolymers. We find evidence of melting of the dynamically arrested state of the soft nanocolloids with addition of linear polymers followed by a re-entrant slowing down of the dynamics with further increase in polymer density, depending on the size ratio, delta, of the polymers and the nanocolloids. For higher delta the re-entrant behavior is not observed, even for the highest added polymer density, explored here. Possible explanation of the observed dynamics in terms of the presence of a double - glass phase is provided. (C) 2011 American Institute of Physics. [doi:10.1063/1.3644930]

Anomalous structural and dynamical phase transitions of soft colloidal binary mixtures

We report microscopic structural and dynamical measurements on binary mixtures of homopolymers and polymer grafted nanoparticles at high densities in good solvent. We find strong and unexpected anomalies in the structure and dynamics of these binary mixtures, including appearance of spontaneous orientational alignment, as a function of added homopolymers of different molecular weights. Our experiments point to the possibility of exploiting the phase space in density and homopolymer size, of such hybrid systems, to create new materials with novel structural and physical properties.

Stability of fluctuating and transient aggregates of amphiphilic solutes in aqueous binary mixtures: Studies of dimethylsulfoxide, ethanol, and tert-butyl alcohol

In aqueous binary mixtures, amphiphilic solutes such as dimethylsulfoxide (DMSO), ethanol, tertbutyl alcohol (TBA), etc., are known to form aggregates (or large clusters) at small to intermediate solute concentrations. These aggregates are transient in nature. Although the system remains homogeneous on macroscopic length and time scales, the microheterogeneous aggregation may profoundly affect the properties of the mixture in several distinct ways, particularly if the survival times of the aggregates are longer than density relaxation times of the binary liquid. Here we propose a theoretical scheme to quantify the lifetime and thus the stability of these microheterogeneous clusters, and apply the scheme to calculate the same for water-ethanol, water-DMSO, and water-TBA mixtures. We show that the lifetime of these clusters can range from less than a picosecond (ps) for ethanol clusters to few tens of ps for DMSO and TBA clusters. This helps explaining the absence of a strong composition dependent anomaly in water-ethanol mixtures but the presence of the same in water-DMSO and water-TBA mixtures. (C) 2013 AIP Publishing LLC.

Anomalous phase transitions in soft colloid-polymer binary mixtures

We have shown earlier [1] that these PGNPs resemble star polymers or spherical brushes in terms of their morphology in the melt. However, these particles show dynamics in melt which is quite different from other soft colloidal particles. Since most of the work on soft colloidal particles have been performed in solutions we have now explored the phase behavior of the PGNPs in good solvent using microscopic structural and dynamical measurements on binary mixtures of homopolymers and soft colloids consisting of polymer grafted nanoparticles. We observe anomalous structural and dynamical phase transitions of these binary mixtures, including appearance of spontaneous orientational alignment and logarithmic structural relaxations, as a function of added homopolymers of different molecular weights. Our experiments points to the possibility of exploiting the phase space in density and homopolymer size, of such hybrid systems, to create new materials with unique properties.

Effect of adsorbate loading on selectivity during adsorption of C/C and C/C n-alkane binary mixtures in silicalite

Adsorption experiments of mixtures of long chain alkanes into silicalite under liquid phase conditions show selectivity inversion and azeotrope formation. These effects are due to the subtle interplay between the size of the adsorbed molecules and pore topology of the adsorbent. In this study, the selective uptake of lighter component during liquid phase adsorption of C/C and C/C n-alkane binary mixtures in the zeolite silicalite is understood through configurational bias grand-canonical Monte Carlo molecular simulation technique and a coarse-grained siting analysis. The simulations are conducted under conditions of low and intermediate levels of loading. The siting pattern of the adsorbates inside the zeolite pores explain the selectivity as seen in experiments.