Combination of (M)DSC and surface analysis to study the phase behaviour and drug distribution of ternary solid dispersions

Purpose: Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix. Methods: MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed. Results: The distribution of the API in the ternary solid dispersions depended on formulation parameters. The extent of API surface coverage and therefore the distribution of the API over both polymeric phases differed significantly for the three formulations. Conclusions: Combining (M)DSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions

Dielectric and thermal characterization of electroactive sol gel polymer composites

The dielectric characterization of silica gel-poly (methyl methacrylate)-organic dye composites has identified three relaxation mechanisms which give rise to partially overlapping thermocurrent bands in the range 10-320K of the Thermally Stimulated Depolarization Currents (TSDCs) spectra: a relatively low intensity relaxation band maximized at around 130K, a broad band around 225Y and intense signals above 275K. Spectral results show that these relaxations are mainly bulk rather electrode interfacial effects, and are discussed in terms of intrinsic dipolar (e.g. rotations of H2O molecules and conformational motions of the polymer side chain segments), Maxwell-Wagner-Sillars interfacial polarizations, and other types of compositional/structural defects. Differential Scanning Calorimetry (DSC) analysis of PMMA/Sol-gel composites has shown that the impregnated polymer’s transition temperature increases by about 15 degrees, compared to bulk PMMA. The effect is attributed to hydrogen bonding between the pore surface silanols and the polymer side chains, based on additional Raman and NMR measurements

Polarizing-field orientation and thermal treatment effects on the dielectric behavior of fluorapatite

A thermally stimulated depolarization currents (TSDC) study in natural fluorapatite single crystals has established different relaxation mechanisms for two polarization orientations (E-p parallel and perpendicular to the crystallographic c axis), which are discussed in relation to the defect chemistry and the specific columnar structure in apatite. The intensities of the thermostimulated current signals between the two poling field orientations demonstrate a difference of at least one order of magnitude, with the higher one recorded for the electric field parallel to the c axis. The TSDC thermogram appearing with the electric field parallel to c axis, in the 10-320 K range, consists of a broad and complex band (HT), with a maximum around 300 K. The relative intensity of associated current signals is indicative of extensive dipole-like ionic motions along c axis with a distribution in their activation energies ranging between 0.14 and 0.85 eV. The microdomain structure of fluorapatite along c axis permits the formation of charge layers at the interfaces. After annealing, the induced changes of size and/or shape of the interfaces could explain the observed changes of band intensity and location. With the electric field perpendicular to c axis, the spectrum consists of at least five well-defined relaxation bands, the high temperature ones (HT1, HT2, HT3) decreasing after heating at 673-873 K. The most dramatic change was recorded for an intermediate LT2 single-relaxation band located around 185 K, with a high activation energy of 1.06 eV, which manifested a significant growth after annealing. Rietvelt analysis of the x-ray diffraction patterns of the original and annealed apatite powders, indicates change in the unit cell parameters of the hexagonal structure (i.e., a increases from 9.3921 to 9.3940 Angstrom after annealing), which can be related to the establishment of a new equilibrium distribution of the abundant trivalent rare-earth (Ce, La, Nd, Pr,...) impurity ions. The origin of the TSDC bands is discussed and tentative correlations are suggested, in terms of substitute aliovalent ions-vacancy dipoles. The thermal response of the high temperature relaxation bands in the case of E-p perpendicular to c axis, is characteristic of dipole clustering phenomena - although an explanation based on localized changes in the structural environment of the pertinent dipoles/ions cannot be disregarded. (C) 1999 American Institute of Physics. [S00218979(99)10001- X]

Comparative dielectric studies of segmental mobility in novel polyurethanes

Molecular dynamics in selected novel linear/low-branched polyurethanes (PUs), based on oligo(oxytetramethylene glycol), 4,4′- diphenylmethanediisocyanate (MDI) or 2,6-toluenediisocyanate (TDI), and unsymmetrical dimethyl-hydrazine (I) and a derivative of that (II) as chain extenders (CE), were studied by dielectric techniques. Special attention was paid to the investigation of the a relaxation, associated to the glass transition, by dielectric relaxation spectroscopy (DRS) and thermally stimulated depolarization currents (TSDC). The TSDC method was used to study the interfacial Maxwell-Wagner-Sillars (MWS) relaxation, related to the accumulation of charges at the interfaces between soft-segment and hard-segment microdomains. The results obtained by DRS and TSDC were in good agreement with each other and in reasonable agreement with results for the micro-phase separation (MS) obtained by small-angle X-ray scattering and differential scanning calorimetry. TSDC proved to be an attractive complementary technique to DRS for the study of MS in PUs. The results suggest that the position of the MWS band, as well as its separation from the a band, is a good measure of the degree of MS. As regards the PUs studied here, the degree of MS enhances by increasing the mole ratio of CE, and by replacing MDI by TDI or CE I by CE II