Impact of Hot-Melt Extrusion on Glibenclamide's Physical and Chemical States and Dissolution Behavior: Case Studies with Three Polymer Blend Matrices.

This research work dives into the complexity of hot-melt extrusion (HME) and its influence on drug stability, focusing on solid dispersions containing 30% of glibenclamide and three 50:50 polymer blends. The polymers used in the study are Ethocel Standard 10 Premium, Kollidon SR and Affinisol HPMC HME 4M. Glibenclamide solid dispersions are characterized using thermal analyses (thermogravimetric analysis (TGA) and differential scanning calorimetry), X-ray diffraction and scanning electron microscopy.

Impact of the polymer dispersity on the properties of curcumin/polyvinylpyrrolidone amorphous solid dispersions.

Amorphous solid dispersions (ASD) are known to enhance the absorption of poorly water-soluble drugs. In this work we synthesise well-defined Polyvinylpyrrolidone (PVP) to establish the impact of dispersity and chain-end functionality on the physical properties of Curcumin (CUR)/PVP ASD. Thermodynamic characterisation of synthesised PVP emphasises a strong effect of the dispersity on the glass transition temperature (T), 50 °C higher for synthesised PVP than for commercial PVP K12 of same molar mass.

Impact of Low Concentration of Strongly Hydrogen-Bonded Water Molecules on the Dynamics of Amorphous Terfenadine: Insights from Molecular Dynamics Simulations and Dielectric Relaxation Spectroscopy.

The impact of low water concentration of strongly hydrogen-bonded water molecules on the dynamical properties of amorphous terfenadine (TFD) is investigated through complementary molecular dynamics (MD) simulations and dielectric relaxation spectroscopy (DRS) experiments. In this article, we especially highlight the important role played by some residual water molecules in the concentration of 1-2% (w/w) trapped in the TFD glassy matrix, which are particularly difficult to remove experimentally without a specific heating/drying process. From MD computations and analyses of the hydrogen bonding (HB) interactions, different categories of water molecules are revealed and particularly the presence of strongly HB water molecules.

Molecular Mobility of Terfenadine: Investigation by Dielectric Relaxation Spectroscopy and Molecular Dynamics Simulation.

The molecular mobility of an amorphous active pharmaceutical ingredient, terfenadine, was carefully investigated by dielectric relaxation spectroscopy and molecular dynamics simulation for the first time. Comprehensive characterization on a wide frequency (10 to 10 Hz) and temperature (300 K) range highlights the fragile nature of this good glass-former ( = 112) and the relatively large nonexponentiality of the main relaxation (β = 0.53 ± 0.

Transformation of an active pharmaceutical ingredient upon high-energy milling: A process-induced disorder in Biclotymol.

This study investigates for the first time the thermodynamic changes of Biclotymol upon high-energy milling at various levels of temperature above and below its glass transition temperature (Tg). Investigations have been carried out by temperature modulated differential scanning calorimetry (TM-DSC) and X-ray powder diffraction (XRPD). Results indicate that Biclotymol undergoes a solid-state amorphization upon milling at Tg-45 °C.

Crystallization from the amorphous state: nucleation-growth decoupling, polymorphism interplay, and the role of interfaces.

The physical stability of the amorphous state is governed by crystallization, which results from the complex interplay of nucleation and growth processes. These processes can be further complicated by the preferred initial nucleation of less-stable phases, and interpretation requires the evaluation of the relative roles of structure, dynamics, and thermodynamics on the kinetics of the recrystallization. As a contribution to this issue, we reanalyze data sets concerning recrystallization of two pharmaceutical compounds: L-arabitol and RS ibuprofen.

A new protocol to determine the solubility of drugs into polymer matrixes.

In this paper we present a new protocol to determine faster the solubility of drugs into polymer matrixes. The originality of the method lies in the fact that the equilibrium saturated states are reached by demixing of supersaturated amorphous solid solutions and not by dissolution of crystalline drug into the amorphous polymer matrix as for usual methods. The equilibrium saturated states are thus much faster to reach due to the extra molecular mobility resulting from the strong plasticizing effect associated with the supersaturation conditions.

On the polymorphism of griseofulvin: identification of two additional polymorphs.

In this paper, we present an investigation of the polymorphism of griseofulvin. In addition to the only reported crystalline form (form I), two new polymorphic forms (II and III) have been identified and characterized by differential scanning calorimetry and powder X-ray diffraction. Reasons why these two polymorphs were isolated during the present study, but not detected during the numerous previous studies on this drug, are also discussed.

Solid-solid transformation in racemic Ibuprofen.

Purpose: To clarify the polymorphism of racemic Ibuprofen and to determine the kinetic of the phase transformation that follows crystallisation of phase II.

Methods: Differential Scanning Calorimetry (DSC), X-ray powder diffraction and Hot Stage Microscopy are complementarily used to perform a kinetic investigation of the particular temperature range where competition between the occurrence of phases I and II is suspected.

Results: Experiments performed with the three techniques reveal that at 273 K the crystallisation to phase II is then followed by a solid-solid transition towards phase I.

Raman spectroscopy of racemic ibuprofen: evidence of molecular disorder in phase II.

Low- and high-frequency Raman experiments in the 5-200 cm(-1) and 600-1800 cm(-1) ranges were carried out in the crystalline and amorphous states of ibuprofen. Low-frequency investigations indubitably reveal the existence of a molecular disorder in the metastable phase (phase II), through the observation of quasielastic contribution below 30 cm(-1), and the absence of phonon peaks in the Raman susceptibility which mimics the density of vibrational states of an amorphous state. High-frequency Raman spectra indicate a local order in phase II similar to that in the glassy state.

Characterization of the hidden glass transition of amorphous cyclomaltoheptaose.

An amorphous solid of cyclomaltoheptaose (β-cyclodextrin, β-CD) was formed by milling its crystalline form using a high-energy planetary mill at room temperature. The glass transition of this amorphous solid was found to occur above the thermal degradation point of the material preventing its direct observation and thus its full characterization. The corresponding glass transition temperature (T(g)) and the ΔC(p) at T(g) have, however, been estimated by extrapolation of T(g) and ΔC(p) of closely related amorphous compounds.

Ab initio structure determination of phase II of racemic ibuprofen by X-ray powder diffraction.

Annealing of the quenched ibuprofen at 258 K yielded a new crystalline form, called phase II. Powder X-ray diffraction patterns of this phase II were recorded with a laboratory diffractometer equipped with an INEL G3000 goniometer and a curved position-sensitive detector CPS120. The starting structural model was found by a Monte-Carlo simulated annealing method.

Evidence for a new crystalline phase of racemic Ibuprofen.

Purpose: The aim of this work is to search for the existence of crystalline polymorphism for racemic Ibuprofen.

Methods: The pharmaceutical material was studied by X-ray diffraction to identify crystalline phases, and by Differential Scanning Calorimetry to follow the thermodynamic evolution of these forms versus temperature.

Results: Results presented here show that, in addition to the already known conventional crystalline phase, whose nucleation domain extends between 233 K and 263 K and which melts at 349 K, racemic Ibuprofen can crystallize in another polymorphic phase.