A Strategy for Co-former Selection to Design Stable Co-amorphous Formations Based on Physicochemical Properties of Non-steroidal Inflammatory Drugs.

Purpose: This study aimed to investigate the physicochemical factors contributing to stable co-amorphous formations and to design a co-former selection strategy.

Methods: Non-steroidal inflammatory drugs were used as main components and/or co-formers. Physical mixtures of the materials were melted.

Anomalous role change of tertiary amino and ester groups as hydrogen acceptors in eudragit E based solid dispersion depending on the concentration of naproxen.

Eudragit E (EGE) is a basic polymer incorporating tertiary amino and ester groups. The role of the functional groups of EGE in the formation of solid dispersion (SD) with Naproxen (NAP) was investigated. The glass transition temperature (Tg) of EGE decreased with the plasticizing effect of NAP up to 20% weight ratio.

Anti-plasticizing effect of amorphous indomethacin induced by specific intermolecular interactions with PVA copolymer.

The mechanism of how poly(vinyl alcohol-co-acrylic acid-co-methyl methacrylate) (PVA copolymer) stabilizes an amorphous drug was investigated. Solid dispersions of PVA copolymer, poly(vinyl pyrrolidone) (PVP), and poly(vinyl pyrrolidone-co-vinyl acetate) (PVPVA) with indomethacin (IMC) were prepared. The glass transition temperature (Tg)-proportion profiles were evaluated by differential scanning calorimetry (DSC).

Raman mapping for kinetic analysis of crystallization of amorphous drug based on distributional images.

The feasibility of Raman mapping for understanding the crystallization mechanism of an amorphous drug was investigated using described images. The crystallization tendency of amorphous indomethacin under dry condition at 30 °C was kinetically evaluated by means of Raman mapping and X-ray powder diffraction (XRPD) with change in the calculated crystallinities. Raman images directly revealed the occurrence of particle size-dependent non-uniform crystallization; slow crystallization of large particles, but fast crystallization of small particles.

Process monitoring of ultrasound compaction as a small-scale heating process.

Ultrasound compaction is a simple small-scale heating process. The aim of this study was to elucidate the polymer phase transition process during ultrasound compaction by process monitoring. Morphological change with heat occurs when ultrasound energy is supplied.

Physicochemical characterization and structural evaluation of a specific 2:1 cocrystal of naproxen-nicotinamide.

Physicochemical characterization and structural evaluation of a 2:1 naproxen-nicotinamide cocrystal were performed. The 2:1 cocrystal showed rapid naproxen dissolution and less water vapor adsorption, indicating better pharmaceutical properties of naproxen. The unique 2:1 cocrystal formation was evaluated by solid-state nuclear magnetic resonance (NMR).

Crystallization of sucrose glass under ambient conditions: evaluation of crystallization rate and unusual melting behavior of resultant crystals.

Isothermal crystallization of sucrose glass under ambient condition was investigated by powder X-ray diffraction, isothermal microcalorimetry, and water sorption/desorption analysis. Isothermal microcalorimetry measurements showed that the crystallization behavior was affected by the compression force applied to starting amorphous materials. The crystallization rate was analyzed by X-ray diffraction measurements to establish that the rate could well be explained by the Avrami-Erofeev equation.

Solubilization behavior of a poorly soluble drug under combined use of surfactants and cosolvents.

The solubilization behavior of a poorly soluble model drug, phenytoin (PHT), under combined use of surfactants (sodium dodecyl sulfate (SDS), Tween 80) and cosolvents (dimethylacetoamide (DMA), ethanol, poly(ethylene glycol) 400 (PEG), glycerol) was examined. The solubility of PHT in the aqueous surfactant solutions increased linearly with increase of the surfactant concentration. The solubility of PHT in water-cosolvent mixtures roughly followed the log-linear model, which is widely accepted to explain the solubilization behavior of poorly soluble compounds in water-cosolvent mixtures, except for the case of glycerol, in which the solubility was minimal at 10% (w/v) of glycerol.

Impact of the amount of excess solids on apparent solubility.

Purpose: The impact of excess solids on the apparent solubility is examined.

Methods: The apparent solubility of some model drugs was measured in various buffered solutions, with various amounts of excess solid. To help understand the dependence of the solubility on the amount of solid, we evaluated the dissolution and crystallization rates of indomethacin (IDM), one of the model drugs, at near-equilibrium conditions.

Effect of salt type on hygroscopicity of a new cephalosporin S-3578.

Purpose: Effect of salt type on hygroscopicity was evaluated using S-3578 salts.

Methods: The hydration behavior of a sulfate and a nitrate salt of S-3578 were evaluated by powder X-ray diffraction (PXRD), simultaneous measurement of PXRD-differential scanning calorimetry (DSC), moisture sorption analysis, simultaneous measurement of thermogravimetric/differential thermal analyses, and solid state 13C-nuclear magnetic resonance (C-NMR).

Results: The sulfate salt incorporated two types of lattice water to form a monohydrate or a trihydrate.

Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent.

Gelucire 44/14 is a surface-active excipient that can solubilize poorly soluble drugs. We investigated its solubilization behavior when coexisting with dimethylacetoamide (DMA) or dimethylsulfoxide (DMSO), both of which are also expected to enhance drug solubility. Gelucire was confirmed to form micelles by surface tension and fluorescence measurements both in water and water/cosolvent mixtures.

Direct observation of the enthalpy relaxation and the recovery processes of maltose-based amorphous formulation by isothermal microcalorimetry.

Purpose: The applicability of isothermal microcalorimetry (IMC) for evaluating enthalpy relaxation and recovery processes of amorphous material was assessed.

Methods: A maltose-based formulation was prepared by freeze-dry method. Differential scanning calorimetry (DSC) was used to investigate its glass transition and relaxation behaviors.

Assessment of amorphous content by microcalorimetry.

The amorphous content of model drugs was evaluated by isotherm microcalorimetry. Two model drugs were employed; lactose as a hydrophilic one and erythromycin as a hydrophobic one. When amorphous lactose was loaded in a sample cell with a water vial, a sharp exothermic peak due to the crystallization was observed.