Generality of Enhancing the Dissolution Rates of Free Acid Amorphous Solid Dispersions by the Incorporation of Sodium Hydroxide.

The incorporation of a counterion into an amorphous solid dispersion (ASD) has been proven to be an attractive strategy to improve the drug dissolution rate. In this work, the generality of enhancing the dissolution rates of free acid ASDs by incorporating sodium hydroxide (NaOH) was studied by surface-area-normalized dissolution. A set of diverse drug molecules, two common polymer carriers (copovidone or PVPVA and hydroxypropyl methylcellulose acetate succinate or HPMCAS), and two sample preparation methods (rotary evaporation and spray drying) were investigated.

Effect of Buffer pH and Concentration on the Dissolution Rates of Sodium Indomethacin-Copovidone and Indomethacin-Copovidone Amorphous Solid Dispersions.

The incorporation of counterions into amorphous solid dispersions (ASDs) has been proven to be effective for improving the dissolution rates of ionizable drugs in ASDs. In this work, the effect of dissolution buffer pH and concentration on the dissolution rate of indomethacin-copovidone 40:60 (IMC-PVPVA, w/w) ASD with or without incorporated sodium hydroxide (NaOH) was studied by surface area-normalized dissolution to provide further mechanistic understanding of this phenomenon. Buffer pH from 4.

Effect of Counterions on Dissolution of Amorphous Solid Dispersions Studied by Surface Area Normalized Dissolution.

Solubility enhancement has become a common requirement for formulation development to deliver poorly water soluble drugs. Amorphous solid dispersions (ASDs) and salt formation have been two successful strategies, yet there are opportunities for further development. For ASDs, drug-polymer phase separation may occur at high drug loadings during dissolution, limiting the increase of drug loadings in ASD formulations.

Improving Stability and Dissolution of Amorphous Clofazimine by Polymer Nano-Coating.

Purpose: To inhibit the surface crystallization and enhance the dissolution of the basic amorphous drug clofazimine by polymer nano-coating.

Methods: The free surface of amorphous clofazimine was coated by dip coating in an alginate solution at pH 7. The stability of the coated amorphous drug against crystallization was evaluated by X-ray diffraction and light microscopy.

Effect of molecular size and hydrogen bonding on three surface-facilitated processes in molecular glasses: Surface diffusion, surface crystal growth, and formation of stable glasses by vapor deposition.

Recent work has shown that diffusion and crystal growth can be much faster on the surface of molecular glasses than in the interior and that the enhancement effect varies with molecular size and intermolecular hydrogen bonds (HBs). In a related phenomenon, some molecules form highly stable glasses when vapor-deposited, while others (notably those forming extensive HBs) do not. Here we examine all available data on these phenomena for quantitative structure-property relations.

Influence of Hydrogen Bonding on the Surface Diffusion of Molecular Glasses: Comparison of Three Triazines.

Surface grating decay measurements have been performed on three closely related molecular glasses to study the effect of intermolecular hydrogen bonds on surface diffusion. The three molecules are derivatives of bis(3,5-dimethyl-phenylamino)-1,3,5-triazine and differ only in the functional group R at the 2-position, with R being CH, OCH, and NHCH, and referred to as "Et", "OMe", and "NHMe", respectively. Of the three molecules, NHMe forms more extensive intermolecular hydrogen bonds than Et and OMe and was found to have slower surface diffusion.

Tensile Fracture of Molecular Glasses Studied by Differential Scanning Calorimetry: Reduction of Heat Capacity by Lateral Constraint.

Molecular glasses indomethacin and ortho-terphenyl were formed and fractured by cooling a liquid on a less thermally expansive substrate. In-plane tension was created by the mismatch of thermal expansion coefficients and accumulated to cause catastrophic network fracture. Differential scanning calorimetry was used to characterize the process.

Hydrogen Bonding Slows Down Surface Diffusion of Molecular Glasses.

Surface-grating decay has been measured for three organic glasses with extensive hydrogen bonding: sorbitol, maltitol, and maltose. For 1000 nm wavelength gratings, the decay occurs by viscous flow in the entire range of temperature studied, covering the viscosity range 10(5)-10(11) Pa s, whereas under the same conditions, the decay mechanism transitions from viscous flow to surface diffusion for organic glasses of similar molecular sizes but with no or limited hydrogen bonding. These results indicate that extensive hydrogen bonding slows down surface diffusion in organic glasses.

Fast Crystal Growth in o-Terphenyl Glasses: A Possible Role for Fracture and Surface Mobility.

Molecular liquids can develop a fast mode of crystal growth ("GC growth") near the glass transition temperature. This phenomenon remains imperfectly understood with several explanations proposed. We report that GC growth in o-terphenyl conserves the overall volume, despite a 5% higher density of the crystal, and produces fine crystal grains with the same unit cell as normally grown crystals.