Molecular indicators of surface and bulk instability of hot melt extruded amorphous solid dispersions.

Purpose: To identify molecular indicators of bulk and surface instabilities of amorphous dispersions prepared by hot melt extrusion.

Methods: Four model drugs with different physicochemical properties were formulated with EUDRAGIT(®) E PO using hot melt extrusion. Samples were aged under a range of conditions for up to 6 months and characterized using SEM, ATR-FTIR, PXRD and MTDSC.

The effect of processing on the surface physical stability of amorphous solid dispersions.

The focus of this study was to investigate the effect of processing on the surface crystallization of amorphous molecular dispersions and gain insight into the mechanisms underpinning this effect. The model systems, amorphous molecular dispersions of felodipine-EUDRAGIT® E PO, were processed both using spin coating (an ultra-fast solvent evaporation based method) and hot melt extrusion (HME) (a melting based method). Amorphous solid dispersions with drug loadings of 10-90% (w/w) were obtained by both processing methods.

Molecular implications of drug-polymer solubility in understanding the destabilization of solid dispersions by milling.

The solubility of drugs in polymer matrixes has been recognized as one of the key factors governing the physical stability of solid dispersions. This study has explored the implications of drug solubility on the destabilization that occurs on milling, which is often used as an additional process for hot melt extruded (HME) solid dispersions. The theoretical drug solubility in the polymer was first predicted using various theoretical and experimental approaches.

Poly(meth)acrylate-based coatings.

Poly(meth)acrylate coatings for pharmaceutical applications were introduced in 1955 with the launch of EUDRAGIT(®) L and EUDRAGIT(®) S, two types of anionic polymers. Since then, by introducing various monomers into their polymer chains and thus altering their properties, diverse forms with specific characteristics have become available. Today, poly(meth)acrylates function in different parts of the gastrointestinal tract and/or release the drug in a time-controlled manner.

Microstructure of an immiscible polymer blend and its stabilization effect on amorphous solid dispersions.

This study proposes use of the phase separation of immiscible polymer blends as a formulation approach to improve the stabilization and solubilization of amorphous molecular dispersions of poorly soluble drugs. This approach uses the phase separation and different drug solubilization properties of the two immiscible polymers in the blend to optimize drug loading and stabilization. The model system tested in this study is a EUDRAGIT E PO-PVP-VA 50/50 (w/w) blend loaded with felodipine via hot melt extrusion.

Characterisation and prediction of phase separation in hot-melt extruded solid dispersions: a thermal, microscopic and NMR relaxometry study.

Purpose: To develop novel analytical approaches for identifying both miscibility and phase separation in hot-melt extruded formulations.

Methods: Felodipine-Eudragit E PO solid dispersions were prepared using hot-melt extrusion. The fresh and aged formulations were characterised using scanning electron microscopy, differential scanning calorimetry, heat capacity (C(p)) measurements using modulated temperature DSC and nuclear magnetic resonance relaxometry.