Evaluation of Three Amorphous Drug Delivery Technologies to Improve the Oral Absorption of Flubendazole.

This study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH.

Insights into the role of polymer-surfactant complexes in drug solubilisation/stabilisation during drug release from solid dispersions.

Purpose: To evaluate the role of polymer-surfactant interactions in drug solubilisation/stabilisation during the dissolution of spray-dried solid dispersions and their potential impact on in vivo drug solubilisation and absorption.

Methods: Dissolution/precipitation tests were performed on spray-dried HPMC-Etravirine solid dispersions to demonstrate the impact of different surfactants on the in vitro performance of the solid dispersions. Interactions between HPMC and bio-relevant and model anionic surfactants (bile salts and SDS respectively) were further characterised using surface tension measurements, fluorescence spectroscopy, DLS and SANS.

Physicochemical properties of the amorphous drug, cast films, and spray dried powders to predict formulation probability of success for solid dispersions: etravirine.

Solid dispersion technology represents an enabling approach to formulate poorly water-soluble drugs. While providing for a potentially increased oral bioavailability secondary to an increased drug dissolution rate, amorphous dispersions can be limited by their physical stability. The ability to assess formulation risk in this regard early in development programs can not only help in guiding development strategies but can also point to critical design elements in the configuration of the dosage form.

An investigation into the crystallisation behaviour of an amorphous cryomilled pharmaceutical material above and below the glass transition temperature.

The aim of this study was to evaluate the glass transition and recrystallisation of a cryomilled drug, TMC125 (Etravirine), with particular emphasis on assessing the physical stability of the drug above and below the glass transition temperature. DSC (conventional, fast and modulated temperature) and variable temperature ATR-FTIR spectroscopy were employed to monitor the glass transition and crystallisation behaviour of the material. The isothermal crystallisation behaviour was investigated at temperatures below T(g).

Evaluation of Inutec SP1 as a new carrier in the formulation of solid dispersions for poorly soluble drugs.

Solid dispersions made up of itraconazole and Inutec SP1, a new polymeric surfactant, were prepared by spray drying and hot-stage extrusion. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) were used to evaluate the miscibility of the components of the dispersions, and dissolution experiments were performed in simulated gastric fluid without pepsin (SGFsp) to evaluate the pharmaceutical performance of itraconazole from the solid dispersions. DSC analysis showed that the solid dispersions are phase separated systems made up of glassy and crystalline itraconazole and amorphous Inutec SP1.

Physical stability of the amorphous state of loperamide and two fragment molecules in solid dispersions with the polymers PVP-K30 and PVP-VA64.

The purpose of the present study was to investigate the impact of intermolecular forces on the stability of the amorphous state of loperamide and two of its fragment molecules (4-dimethylamino-N,N-dimethyl-2,2-diphenyl-butyramide (F1) and 4-(4-chlorophenyl)-4-piperidinol (F2)) in solid dispersions with PVP-K30 and PVP-VA64. The stability of originally homogeneous and amorphous dispersions was investigated under different storage conditions. The chemical stability of the compounds was evaluated with HPLC.

Salt formation in solid dispersions consisting of polyacrylic acid as a carrier and three basic model compounds resulting in very high glass transition temperatures and constant dissolution properties upon storage.

The purpose of the study was to investigate the suitability of polyacrylic acid (PAA) as a carrier in solid dispersions, with the aim to delay crystallization of basic drugs and improve their dissolution behaviour. The physicochemical properties were investigated in order to link the physical state of some model compounds to their dissolution properties. Loperamide and two structurally related substances were selected as model compounds.

Study of the physicochemical properties and stability of solid dispersions of loperamide and PEG6000 prepared by spray drying.

Solid dispersions of PEG6000 and loperamide-a poorly water-soluble agent-were prepared by spray drying. Their physicochemical properties were evaluated immediately after preparation. The dissolution was higher than that of pure crystalline loperamide.

Phase behaviour analysis of solid dispersions of loperamide and two structurally related compounds with the polymers PVP-K30 and PVP-VA64.

The purpose of the present study was to investigate the influence of the structure of a poorly water soluble model drug (loperamide) on the phase behaviour in solid dispersions with PVP-K30. Dispersions with PVP-VA64, a less hydrophilic polymer, were investigated as well in order to study the influence of differences in polymer structure and water content of the samples. The solid dispersions of PVP-K30 or PVP-VA64 with loperamide as well as with two fragments of this molecule were prepared by spray drying.

Identification of phase separation in solid dispersions of itraconazole and Eudragit E100 using microthermal analysis.

Purpose: To evaluate the phase separation in itraconazole/Eudragit E100 solid dispersions prepared by hot-stage extrusion.

Methods: Extrudates were prepared using a corotating twin-screw extruder at 180 degrees C. Micro-TA was used to evaluate the phase separation, where the AFM mode is used to visualize the different phases and local thermal analysis (LTA) to characterize the different phases

Results: Itraconazole formed a homogeneous mixture with Eudragit E100 with drug concentrations up to approximately 20%.