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.

Prediction of blood-brain barrier penetration of poorly soluble drug candidates using surface activity profiling.

The aim of this study was to determine whether transepithelial transport across the blood-brain barrier (BBB) [expressed as the logarithm of blood/brain partitioning coefficient (logbb)] could be correlated to surface tension properties for a series of new chemical entities (NCEs) having extremely low solubility in aqueous media. Surface tension data were generated by the "Du Nouy maximum pull force method" using an automated, small volume Kibron Delta 8 Multi-channel tensiometer. Using the surface pressure/concentration profiles, parameters such as the maximum surface pressure, cross-sectional area and the air-water partitioning coefficient were calculated for the individual compounds and correlated with their in vivo logbb values.

Solid state characterization of the anti-HIV drug TMC114: interconversion of amorphous TMC114, TMC114 ethanolate and hydrate.

The interconversion of the ethanolate, hydrate and amorphous form of TMC114 ((3-[(4-amino-benzenesulfonyl)-isobutyl-amino]-1-benzyl-2-hydroxypropyl)-carbamic acid hexahydrofuro-[2,3-b]furan-3-yl ester) in open conditions was characterized. TMC114 hydrate and ethanolate form isostructural channel solvates. The crystal structure of TMC114 was obtained from single crystal X-ray diffraction, confirming that it is a channel solvate.

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).