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A novel amorphous solid dispersion based on drug-polymer complexation
Abstract: Rafoxanide (RAF) is a poorly water-​soluble drug that forms a complex with povidone K25 (PVP) in a cosolvent system containing acetone and an alkaline aqueous medium.ÌýThis study aims to investigate the impact of RAF-​PVP complexation on in vitro and in vivo release of RAF.ÌýWe prepared two RAF amorphous solid dispersions (ASDs) spray-​dried from these two cosolvents.ÌýThe first is a complexation-​based spray-​drying using a 70​% 0.1 N NaOH solution with 30​% acetone.ÌýThe second is a traditional spray-​dried formulation containing 80​% acetone and 20​% ethanol.ÌýEvidence from multiple solid-​state characterization techniques indicated that ASDs spray-​dried using both methods were amorphous.ÌýHowever, RAF ASDs based on drug-​polymer complexation in the feed solution demonstrated not only faster drug release during dissolution testing but also higher in vivo absorption in an animal model.ÌýThe improved RAF release in the complexation-​based ASD is due to (1) high energy state of RAF owing to the amorphous form, (2) high pH in the microenvironment due to the ionized state of RAF and residual sodium hydroxide, (3) increased apparent solubility of RAF results from RAF-​PVP complexation in dissolution media and biological media, and (4) improved wettability.
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