Physical stabilization of amorphous itraconazole in solid dispersions for improved dissolution profile

Abstract

The main objective of the present investigation was to improve dissolution efficiency and stabilize amorphous form of itraconazole (ITR) through formulation of ternary solid dispersion system (SDs) with polyvinylpyrrolidone K30 (PVP K30) and sylysia ® 350 using spray drying technique. The prepared ternary SD system was characterized for solid state properties, in vitro dissolution efficiency and accelerated stability study at 40 °C/75% RH for the period of 3 months to explore extent of stabilization of amorphous itraconazole (AITR). Surprisingly, AITR was found to have no significant improvement in its dissolution characteristics compared to pure drug. The formation of cohesive supercooled liquid state might be the reason for poor solubility. Hence a combined approach of SD system with an antiplasticizing agent and surface adsorption technique was employed to prevail over functional inabilities of AITR. The binary and ternary SDs of AITR were prepared employing PVP K30 as antiplasticizer and/or sylysia ® 350 as adsorbent in the ratio 1:1:1 w/w using spray drying technique. The prepared systems have shown significant improvement in dissolution characteristics when compared to pure drug. Accelerated stability studies confirmed the absence of crystallization events over a period of 3 months endorsing excellent stabilization of AITR.

Prediction of Solid-State Form of SLS 3D Printed Medicines Using NIR and Raman Spectroscopy

“…It is well known that quench-cooled amorphous compounds can be prone to recrystallisation inside the DSC, due to elevated temperatures, enabling the free movement and reordering of molecules into a regular crystalline arrangement [51]. As such, a recrystallisation exotherm can be observed at 130 °C, followed by a melting endotherm at 170 °C of the now partially crystalline form of itraconazole, a phenomenon which has been reported elsewhere [52].…”