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

Yogesh Pore,Vikram Shinde,J Rao

doi:10.7324/japs.2016.601005

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.

Highlights

Crystallinity of an active pharmaceutical ingredient (API) offers potential benefit in ease of formulation design and contributes to thermodynamic stability (Paul et al, 2011; Byrn et al, 1999; Brittain, 1999)
Some APIs exist in different crystalline phases and exhibit polymorphism which can adversely influence solubility and dissolution rate leading to poor oral bioavailability and reduced therapeutic efficacy (Llinas and Goodman, 2008; Yadav et al, 2009)
Thin-layer chromatography TLC studies were performed to identify any degradation of ITR during melting

Summary

INTRODUCTION

Crystallinity of an active pharmaceutical ingredient (API) offers potential benefit in ease of formulation design and contributes to thermodynamic stability (Paul et al, 2011; Byrn et al, 1999; Brittain, 1999). ITR, classified as a BCS class II drug, has poor solubility in aqueous media (less than 0.001 mg mL-1 at 25 °C) (Shete et al, 2015) and has a dissolution rate limited poor oral bioavailability with pKa of 3.7 (Heykants et al, 1989) with due consideration of its relatively low Tg. Some investigations have reported formulation of solid dispersion systems (SDs) of crystalline ITR (CITR) (Jung et al, 1999; Verreck et al, 2003; Wang et al, 2005; Tao et al, 2009). The main objective of the present investigation was to improve dissolution efficiency and stabilize AITR through formulation of ternary SDs with PVP K30 and/or sylysia®350 using spray drying technique

MATERIALS AND METHODS

RESULTS AND DISCUSSION

CONCLUSION