Solubility and dissolution enhancement of efavirenz hot melt extruded amorphous solid dispersions using combination of polymeric blends: A QbD approach

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• 作者：Jaywant Pawar ; ^{jaywantpawar.ict@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Apurva Tayade ; Avinash Gangurde ; Kailas Moravkar ; Purnima Amin
• 关键词：Efavirenz ; Soluplus® ; HPMCAS-HF ; Hot melt extrusion ; Solubility ; FTIR imaging
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：10 June 2016
• 年：2016
• 卷：88
• 期：Complete
• 页码：37-49
• 全文大小：1957 K

文摘

Efavirenz is a non-nucleoside reverse transcriptase inhibitor and categorized in to BCS class II drug. The aim of the present investigation was to apply quality by design approach to enhance the solubility, dissolution and stability of amorphous solid dispersions (ASDs) of efavirenz using a combination of Soluplus® and HPMCAS-HF polymers. In design of experiments, the user defined quadratic model was used to study the effect of variable concentrations of Soluplus® and HPMCAS-HF for the formation of ASDs of efavirenz. Similarly, a prototype ASD was made using Soluplus® as a carrier with efavirenz loading of 30%. The efavirenz ASDs granular extrudates were evaluated for saturation solubility as well as dissolution rate studies. X-ray powder diffraction, Differential scanning calorimetry, Fourier transform infrared, Atomic force microscopy and FTIR imaging to determine the solid state of efavirenz in the ASDs. DSC and XRD data confirmed that bulk crystalline efavirenz transformed to the amorphous form during the hot melt extrusion processing. Prototype ASD batch showed instability upon storage as per ICH guidelines over a period of 6 months, observations inferred from DSC, XRD and in vitro dissolution studies. The maximum dissolution rate was observed when Soluplus® and HPMCAS-HF was in ratio of (60:20) as optimized by design of experiments study. Moreover, the optimized ASDs batch were stable at 40°C, 75% RH for a period of 6 months without any dissolution rate changes, and remained into amorphous state.