Evaluation of Dissolution Enhancement of Aprepitant Drug in Ternary Pharmaceutical Solid Dispersions with Soluplus® and Poloxamer 188 Prepared by Melt Mixing

Abstract

In the present study Aprepitant (APT) ternary solid dispersions (SDs) were developed and evaluated for the first time. Specifically, ternary SDs of APT with Poloxamer 188 and Soluplus® (SOL) were prepared via melt mixing and compared to binary APT/Poloxamer 188 and APT/SOL SDs. Initially, combined thermo-gravimetric and hot-stage polarized light microscopy studies indicated that all tested compounds were thermally stable up to 280 °C, while Poloxamer 188 acted as a plasticizer to SOL by significantly reducing the temperature required to fully solubilize the API during SD preparation. Differential scanning calorimetry combined with wide angle X-ray diffraction studies showed that crystalline API was dispersed in both binary and ternary SDs, while Fourier transformation-infrared spectroscopy studies revealed no molecular interactions among the components. Scanning electron microscopy combined with EDAX element analysis showed that the API was dispersed in nano-scale within the polymer matrices, while increasing APT content led to increasing API nano-crystals within the SDs. Finally, dissolution studies showed that the prepared formulations enhanced dissolution of Aprepitant and its mechanism analysis was further studied. A mathematical model was also investigated to evaluate the drug release mechanism.

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“…The sharp endothermic peak observed in the thermogram of IBU at 72 ºC represents the drug's endothermic melting 41 . The DSC thermogram of pure copolymer showed a broad endothermic event ranging from 50 ºC to 75 ºC, similar to the reported glass transition temperature (Tg) of the copolymer 38 . The shifting and broadening of the IBU melting point in the IBU-PMs suggest additional physical attractive bonds between the drug and the polymer 42 .…”

Preparation and Characterization of Aprepitant Solid Dispersion with HPMCAS-LF

“…Therefore, this study focused on preparing the solid dispersion (SD) for aprepitant to maximally increase its oral bioavailability and dissolution using the least carrier amount. Specifically, an in-depth evaluation of the binary SD of APT with Soluplus (an amphiphilic copolymer) was recently performed by several different research groups. , Aprepitant is absorbed in the intestine. − The preparation of aprepitant solid dispersions using enteric-soluble materials as carriers has not been reported. An amphiphilic polymer LF was explored as the carrier to prepare SD.…”

“…Specifically, an in-depth evaluation of the binary SD of APT with Soluplus (an amphiphilic copolymer) was recently performed by several different research groups. 32 , 33 Aprepitant is absorbed in the intestine. 34 − 36 The preparation of aprepitant solid dispersions using enteric-soluble materials as carriers has not been reported.…”

Drug crystal growth in ternary amorphous solid dispersions: Effect of surfactants and polymeric matrix-carriers

“…Specifically, it is critical for the prepared system to enhance the drug solubility and, at the same time, to stabilize the amorphous drug and prevent its recrystallization during processing or storage ( Davis et al, 2018 ; Kyaw Oo et al, 2017a ). Consequently, given that it is not possible for a single polymer to fulfil all requirements, an upsurge of research into ternary ASDs in the recent years is notable ( Ghebremeskel et al, 2007 ; Kyaw Oo et al, 2017b ; Nanaki et al, 2019 ; Prasad et al, 2014 ; Xie and Taylor, 2016 ).…”