Extruded Soluplus/SIM as an oral delivery system: characterization, interactions,in vitroandin vivoevaluations

Abstract

The aim of this study was to obtain a stable, amorphous solid dispersion (SD) with Soluplus, prepared by hot-melt extrusion (HME) as an effective and stable oral delivery system to improve the physical stability and bioavailability of the poorly water-soluble simvastatin (SIM), a drug with relatively low Tg. The drug was proved to be miscible with Soluplus by calculation and measurements. The solubility, dissolution, thermal characteristics, interactions and physical stability of the SIM/Soluplus SDs were investigated. The crystal state of simvastatin in the SD was found to change from crystalline to amorphous form during the HME process and also hydrogen bonds were observed between SIM and the extruded Soluplus. The phase solubility showed the solubilization effect of Soluplus was strong and spontaneous. The equilibrium solubility illustrated that Soluplus/SIM SDs gained much higher solubility than its corresponding physical mixtures (PMs). Both of the dissolution profiles and in-vivo performance showed that the SIM/Soluplus SD obtained a marked enhancement, compared with the PM. There was a little change in the SIM/Soluplus SD during a 3-month storage period (40 C, 75%), indicating the good physicochemical stability. The extruded Soluplus system prepared by HME is a good alternative for the water-insoluble SIM to improve the stability and bioavailability.

A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products

“…This behaviour is responsible for the gel forming property of Soluplus ® (Cavallari et al, 2016). Due to the polymer gelling and swelling it is possible that the intrinsic dissolution/constant surface area model is not suitable for dissolution testing with Soluplus ® polymer even though it has been reported in the literature that Soluplus ® has been shown to increase the solubility and dissolution rate of some APIs (Djuris et al, 2013;Homayouni et al, 2015;Linn et al, 2012;Shamma and Basha, 2013;Zhang et al, 2014).…”

Mechanisms of increased bioavailability through amorphous solid dispersions: a review

“…The use of ASDs in oral drug delivery has shown to enhance in vitro performance as well as in vivo bioavailability in animals (Yu et al, 2013;Fule et al, 2015Fule et al, , 2016Agrawal et al, 2016;Kate et al, 2016;Mitra et al, 2016;Xia et al, 2016;Zhang et al, 2016;Knopp et al, 2018;Liu et al, 2018) and in humans (Six et al, 2005;Weiss et al, 2009;Moes et al, 2011;Aboelwafa & Fahmy, 2012;Krishna et al, 2012;Marchetti et al, 2012;Zayed et al, 2012;Othman et al, 2012a,b;Moes et al, 2013;Prasannaraju et al, 2013;Shah et al, 2013;Anon, 2014). An overall statistically positive effect of ASD on bioavailability was measured in a recent meta-analysis (Fong et al, 2017).…”

Fabrication and Characterizations of Hot-Melt Extruded Nanocomposites Based on Zinc Sulfate Monohydrate and Soluplus

“…Of note, it has been widely used as a main matrix for the production of HME formulations due to its thermodynamic properties [14,15]. Conclusively, the use of SP in HME processing can improve solubility and the bioavailability of poorly water-soluble drugs [9,14,16,17]. So far, the HME technique has been used principally to make solid dispersions of organic molecules, which have low molecular weight and poor water solubility, with appropriate polymers (i.e., cellulose derivatives, poly (ethylene-co-vinyl acetate), polyethylene glycol, polyvinylpyrrolidone, and SP) [9,14,16,18].…”