Exploring novel carrier for improving bioavailability of Itraconazole: Solid dispersion through hot-melt extrusion

Chivate, Amit; Garkal, Atul; Hariharan, Kartik; Mehta, Tejal

doi:10.1016/j.jddst.2021.102541

Cited by 17 publications

(2 citation statements)

References 58 publications

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“…After the SDs were subjected to the environment of 40 • C and RH75% for a period of time, the stability of the SDs were determined using DSC, and the results are shown in Figure 11. The DSC curves confirmed no recrystallization of the amorphous drug in the SDs, suggesting good physical stability [49]. This phenomenon could be ascribed to the molecular interaction and good miscibility between the drug and carrier.…”

Section: Acceleration Of Stability Studymentioning

confidence: 83%

Preparation of Curcumin-Eudragit® E PO Solid Dispersions with Gradient Temperature through Hot-Melt Extrusion

Zhang

Zhu

et al. 2021

Molecules

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Hot-melt extrusion (HME) has great advantages for the preparation of solid dispersion (SD), for instance, it does not require any organic solvents. Nevertheless, its application to high-melting-point and thermosensitive drugs has been rarely reported. In this study, thermally unstable curcumin (Cur) was used as a drug model. The HME process was systematically studied by adjusting the gradient temperature mode and residence time, with the content, crystallinity and dissolution of Cur as the investigated factors. The effects of barrel temperature, screw speed and cooling rate on HME were also examined. Solubility parameters and the Flory–Huggins method were used to evaluate the miscibility between Cur and carriers. Differential scanning calorimetry, X-ray diffraction, Fourier transform infrared spectroscopy, equilibrium solubility and in vitro and in vivo experiments were used to characterize and evaluate the results. An amorphous Cur SD was successfully obtained, increasing the solubility and release of Cur. In the optimal process, the mass ratio of Cur to Eudragit® E PO (EPO) was 1:4 and the barrel temperature was set at a gradient heating mode (130 °C–135 °C–140 °C–145 °C–150 °C–155 °C–160 °C) at 100 rpm. Related pharmacokinetic test results also showed the improved bioavailability of the drug in rats. In a pharmacodynamic analysis of Sprague–Dawley rats, the Cmax and the bioavailability of the Cur-EPO SD were 2.6 and 1.5 times higher than those of Cur, respectively. The preparation of the amorphous SD not only provided more solubility but also improved the bioavailability of Cur, which provides an effective way to improve the bioavailability of BCS II drugs.

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Section: Acceleration Of Stability Studymentioning

confidence: 83%

Preparation of Curcumin-Eudragit® E PO Solid Dispersions with Gradient Temperature through Hot-Melt Extrusion

Zhang

Zhu

et al. 2021

Molecules

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“…Different features and applications of HME have been reviewed recently by various other researchers [ 63 , 64 ]. HME’s application has largely propagated to formulate ASD and to enhance oral bioavailability of poorly water-soluble drugs, mainly BCS class II [ 65 , 66 ]. This technique’s clinical and commercial success is indicated by the presence of several melt-extruded ASD products in the market [ 66 ].…”

Section: Methods Of Preparing Transdermal Coamorphous Systemmentioning

confidence: 99%

Amorphization of Drugs for Transdermal Delivery-a Recent Update

et al. 2022

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Amorphous solid dispersion is a popular formulation approach for orally administered poorly water-soluble drugs, especially for BCS class II. But oral delivery could not be an automatic choice for some drugs with high first-pass metabolism susceptibility. In such cases, transdermal delivery is considered an alternative if the drug is potent and the dose is less than 10 mg. Amorphization of drugs causes supersaturation and enhances the thermodynamic activity of the drugs. Hence, drug transport through the skin could be improved. The stabilization of amorphous system is a persistent challenge that restricts its application. A polymeric system, where amorphous drug is dispersed in a polymeric carrier, helps its stability. However, high excipient load often becomes problematic for the polymeric amorphous system. Coamorphous formulation is another approach, where one drug is mixed with another drug or low molecular weight compound, which stabilizes each other, restricts crystallization, and maintains a single-phase homogenous amorphous system. Prevention of recrystallization along with enhanced skin permeation has been observed by the transdermal coamorphous system. But scalable manufacturing methods, extensive stability study and in-depth in vivo evaluation are lacking. This review has critically studied the mechanistic aspects of amorphization and transdermal permeation by analyzing recent researches in this field to propose a future direction.

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