Process analytical quality control of tailored drug release formulation prepared via hot-melt extrusion technology

Park, Jun-Bom; Lee, Beom‐Jin; Kang, Chin-Yang; Repka, Michael A.

doi:10.1016/j.jddst.2017.01.007

Cited by 20 publications

(5 citation statements)

References 33 publications

(32 reference statements)

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“…The use of the release modifier (water-soluble carrier) can effectively improve the release of the drug in the SRSD [ 32 ], and the selection of different types of release modifier greatly influenced drug release. After determining the drug-carrier ratio, the effects of different release modifiers on drug release were compared using poloxamer (P188), povidone (PVP), and polyethylene glycol (PEG6000).…”

Section: Resultsmentioning

confidence: 99%

Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Zhu

Zhang

et al. 2021

Molecules

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This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic–hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.

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Section: Resultsmentioning

confidence: 99%

Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Zhu

Zhang

et al. 2021

Molecules

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“…Polymers from the Eudragit family have also been used to produce dosage forms by HME other than those discussed in the previous sections, such as ocular inserts [109], dry suspensions [105], or actually as extrudates [38,108]. These reports are summarized in Table 4, and the most relevant data is discussed below.…”

Section: Other Dosage Forms Obtained By Hmementioning

confidence: 99%

“…On the other hand, ERS may result in an undesired controlled release of the drug over many hours. Whilst they have similar structures, ERL has a higher proportion of ammonium quaternary groups in its chemical structure than ERS, making the former more permeable [ 38 ]. However, the approach of using ERL and ERS blends has been reported as an interesting rational to obtain moderate burst release of the drug and faster sustained release, when compared with formulations composed of the single polymers [ 83 ].…”

Section: Hot Melt Extrusionmentioning

confidence: 99%

“…On the other hand, Eudragit RS (ERS) has the same molecular structure and the same particularities as ERL, with the exception of its permeability, which is much lower [ 37 ]. The only difference between ERS and ERL is, therefore, their ammonium functional group content, which controls the permeability of the polymers [ 38 ]. ERS has 5% of quaternary ammonium groups, which is 2× lower than ERL.…”

Section: Introductionmentioning

confidence: 99%

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Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics

et al. 2021

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Eudragit® polymers are polymethacrylates highly used in pharmaceutics for the development of modified drug delivery systems. They are widely known due to their versatility with regards to chemical composition, solubility, and swelling properties. Moreover, Eudragit polymers are thermoplastic, and their use has been boosted in some production processes, such as hot melt extrusion (HME) and fused deposition modelling 3D printing, among other 3D printing techniques. Therefore, this review covers the studies using Eudragit polymers in the development of drug delivery systems produced by HME and 3D printing techniques over the last 10 years. Eudragit E has been the most used among them, mostly to formulate immediate release systems or as a taste-masker agent. On the other hand, Eudragit RS and Eudragit L100-55 have mainly been used to produce controlled and delayed release systems, respectively. The use of Eudragit polymers in these processes has frequently been devoted to producing solid dispersions and/or to prepare filaments to be 3D printed in different dosage forms. In this review, we highlight the countless possibilities offered by Eudragit polymers in HME and 3D printing, whether alone or in blends, discussing their prominence in the development of innovative modified drug release systems.

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“…If the miscibility between the drug and the polymer is low, then the content uniformity of the drug in the HME formulation would drop significantly during the process. Additionally, the distribution and homogeneity of the drug in the HME formulation could be evaluated using spectroscopic imaging techniques [48,49]. In fact, the compatibility between the drug and the polymer can be the critical parameter for maintaining the assay of the drug.…”

Section: Determination Of Drug Content In Sdsmentioning

confidence: 99%

Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition

et al. 2021

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Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC0–48h of the commercial formulation, Sporanox®, was 1073.9 ± 314.7 ng·h·mL−1, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL−1) was three-fold higher than that of Sporanox® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL−1 and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL−1. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area.

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Process analytical quality control of tailored drug release formulation prepared via hot-melt extrusion technology

Cited by 20 publications

References 33 publications

Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Eudragit®: A Versatile Family of Polymers for Hot Melt Extrusion and 3D Printing Processes in Pharmaceutics

Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition

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