Rheological analysis of itraconazole-polymer mixtures to determine optimal melt extrusion temperature for development of amorphous solid dispersion

Solanki, Nayan G.; Gupta, Simerdeep Singh; Serajuddin, Abu T.M.

doi:10.1016/j.ejps.2017.10.034

Cited by 38 publications

(24 citation statements)

References 27 publications

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“…The best representatives of such methods are hot melt extrusion (HME) or 3D printing (3DP). This kind of manufacturing processes typically includes three stages: (i) Heating and softening of a physical mixture containing API and thermoplastic polymer; (ii) pressurization of molten mass through a die, and (iii) sample solidification, during which the final dosage form is formulated [46,47,48,49,50,51]. To obtain the desired shape of a final product, samples besides high physical stability needs to be characterized by suitable melt viscosity.…”

Section: Resultsmentioning

confidence: 99%

Physical Stability and Viscoelastic Properties of Co-Amorphous Ezetimibe/Simvastatin System

et al. 2019

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The purpose of this paper is to examine the physical stability as well as viscoelastic properties of the binary amorphous ezetimibe–simvastatin system. According to our knowledge, this is the first time that such an amorphous composition is prepared and investigated. The tendency toward re-crystallization of the amorphous ezetimibe–simvastatin system, at both standard storage and elevated temperature conditions, have been studied by means of X-ray diffraction (XRD). Our investigations have revealed that simvastatin remarkably improves the physical stability of ezetimibe, despite the fact that it works as a plasticizer. Pure amorphous ezetimibe, when stored at room temperature, begins to re-crystallize after 14 days after amorphization. On the other hand, the ezetimibe-simvastatin binary mixture (at the same storage conditions) is physically stable for at least 1 year. However, the devitrification of the binary amorphous composition was observed at elevated temperature conditions (T = 373 K). Therefore, we used a third compound to hinder the re-crystallization. Finally, both the physical stability as well as viscoelastic properties of the ternary systems containing different concentrations of the latter component have been thoroughly investigated.

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Section: Resultsmentioning

confidence: 99%

Physical Stability and Viscoelastic Properties of Co-Amorphous Ezetimibe/Simvastatin System

et al. 2019

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“…By employing a high drug load, even with drug-saturated micelles, a relatively high extent of drug may be released (e.g., the FM-saturated micelles released around 4 mg per hour in PBS (pH 7.4)). Even considering solid dosage forms consisting of SP solid dispersions, whether they are prepared by hot-melt extrusion, spray drying or electrospinning, they will eventually disintegrate and dissolve into the gastrointestinal fluids [4,5,7,36]. The micellar SP systems that then form could be expected to behave somewhat similarly to the mostly liquid formulations described in this study and thereby be dependent on the polymer concentration and the pH, as well as the composition of the media at the site.…”

Section: Discussionmentioning

confidence: 99%

“…It has a PEG 6000 backbone with one or two sidechains consisting of vinyl acetate randomly copolymerised with vinyl caprolactam. SP was originally developed as an excipient for hot-melt extrusion [2] and has been reported in many studies to form amorphous solid dispersions [2,3,4,5]; commonly used techniques for forming amorphous solid dispersions include spray drying, electrospinning and solvent evaporation technique [5,6,7]. Due to the amphiphilic character of the polymer, it forms micelles in aqueous media (Figure 1) and can be used to solubilise poorly water-soluble drugs [8].…”

Section: Introductionmentioning

confidence: 99%

Micellisation Mechanism and Behaviour of Soluplus®–Furosemide Micelles: Preformulation Studies of an Oral Nanocarrier-Based System

2019

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: In this study, self-assembling Soluplus® micelles were examined for inherent properties. Through calorimetric analysis, the critical micelle concentration (CMC) could be determined at 25 and 37 °C, and the influence of three media (Milli-Q water, phosphate-buffered saline (PBS) with a pH of 7.4 and 0.1 M HCl) on the lower critical solution temperature (LCST) was detected. Furthermore, the solubilisation of a poorly soluble drug, furosemide, into the Soluplus® micelles was studied. The concentration-dependent properties of the micellar system were assessed through an examination of the micellar size, polydispersity, morphology, viscosity and solubilising properties, which were all found to be affected by the concentration, but temperature, pH and the composition of the test medium were also found to have an effect. Homogeneity in the estimated micellar size and morphology was shown for monophasic micelle dispersions in lower concentrations and with a shift towards more complex structures or aggregates in higher concentrations. The micelles were further investigated in terms of drug release and biocompatibility with mucus-producing HT29-MTX cells, where no biocompatibility issues were found. In this research, the implications for oral drug delivery are discussed and valuable preformulation information is provided on the micellar properties of a Soluplus® drug system in a liquid or semi-solid form.

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“…Soluplus ® [59][60][61], Eudragit ® L [62], polyvinylpyrrolidone (PVP) [63], Kollidon ® VA64 [64,65], polyvinyl alcohol (PVA) [65,66], as well as semi-synthetic cellulose derivatives such as hydroxypropyl cellulose [67] and hydroxypropyl methylcellulose acetate succinate [53,54,[68][69][70], are examples of pharmaceutical polymers tested for preparing itraconazole amorphous solid dispersions (ASD) and also suitable as filament-forming polymers for FDM. Although many papers described the formation of amorphous solid dispersions with ITR, including the use of the hot-melt extrusion process [61], only two considered the formation of dosage forms using 3D printing. Kimura et al reported that it is possible to use fused deposition modeling to prepare zero-order sustained-release floating tablets containing itraconazole [43].…”

Section: Introductionmentioning

confidence: 99%

Multivariate Design of 3D Printed Immediate-Release Tablets with Liquid Crystal-Forming Drug—Itraconazole

et al. 2020

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The simplicity of object shape and composition modification make additive manufacturing a great option for customized dosage form production. To achieve this goal, the correlation between structural and functional attributes of the printed objects needs to be analyzed. So far, it has not been deeply investigated in 3D printing-related papers. The aim of our study was to modify the functionalities of printed tablets containing liquid crystal-forming drug itraconazole by introducing polyvinylpyrrolidone-based polymers into the filament-forming matrices composed predominantly of poly(vinyl alcohol). The effect of the molecular reorganization of the drug and improved tablets’ disintegration was analyzed in terms of itraconazole dissolution. Micro-computed tomography was applied to analyze how the design of a printed object (in this case, a degree of an infill) affects its reproducibility during printing. It was also used to analyze the structure of the printed dosage forms. The results indicated that the improved disintegration obtained due to the use of Kollidon®CL-M was more beneficial for the dissolution of itraconazole than the molecular rearrangement and liquid crystal phase transitions. The lower infill density favored faster dissolution of the drug from printed tablets. However, it negatively affected the reproducibility of the 3D printed object.

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Rheological analysis of itraconazole-polymer mixtures to determine optimal melt extrusion temperature for development of amorphous solid dispersion

Cited by 38 publications

References 27 publications

Physical Stability and Viscoelastic Properties of Co-Amorphous Ezetimibe/Simvastatin System

Physical Stability and Viscoelastic Properties of Co-Amorphous Ezetimibe/Simvastatin System

Micellisation Mechanism and Behaviour of Soluplus®–Furosemide Micelles: Preformulation Studies of an Oral Nanocarrier-Based System

Multivariate Design of 3D Printed Immediate-Release Tablets with Liquid Crystal-Forming Drug—Itraconazole

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