Evaluation of solid state properties of solid dispersions prepared by hot-melt extrusion and solvent co-precipitation

Dong, Zedong; Chatterji, Ashish; Sandhu, Harpreet; Choi, Duk Soon; Chokshi, Hitesh; Shah, Navnit

doi:10.1016/j.ijpharm.2007.12.017

Cited by 113 publications

(55 citation statements)

References 13 publications

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“…It is worth noting that as these windows are defined for neat polymers, many polymers that exhibit viscosities just above the defined maximum viscosity limit will be sufficiently plasticized with the addition of API to bring down the viscosity to extrudable levels. For example, low molecular weight grades of HPMC and HPMC AS have been extensively investigated by hot-melt extrusion in ASDs (57,(59)(60)(61). Additionally, the complex viscosity range was correlated to the torque limitation for a small-scale extruder, and higher torque capacity will often be achievable in larger scale extruders.…”

Section: Discussionmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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Abstract. Thermal processing of amorphous solid dispersions continues to gain interest in the pharmaceutical industry, as evident by several recently approved commercial products. Still, a number of pharmaceutical polymer carriers exhibit thermal or viscoelastic limitations in thermal processing, especially at smaller scales. Additionally, active pharmaceutical ingredients with high melting points and/or that are thermally labile present their own specific challenges. This review will outline a number of formulation and process-driven strategies to enable thermal processing of challenging compositions. These include the use of traditional plasticizers and surfactants, temporary plasticizers utilizing sub-or supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion processing, and KinetiSol® Dispersing technology. Recent case studies of each strategy will be described along with potential benefits and limitations.

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Section: Discussionmentioning

confidence: 99%

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

2015

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“…It has also been implemented in a twin screw extrusion process to determine the concentration of Irganox additive in polypropylene [12] . Raman spectroscopy has also been applied for off-line confirmation of drug dispersion within PEO and interaction with PEO in extrudates [13] , for characterization of the hydrogen bonding nature in α and amorphous indomethacin [14] , and for comparison of the solid state properties of solid dispersions prepared by HME and solvent co-precipitation processes [15] .…”

Section: Introductionmentioning

confidence: 99%

Raman spectroscopy for the in-line polymer–drug quantification and solid state characterization during a pharmaceutical hot-melt extrusion process

Saerens

Dierickx

Lenain³

et al. 2011

European Journal of Pharmaceutics and Biopharmaceutics

135

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The aim of this study was to evaluate the suitability of Raman spectroscopy as a Process Analytical Technology (PAT) tool for the in-line determination of the active pharmaceutical ingredient (API) concentration and the polymer-drug solid state during a pharmaceutical hot-melt extrusion process. For in-line API quantification, different metoprolol tartrate (MPT) -Eudragit ® RL PO mixtures, containing 10, 20, 30, and 40% MPT respectively, were extruded and monitored in-line in the die using Raman spectroscopy. A PLS model, regressing the MPT concentrations versus the in-line collected Raman spectra, was developed and validated, allowing real-time API concentration determination. The correlation between the predicted and real MPT concentrations of the validation samples is acceptable (R²=0.997) The predictive performance of the calibration model is rated by the root mean square error of prediction (RMSEP), which is 0.59%. Two different polymer-drug mixtures were prepared to evaluate the suitability of Raman spectroscopy for in-line polymer-drug solid state characterization. Mixture 1 contained 90% Eudragit ® RS PO and 10% MPT, and was extruded at 140°C, hence producing a solid solution. Mixture 2 contained 60% Eudragit ® RS PO and 40% MPT, and was extruded at 105°C, prod ucing a solid dispersion. The Raman spectra collected during these extrusion processes provided two main observations. First, the MPT Raman peaks in the solid solution broadened compared to the corresponding solid dispersion peaks, indicating the presence of amorphous MPT. Secondly, peak shifts appeared in the spectra of the solid dispersion and solid solution compared to the physical mixtures, suggesting interactions between Eudragit ® RS PO and MPT, most likely hydrogen bonds. These shifts were larger in the spectra of the solid solution. DSC analysis confirmed these Raman solid state observations and the interactions seen in the spectra. Raman spectroscopy is a potential PAT-tool for in-line determination of the API-concentration and the polymer-drug solid state during pharmaceutical hot-melt extrusion.

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“…Soluplus in fact does not show a sharp melting point, rather it progressively softens at increasing temperatures; moreover its relatively high Tg (about 70°C) suggests stability for the possible amorphous forms embedded inside the final matrix. All these properties explain the successful use of soluplus as drug release enhancer for a range of drugs [11,[28][29][30][31] even taking into account possible variants [32,34] . The gelling tendency of soluplus, which could impact on release performances of formulations where it was inserted, was rarely reported.…”

Section: Discussionmentioning

confidence: 99%

Release Problems for Nifedipine in the Presence of Soluplus

Fini¹,

Cavallari²,

Ternullo³

et al. 2016

JPP

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Nifedipine/soluplus co-precipitates were prepared at 1:9 and 1:1 weight ratios, using the solvent method, with the aim to obtain an improvement of the drug release. The release, though accelerated with respect to physical mixtures and pure drug, resulted slow with respect to similar systems containing soluplus and are characterized by the appearance in suspension of micro-particulates that, at the optical microscope, revealed a large variety of shapes typical of flower-like aggregates, not previously reported. For comparison systems were also prepared with PVP K30 and sucrester P1670 and two mixtures, without any evidence of this last phenomenon. The systems were studied by thermal (differential scanning calorimetry -DSC, thermomicroscopy -HSM) and spectroscopic (SEM, FT-IR, micro-Raman) analysis. Slow release of nifedipine and formation of colloidal micro-particulates were hypothesized due to the gelling tendency of soluplus associated to drug/polymer multi-site-interactions: when one of these parameters is absent in the system the two phenomena could not be observed together, such as in the case of PVP K30 or sucrester P1670, when used as carriers for nifedipine release.

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Evaluation of solid state properties of solid dispersions prepared by hot-melt extrusion and solvent co-precipitation

Cited by 113 publications

References 13 publications

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

Raman spectroscopy for the in-line polymer–drug quantification and solid state characterization during a pharmaceutical hot-melt extrusion process

Release Problems for Nifedipine in the Presence of Soluplus

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