Probing the Effects of Experimental Conditions on the Character of Drug-Polymer Phase Diagrams Constructed Using Flory-Huggins Theory

Donnelly, Conor; Tian, Yiwei; Potter, Catherine B.; Jones, David S.; Andrews, Gavin

doi:10.1007/s11095-014-1453-9

Cited by 54 publications

(54 citation statements)

References 38 publications

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“…2, enabling the calculation of entropic (A) and enthalpic (B) contributions to χ in the FD-EPO system. In agreement with our previous work, positive values of the calculated B term indicated upper critical solution temperature (UCST) behaviour and corresponded to decreasing χ values with increasing temperature (18). The calculated values for constants A (−126.557) and B (53038.616) were subsequently used in Eq.…”

Section: Melting Point Depression Measurements and The Construction Osupporting

confidence: 86%

“…The use of Flory-Huggins lattice theory to construct a T-ϕ phase diagram thus determining drug-polymer solubility as a function of temperature has been well established in the current literature (13)(14)(15)(16)(17)(18)20,21). Accordingly, Gibb's free energy of mixing ΔG mix can be expressed as (22):…”

Section: Treatment Of Data and Construction Of Phase Diagrammentioning

confidence: 99%

“…Previously, our group employed an 8 min milling cycle (16)(17)(18) in preparing physical mixtures of drug and polymer. Intimate mixing of raw materials prior to extrusion is an ideal scenario but not always the case in practice.…”

Section: Melting Point Depression Measurements and The Construction Omentioning

confidence: 99%

“…A number of recent publications have successfully defined the mixing behaviour of drug-polymer binary mixtures from a thermodynamic perspective (12)(13)(14)(15). Our group has also published a series of articles, utilising Flory-Huggins (F-H) theory in combination with the measurement of melting temperature depression to understand drug-polymer phase behaviour (16)(17)(18). In doing so, thermodynamic miscibility is expressed as a temperature/composition phase diagram, whilst Gibb's free energy of mixing may be expressed as a function of both temperature and composition.…”

Section: Introductionmentioning

confidence: 99%

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Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters

et al. 2016

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Abstract. The aim of this article was to construct a T-ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature-composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)-Eudragit ® EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10 wt% FD-EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperaturecomposition (T-ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid-solid curve in a F-H T-ϕ phase diagram. If extruded between the spinodal and liquid-solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F-H T-ϕ phase diagrams are valuable not only in the understanding drug-polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.

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Section: Melting Point Depression Measurements and The Construction Osupporting

confidence: 86%

Section: Treatment Of Data and Construction Of Phase Diagrammentioning

confidence: 99%

Section: Melting Point Depression Measurements and The Construction Omentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters

et al. 2016

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“…Thermal analysis has been used as a valuable tool to predict drug-polymer miscibility 19,[32][33][34] .…”

Section: Flory Huggins (F-h) Theory For the Prediction Of Drug/polymementioning

confidence: 99%

Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

et al. 2015

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In this study molecular modelling is introduced as a novel approach for the development of pharmaceutical solid dispersions. A computational model based on quantum mechanical (QM) calculations was used to predict the miscibility of various drugs in various polymers by predicting the binding strength between the drug and dimeric form of the polymer. The drug/polymer miscibility was also estimated by using traditional approaches such as Van Krevelen/Hoftyzer and Bagley solubility parameters or Flory Huggins interaction parameter in comparison to the molecular modelling approach.The molecular modelling studies predicted successfully the drug-polymer binding energies and the preferable site of interaction between the functional groups. The drug-polymer miscibility and the physical state of bulk materials, physical mixtures and solid dispersions were determined by thermal analysis (DSC/MTDSC) and X-ray diffraction. The produced solid dispersions were analysed by X-ray photoelectron spectroscopy (XPS), which confirmed not only the exact type of the intermolecular interactions between the drugpolymer functional groups but also the binding strength by estimating the N-coefficientvalues. The findings demonstrate that QM-based molecular modelling is a powerful tool to predict the strength and type of intermolecular interactions in a range of drug/polymeric systems for the development of solid dispersions.

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Amorphous Solid Dispersions: Utilization and Challenges in Drug Discovery and Development

He¹,

Ho²

2015

Journal of Pharmaceutical Sciences

209

115

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Probing the Effects of Experimental Conditions on the Character of Drug-Polymer Phase Diagrams Constructed Using Flory-Huggins Theory

Abstract: The potential implications of these findings when applied to a non-ambient processing method such as Hot Melt Extrusion (HME) are also discussed.

Cited by 54 publications

References 38 publications

Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters

Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters

Molecular Modeling as a Predictive Tool for the Development of Solid Dispersions

Amorphous Solid Dispersions: Utilization and Challenges in Drug Discovery and Development

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