Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems

Yoo, Seung-uk; Krill, Steven L.; Wang, Zeren; Telang, Chitra

doi:10.1002/jps.21779

Cited by 80 publications

(39 citation statements)

References 15 publications

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“…Ionic interactions have also been seen to play a role in the physical stability of a number of pharmaceutically relevant compounds including dexamethasone phosphate [40] and indometacin. [41] Yoo et al [42] reported that ionic interactions play a significant role for both drug-polymer miscibility and drug physical stability; systems with ionic interactions were stable for up to 50 days at 60% RH and 25°C, while other systems lacking ionic interactions tended to recrystallize. These reports demonstrate the significant influence of acid-base ionic interactions on the physical stability of amorphous solid dispersions.…”

Section: Discussionmentioning

confidence: 99%

Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions

Wegiel

Mauer

Edgar

et al. 2013

Journal of Pharmacy and Pharmacology

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Based on the observed ability of mid-IR analysis to enable the characterization of intermolecular polyphenol-polymer interactions and based on the correlation between the extent of intermolecular interactions and the crystallization-inhibiting performance of polymers, it can be concluded that this technique is an important tool for the rational formulation of solid dispersions with optimized physical stability.

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Section: Discussionmentioning

confidence: 99%

Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions

Wegiel

Mauer

Edgar

et al. 2013

Journal of Pharmacy and Pharmacology

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“…Since both formation and physical stability of solid dispersions rely on solidification from a mutually miscible API and polymer mixture, research in this area has focused on predicting how the interactions between API and carrier enable dispersability . Despite predictive advances, dispersion formulation still relies on the analytical techniques to confirm that a true dispersion has been formed.…”

Section: Introductionmentioning

confidence: 99%

Physical Characterization of Drug:Polymer Dispersion Behavior in Polyethylene Glycol 4000 Solid Dispersions using a Suite of Complementary Analytical Techniques

Vasa

Dalal

Katz

et al. 2014

Journal of Pharmaceutical Sciences

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Fifteen model drugs were quenched from 3:1 (w/w) mixtures with polyethylene glycol 4000 (PEG4000). The resulting solids were characterized using powder X-ray diffraction (PXRD), analysis of pair distribution function-transformed PXRD data (where appropriate), hot-stage polarized light microscopy, and differential scanning calorimetry (DSC). Drug/polymer dispersion behavior was classified using the data from each technique, independent of the others, and limitations to single-method characterization of PEG-based systems are highlighted. The data from all characterization techniques were collectively used to classify dispersion behavior, which was compared with single-technique characterization. Of the 15 combinations, only six resulted in solids whose dispersion behavior was consistently described using each standalone technique. The other nine were misclassified using at least one standalone technique, mainly because the phase behavior was ambiguously interpreted when only the data from one technique were considered. The data indicated that a suite of complementary techniques provided better classifications of the phase behavior. Of all the quenched solids, only cimetidine was fully dispersed in PEG4000, suggesting that it solidified from a completely miscible mixture of molten drug and polymer that did not phase separate upon cooling. In contrast, ibuprofen and PEG4000 completely recrystallized during preparation, whereas the remaining 13 drugs were partially dispersed in PEG4000 at this composition.

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“…The significance of drug-polymer interactions in the process and product properties of HME has become an inspiring point. [3,[5][6][7][8] The general interactions between drug and polymer include ionic interaction, [9][10][11] hydrogen bond, [2,12,13] dipoledipole interaction [14,15] and Van der Waals interaction. [14] Ionic interaction, one of the electrostatic interactions, specifically refers to the strong and nondirective attraction or repulsion between ionized molecules.…”

Section: Introductionmentioning

confidence: 99%

Interactions between drugs and polymers influencing hot melt extrusion

Pang

Guo

et al. 2013

Journal of Pharmacy and Pharmacology

112

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Objectives Hot melt extrusion (HME) as a technique for producing amorphous solid dispersion (ASD) has been widely used in pharmaceutical research. The biggest challenge for the application of HME is the thermal degradation of drug, poor physical stability of ASD and precipitation of drug during dissolution. Interactions between drugs and polymers may play an important role in overcoming these barriers. In this review, influence of drug-polymer interactions on HME and the methods for characterizing the drug-polymer interactions were reviewed. Key findings Strong drug-polymer interactions, especially ionic interactions and hydrogen bonds, are helpful to improving the thermal stability of drug during HME, enhancing the physical stability of ASD during storage and maintaining supersaturated solution after dissolution in gastrointestinal tract. The interactions can be quantitatively and qualitatively characterized by many analysing methods. Conclusions As many factors collectively determine the properties of HME products, drug-polymer interactions play an extremely important role. However, the action mechanisms of drug-polymer interactions need intensive investigation to provide more useful information for optimizing the formulation and the process parameters of HME.

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Miscibility/stability considerations in binary solid dispersion systems composed of functional excipients towards the design of multi-component amorphous systems

Cited by 80 publications

References 15 publications

Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions

Mid-infrared spectroscopy as a polymer selection tool for formulating amorphous solid dispersions

Physical Characterization of Drug:Polymer Dispersion Behavior in Polyethylene Glycol 4000 Solid Dispersions using a Suite of Complementary Analytical Techniques

Interactions between drugs and polymers influencing hot melt extrusion

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