Journal ArticleDOI
What is the true solubility advantage for amorphous pharmaceuticals
Bruno C. Hancock,Michael Parks +1 more
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TLDR
Amorphous pharmaceuticals are markedly more soluble than their crystalline counterparts, however, their experimental solubility advantage is typically less than that predicted from simplethermodynamic considerations.Abstract:
Purpose To evaluate the magnitude of the solubility advantage foramorphous pharmaceutical materials when compared to their crystallinecounterpartsMethods The thermal properties of several drugs in their amorphousand crystalline states were determined using differential scanningcalorimetry From these properties the solubility advantage for theamorphous form was predicted as a function of temperature using a simplethermodynamic analysis These predictions were compared to theresults of experimental measurements of the aqueous solubilities of theamorphous and crystalline forms of the drugs at several temperaturesResults By treating each amorphous drug as either an equilibriumsupercooled liquid or a pseudo-equilibrium glass, the solubilityadvantage compared to the most stable crystalline form was predicted to bebetween 10 and 1600 fold The measured solubility advantage wasusually considerably less than this, and for one compound studied indetail its temperature dependence was also less than predicted It wascalculated that even for partially amorphous materials the apparentsolubility enhancement (theoretical or measured) is likely to influencein-vitro and in-vivo dissolution behaviorConclusions Amorphous pharmaceuticals are markedly more solublethan their crystalline counterparts, however, their experimental solubility advantage is typically less than that predicted from simplethermodynamic considerations This appears to be the result of difficulties indetermining the solubility of amorphous materials under trueequilibrium conditions Simple thermodynamic predictions can provide a useful indication of the theoretical maximum solubility advantage foramorphous pharmaceuticals, which directly reflects the driving forcefor their initial dissolutionread more
Citations
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Effect of the preparation method on crystallinity, particle size, aqueous solubility and dissolution of different samples of the poorly water-soluble fenofibrate with HP-β-CD
Abid Mehmood Yousaf,Dong Wuk Kim,Kwan Hyung Cho,Kwan Hyung Cho,Jong Oh Kim,Chul Soon Yong,Han-Gon Choi +6 more
TL;DR: In this article, the physicochemical properties of poorly water-soluble fenofibrate with HP-β-cyclodextrin were analyzed using particle size determination, powder x-ray diffraction, differential scanning calorimetry and thermogravimetry.
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A phase space approach to supercooled liquids and a universal collapse of their viscosity
Nicholas B. Weingartner,Chris Pueblo,Flavio S. Nogueira,Kenneth F. Kelton,Zohar Nussinov,Zohar Nussinov +5 more
TL;DR: In this article, the authors describe a classical framework for explaining the dynamical behavior of supercooled liquids based on statistical mechanical considerations, and possessing only a single variable parameter, which varies weakly from liquid to liquid.
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Synergistic Computational Modeling Approaches as Team Players in the Game of Solubility Predictions.
TL;DR: It is concluded that the field of computational pharmaceutics is in its early days but with a bright future ahead, and education of computational formulators with broad knowledge of modelling and simulation approaches is imperative if computational pharmaceuticals is to reach its full potential.
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Preparation of polyphenol fine particles potent antioxidants by a supercritical antisolvent process using different extracts of Olea europaea leaves
Chandrasekar Chinnarasu,Chandrasekar Chinnarasu,A. Montes,Clara Pereyra,Lourdes Casas,M.T. Fernández-Ponce,Casimiro Mantell,Sangma Pattabhi,Enrique J. Martínez de la Ossa +8 more
TL;DR: In this paper, a supercritical antisolvent (SAS) process was used to evaluate the possibility of producing polyphenol fine particles with controlled size and size distribution from Olive leaves.
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Amorphization of crystalline active pharmaceutical ingredients via formulation technologies
TL;DR: Amorphous solid dispersions (ASDs) were formulated to stabilize amorphous Active Pharmaceutical Ingredients (APIs) in this article, and spray-drying was used to generate them.
References
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Journal ArticleDOI
Characteristics and Significance of the Amorphous State in Pharmaceutical Systems
Bruno C. Hancock,George Zografi +1 more
TL;DR: The amorphous state is critical in determining the solid-state physical and chemical properties of many pharmaceutical dosage forms and some of the most common methods that can be used to measure them are described.
Book
Polymorphism in Pharmaceutical Solids
TL;DR: Brittain et al. as mentioned in this paper applied the phase rule to the characterisation of polymorphic and solvatomorphic systems, and proposed a computational method to predict polymorphism.
Journal ArticleDOI
Pharmaceutical Solids: A Strategic Approach to Regulatory Considerations
TL;DR: It is hoped that this review will lead to a more direct approach to the characterization of pharmaceuticalsolids and ultimately to faster approval of regulatory documents containing information on pharmaceutical solids.
Journal ArticleDOI
Crystallization of Indomethacin from the Amorphous State below and above Its Glass Transition Temperature
TL;DR: It was shown that in both samples significant crystallization to the most stable polymorphic form occurred over several days when stored below Tg, and in some cases this process was preceded by the relaxation of one amorphous form to the other.
Journal ArticleDOI
Characterization of the time scales of molecular motion in pharmaceutically important glasses
TL;DR: In this paper, the authors characterized the molecular mobility of selected amorphous systems (i.e., indomethacin, sorbitol, sucrose, and trehalose) below Tg using a combined experimental and theoretical approach.
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