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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Surfactant-Free Solid Dispersions of Hydrophobic Drugs in an Amorphous Sugar Matrix Dried from an Organic Solvent.
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TL;DR: Results indicated that the Cmax and AUC0-60 min of the hydrophobic drug in water were increased when the surfactant-free solid dispersion was used, and the model drug with a lower water solubility tended to exhibit a greater extent of over-dissolution.
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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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