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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Journal ArticleDOI
Data Requirements for the Reliable Use of Atomic Pair Distribution Functions in Amorphous Pharmaceutical Fingerprinting
TL;DR: The ambiguities make data measured using low energy x-rays unsuitable for fingerprinting active pharmaceutical ingredients and small molecule systems, and, in general, copper anode diffractometers are undesirable for this purpose; however, laboratory x-ray sources with either Mo or Ag anodes are well suited for this application.
Journal ArticleDOI
Shear-Triggered Crystallization and Light Emission of a Thermally Stable Organic Supercooled Liquid.
Kyeongwoon Chung,Min Sang Kwon,Brendan M. Leung,Antek G. Wong-Foy,Min Su Kim,Jeongyong Kim,Shuichi Takayama,Johannes Gierschner,Adam J. Matzger,Jinsang Kim +9 more
TL;DR: Molecular design of thermally stable supercooled liquid of diketopyrrolopyrrole (DPP) derivatives and their intriguing shear-triggered crystallization with dramatic optical property changes is reported and the origin is a subtle force balance between aromatic interactions among the core units and van der Waals interactionsamong the aliphatic side chains acting in opposite directions.
Journal ArticleDOI
Fluorescent Polymeric Nanoparticles: Aggregation and Phase Behavior of Pyrene and Amphotericin B Molecules in Nanoparticle Cores
TL;DR: Fluorescence measurements are used to probe the state of aggregation and dynamics of rearrangement of pyrene, Hostasol Yellow (HosY), and amphotericin B (AmpB) in NP cores and show stability of the microphase-separated fluorophores, which is consistent with the Flory-Huggins theory calculations.
Journal ArticleDOI
Polyamorphism: a pharmaceutical science perspective.
TL;DR: The use of the term polyamorphism has been restricted to describe only those systems where multiple super-cooled thermodynamic liquid states have been shown to exist, and the occurrence of true polyamorphs appears to be quite rare for typical pharmaceutical materials.
Patent
Solid forms of n-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide
Patricia Hurter,William Rowe,Christopher R. Young,Adriana Costache,Patrick R. Connelly,Krawiec Mariusz,Gong Yuchuan,Yushi Feng,Martin Trudeau +8 more
TL;DR: In this article, solid state forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1, 4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.
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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