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
Preparation and Characterization of Co-Grinded Mixtures of Aceclofenac and Neusilin US2 for Dissolution Enhancement of Aceclofenac
TL;DR: In vitro dissolution rate of acecl ofenac from co-ground mixture was significantly higher compared to pure aceclofenac and there was no reversion from amorphous to crystalline form, indicating that it is advantageous to use a porous carrier like Neusilin US2 in improvement of dissolution of poorly soluble drugs.
Journal ArticleDOI
Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation
Karthik Nagapudi,Janan Jona +1 more
TL;DR: In this article, a review of methods to generate the amorphous phase, estimate the degree of crystallinity of the polymeric phase, predict the stability of the ammorphous phase against crystallization, and choose the polymers carrier and formulation of the preclinical phase for preclinical studies is presented.
Journal ArticleDOI
The Biopharmaceutics Risk Assessment Roadmap for Optimizing Clinical Drug Product Performance
Arzu Selen,Paul A. Dickinson,Anette Müllertz,John R. Crison,Hitesh Mistry,Maria T. Cruanes,Marilyn N. Martinez,Hans Lennernäs,Timothy Wigal,David C. Swinney,James E. Polli,Abu T.M. Serajuddin,Jack Cook,Jennifer B. Dressman +13 more
TL;DR: The biopharmaceutics risk assessment roadmap (BioRAM) optimizes drug product development and performance by using therapy-driven target drug delivery profiles as a framework to achieve the desired therapeutic outcome.
Journal ArticleDOI
Nanoparticle Formation and Growth During In Vitro Dissolution of Ketoconazole Solid Dispersion
Parijat Kanaujia,Grace Lau,Wai Kiong Ng,Effendi Widjaja,Andrea Hanefeld,Matthias Fischbach,Mario Maio,Reginald B. H. Tan +7 more
TL;DR: The results suggested that the release of KC from the solid dispersions was carrier controlled initially, and PVP 17 PF is more efficient in inhibiting particle growth as compared with PVP-VA64, which may be an important consideration to achieve the full benefits of dissolution enhancement of solid dispersion.
Journal ArticleDOI
Dry powder insufflation of crystalline and amorphous voriconazole formulations produced by thin film freezing to mice.
TL;DR: High concentrations ofVRC in lung tissue coupled with clinically relevant plasma concentrations suggest that pulmonary delivery of microstructured crystalline VRC could potentially be a beneficial strategy for administration of VRC to patients with invasive pulmonary fungal infections.
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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