Author
George Zografi
Other affiliations: Columbia University, Merck & Co., University of Michigan ...read more
Bio: George Zografi is an academic researcher from University of Wisconsin-Madison. The author has contributed to research in topics: Amorphous solid & Glass transition. The author has an hindex of 59, co-authored 165 publications receiving 15836 citations. Previous affiliations of George Zografi include Columbia University & Merck & Co..
Papers published on a yearly basis
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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.
1,864 citations
TL;DR: In the temperature range studied the model amorphous solids were in a transition zone between regions of very high molecular mobility above Tg and very low molecular mobility much further below Tg, which should be expected to experience significant molecular mobility at temperatures up to fifty degrees below their glass transition temperature.
Abstract: Purpose. To measure the molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures (Tg), using indomethacin, poly (vinyl pyrrolidone) (PVP) and sucrose as model compounds.
Methods. Differential scanning calorimetry (DSC) was used to measure enthalpic relaxation of the amorphous samples after storage at temperatures 16-47 K below Tg for various time periods. The measured enthalpy changes were used to calculate molecular relaxation time parameters. Analogous changes in specimen dimensions were measured for PVP films using thermomechanical analysis.
Results. For all the model materials it was necessary to cool to at least 50 K below the experimental Tg before the molecular motions detected by DSC could be considered to be negligible over the lifetime of a typical pharmaceutical product. In each case the temperature dependence of the molecular motions below Tg was less than that typically reported above Tg and was rapidly changing.
Conclusions. In the temperature range studied the model amorphous solids were in a transition zone between regions of very high molecular mobility above Tg and very low molecular mobility much further below Tg. In general glassy pharmaceutical solids should be expected to experience significant molecular mobility at temperatures up to fifty degrees below their glass transition temperature.
926 citations
TL;DR: A comparison of the carbonyl stretching region of γ indomethacin, known to form carboxylic acid dimers, with that of amorphous indometHacin indicated that the amorphously phase exists predominantly as dimers.
Abstract: Purpose. To study the molecular structure of indomethacin-PVP amorphous solid dispersions and identify any specific interactions between the components using vibrational spectroscopy.
904 citations
TL;DR: It was found that there is a rapid initial reduction in the glass transition temperature from the dry state as water is absorbed, followed by a gradual leveling off of the response at higher water contents, indicating that water acts as a plasticizer in a way similar to that of other small molecules and not through any specific or stoichiometric interaction process(es).
Abstract: The glass transition temperature of an amorphous pharmaceutical solid is a critical physical property which can dramatically influence its chemical stability, physical stability, and viscoelastic properties. Water frequently acts as a potent plasticizer for such materials, and since many amorphous solids spontaneously absorb water from their surroundings the relationship between the glass transition temperature and the water content of these materials is important. For a wide range of amorphous and partially amorphous pharmaceutical solids, it was found that there is a rapid initial reduction in the glass transition temperature from the dry state as water is absorbed, followed by a gradual leveling off of the response at higher water contents. This plasticization effect could generally be described using a simplified form of the Gordon–Taylor/ Kelley–Bueche relationships derived from polymer free volume theory. Most of the systems considered showed a nearly ideal volume additivity and negligible tendency to interact. This is consistent with the hypothesis that such mixtures behave as concentrated polymer solutions and indicates that water acts as a plasticizer in a way similar to that of other small molecules and not through any specific or stoichiometric interaction process(es).
689 citations
TL;DR: In this paper, the role of water in affecting drug entities that are believed to exist predominantly in the crystalline state, in the absence and presence of excipients and other drugs in the formulation.
559 citations
Cited by
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TL;DR: The historical background and definitions of the various systems including eutectic mixtures, solid dispersions and solid solutions, as well as the production, the different carriers and the methods used for the characterization of solid dispersion are outlined.
2,695 citations
TL;DR: Concentrating on recent advances, this article covers industrial aspects, inorganic materials, organic synthesis, cocrystallisation, pharmaceutical aspects, metal complexes, supramolecular aspects and characterization methods.
Abstract: The aim of this critical review is to provide a broad but digestible overview of mechanochemical synthesis, i.e. reactions conducted by grinding solid reactants together with no or minimal solvent. Although mechanochemistry has historically been a sideline approach to synthesis it may soon move into the mainstream because it is increasingly apparent that it can be practical, and even advantageous, and because of the opportunities it provides for developing more sustainable methods. Concentrating on recent advances, this article covers industrial aspects, inorganic materials, organic synthesis, cocrystallisation, pharmaceutical aspects, metal complexes (including metal–organic frameworks), supramolecular aspects and characterization methods. The historical development, mechanistic aspects, limitations and opportunities are also discussed (314 references).
2,102 citations
Book•
01 Jan 1971
TL;DR: In this paper, Ozaki et al. describe the dynamics of adsorption and Oxidation of organic Molecules on Illuminated Titanium Dioxide Particles Immersed in Water.
Abstract: 1: Magnetic Particles: Preparation, Properties and Applications: M. Ozaki. 2: Maghemite (gamma-Fe2O3): A Versatile Magnetic Colloidal Material C.J. Serna, M.P. Morales. 3: Dynamics of Adsorption and Oxidation of Organic Molecules on Illuminated Titanium Dioxide Particles Immersed in Water M.A. Blesa, R.J. Candal, S.A. Bilmes. 4: Colloidal Aggregation in Two-Dimensions A. Moncho-Jorda, F. Martinez-Lopez, M.A. Cabrerizo-Vilchez, R. Hidalgo Alvarez, M. Quesada-PMerez. 5: Kinetics of Particle and Protein Adsorption Z. Adamczyk.
1,870 citations
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TL;DR: Lipson and Steeple as mentioned in this paper interpreted X-ray powder diffraction patterns and found that powder-diffraction patterns can be represented by a set of 3-dimensional planes.
Abstract: Interpretation of X-ray Powder Diffraction Patterns . By H. Lipson and H. Steeple. Pp. viii + 335 + 3 plates. (Mac-millan: London; St Martins Press: New York, May 1970.) £4.
1,867 citations
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.
1,864 citations