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Journal ArticleDOI

Pharmaceutical Applications of Polymorphism

01 Aug 1969-Journal of Pharmaceutical Sciences (Elsevier)-Vol. 58, Iss: 8, pp 911-929
TL;DR: Polymorphism is the ability of any element or compound to crystallize as more than one distinct crystal species (e.g., carbon as cubic diamond or hexagonal graphite).
About: This article is published in Journal of Pharmaceutical Sciences.The article was published on 1969-08-01. It has received 894 citations till now. The article focuses on the topics: Polymorphism (materials science) & Crystal.
Citations
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Book ChapterDOI
TL;DR: A wide variety of techniques appropriate to the study of organic crystalline polymorphism and pseu-dopolymorphism is then surveyed, ranging from simple crystal density measurement to observation of polymorphic transformations using variable-temperature synchrotron X-ray diffraction methods.
Abstract: Crystal polymorphism is encountered in all areas of research involving solid substances. Its occurrence introduces complications during manufacturing processes and adds another dimension to the complexity of designing materials with specific properties. Research on polymorphism is fraught with unique difficulties due to the subtlety of polymorphic transformations and the inadvertent formation of pseudopolymorphs. In this report, a summary of thermodynamic, kinetic and structural considerations of polymorphism is presented. A wide variety of techniques appropriate to the study of organic crystalline polymorphism and pseu-dopolymorphism is then surveyed, ranging from simple crystal density measurement to observation of polymorphic transformations using variable-temperature synchrotron X-ray diffraction methods. Application of newer methodology described in this report is yielding fresh insights into the nature of the crystallization process, holding promise for a deeper understanding of the phenomenon of polymorphism and its practical control.

1,444 citations

Journal ArticleDOI
Lian Yu1
TL;DR: Current research in the stabilization of amorphous solids focuses on the stabilize of labile substances during processing and storage using additives, the prevention of crystallization of the excipients that must remainAmorphous for their intended functions, and the selection of appropriate storage conditions under which amorphously solids are stable.

1,367 citations

Journal ArticleDOI
TL;DR: The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology where required.
Abstract: Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each case, the theoretical basis for utility is described along with a detailed review of recent advances in the field. The article provides an integrated and contemporary discussion of current approaches to solubility and dissolution enhancement but has been deliberately structured as a series of stand-alone sections to allow also directed access to a specific technology (e.g., solid dispersions, lipid-based formulations, or salt forms) where required.

1,201 citations


Cites background from "Pharmaceutical Applications of Poly..."

  • ...Particles are also prone to phase transformations during dry milling, especially over extended processing times (Haleblian and McCrone, 1969; Elamin et al., 1994; Mackin et al., 2002; Descamps et al., 2007), precluding application to thermally labile and low melting materials....

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Journal ArticleDOI
TL;DR: This Perspective provides a brief historical introduction to crystal engineering itself and an assessment of the importance and utility of the supramolecular synthon, which is one of the most important concepts in the practical use and implementation of crystal design.
Abstract: How do molecules aggregate in solution, and how do these aggregates consolidate themselves in crystals? What is the relationship between the structure of a molecule and the structure of the crystal it forms? Why do some molecules adopt more than one crystal structure? Why do some crystal structures contain solvent? How does one design a crystal structure with a specified topology of molecules, or a specified coordination of molecules and/or ions, or with a specified property? What are the relationships between crystal structures and properties for molecular crystals? These are some of the questions that are being addressed today by the crystal engineering community, a group that draws from the larger communities of organic, inorganic, and physical chemists, crystallographers, and solid state scientists. This Perspective provides a brief historical introduction to crystal engineering itself and an assessment of the importance and utility of the supramolecular synthon, which is one of the most important concepts in the practical use and implementation of crystal design. It also provides a look to the future from the viewpoint of the author, and indicates some directions in which this field might be moving.

1,148 citations

References
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Journal ArticleDOI
TL;DR: The analyses suggest that for the latter system the time required to release 50% of the drug would normally be expected to be approximately 10 per cent of that required to dissolve the last trace of the solid drug phase in the center of the pellet.

4,383 citations

Journal ArticleDOI
04 Jan 1908-JAMA
TL;DR: The Pharmacopeia was called into being by physicians in 1820, and in 1850 pharmacists were admitted to the convention; since then physicians have gradually relinquished control to pharmacists, and to-day the authors are confronted with an anomalous condition.
Abstract: It is not my present purpose to add to the many reviews or criticisms of the Pharmacopeia, but to call attention to two conditions, hoping that steps may be taken by this Section looking to their improvement. The first is the general loss of interest on the part of physicians in the revision of the Pharmacopeia. The Pharmacopeia was called into being by physicians in 1820, and in 1850 pharmacists were admitted to the convention; since then physicians have gradually relinquished control to pharmacists, and to-day we are confronted with an anomalous condition, in that the committee of revision of 1900, consisting of twenty-five men, numbered nineteen pharmacists or men identified with pharmaceutic institutions, and but six whose interests were entirely with medicine. For example, Dr. Squibb was almost universally known as a manufacturing pharmacist. Only ten members of the committee of revision had the title of M.D. This condition

1,350 citations

Book
01 Jan 1963

1,068 citations

Book
01 Jan 1964
TL;DR: In this article, a revised edition necessitated by the phenomenal growth of the field during the past decade contains 90% new material, focusing on tech niques and applications of thermal analysis.
Abstract: Contents include: Thermogravimetry. Thermobalances. Applications of thermogravimetry. Differential thermal analysis and differential scanning calorimetry. Evolved gas detection and evolved gas analysis. Spectroscopic, photometric, and optical thermal techniques. Miscellaneous thermal analysis techniques. This revised edition necessitated by the phenomenal growth of the field during the past decade contains 90% new material. Emphasis is on tech niques and applications of thermal analysis. Author now with University of Houston. -- AATA

961 citations