Physicochemical characterization of the various solid forms of carbovir, an antiviral nucleoside. 1994

N A Nguyen, and S Ghosh, and L A Gatlin, and D J Grant
Pharmaceutical Development, Glaxo Inc., Research Triangle Park, NC 27709.

Carbovir, which exhibits promising in-vitro activity against HIV, is shown to exist in five forms: I, II, III, IV, and V. Forms I-III and V were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), hot-stage microscopy (HSM), Karl Fischer titrimetry (KFT), powder X-ray diffraction (PXD), intrinsic dissolution rate (IDR) studies, heat of solution measurements (SC), scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and water uptake at various relative humidities (water activities). Form IV could not be characterized fully, as it is stable only over a narrow temperature range (267-275 degrees C) which is immediately followed by melting and decomposition. With increasing temperature in DSC, forms I and V transformed successively to form III (195 degrees C), then to form II (220 degrees C), and then to form IV (275 degrees C). The PXD patterns, FTIR spectroscopy, IDR, and SC showed significant differences between these polymorphs. For each of the forms I, II, and III, there exists a critical value of relative humidity above which absorption of water proceeds steeply, leading to the formation of form V, which is more heavily hydrated than any of the other forms. Forms I and V each showed a two-step weight loss in TGA (24-120 degrees C), suggesting the presence of water molecules with two different binding energies probably corresponding to two different locations in the crystal lattice; HSM confirmed the dehydration.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D008855 Microscopy, Electron, Scanning Microscopy in which the object is examined directly by an electron beam scanning the specimen point-by-point. The image is constructed by detecting the products of specimen interactions that are projected above the plane of the sample, such as backscattered electrons. Although SCANNING TRANSMISSION ELECTRON MICROSCOPY also scans the specimen point by point with the electron beam, the image is constructed by detecting the electrons, or their interaction products that are transmitted through the sample plane, so that is a form of TRANSMISSION ELECTRON MICROSCOPY. Scanning Electron Microscopy,Electron Scanning Microscopy,Electron Microscopies, Scanning,Electron Microscopy, Scanning,Electron Scanning Microscopies,Microscopies, Electron Scanning,Microscopies, Scanning Electron,Microscopy, Electron Scanning,Microscopy, Scanning Electron,Scanning Electron Microscopies,Scanning Microscopies, Electron,Scanning Microscopy, Electron
D002151 Calorimetry The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
D002152 Calorimetry, Differential Scanning Differential thermal analysis in which the sample compartment of the apparatus is a differential calorimeter, allowing an exact measure of the heat of transition independent of the specific heat, thermal conductivity, and other variables of the sample. Differential Thermal Analysis, Calorimetric,Calorimetric Differential Thermal Analysis,Differential Scanning Calorimetry,Scanning Calorimetry, Differential
D002627 Chemistry, Physical The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes. Physical Chemistry,Chemistries, Physical,Physical Chemistries
D006813 Humidity A measure of the amount of WATER VAPOR in the air. Humidities
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D013055 Spectrophotometry, Infrared Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) IR Spectra,Infrared Spectrophotometry,IR Spectras,Spectra, IR
D013056 Spectrophotometry, Ultraviolet Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Ultraviolet Spectrophotometry
D013816 Thermodynamics A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed) Thermodynamic

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