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Characterization Of Tolbutamide Polymorphs (Burger's Forms II And IV) And Polymorphic Transition Behavior.

K. Kimura, F. Hirayama, K. Uekama
Published 1999 · Chemistry, Medicine

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Burger's two polymorphs of tolbutamide (TB), an oral hypoglycemic agent, were obtained by spray-drying the drug dissolved in a mixed solvent of ethanol/dichloromethane (Form IV) and allowing Form IV to stand at constant temperatures and humidities (Form II). These polymorphs were characterized by various physical methods [e.g., powder X-ray diffractometry, differential scanning calorimetry, infrared spectrometry, and solid-state carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy] and compared with two other TB polymorphs Forms I and III. The 13C NMR spectra showed that the chemical shift and the peak shape of resonance associated with the toluene and n-butyl moieties of TB were different for each of the four polymorphs, whereas the carbonyl carbon was unchanged, indicating different conformations and molecular motions of the toluene and n-butyl moieties in the solid states. Form IV converted itself to Form II within 3 h when it was stored at 45 degrees C and 75% relative humidity (RH) and, in turn, Form II transformed to Form I at higher temperatures. The conversion of Form IV to Form II proceeded according to a zero-order equation (Polany-Winger equation), and that of Form II to Form I according to a first-order equation. The increase in RH accelerated the polymorphic transition of Form IV. Both the apparent dissolution rate and the solubility of Form IV were nearly identical with those of Form II, because the former changed to the latter during the dissolution, but their dissolution rates and solubility were higher than those of Forms I and III. These dissolution characteristics of TB polymorphs were reflected in the oral absorption behavior in dogs; that is, the bioavailability increased in the order Form I < Form III < Form II approximately Form IV.
This paper references
On the polymorphism of pharmaceuticals and other molecular crystals. II
A. Burger (1979)
X-ray structural studies and physicochemical properties of cimetidine polymorphism.
M. Shibata (1983)
The structure of the orthorhombic form of tolbutamide (1-n-butyl-3-p-toluenesulphonylurea)
J. Donaldson (1981)
Nuclear Magnetic Resonance (NMR) Spectroscopy of Inclusion Compounds of Tolbutamide and Chlorpropamide with β-Cyclodextrin in Aqueous Solution
H. Ueda (1980)
Solutions for Maintaining Constant Relative Humidity
D. Carr (1949)
Pharmaceutical applications of polymorphism.
J. Haleblian (1969)
Method of Comparing Solid‐State Kinetic Data and Its Application to the Decomposition of Kaolinite, Brucite, and BaCO3
J. Hancock (1972)
Untersuchungen zur Polymorphie von Tolbutamid
M. Georgarakis (1989)
Review on crystal polymorphism of substances in the European pharmacopoeia.
L. Borka (1991)
Physicochemical characterization of spray-dried phenylbutazone polymorphs.
Y. Matsuda (1984)
Solid-state investigation of the tautomerism of acetohexamide
G. Stephenson (1997)
Thermodynamic studies of tolbutamide polymorphs.
E. L. Rowe (1984)
Influence of the presence of trace amounts of metals on the polymorphism of tolbutamide.
A. Olives (1996)
Saturated salt solutions for maintaining specified relative humidities.
H. Nyqvist (1983)
The metabolic fate of tolbutamide in man and in the rat.
R. Thomas (1966)
Solid-State Nuclear Magnetic Resonance Spectroscopy and Raman Spectroscopy of the Inclusion Compound of Tolbutamide with β-Cyclodextrin
H. Ueda (1981)
Untersuchungen zur Polymorphie von Arzneistoffen in Pulvern und Tabletten. VI: Röntgendiffraktometrische Untersuchungen polymorpher Formen des Tolbutamids
J. Traue (1987)
Dissolution Phenomena of Organic Medicinals involving Simultaneous Phase Changes
H. Nogami (1969)
A kinetic study on the isothermal transition of polymorphic forms of tolbutamide and mefenamic acid in the solid state at high temperatures.
T. Umeda (1985)
Crystallization and polymorphic transition behavior of chloramphenicol palmitate in 2-hydroxypropyl-β-cyclodextrin matrix
F. Hirayama (1997)

This paper is referenced by
Cyclodextrin-based isolation of Ostwald's metastable polymorphs occurring during crystallization.
Yoh Sonoda (2006)
Solid-State 13C Nuclear Magnetic Resonance Spectroscopic Study on Amorphous Solid Complexes of Tolbutamide with 2-Hydroxypropyl-α-and -β-Cyclodextrins
K. Kimura (2004)
Polymorphs, Solvates and Hydrates
T. Threlfall (2006)
Effects of Self-Assembled Monolayers on Selective Crystallization of Tolbutamide
J. Zhang (2011)
Deformation Behaviors of Tolbutamide, Hydroxypropyl-β-Cyclodextrin, and Their Dispersions
E. Suihko (2004)
Dissolution Rate Enhancement of Tolbutamide by in-situ-Micronization Using Sodium Lauryl Sulphate
Rajesh A. Keraliya (2013)
Study of retinoic acid polymorphism.
G. Caviglioli (2006)
Physicochemical and crystal structure analyses of the antidiabetic agent troglitazone.
K. Kobayashi (2003)
Polymorphism : The Phenomenon Affecting the Performance of Drugs
K. Raza (2014)
Adding anisotropy to the standard quasi-harmonic approximation still fails in several ways to capture organic crystal thermodynamics
N. S. Abraham (2019)
Solid‐State NMR Studies of Pharmaceutical Systems
M. Geppi (2008)
The Potential of Small-Scale Fusion Experiments and the Gordon-Taylor Equation to Predict the Suitability of Drug/Polymer Blends for Melt Extrusion
A. Forster (2001)
Novel form V of tolbutamide and a high Z′ crystal structure of form III
Naba K Nath (2011)
Reevaluation of solubility of tolbutamide and polymorphic transformation from Form I to unknown crystal form.
Gen Hasegawa (2009)
Solvent effect on tolbutamide crystallization induced by compressed CO2 as antisolvent
P. Subra-Paternault (2007)
Polymorphism: The Phenomenon Affecting the Performance of Drugs
K. Raza (2014)
Different BCS Class II Drug-Gelucire Solid Dispersions Prepared by Spray Congealing: Evaluation of Solid State Properties and In Vitro Performances
Serena Bertoni (2020)
Supercritical carbon dioxide processing of active pharmaceutical ingredients for polymorphic control and for complex formation.
K. Moribe (2008)
[Pharmaceutical application of cyclodextrins as multi-functional drug carriers].
K. Uekama (2004)
Quantitative determination of amorphous cyclosporine in crystalline cyclosporine samples by Fourier transform infrared spectroscopy.
V. Bertacche (2006)
Use of Glancing Angle X-Ray Powder Diffractometry to Depth-Profile Phase Transformations During Dissolution of Indomethacin and Theophylline Tablets
S. Debnath (2004)
Conformational polymorphism of tolbutamide: A structural, spectroscopic, and thermodynamic characterization of Burger's forms I-IV.
Satyanarayana Thirunahari (2010)
Estimation of Initial Dissolution Rate of Drug Substance by Thermal Analysis: Application for Carbamazepine Hydrate
Y. Yoshihashi (2002)
Selective Crystallization of the Metastable Form IV Polymorph of Tolbutamide in the Presence of 2,6-Di-O-methyl-β-cyclodextrin in Aqueous Solution
Yoh Sonoda (2006)
Solid state characterization of E2101, a novel antispastic drug.
Ikuo Kushida (2002)
Particle characterization of poorly water-soluble drugs using a spray freeze drying technique.
M. Kondo (2009)
In Vitro–In Vivo Correlation for Low-Clearance Compounds Using Hepatocyte Relay Method
Li Di (2013)
Recent progress of structural study of polymorphic pharmaceutical drugs.
K. Higashi (2017)
Solid dispersion particles of tolbutamide prepared with fine silica particles by the spray-drying method
H. Takeuchi (2004)
Crystal structure and dehydration behavior of E6070, a novel IKKβ protein kinase inhibitor for the treatment of rheumatoid arthritis.
Ikuo Kushida (2013)
Phase Transition Enthalpy Measurements of Organic and Organometallic Compounds and Ionic Liquids. Sublimation, Vaporization, and Fusion Enthalpies from 1880 to 2015. Part 2. C11–C192
W. Acree (2017)
Isoenergetic Polymorphism: The Puzzle of Tolazamide as a Case Study.
E. Boldyreva (2015)
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