Spectroscopic and X-ray Diffraction Study of Structural Disorder in Cryomilled and Amorphous Griseofulvin

$29.00 plus tax (Refund Policy)

Buy Article:

Abstract:

Structural disorder induced by cryogenic milling and by heating to the amorphous phase in the active pharmaceutical ingredient Griseofulvin has been studied using Raman spectroscopy, X-ray powder diffraction (XRPD), and fluorescence spectroscopy. A broad, exciting-frequency-independent scattering background in the Raman spectra and changes in intensities and splitting of some of the Raman lines due to lattice and molecular modes have been observed. In the cryomilled samples this strong background is deconvoluted into two components: one due to lattice disorder induced by cryomilling and the other due to Mie scattering from nanosized crystallites. A single-component background scattering attributed to lattice disorder is seen in the Raman spectrum of the amorphous sample. Fluorescence measurements showed an intrinsic fluorescence signal in as-received Griseofulvin that does not correspond to the inelastic background in the Raman spectra and, moreover, decreases in intensity upon cryomilling, thus excluding an assignment of the Raman background intensity to impurity- or molecular-defect-induced fluorescence. Wide-angle XRPD measurements on cryomilled Griseofulvin shows a broad two-component background consistent with the background-scattering component in the Raman data associated with lattice disorder, but at longer correlation lengths. Persistence of this disorder to even longer lengths is evident in small-angle synchrotron XRPD data on micronized Griseofulvin taken as a function of temperature from the crystalline to the amorphous phase.

Keywords: ACTIVE PHARMACEUTICAL INGREDIENT; AMORPHOUS PHASE; API; CRYOMILLING; CRYSTALLINE DEFECTS; DISORDER; FLUORESCENCE SPECTROSCOPY; GRISEOFULVIN; LATTICE DISORDER; MILLING; RAMAN SPECTROSCOPY; X-RAY POWDER DIFFRACTION; XRPD

Document Type: Research Article

DOI: http://dx.doi.org/10.1366/10-06024

Affiliations: 1: Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, New Jersey 07102, USA 2: Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907, USA 3: Otto York Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, New Jersey 07102, USA

Publication date: February 1, 2011

More about this publication?
Related content

Tools

Favourites

Share Content

Access Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content
Cookie Policy
X
Cookie Policy
ingentaconnect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more