Next Article in Journal / Special Issue
Ingredient Consistency of Commercially Available Polyphenol and Tocopherol Nutraceuticals
Previous Article in Journal
Determination of the Pharmacokinetics and Oral Bioavailability of Salicylamine, a Potent γ-Ketoaldehyde Scavenger, by LC/MS/MS
Previous Article in Special Issue
Investigation of Formulation and Process of Lyophilised Orally Disintegrating Tablet (ODT) Using Novel Amino Acid Combination
Pharmaceutics 2010, 2(1), 30-49; doi:10.3390/pharmaceutics2010030
Article

Quantification of Process Induced Disorder in Milled Samples Using Different Analytical Techniques

1
, 1,2
, 3
, 3
, 4
 and 1,*
Received: 10 December 2010; in revised form: 4 February 2010 / Accepted: 12 February 2010 / Published: 16 February 2010
(This article belongs to the Special Issue What's on Board in Pharmaceutics)
View Full-Text   |   Download PDF [1392 KB, uploaded 16 February 2010]   |   Browse Figures
Abstract: The aim of this study was to compare three different analytical methods to detect and quantify the amount of crystalline disorder/ amorphousness in two milled model drugs. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman spectroscopy were used as analytical methods and indomethacin and simvastatin were chosen as the model compounds. These compounds partly converted from crystalline to disordered forms by milling. Partial least squares regression (PLS) was used to create calibration models for the XRPD and Raman data, which were subsequently used to quantify the milling-induced crystalline disorder/ amorphousness under different process conditions. In the DSC measurements the change in heat capacity at the glass transition was used for quantification. Differently prepared amorphous indomethacin standards (prepared by either melt quench cooling or cryo milling) were compared by principal component analysis (PCA) to account for the fact that the choice of standard ultimately influences the quantification outcome. Finally, the calibration models were built using binary mixtures of crystalline and quench cooled amorphous drug materials. The results imply that the outcome with respect to crystalline disorder for milled drugs depends on the analytical method used and the calibration standard chosen as well as on the drug itself. From the data presented here, it appears that XRPD tends to give a higher percentage of crystalline disorder than Raman spectroscopy and DSC for the same samples. For the samples milled under the harshest milling conditions applied (60 min, sixty 4 mm balls, 25 Hz) a crystalline disorder/ amorphous content of 44.0% (XRPD), 10.8% (Raman spectroscopy) and 17.8% (DSC) were detected for indomethacin. For simvastatin 18.3% (XRPD), 15.5% (Raman spectroscopy) and 0% (DSC, no glass transition) crystalline disorder/ amorphousness were detected.
Keywords: indomethacin; simvastatin; amorphous; process induced disorder; ball milling; DSC; XRPD; Raman spectroscopy; multivariate analysis; principal component analysis (PCA); partial least squares regression (PLS) indomethacin; simvastatin; amorphous; process induced disorder; ball milling; DSC; XRPD; Raman spectroscopy; multivariate analysis; principal component analysis (PCA); partial least squares regression (PLS)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Zimper, U.; Aaltonen, J.; McGoverin, C.M.; Gordon, K.C.; Krauel-Goellner, K.; Rades, T. Quantification of Process Induced Disorder in Milled Samples Using Different Analytical Techniques. Pharmaceutics 2010, 2, 30-49.

AMA Style

Zimper U, Aaltonen J, McGoverin CM, Gordon KC, Krauel-Goellner K, Rades T. Quantification of Process Induced Disorder in Milled Samples Using Different Analytical Techniques. Pharmaceutics. 2010; 2(1):30-49.

Chicago/Turabian Style

Zimper, Ulrike; Aaltonen, Jaakko; McGoverin, Cushla M.; Gordon, Keith C.; Krauel-Goellner, Karen; Rades, Thomas. 2010. "Quantification of Process Induced Disorder in Milled Samples Using Different Analytical Techniques." Pharmaceutics 2, no. 1: 30-49.


Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert