Internal standard for amorphous pharmaceuticals products quantification and an application of Parametric Rietveld refinement using time, temperature and relative humidity as 'non-crystallographic' parameters

Author(s)

Rafael Silva Nunes

• Document type: Doctoral Thesis
• Press: Araraquara. 2015-03-03.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Química. Araraquara
• Defense date: 2014-09-25
• Advisor: Carlos de Oliveira Paiva Santos

Abstract

Recent studies on solid polycrystalline drugs by x-ray powder diffraction (XRPD) in Brazil, has demonstrated how important this technique can be, especially joined to Rietveld method, for structural understanding of these materials. Amorphous material has a higher internal energy than crystalline materials, what alters their therapeutic effects and it makes of amorphous quantification an important study. As an internal standard with international recognition for this purpose, such as NIST SRM-676a (Al2O3), can be economically unviable, a systematic characterization, mainly by XRPD, of a cheap material with liner coefficient absorption of same order of this organic products, to use as internal standard for quantitative phase analysis was made. Good results obtained with LiF, as internal standard, for amorphous pharmaceutical quantification at room temperature, shows its potential for a large-scale application (when compared to results obtained using NIST standard SRM-676a, considering microabsorption effect). Other important focus of this work was in situ XRPD applied to pharmaceutical products and had as highlights: a chamber called TUCANO, to use relative humidity in experiments of in situ XRPD, developed with cooperation of Brazilian Synchrotron Light Source (LNLS); the Parametric Rietveld refinement, pioneered applied in Brazil; the first use of relative humidity as ‘non-crystallographic’ parameter in this refinement; and the application of internal standards (SRM-676a and LiF) during experiments in function of time (at constant temperature), temperature and relative humidity (RH). Norfloxacin (NF, C16H18FN3O3), has a high structural susceptibility to RH and after crystallization of Norfloxacin sesquihydrate form (the only with known crystal structure) starts, at high RH, the behaviour of its cell parameters were parameterized to obtain a smoothly behaviour between all powder patterns... (AU)

• FAPESP's process: 10/08789-4 - Preparation of a standard material for quantification of amorphous in crystalline pharmaceuticals without knowledge of the crystal structure
• Grantee: Rafael Silva Nunes
• Support Opportunities: Scholarships in Brazil - Doctorate