Development of Green Methods for the Determination of Elemental Impurities in Commercial Pharmaceutical Tablets

In this study, two methods based on the use of diluted acids were developed: microwave-assisted wet digestion (MAWD) and microwave-assisted ultraviolet digestion (MAWD-UV). These methods are evaluated for the digestion of oral pharmaceutical drugs and further determination of elemental impurities from classes 1 (As, Cd, Hg and Pb) and 2A (Co, Ni and V) by inductively coupled plasma optical emission spectrometry (ICP-OES). Commercial drugs for the treatment of type 2 diabetes are used. No prior comminution is performed. For MAWD, the optimized conditions were 2 mol L−1 or 3 mol L−1 HNO3, 1 mL of 50% H2O2 and a 45 min or 55 min irradiation program. For MAWD-UV, the condition using 1 mol L−1 HNO3, 1.6 mL of 50% H2O2 and a 55 min irradiation program enabled the digestion of all samples. In this way, efficient methods are proposed for the digestion of commercial pharmaceutical tablets for further determination of class 1 and 2A elemental impurities (ICH Q3D guidelines).

Modeling of High-Density Compaction of Pharmaceutical Tablets Using Multi-Contact Discrete Element Method

The purpose of this work is to simulate the powder compaction of pharmaceutical materials at the microscopic scale in order to better understand the interplay of mechanical forces between particles, and to predict their compression profiles by controlling the microstructure. For this task, the new framework of multi-contact discrete element method (MC-DEM) was applied. In contrast to the conventional discrete element method (DEM), MC-DEM interactions between multiple contacts on the same particle are now explicitly taken into account. A new adhesive elastic-plastic multi-contact model invoking neighboring contact interaction was introduced and implemented. The uniaxial compaction of two microcrystalline cellulose grades (Avicel® PH 200 (FMC BioPolymer, Philadelphia, PA, USA) and Pharmacel® 102 (DFE Pharma, Nörten-Hardenberg, Germany) subjected to high confining conditions was studied. The objectives of these simulations were: (1) to investigate the micromechanical behavior; (2) to predict the macroscopic behavior; and (3) to develop a methodology for the calibration of the model parameters needed for the MC-DEM simulations. A two-stage calibration strategy was followed: first, the model parameters were directly measured at the micro-scale (particle level) and second, a meso-scale calibration was established between MC-DEM parameters and compression profiles of the pharmaceutical powders. The new MC-DEM framework could capture the main compressibility characteristics of pharmaceutical materials and could successfully provide predictions on compression profiles at high relative densities.

SIMULTANEOUS DETERMINATION OF PARACETAMOL AND TAPENTADOL IN TABLETS BY RATIO SPECTRA DERIVATIVE SPECTROPHOTOMETRY

The application of the ratio spectra derivative spectrophotometry to the simultaneous determination of Paracetamol (PCM) and Tapentadol (TAP) in combined pharmaceutical tablets is presented. The spectrophotometric procedure is based on the use of the first derivative of the ratio spectra obtained by dividing the absorption spectrum of the binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes were measured at 220 and 232 nm for the assay of TAP and PCM, respectively. Calibration graphs were established for 1-5 μg mL-1 for TAP and 6.5-32.5 μg mL-1 for PCM in binary mixture. The detection limits for TAP and PCM were found 0.098 and 0.595 μg mL-1, respectively, while the quantification limits were 0.298 μg mL-1 for TAP and 1.805 μg/ml for PCM. The relative standard deviations were found to be less than 2%, indicating reasonable repeatability of both methods. The proposed methods were hence validated as per ICH guidelines and successfully applied to the determination of these drugs in commercial tablets.