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.

Preparation, analytical Studies and application of a New Azodye Derived from Pharmaceutical Materials (Procaine Hydrochloride & Salicylic acid)

Procaine hydrochloride was used as an aromatic amine, and salicylic acid (5-[2-(diethylamino)-4-benzoateazo]-2-hydroxybenzoic acid) was used to make a new azodye derived from pharmaceutical materials ( PS ).C.H.N., H1-NMR, I.R., and visible spectroscopic techniques have also been used to characterize dye. At different pH values ( 2 - 12 ), the electronic spectra of this azo dye was investigated in terms of acid-base properties, which included defining isobestic points and determining protonation and ionization constants. The effect of different polarities of solvents on the electronic spectra was the subject of another study. The dye has been used in a variety of applications, including as an indicator for strong acid with strong base and for nitrite determination.

Spectral imaging of pharmaceutical materials with a compact terahertz difference-frequency generation semiconductor source

We demonstrated the ability to perform spectroscopic imaging of pharmaceutical material using a compact ultra-broadband THz DFG source.

Interconvertible Hydrochlorothiazide–Caffeine Multicomponent Pharmaceutical Materials: A Solvent Issue

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions.