Newly developed active pharmaceutical ingredients (APIs) are often poorly soluble in water. As a result the bioavailability of the API in the human body is reduced. One approach to overcome this restriction is the formulation of amorphous solid dispersions (ASDs), e.g., by hot-melt extrusion (HME). Thus, the poorly soluble crystalline form of the API is transferred into a more soluble amorphous form. To reach this aim in HME, the APIs are embedded in a polymer matrix. The resulting amorphous solid dispersions may contain small amounts of residual crystallinity and have the tendency to recrystallize. For the controlled release of the API in the final drug product the amount of crystallinity has to be known. This review assesses the available analytical methods that have been recently used for the characterization of ASDs and the quantification of crystalline API content. Well-established techniques like near- and mid-infrared spectroscopy (NIR and MIR, respectively), Raman spectroscopy, and emerging ones like UV/VIS, terahertz, and ultrasonic spectroscopy are considered in detail. Furthermore, their advantages and limitations are discussed with regard to general practical applicability as process analytical technology (PAT) tools in industrial manufacturing. The review focuses on spectroscopic methods which have been proven as most suitable for in-line and on-line process analytics. Further aspects are spectroscopic techniques that have been or could be integrated into an extruder.
Two solid solution series exist in the system MgMoO 4 -NiMoO 4 . The α-Ni 1-y Mg y MoO 4 solution series, isostructural to α-NiMoO 4 , is thermodynamically stable at ambient conditions for compositions between 0 % and about 75 % magnesium content. The solution series β-Mg 1-x Ni x MoO 4 , isostructural to MgMoO 4 and the high temperature β modification of NiMoO 4 , is thermodynamically stable at ambient conditions for compositions with Ͻ 25 % nickel content. A complete solid solution series β-Mg 1-x Ni x MoO 4 exists at higher temperatures (Ͼ 823 K). The transition temperature for the α Ǟ β transition decreases with increasing magnesium content. The coexist-
For optimization of production processes and product quality, often knowledge of the factors influencing the process outcome is compulsory. Thus, process analytical technology (PAT) that allows deeper insight into the process and results in a mathematical description of the process behavior as a simple function based on the most important process factors can help to achieve higher production efficiency and quality. The present study aims at characterizing a well-known industrial process, the transesterification reaction of rapeseed oil with methanol to produce fatty acid methyl esters (FAME) for usage as biodiesel in a continuous micro reactor set-up. To this end, a design of experiment approach is applied, where the effects of two process factors, the molar ratio and the total flow rate of the reactants, are investigated. The optimized process target response is the FAME mass fraction in the purified nonpolar phase of the product as a measure of reaction yield. The quantification is performed using attenuated total reflection infrared spectroscopy in combination with partial least squares regression. The data retrieved during the conduction of the DoE experimental plan were used for statistical analysis. A non-linear model indicating a synergistic interaction between the studied factors describes the reactor behavior with a high coefficient of determination (R²) of 0.9608. Thus, we applied a PAT approach to generate further insight into this established industrial process.
Powder samples of solid solutions in the MgMoO4—NiMoO4 system are prepared from stoichiometric mixtures of MgO, MoO3, and NiO (quartz crucible, 1173 K, 60 h).
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