This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche. Furthermore, the paper discusses the PAT paradigm from the regulatory science perspective. Given the multidisciplinary nature of PAT, such an endeavour would be almost impossible for a single author, so the concept of a multiauthor review was born. Each section of the multiauthor review has been written by a single expert or group of experts with the aim to report on its own research results. This paper also serves as a comprehensive source of information on PAT topics for the novice reader.

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The solubility of 2-chloro-N-(4-methylphenyl)propanamide (S1) in ethyl acetate + hexane mixtures between the temperatures of 273.43 to 327.67 K, in toluene + hexane mixtures from 273.24 to 331.62 K, in acetone + hexane mixtures from 269.81 to 318.8 butanone + hexane mixtures between 267.10 and 322.92 were determined using the polythermal method. In situ focused beam reflectance measurement (FBRM) was used to characterize the dissolution properties and to provide S1's saturation temperature profile as a function of concentration. It was demonstrated that the solubility of S1 increases with increasing temperature at constant solvent composition. The experimental solubility data were correlated using Apelblat, λh, and phase equilibria with NRTL (nonrandom two liquid) model equations, and the predicted solubility data obtained agree sufficiently with the experimental data based on the relative deviation (RD%) and average relative deviation (ARD%) values. The Apelblat and λh model equation provides a convenient operational model of engineering interest to calculate the solubility of S1 quickly and easily, although it does not take the solvent composition into account, therefore needing separate parameters for each different solvent compositions. Therefore, the phase equilibria with NRTL model equation is used to provide a more comprehensive model that illustrates the effect of solvent composition on the solubility more apparently. One general set of NRTL parameters has the capability of describing all solvent compositions. Additionally, the melting temperature, T m and the molar fusion enthalpy, Δ fus H, (394.83 K and 26.77 kJ mol −1 respectively) of S1 were determined by differential scanning calorimetry (DSC).

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The integration of an in situ wet mill and continuous mixed suspension mixed product removal crystallizer (MSMPR) is studied in this work for the cooling crystallization of paracetamol from an aqueous isopropanol mixture. The continuous operation was monitored using focused beam reflectance measurements (FBRM) to determine the onset of the steady state. The impact of various operational conditions of both continuous in situ mill and MSMPR unit is studied. The paper demonstrates that the operational conditions (i.e., residence time, operational temperature) of the crystallization process affect the achievable steady state product characteristics. In addition, the influence of in situ mill operating conditions (i.e., rotor speed) on important product and process qualities such as mean particle size, yield, and particle number is also discussed. Furthermore, breakage kernels were evaluated and validated through a parameter estimation routine. The in situ mill process can be assumed to be a combination of a nucleator generator and mill due to its impact on the mixing conditions as demonstrated by the parameter estimation framework. The model developed shows significant promise for process intensification and optimization studies in continuous crystallization process.

This paper presents a laboratory study examining the dissolution kinetics of ibuprofen crystals in water containing a phosphate buffer (pH 7.20) at 37 °C, examining the influences of initial undersaturation ratio, agitation rate, crystal habit, and particle size. For each experiment, the concentration during the dissolution process was followed using UV spectroscopy, ATR-FTIR, and FBRM methods. The dissolution profiles were correlated using eight mathematical models, and the dissolution rate parameters were determined. The Weibull model, the Korsmeyer−Peppas model, and the first-order kinetics model gave better correlation results than the other models used in this paper for the dissolution of ibuprofen crystals. The particle size distribution slightly shifted to the right after dissolution, confirming that smaller particles with higher surface areas dissolved more rapidly. During dissolution, two distinct behaviors were obtained at different levels of undersaturation ratio; therefore, it is postulated that the mechanism of dissolution switches from being mass-transfer-limited at higher levels of undersaturation ratio to being limited by the rate of surface detachment at lower undersaturation ratio levels.

The knowledge of crystallization kinetics, especially crystal nucleation, is crucial for crystallization process design and control. In the present paper, the primary nucleation kinetics of benzoic acid in water−ethanol solution was estimated from induction time measurements, where focused beam reflectance measurement was utilized to detect the onset point of nucleation. As a result, the induction times have been found to decrease with increasing mass fraction of water under the same supersaturation. These data were then used to determine the interfacial energy together with critical size and activation energy for nucleation based on classical nucleation theory. The resulting interfacial energy differed from 1.83 to 6.46 mJ/m 2 at various solvent compositions. Also, it has been demonstrated that the interfacial energy increased with increasing water mass fraction, which finally caused the increase of the critical size and activation energy for nucleation, suggesting significant effects of water mass fraction on nucleation kinetics.

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