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Flufenamic acid (FFA) is a Biopharmaceutical Classification System- II (BCS-II) class drug with poor bioavailability and a lower dissolution rate. Particle size reduction is one of the conventional approaches to increase the dissolution rate and subsequently the bioavailability. The use of the liquid antisolvent method for particle size reduction of FFA was studied in this work. Ethanol and water were used as solvent and antisolvent, respectively. Experimental parameters such as solution concentration (10–40 mg/ml), flow rate (120–480 ml/h), temperature (298–328 K) and stirring speed (200–800 rpm) were investigated. Furthermore, the solid dispersion of FFA was prepared with polyvinylpyrrolidone K-30 (PVP K-30) with different weight ratios (1:1, 1:2, 1:3 and 1:4) and samples were characterized using SEM, FTIR and XRD techniques. The experimental investigation revealed that higher values of concentration, injection rate, stirring speed, along with lower temperature favored the formation of fine particles. SEM analysis revealed that the morphology of raw FFA changed from rock-like to rectangular-like after liquid antisolvent recrystallization. FTIR analysis validated the presence of hydrogen bonding between FFA and PVP in solid dispersion. XRD analysis showed no significant change in the crystallinity of the processed FFA. [ABSTRACT FROM AUTHOR]

[Display omitted] • System thermodynamics of the antisolvent crystallization is discussed. • Supersaturation, MSZW, induction time, crystallization kinetics are critically analysed. • Hydrodynamic modeling and CFD-based approach for LASC are critically reviewed. • A complete outlook of LASC is presented. • Modeling based LASC scale-up guidelines and challenges are discussed. Fine particles are in great demand in the pharmaceutical industry due to their versatile applications. Liquid antisolvent crystallization (LASC) is one of the promising approaches to prepare fine particles without requiring high energy. The interdependence of system thermodynamics, mass transfer kinetics, and the multi-phase hydrodynamics in the liquid antisolvent crystallization process is not well understood. In this review, the different modeling aspects of LASC are described from a fundamental perspective. The system thermodynamics of LASC is discussed and several models used in literature to predict the solubility in pure solvents and binary solvent mixtures are summarized. A detailed description of supersaturation, metastable zone width and induction time in antisolvent crystallization are presented and critically analyzed. The nucleation and growth kinetics are discussed and interpreted in terms of process variables. The hydrodynamic aspect of LASC which involves the mixing at different length scales is discussed and analyzed in detail. The CFD simulation-based approach to describe the interaction among different phenomena is critically reviewed. The crystallization scale-up, which is a major challenge in the LASC process, is discussed. A guideline for crystallization scale-up using the CFD-based modeling approach is presented which will be helpful to prospective researchers. [ABSTRACT FROM AUTHOR]

[Display omitted] The novel particle generation processes of Active Pharmaceutical Ingredient (API)/drug have been extensively explored in recent decades due to their wide-range applications in the pharmaceutical industry. The Rapid Expansion of Supercritical Solutions (RESS) is one of the promising techniques to obtain the fine particles (micro to nano-size) of APIs with narrow particle size distribution (PSD). In RESS, supercritical carbon dioxide (SC CO 2) and API are used as solvent and solute respectively. In this literature survey, the application of RESS in the formation of fine particles is critically reviewed. Solubility of API in SC CO 2 and supersaturation are the key factors in tuning the particle size. The different approaches to model and predict the solubility of API in SC CO 2 are discussed. Then, the effect of process parameters on mean particle size and the particle size distribution are interpreted in the context of solubility and supersaturation. Furthermore, the less-explored applications of RESS in preparation of solid-lipid nanoparticles, liposome, polymorphic conversion, cocrystallization and inclusion complexation are compared with traditional processes. The solubility enhancement of API in SC CO 2 using co-solvent and its applications in particle generation are explored in published literature. The development and modifications in the conventional RESS process to overcome the limitations of RESS are presented. Finally, the perspective on RESS with special attention to its commercial operation is highlighted. [ABSTRACT FROM AUTHOR]