Liquid antisolvent recrystallization and solid dispersion of flufenamic acid with polyvinylpyrrolidone K-30

Abstract 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.

[1]  A. Thakur,et al.  Particle Size Reduction Techniques of Pharmaceutical Compounds for the Enhancement of Their Dissolution Rate and Bioavailability , 2021, Journal of Pharmaceutical Innovation.

[2]  L. Kumar,et al.  Rapidly dissolving Felodipine nanoparticle strips -Formulation using Design of Experiment and Characterisation , 2020 .

[3]  Seon-Kwang Lee,et al.  Solubility of bisacodyl in fourteen mono solvents and N-methyl-2-pyrrolidone + water mixed solvents at different temperatures, and its application for nanosuspension formation using liquid antisolvent precipitation , 2020 .

[4]  Shuang Zhang,et al.  Preparation and physicochemical characterization of soy isoflavone (SIF) nanoparticles by a liquid antisolvent precipitation method , 2019, Advanced Powder Technology.

[5]  V. Rathod,et al.  Continuous preparation of nimesulide nanoparticles by liquid antisolvent precipitation using spinning disc reactor , 2018, Journal of Chemical Technology & Biotechnology.

[6]  Y. Zu,et al.  Preparation, characterization and antitumor activity evaluation of silibinin nanoparticles for oral delivery through liquid antisolvent precipitation , 2017 .

[7]  Ho-mu Lin,et al.  Phase equilibrium and micronization for flufenamic acid with supercritical carbon dioxide , 2017 .

[8]  Li Wang,et al.  Preparation, characterization and antitumor activity evaluation of apigenin nanoparticles by the liquid antisolvent precipitation technique , 2017, Drug delivery.

[9]  S. Yeo,et al.  Liquid antisolvent crystallization of griseofulvin from organic solutions , 2015 .

[10]  Y. Zu,et al.  Enhancement of solubility, antioxidant ability and bioavailability of taxifolin nanoparticles by liquid antisolvent precipitation technique. , 2014, International journal of pharmaceutics.

[11]  N. Sheth,et al.  Application of Plackett-Burman screening design for preparing glibenclamide nanoparticles for dissolution enhancement , 2013 .

[12]  A. Hezave,et al.  Fabrication of Micron Level Particles of Amoxicillin by Rapid Expansion of Supercritical Solution , 2012 .

[13]  Jianfeng Chen,et al.  Nanonization of Megestrol Acetate by Liquid Precipitation , 2009 .

[14]  Ali Abbas,et al.  Antisolvent crystallization: Model identification, experimental validation and dynamic simulation , 2008 .

[15]  Pardeep Gupta,et al.  Effect of arginine hydrochloride and hydroxypropyl cellulose as stabilizers on the physical stability of high drug loading nanosuspensions of a poorly soluble compound. , 2008, International journal of pharmaceutics.

[16]  Su-Jin Park,et al.  Antisolvent Crystallization of Sulfa Drugs and the Effect of Process Parameters , 2007 .

[17]  L. Hovgaard,et al.  Characterization and Physical Stability of Tolfenamic Acid-PVP K30 Solid Dispersions , 2007, Pharmaceutical development and technology.

[18]  Panos Macheras,et al.  A century of dissolution research: from Noyes and Whitney to the biopharmaceutics classification system. , 2006, International journal of pharmaceutics.

[19]  R. Gilpin,et al.  Infrared studies of the polymorphic states of the fenamates. , 2005, Journal of pharmaceutical and biomedical analysis.

[20]  Jong-Chan Lee,et al.  Crystallization of sulfamethizole using the supercritical and liquid antisolvent processes , 2004 .

[21]  N. Rasenack,et al.  Preparation of microcrystals by in situ micronization , 2004 .

[22]  Martial Sauceau,et al.  Particle generation for pharmaceutical applications using supercritical fluid technology , 2004 .

[23]  E. Matijević,et al.  Preparation of monodisperse colloids of biologically active compounds 1. Naproxen , 1997 .