Monodisperse Particles from Single Emulsions with Microfluidic Device
DOI:
https://doi.org/10.14738/aivp.1301.18255Keywords:
monodisperse crystal, microcrystal, microfluidic deviceAbstract
The goal of this study was to develop a microfluidic device, establish the optimal conditions, and adapt an antisolvent technique into microfluidic microcapillary device to produce API microparticles with uniform particle size, generated from monodisperse single emulsions, using griseofulvin as the model compound. Griseofulvin monodispersed crystals were produced using a microfluidic microcapillary device. Three different fluids mixtures were used to both create an antisolvent environment and generate monodisperse drops within the microcapillary device. Single emulsion generation was visualized using an inverted microscope equipped with a high-speed camera. Finally, the griseofulvin crystals were collected, and their particle size was measured through microscopy image analysis.
An antisolvent technique was adapted into the microfluidic capillary device. The inner, middle, and outer fluids consisted of 7% griseofulvin, SDS in ultrapure water, and polysorbate 80 in ultrapure water, respectively. The optimal flow conditions were determined to generate monodisperse single emulsion drops, resulting in griseofulvin microcrystals with an average particle size of 11 µm. A novel microcapillary device process was developed, applying an antisolvent technique to generate monodisperse griseofulvin crystals starting from monodisperse single emulsions. Established the constituents and flow rates of each fluid, allowing for complete control of the system. Single emulsions of GF in triacetin were produced with an average diameter of 75.2 ± 2.9 µm. Finally, monodispersed griseofulvin crystals with a mean particle size of 11.60 ± 3.64 µm were obtained. Microfluidic method is excellent to obtain monodisperse particles for inhalation process and pulmonary delivery, because the span is better than the other material in the market. Microfluidic method developed is excellent to produce crystals with improved specific surface area and probably with better bioavailability.
References
Griseofulvin. British Pharmacopeia, 2020, I1213
Al-Obaidi H, Buckton G. Evaluation of griseofulvin binary and ternary solid dispersions with HPMCAS. AAPS Pharm Sci Tech. 2009; 10:1172-7.
Ahmed IS, Aboul-Einien MH. In vitro and in vivo evaluation of a fast-disintegrating lyophilized dry emulsion tablet containing griseofulvin. Eur J Pharm Sci. 2007; 32:58-68.
Zili Z, Sfar S, Fessi H. Preparation and characterization of poly- -caprolactone nanoparticles containing griseofulvin. Int J Pharm. 2005; 294:261-267.
Kamiya S, Nozawa Y, Miyagishima A, Kurita T, Sadzuka Y, Sonobe T. Physical characteristics of freeze-dried griseofulvin-lipids nanoparticles. Chem Pharm Bull. 2006; 54:181-4.
Blagden N, de Matas M, Gavan PT, York P. Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Deliv Rev. 2007; 59:617–630.
Knoblauch J, Zimmermann I. Thermochemical analysis of the dissolution process of Griseofulvin. Eur J Pharm Biopharm. 2007; 67:743–751.
Zhao H., Wang JX, Wang QA, Chen JF, Yun J. Controlled liquid antisolvent precipitation of hydrophobic pharmaceutical nanoparticles in a microchannel reactor. Ind. Eng. Chem. Res. 2007;46: 8229-8235.
Shekunov BY, Chattopadhyay P, Seitzinger J, Huff R. Nanoparticles of poorly watersoluble drugs prepared by supercritical Fluid extraction of emulsions. Pharm Res. 2006; 23:196-204.
Feng T, Pinal R, Carvajal MT. Process induced disorder in crystalline materials: differentiating defective crystals from the amorphous form of griseofulvin. J Pharm Sci. 2008; 97:3207-21.
ll J, Lindenberg C, Vicum L, Mazzotti M. Antisolvent precipitation of PDI 747: Kinetics of particle formation and growth. Cristal Grow and Design. 2007; 7:1653-1661.
Murnane D, Marriott C, Martin GP. Comparison of salmeterol xinafoate microparticle production by conventional and novel antisolvent crystallization. Eur J Pharm Biopharm. 2008; 69:94-105.
Jarmer DJ, Lengsfeld CS, Anseth KS, Randolph TW. Supercritical fluid crystallization of griseofulvin: Crystal habit modification with a selective growth inhibitor. J Pharm Sci. 2005; 94:2688-2702.
Kim MS, Jin SJ, Kim JS, Park HJ, Song HS, Neubert RH, Hwang SJ. Preparation, characterization and in vivo evaluation of amorphous atorvastatin calcium nanoparticles using supercritical antisolvent (SAS) process. Eur J Pharm Biopharm. 2008; 68:454-465.
Matteucci ME, Hotze MA, Johnston KP, Williams RO. Drug nanoparticles by antisolvent precipitation: Mixing energy versus surfactant stabilization. Langmuir. 2006; 22:8951-8959. 293
James-Smith MA. Alford K, Shah DO. Effect of long-chain alcohols on SDS partitioning to the oil/water interface of emulsions and on droplet size. J. Colloid Interface Sci. 2007; 315:307-312.
Calafato NR, Picó G. Griseofulvin and ketoconazole solubilization by bile salts studied using fluorescence spectroscopy. Colloids Surf B Biointerfaces. National University of Rosario, Argentina. 2006; 47:198-204.
Ye C, Chen A, Colombo P, Martinez C. Ceramic microparticles and capsules via microfluidic processing of a preceramic polymer. J R Soc Interface. 2010; 7:461-73.
Utada S, Lorenceau E, Link DR, Kaplan PD, Stone HA, Weitz DA. Monodisperse double emulsions generated from a microcapillary device. Science. 2005; 308:537-541.
Shengqing Xu, et al. Generation of Monodisperse Particles by Using Microfluidics: Control over Size, Shape, and Composition. Angew. Chem. 2005, 117, 734 –738
Okushima S, Nisisako T, Torii T, Higuchi T. Controlled Production of monodisperse Double Emulsions by Two-Step Droplet Breakup in Microfluidic Devices. Langmuir. 2004; 20:9905-9908.
Xu JH, Luo GS, Li SW, Chen GG. Shear force induced monodisperse droplet formation in a microfluidic device by controlling wetting properties. Lab Chip. 2006; 6:31–136.
Djerdjev AM, Beattie JK, Hunter RJ. An electroacoustic and high-frequency dielectric response study of stagnant layer conduction in emulsion systems. J Colloid Interface Sci. 2003; 265:56-64.
James-Smith MA. Alford K, Shah DO. A novel method to quantify the amount of surfactant at the oil/water interface and to determine total interfacial area of emulsions. J. Colloid Interface Sci. 2007; 310:590-8.
Ariyaprakai S, Dungan SR. Contribution of molecular pathways in the micellar solubilization of monodisperse emulsion droplets. Langmuir. 2008; 24:3061-3069.
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000; 45:89–121.
https://www.meggle-pharma.com/es/productConfigurator.html
https://dfepharma.com/excipients/
Perez A., Hernández R., Velasco D., Voicu D. and Mijangos C. Poly (lactic-co-glycolic acid) particles prepared by microfluidics and conventional methods. Modulated particle size and rheology. Journal of Colloid and Interface Science 441 (2015) 90–97.
Lurong Qin, Meifang Liu, Yong Yi, Qiang Yin and Ke Cao. Microfluidic preparation of monodisperse hollow polyacrylonitrile microspheres for ICF. Colloids and Surfaces A: Physicochemical and Engineering Aspects 641 (2022) 127955. https://doi.org/10.1016/j.colsurfa.2021.127955
Esther Amstad. Microfluidics: A Tool to Control the Size and Composition of Particles. CHIMIA 2017, 71, No. 6. 334-341.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Edgar Barrera, Carlos Martinez, Efrén Hernandez-Baltazar
This work is licensed under a Creative Commons Attribution 4.0 International License.
