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Solvent Extraction Employing A Static Micromixer: A Simple, Robust And Versatile Technology For The Microencapsulation Of Proteins.

S. Freitas, A. Walz, H. P. Merkle, B. Gander
Published 2003 · Materials Science, Medicine

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The potential of a static micromixer for the production of protein-loaded biodegradable polymeric microspheres by a modified solvent extraction process was examined. The mixer consists of an array of microchannels and features a simple set-up, consumes only very small space, lacks moving parts and offers simple control of the microsphere size. Scale-up from lab bench to industrial production is easily feasible through parallel installation of a sufficient number of micromixers ('number-up'). Poly(lactic-co-glycolic acid) microspheres loaded with a model protein, bovine serum albumin (BSA), were prepared. The influence of various process and formulation parameters on the characteristics of the microspheres was examined with special focus on particle size distribution. Microspheres with monomodal size distributions having mean diameters of 5-30 micro m were produced with excellent reproducibility. Particle size distributions were largely unaffected by polymer solution concentration, polymer type and nominal BSA load, but depended on the polymer solvent. Moreover, particle mean diameters could be varied in a considerable range by modulating the flow rates of the mixed fluids. BSA encapsulation efficiencies were mostly in the region of 75-85% and product yields ranged from 90-100%. Because of its simple set-up and its suitability for continuous production, static micromixing is suggested for the automated and aseptic production of protein-loaded microspheres.
This paper references
10.1002/(SICI)1097-0290(19970620)54:6<503::AID-BIT1>3.0.CO;2-N
Protein denaturation by combined effect of shear and air-liquid interface.
Y. Maa (1997)
10.1007/S002160051397
The potential of micromixers for contacting of disperse liquid phases
V. Haverkamp (1999)
10.1016/S0009-2509(99)00503-5
Effect of preparation conditions on morphology and release profiles of biodegradable polymeric microspheres containing protein fabricated by double-emulsion method
Y. Yang (2000)
10.1023/A:1011968707321
The Production of Uniformly Sized Polymer Microspheres
B. Amsden (2004)
10.3109/02652048809056478
A method for the preparation of polylactic acid microcapsules of controlled particle size and drug loading.
N. Leelarasamee (1988)
Formulation of bovine serum albumin loaded PLGA microspheres influence of the process variables on the loading and in vitro release
H. Marchais (1996)
10.3109/02652049609006803
Microencapsulation reactor scale-up by dimensional analysis.
Y. Maa (1996)
10.1016/S0168-3659(00)00291-1
Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method.
Y. Yang (2000)
10.1016/S0168-3659(01)00289-9
Fabrication of PLG microspheres with precisely controlled and monodisperse size distributions.
C. Berkland (2001)
10.1111/j.2042-7158.1996.tb05995.x
Preparation of Poly(D,L‐lactide) and Copoly(lactide‐glycolide) Microspheres of Uniform Size
K. Shiga (1996)
10.1016/S0168-3659(97)01647-7
Microencapsulation techniques using ethyl acetate as a dispersed solvent: effects of its extraction rate on the characteristics of PLGA microspheres
H. Sah (1997)
10.1002/(SICI)1097-0290(19991220)65:6<659::AID-BIT6>3.0.CO;2-9
Microencapsulation of human growth hormone within biodegradable polyester microspheres: protein aggregation stability and incomplete release mechanism.
H. Kim (1999)
10.1016/0378-5173(93)90052-H
Influence of manufacturing parameters on the size characteristics and the release profiles of nifedipine from poly(DL-lactide-co-glycolide) microspheres
P. Sansdrap (1992)
10.1248/CPB.36.1095
A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic) acid.
Y. Ogawa (1988)
10.1016/S0168-3659(96)01475-7
Protein-loaded poly(dl-lactide-co-glycolide) microparticles for oral administration: formulation, structural and release characteristics
H. Rafati (1997)
10.1016/S0168-3659(96)01547-7
Bovine serum albumin release from poly(α-hydroxy acid) microspheres: effects of polymer molecular weight and surface properties
Franck Boury (1997)
10.1002/1521-4125(200101)24:1<11::AID-CEAT11>3.0.CO;2-Q
Utilization of Micromixers for Extraction Processes
K. Benz (2001)
10.1023/A:1015841715384
Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres
S. Cohen (2004)
10.1016/S0939-6411(98)00011-3
Protein encapsulation and release from poly(lactide-co-glycolide) microspheres: effect of the protein and polymer properties and of the co-encapsulation of surfactants.
D. Blanco (1998)
10.3109/02652049709015335
Effect of primary emulsions on microsphere size and protein-loading in the double emulsion process.
Y. Maa (1997)
10.3109/02652049609026028
Liquid-liquid emulsification by static mixers for use in microencapsulation.
Y. Maa (1996)
10.1021/IE980128D
Characterization of Mixing in Micromixers by a Test Reaction: Single Mixing Units and Mixer Arrays
W. Ehrfeld (1999)
10.1016/S0168-3659(96)01483-6
An examination of factors affecting the size, distribution and release characteristics of polymer microbeads made using electrostatics
B. Amsden (1997)
10.1126/SCIENCE.2218494
New methods of drug delivery.
R. Langer (1990)



This paper is referenced by
Desenvolvimento de microesferas de PLGA contendo interleucina-2 para aplicação na terapia anti-neoplástica
R. Costa (2008)
10.1016/j.jconrel.2008.06.003
Surface coating of PLGA microparticles with protamine enhances their immunological performance through facilitated phagocytosis.
Julia M Martínez Gómez (2008)
10.1016/J.JCONREL.2003.11.005
Ultrasonic atomisation into reduced pressure atmosphere--envisaging aseptic spray-drying for microencapsulation.
S. Freitas (2004)
10.1016/J.EJPB.2005.08.015
Preparation of protein loaded poly(D,L-lactide-co-glycolide) microparticles for the antigen delivery to dendritic cells using a static micromixer.
C. Wischke (2006)
10.1002/ADMA.200803386
The Synthesis and Assembly of Polymeric Microparticles Using Microfluidics
D. Dendukuri (2009)
10.1039/b921430e
Applications of micromixing technology.
G. S. Jeong (2010)
10.1016/j.ejpb.2013.02.017
Biodegradation and heart retention of polymeric microparticles in a rat model of myocardial ischemia.
F. R. Formiga (2013)
10.1016/J.EJPB.2005.05.004
Flow-through ultrasonic emulsification combined with static micromixing for aseptic production of microspheres by solvent extraction.
S. Freitas (2005)
10.1109/CERMA.2006.85
Selection of Micromixers for Biochemical Detection of Pesticides
R. Vargas-Bernal (2006)
10.1021/ja077014q
New avenues to efficient chemical synthesis : emerging technologies
P. Seeberger (2007)
10.1016/J.JCONREL.2004.02.015
Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheres.
M. Blanco-Prieto (2004)
10.1016/J.ADDR.2004.09.002
Formulation aspects of biodegradable polymeric microspheres for antigen delivery.
H. Tamber (2005)
10.1080/02652040400026392
Effect of surfactant HLB and different formulation variables on the properties of poly-D,L-lactide microspheres of naltrexone prepared by double emulsion technique
R. Dinarvand (2005)
10.1016/j.jconrel.2010.05.011
Issues in long-term protein delivery using biodegradable microparticles.
Mingli Ye (2010)
10.2174/157018010790945760
Making Drops in Microencapsulation Processes
L. Martín-Banderas (2010)
Développement d’une protéine à libération prolongée, mise au point du procédé d’encapsulation sans solvant halogéné et optimisation du profil de libération.
Fabien Violet (2015)
10.4071/CICMT-2012-THA13
LTCC 3D MICROMIXER OPTIMIZATION FOR PROCESS INTENSIFICATION
M. R. D. Cunha (2012)
10.1016/J.BIOMATERIALS.2006.10.034
The preservation of phenotype and functionality of dendritic cells upon phagocytosis of polyelectrolyte-coated PLGA microparticles.
S. Fischer (2007)
10.1016/J.JCONREL.2004.10.015
Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology.
S. Freitas (2005)
10.1002/cmmi.442
Multifunctional microbubbles and nanobubbles for photoacoustic imaging.
R. Xu (2011)
10.1016/J.IJMULTIPHASEFLOW.2005.01.006
A computational analysis of the hydrodynamic instability of a liquid jet focused into a converging microchannel
S. Hardt (2005)
10.1016/J.CEJ.2003.11.032
g/l-Dispersion in interdigital micromixers with different mixing chamber geometries
P. Loeb (2004)
10.3929/ETHZ-A-005069007
Novel strategies and technologies for the aseptic microencapsulation of pharmaceutical compounds
S. Freitas (2005)
10.3390/mi9050204
Numerical and Experimental Study on Mixing Performances of Simple and Vortex Micro T-Mixers
M. Ansari (2018)
Encapsulation of Rosmarinic Acid Into Biopolymer-Based Microparticles for Topical Delivery
F. C. C. Bastos (2015)
10.1039/B310802C
An optimised split-and-recombine micro-mixer with uniform chaotic mixing.
F. Schoenfeld (2004)
10.1016/J.JFOODENG.2009.03.030
Manufacture of food grade κ-carrageenan microspheres
Arthur Ellis (2009)
10.1016/J.JCONREL.2006.06.020
Stable cationic microparticles for enhanced model antigen delivery to dendritic cells.
C. Wischke (2006)
10.3929/ETHZ-A-007326128
Immunobiology of surface-assembled poly(I:C) on microspheres as safe and efficacious immunostimulant in vaccination
Annina Maria Hafner (2012)
10.1016/J.CES.2004.11.033
Micromixers—a review on passive and active mixing principles
V. Hessel (2005)
10.1002/9780470571224.PSE351
Progress in Design of Biodegradable Polymer‐Based Microspheres for Parenteral Controlled Delivery of Therapeutic Peptide/Protein
S. Tamilvanan (2010)
10.1016/J.CHERD.2018.04.019
An investigation of mixing performance in helically coiled microchannels by the Villermaux/Dushman reaction
M. Izadi (2018)
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