Solvent extraction employing a static micromixer: A simple, robust and versatile technology for the microencapsulation of proteins

Abstract

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.

A Protective Allergy Vaccine Based on CpG- and Protamine-Containing PLGA Microparticles

“…PLGA MP were made by microextrusion-based w/o/wsolvent extraction using a static multilamination type micromixer (Institut fü r Mikrotechnik Mainz GmbH, Mainz, Germany), as previously described (12), with slight modifications. Three different formulations were prepared.…”

“…Three different PLGA formulations were prepared by a recently developed microextrusion based process (12,15). The size of the particles increased slightly depending on the number of encapsulated components (Table 1).…”

A “twisted” microfluidic mixer suitable for a wide range of flow rate applications

“…Although a number of these micromixers have been built with two or three layers of polydimethylsiloxane (PDMS) or grooves, and are quite small, these are only applicable to high flow rates, which 20,21 favor the transition of the flow within the channels. Micromixer applications are not limited to chemical reactors, 22 but are also helpful in the performance of enzyme reactions, 23 biological analyses, 24,25 and drug delivery, 26 and these applications do not always require fixed flow rates during the process. The demand has therefore arisen for a micromixer that can operate at different flow rates, which are required for a broad range of applications.…”

Applications of micromixing technology

“…Extraction using micromixing techniques has mainly been applied to solvent extraction, also known as liquid-liquid extraction. 15,38,39 From these viewpoints, several micromixers for the extraction process have been evaluated. 38 The main parameter governing this process is mass transport across the phase boundary, which suggests that micromixers should prove useful in assisting the process.…”

“…Extraction processes generally consist of two steps: formation of a dispersion and subsequent phase separation for extraction. 20,38,39 Freitas et al 19,20 employed an interdigital micromixer for the aseptic production of microspheres utilizing solvent extraction method. 38 To achieve phase saturation, both efficient mixing and dispersion methods are required.…”