R&D

As a global leader in fluid formulation processing equipment, MFIC is committed to advancing the formulation field. In the early 2000’s, MFIC focused their business plan to invest heavily in research and discovery. This investment led not only to new product features and equipment offerings, but also to the discovery and development of breakthrough technology, including Micofluidics Reaction Technology (MRT), advancing the field of formulation and further solidifying MFIC’s role as a global leader and innovator.

In 2007, this commitment was reinforced with the creation of a new state-of-the-art research and discovery facility, The Microfluidics Technology Center. The Center serves as an innovation hub for the Company’s highly-specialized research team dedicated to discovering breakthrough technologies, developing new applications for existing technology, creating innovative new products to meet customers’ needs and pursuing groundbreaking work in the field of nanotechnology.

The Microfluidics Technology Center also serves a best-practice in meeting our customers’ needs. At the Center, customers have full access to the best engineers and the most advanced equipment in a single-laboratory setting to prepare, characterize and optimize formulation samples. Engineers will also assist customers in improving their existing products through reformulation using proprietary, leading-edge, high-shear Microfluidizer materials processors.

Microfluidics Reaction Technology

Microfluidics Reaction Technology (MRT) a continuous and scalable microreactor system used for:

• Large scale production of nanoparticles with high purity and efficiency,  and low cost

• Synthesis of fine chemicals through single or multiphase reactions

• Process Intensification

The lab scale capacity is about 0.5 liters/min, but it can be expanded to tens of liters per minute.

MRT ensures mixing of the reactants in the nanometer scale inside a microliter size volume can. Typical applications include:

• Crystallization

• Chemical reactions

• Emulsion formation

Microfluidics has demonstrated successfully all these applications on the lab scale (0.5 liters/min).

MRT solves an issue that conventional mixers/reactors have been unable to overcome. Conventional processes utilize a “top down” method to grind particle sizes to the nano-level through a process of wet-milling, homogenization, micronization, and other techniques. This top-down process does not allow for optimal and consistent sizing of the particles and is often unable to produce particles sizes small enough to be effective. MRT utilizes a “bottoms up” proprietary approach whereby the particle is built up molecule by molecule in seconds allowing not only for optimal and consistent sizing of the particles but also for the creation of smaller particle sizes not previously achievable. The process is both continuous (versus batch) and results in extreme phase purity of products. In the lab, MRT was demonstrated to be more effective in producing optimally-sized, consistent nanosuspensions than standard particle size reducing methods for a variety of drugs using solvent and anti-solvent crystallization, including two antibiotics, an antihistamine, an anticonvulsant and a non-steroidal anti-inflammatory. MRT was presented during a poster presentation at the Nano Science and Technology Institute (NSTI) Nanotech 2007 Conference and won a Nanotech50 Award.  The core of this technology is a continuous microreactor (reaction chamber) based on impinging jet design. Two opposing jets form as fluids flow through two microchannels within the chamber. The jets collide inside a microliter volume where the fluids mix at the nanometer scale.  Average fluid velocities inside the channels may exceed 400 m/s, which is orders of magnitude higher than existing impinging jet reactors. A planar array of opposed pairs of such channels ensures effective scaling up of the technology.

High velocities through the channels are achieved by applying high pressures to the fluid upstream of the channels. Pressures up to 207 MPa (30,000 psi) are required for such velocities generated using a hydraulically or pneumatically driven pressure multiplier referred to as an intensifier.

Two opposing jets form as fluids flow through two microchannels within the chamber. The jets collide inside a microliter volume where the fluids mix in the nanometer scale.  Typical dimensions of channel depth and width are in the range of 75 to 150 microns. Average fluid velocities inside the channels may exceed 400 m/s. A planar array of opposed pairs of such channels ensures effective scaling up of the technology.

Impinging jet reactors have been used in the past for a variety of reactions. The flow inside Microfluidics chamber is intensely turbulent, unlike the flow in other reactors. The average channel velocities, jet Reynolds numbers and energy dissipation levels are orders of magnitude higher in Microfluidics chambers than in these other reactors. Typical values for jet Reynolds numbers of Microfluidics chambers are over 20,000, as compared to only 100-2000 in existing technologies.

Publications

Production of Stable Drug Nanospensions Using Microfluidics Reaction Technology

T. Panagiotou, S. Mesite, R. Fisher and I. Gruverman

Many hydrophobic drugs are difficult to formulate in ways that ensure high bioavailability. The formation of stable drug nanosuspensions is an attractive formulation strategy that does not limit the dosage amount. Microfluidics Reaction Technology (MRT) was used to produce drug nanosuspensions via solvent and anti-solvent crystallization. The core of this technology is a continuous and scalable microreactor based on impinging jets. Inside the reactor, liquid reactants encounter highly turbulent conditions and interact at the nanometer level. Download >

Presentations

Production Of Crystalline Nanoparticles Using Microfluidics Reaction Technology as presented at the Crystallization Summit, 2008, Netherlands

Dr. T. Panagiotou, and S.V. Mesite  (of Microfluidics) Dr. R J. Fisher (of MIT)  

A continuous, “bottom-up” process was developed that utilizes solvent/antisolvent crystallization in conjunction with Microfluidics Reaction Technology (MRT) to produce crystalline nanoparticles. The concept is to create nanosuspensions of crystalline materials by achieving uniform supersaturation in the nanometer level, through intense and localized mixing of a solvent with an antisolvent stream. The core of MRT is a continuous microreactor which uses impinging jet technology. This particular impinging jet reactor maintains jet velocities up to 500 m/s, which are achieved by operating at pressures 50-200 MPa, and therefore energy dissipation levels are orders of magnitude higher than those of conventional impinging jet reactors. MRT was demonstrated using the drug carbamazepine (CBZ). The effect of degree of superstaturation, energy dissipation, and solvent/antisolvent types were examined. Results from this effort were compared to crystallization under low mixing conditions in a beaker, and also to conventional “top-down” particle size reduction of large CBZ particles produced in a beaker. The main results are as follows: (a) The particle size using MRT decreased with increasing energy input (process pressure) and degree of supersaturation, from micron size to a few hundred nanometers. (b) When compared with low mixing crystallization, MRT often resulted in 5-10 times smaller particles. (c) Comparison of the MRT “bottom- up” process with the conventional  “top-down” particle size reduction indicate that MRT results in substantially smaller particle size (median size of 304 nm versus 604 nm). The “bottom-up” process required a single processing cycle, while a “top-down” process that required 25 processing cycles. (d) Highly crystalline particles were achieved by both MRT and beaker crystallization. The polymorphs obtained with this particular drug depended primarily upon the solvent/antisolvent system used. (e) The use of MRT is consistent with the concepts of Process Intensification (PI) currently being implemented in various industrial settings to enhance overall system performance. Download >

NSTI 2008, Boston, MA Presentation by Thomai Panagiotou, Ph.D.

Polymer nanoparticles are often used for controlled drug delivery of active pharmaceutical ingredients (APIs). Microfluidizer processor based technologies offer two options for production of polymer nanoparticles. The first is an emulsion method, which involves dissolving the polymer and API in the oil phase of an emulsion and then subsequent removal of the oil. The second is a precipitation method, in which the polymer and API are dissolved in a solvent and then forced to precipitate inside the high shear mixing zone when mixed with an anitsolvent. These methods are compatible with a wide variety of polymer/API systems. The focus of this work is to identify the effects of varying key parameters such as process pressure, relative flow rates of the streams, and formations on the particle size distribution.

This article showcases polymer nanosuspensions in the range of 50-500 nm that were prepared with two different polymers, using both techniques. Furthermore, these tests indicate that an API was successfully encapsulated within the nanoparticles. Download >

Nano-encapsulation using Microfluidizer Technology Platform

Thomai Panagiotou, Ph.D.

PowerPoint presentation of nanoencapsulation using Microfluidizer high-shear processors and Microfluidics Reaction Technology (MRT) Download >

Microfluidizer Mixer-Reactor (MMR) system

The patented Microfluidizer Mixer-Reactor (MMR) system is a high-performing, continuous chemical reactor utilizing multiple reactant fluid streams. In most conventional chemical reactors, inadequate mixing and mass-transfer rates limit the value and performance of a fast chemical reaction. As a result, product yields are low, and unwanted by-products are produced. Building upon basic Microfluidics technology, computer controlled flow rates of multiple streams of pressurized reactants are brought together in a proprietary MMR mixing chamber with residence times of a few hundred microseconds to a few hundred milliseconds. By optimizing the fast chemical reactions required in many of today’s chemical processes, MMR enables the production of uniform nanoparticles on a continuous basis with phase purity previously unachievable with conventional batch reaction technology.