Innovation through nanotechnology – Biotechnology/pharmaceutical

Overview - biotechnology

From the gentle disruption of cultured cells for virus isolation to the challenging disruption of yeast cells, Microfluidizer® processors meet the variable and demanding needs for cell disruption. The Microfluidics technology provides exacting process control, thus permitting highly reproducible results.  It delivers more effective cell breakage and higher disruption efficiencies than any other means (e.g. using fewer passes to break the cells, thereby reducing the risk of pulverized fragments), while keeping temperatures under precise control to prevent denaturing. 

In short: Microfluidizer processors are tough on cells and gentle on proteins, enabling you to release proteins without denaturing them.  Microfluidizer processors work effectively with a wide range of biotechnology applications including yeast, mold, E.coli, penicillium, algae, meningococcal cells, mammalian cells, bacteria, fungi and insect cells.  From the smallest lab scale systems to production units, the Microfluidics processor technology provides the optimum methods for cell disruption.

Overview – pharmaceutical

By significantly reducing the particle size of active pharmaceutical ingredients, Microfluidics’ high shear fluid processors can assist in the creation of formulations for drug delivery with improved bioavailability.  In addition, these uniformly small particles may enable formulations to be filter-sterilized. The resulting drugs are more stable, can be efficiently administered and have a longer shelf life.

Microfluidizer® processors are a highly efficient and reproducible means to prepare a wide range of pharmaceutical applications including nanoemulsions, nanodispersions, liposomes and nano/microencapsulations; cancer therapeutics, anesthetics, antibiotics, steroids, vaccines, vaccine adjuvants, artificial blood, controlled release drugs, ointments and vitamins; and injectables, inhalables, parenterals and transdermals. 

Scaleup from lab to pilot to production is guaranteed.  The processors can be used in FDA-approvable and cGMP processes.  They currently are used to manufacture a wide array of drugs that are FDA-approved and on the market.

Using nanotechnology to improve bioavailability

As a result of recent advances in high throughput screening and drug discovery, many new chemical compounds have been identified as possible drug candidates.  Unfortunately, many of these compounds show poor water solubility and often are only marginally soluble in oil-based solvents.  In short: their bioavailability is limited.

So you may make a great discovery, only to conclude there is no way to deliver the product usefully. Perhaps you have found a drug to reduce tumors, but there is no way to encapsulate the active ingredients for targeted delivery or controlled release.

Strategies often employed to overcome these challenges include 1) using a suspension for materials that are not soluble in water or oil, 2) using an emulsion for oil-soluble materials and 3) using liposomal formulations.

Creating a suspension of a solid material generally requires significant reduction of the particle size and the addition of surfactants and other materials to prevent particle agglomeration. The ultrahigh shear developed by the Microfluidizer® processor reduces the particle size of active pharmaceutical ingredients to useful sizes and the high turbulence ensures that the resulting particles are efficiently coated. A major advantage of the Microfluidizer technology is that the processor produces the desired small particles with a narrower size distribution than other methods resulting in a very stable product with a long shelf life.

When formulating emulsions, especially oil-in-water emulsions for oil-soluble pharmaceuticals, a common objective is that the resulting emulsion be sterilized by filtration. In practical terms, this means that virtually all of the particles in the emulsion are sufficiently small as to not clog the filtration device.  The high shear forces and flexible design of the Microfluidizer processor permit efficient formation of emulsions and produce products that can be filter-sterilized.

In addition, Microfluidics processor technology has been used for many years by a number of pharmaceutical companies to prepare liposomes containing active pharmaceuticals.

Articles

Nanoemulsions Improve Cancer Treatment - Small Times, November 2007

The efficacy of nutrients, drugs, and even cancer treatments dependsnot only on their chemical composition, but also on their formulation and delivery method. Researchers at the Center for Health & DiseaseResearch at the University of Massachusetts, Lowell, Department ofClinical Laboratory and Nutritional Sciences, have demonstrated thatnanoemulsions—which encapsulate drug or nutrient molecules in submicronsize oil droplets suspended in water—can dramatically increase the rateand level of absorption into the body. Further, nanoemulsions offerbenefits such as side-effects mitigation and anitviral/antibacterialaction. Download>

High-Shear Fluid Processing - Achieving More Precise Homogenization - Quality Digest

by Christopher Werner

Although conventional homogenization has served the needs of the dairyindustry and other industries for more than a century, the producers ofpharmaceutical, personal care, chemical and food products areincreasingly turning to high-shear fluid processing when highly preciseprocessing is required. Download>

BioPharm Applications List

BioPharmaceutical Formulations

Yeast cells offer many advantages for the preparation of biologically relevant molecules.  The genetics of yeast has been extensively studied and the genome of the common budding yeast, Saccharomyces cerevisiae, was first eukaryote sequenced in 1996 and is widely advocated as a model system for interpreting and understanding eukaryotic systems.  Many methods and vectors exist that facilitate cloning and expressing proteins in yeast.  The ease of the genetic manipulations coupled with the ability to conveniently grow yeast on both laboratory and production scale permit a straightforward method of producing materials for research and pharmaceutical processes.  Download>

Laboratory Test Results

Nanosuspension Report Prepared for a Drug Company

A drug developer has a need to reduce the particle size of their active pharmaceutical ingredient (API) dispersion. The objective of this test was to use Microfluidizer technology to reduce the mean particle size of an API dispersion to a size between 0.2 to 0.5 microns. A bench model Microfluidizer processor, the M-110Y, was used for these tests. This unit is capable of reaching pressures of up to 23,000 psi. Processing was done under maximum pressure attainable. Two (2) formulations were processed with concentrations 10% and 20% The quality of this API dispersion was assessed based on its respective particle size distribution. The particle size distribution was measured using a Horiba LA-910 light scattering particle analyzer, with de-ionized water as a diluent. Since this API has limited solubility in water we expect that the results from the particle sizing could be biased towards the larger particles in each sample.

Conclusion: Microfluidizer technology was successful in reducing the mean particle size of the 10% API dispersion concentration down to 0.402 microns within 25 passes at 22,000 psi. The API dispersion progressively reduced in particle size with each pass. Download>

Water and Oil Emulsion Report Prepared for a Pharmaceutical Company

A pharmaceutical company wants to reduce the overall particle size of its oil and water emulsion to a point where d50 is approximately 90 nanometers.

Conclusion: Microfluidizer technology was successful in progressively reducing the particle size of the emulsion from a d50 of 1.825 microns to a d50 in the range of 80 to 96 nanometers within 1 pass. This was achieved by increasing the emulsion temperature in the inlet reservoir to over 65º C just before processing. Download>

Nanoemulsion with 8% Oil Report for a Pharmaceutical Company

A pharmaceutical company wants to use an emulsion with 8% oil. Download>

Materials Processing Data Sheets from the Microfluidics Technology Center

• Test Objective:  Reduce mean droplet size of liposomes that contain a drug for use in a topical cream to ~ 100 nm. Download>

• Test Objective: Reduce mean particle size of iron oxide powder dispersed in a toluene/water mixture. Download>

• Test Objective: Reduce mean particle size of Penicillin suspension to 10-15 µm. Download>

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• Test Objective: Reduce the mean particle size of 25% drug slurry. Download>

• Test Objective: Reduce 99% of Phthalocyanine blue pigment dispersion particles to below 0.5µm.  Download>

• Test Objective: Reduce ophthalmic suspension particle size to 0.7 µm. Download>

• Test Objective: Reduce the particle size of the lipid emulsion to be smaller than the currently used Vortex mixer provides. Download>

• Test Objective: Achieve a high degree of E.coli cell disruption.  Download>

• Test Objective: Produce a stable suspension of Budesonide with a mean particle size below 2.0 µm. Download>

• Test Objective: Determine the optimum conditions for achieving maximum cell lysis.  Download>

Pharmaceutical/Biotech Case Studies

New Intravenous Drug Therapies Possible Due to Microfluidizer Processing

Subject: "Thanks in part to the Microfluidizer® Processor, doctors canadminister new kinds of drugs to patients - drugs that previously couldnot be absorbed through the digestive tract and could not beadministered by injection without risking the blockage of bloodvessels. Earlier work with the Microfluidizer® Processor has alreadyallowed patients to receive intravenous dosages of insoluble fattyoils, giving them more energy during convalescence and prompting fasterrecoveries." Download>

Genetic Researchers Score a Bargain: Free Delivery of DNA

Subject: "A researcher at the University of Pittsburgh has found a wayto deliver virtually any amount of DNA for treatment of any disease,without using viruses as a delivery vehicle." Avoiding the expense of virus-based DNA delivery by usingcheaply produced, less complicated liposomes as a delivery medium. Download>

Helping Cancer Patients Take Their Medicine

Subject: "The purpose of the study is to determine if a new method fordelivering a cytotoxic drug is safe and effective — one that allowssuch drugs to be administered intravenously rather than orally, withfar fewer side effects and much greater patient comfort. Thebreakthrough behind this new approach is the mixing technology embodiedin the Microfluidizer® processor." Download>

Race Is On To Discover Vaccine To Save Salmon

Subject: "Originally we worked with a French press and Gaulinhomogenizer, but they posed contamination and equipment cleaningproblems. After a demonstration here at our lab, the Microfluidizerprocessor's performance and sterilization features convinced us to getone immediately." Download>

Investigating Root Causes of Cancer, Viral Infections and Metabolic Diseases

Subject: Each day a group of multidisciplinary scientists in Dortmund,Germany, gathers to investigate the root causes of life-threateningillnesses. The Max Planck Institute hopes their studies lead toimproved diagnosis and treatment of cancer, AIDS, viral infections andmetabolic diseases.

The group conducts most of its cellular research on E. coli, insect andyeast cells. They must break the cell membranes as quickly andthoroughly as possible to release the highest yields of usable cellularcontents for purification and analysis. Download >

Bacteria May Avert Radioactive Waste Problems

Subject: Closure, remediation and recultivation of former mining sitesin Saxony and Thuringia have been underway since 1991. Conventionalchemical and physical removal methods are useful for highconcentrations of radionuclides and heavy metals, but not for lowconcentrations.  After the initial remediation treatment, the remainingconcentrations of these compounds are still above allowed limit values.

The first step in this bioremediation research was to characterize thecell wall components responsible for metal binding and to study themechanisms of metal complexation extensively. The most efficient way todo this was to disrupt the cells and separate the single components. “[With a Microfluidizer processor] we can process 200 ml of 1:1solution continuously in five to ten minutes versus constantlyrefilling the chambers of other types of equipment over a two- tothree-hour time span” Download >

Presentations

Production of Polymer Nanosuspensions Using Microfluidizer Processor Based Technologies

as presented at NSTI - Nanotech, 2008 by T. 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 antisolvent. These methods are compatible with a wide variety of polymer/API systems. The focus of this work is to identify the effects on the particle size distribution of varying key parameters such as process pressure, relative flow rates of the streams, and formations.

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>

Production of Stable Drug Nanospensions Using Microfluidics Reaction Technology

as presented at NSTI - Nanotech, 2007 by T. Panagiotou, S. Mesite, R. Fisher and I. Gruverman

Many hydrophobic drugs are difficult to formulate in ways that ensurehigh bioavailability. The formation of stable drug nanosuspensions isan attractive formulation strategy that does not limit the dosageamount. Microfluidics Reaction Technology (MRT) was used to producedrug nanosuspensions via solvent and anti-solvent crystallization. Thecore of this technology is a continuous and scalable microreactor basedon impinging jets. Inside the reactor, liquid reactants encounterhighly turbulent conditions and interact at the nanometer level. Download>

Nano-encapsulation using Microfluidizer Technology Platform

T. Panagiotou, Ph.D.

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