Media Milling Nanoparticles for Pharmaceutical Drug Delivery
Of all the potential pharmaceutical applications for nanotechnology, drug delivery is currently the most developed and seems to be the most promising for the long-term. Randy Smith, Vice President for NETZSCH Fine Particle Technology speaks with NWN.
Nanoparticles may be the pharmaceutical industry’s best chance to reduce costs by improving the rate of development successes. Nanotechnologies are being used across all industry sectors and new innovations continue to expand applications, creating a ripple affect on drug delivery possibilities. Of all the potential pharmaceutical applications for nanotechnology, drug delivery is currently the most developed and seems to be the most promising for the long-term. Randy Smith, Vice President for NETZSCH Fine Particle Technology in Exton, PA, answers Nano World News’ questions about nanotechnologies in drug delivery.
NWN: How big is nanotechnology in pharmaceuticals?
Smith: That’s difficult to pinpoint because of the proprietary nature of most drug research. Currently, about 300 companies in the United States are developing drug delivery mechanisms using nanotechnology.
From a dollar-and-cents standpoint, market valuations put nanobiotechnology at more than $3 billion with an annual growth of 28 percent. The combined healthcare products/pharmaceuticals sector is the second largest application for nanotechnology by dollar value. The Freedonia Group, a Cleveland-based research firm, concluded in 2007 that demand for nanotech-based medical supplies and devices in the U.S. market will exceed $110 billion by 2016.
NWN: Why have nanoparticles become so important to the pharmaceutical industry?
Smith: Drug development can take anywhere from 10 to 15 years and can cost more than $2 billion when you factor in failed drugs that never progress past early-stage research. Just one in 5,000 new compounds makes it to the consumer, so pharmaceutical companies need to find ways to improve the odds.
So, for example, a drug company can choose to investigate the use of nanaparticles to reactivate an Active Pharmaceutical Ingredient, (API) which has failed to progress. The company already has a lot invested and owns all the research. A reformulation with the use of nanotechnology may make that drug viable, saving the API and thus company millions in development costs.
NWN: What advantages do nanoparticles offer that larger molecules do not?
Smith: There are countless variables that need to be controlled to make a drug effective and marketable. Nanotechnologies can help:
- improve bioavailability — the body’s ability to take in the active ingredient to the right place in the body or the right system;
- improve solubility;
- extend shelf life;
- improve half life — the time it takes for a dose to be delivered;
- reduce side effects; or
- improve targeting — meaning, for example, that a cancer drug attacks a tumor and not healthy tissue.
NWN: How are these achieved?
Specific nanoparticle shapes can be used to encapsulate or bind drug compounds to improve drugs’ solubility, stability or absorption rates. In other cases, nanoparticles may be used to change the way the drug is delivered. For example, a drug that was ineffective as a pill could potentially be reformulated to use nanotechnology to be usable as capsule or possibly as a skin patch.
NWN: What is NETZSCH’s role in the production of nanoparticles for pharmaceuticals?
For pharmaceutical companies that are making a first foray into the field of nanoparticles or into this method of production, we educate them on the benefits of media milling and how it creates particles at the nano scale. We also endorse mild dispersion, and the two together give formulators many benefits, including:
- excellent particle size control;
- comparative cost effectiveness;
- limited or zero contamination of active: and
- repeatability of process.
Grinding also gives them equipment scalability, from benchtop to production. Fine-bead mills offer lower costs compared to plasma gas and precipitation process techniques, as well as other alternative technologies. Fine-bead mills provide an efficient way to disperse the compounds to primary particle size assuming the proper stabilizing agents are used. Our equipment and processes meet cGMP requirements, which is essential.
NWN: How important is equipment selection?
Smith: Selecting appropriate equipment is essential to developing a repeatable and efficient process in the lab right through to full-scale production. New mills offer adequate product throughput at low-energy/low agitator speeds, which prevents nanoparticle damage, while providing practical methods for handling and separating the grinding media from the product.
NWN: What about materials of construction?
Smith: Grinding-zone parts manufactured completely with yttria zirconia (YTZ) are available. YTZ is a high strength ceramic and allows for processing that’s free of metal contact. The choice of the right material for the application will prevent unwanted reactions and transfer contamination, which could lead to waste of time and API. Grinding beads, which are just as important as the bead mill parts, are available in a wide range of materials such as plastics, glass, and ceramics.
NWN: You just mentioned efficient process in the laboratory. How does that fit in with machine selection?
Smith: Having the right size equipment for the job is critical. Many of the active ingredients that these researchers work with are rare and quite costly, so they have to use lab sized machines. When they look at these mills, they should consider scalability in the evaluation. NETZSCH, for example, offers its lab-sized MicroCer with YTZ grinding zone parts. It handles 75 — 80 ml batches with 0.05 to 0.8 mm grinding media to produce consistent particle reductions down to 200 nm. But it’s fully scalable, from the benchtop right up to full-production.