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October 12, 2017

Leachable Studies of Medical Devices in Complex Biological Environments

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 Thursday, October 12, 2:10 p.m. EST

Adam Kozak, a senior research scientist at Cambridge Polymer Group, presents "Leachable Studies of Medical Devices in Complex Biological Environments" at Eurofins Lancaster Laboratories' Extractables and Leachables Symposium for Drugs and Devices in Pennsylvania.

Detailed Extractables/Leachables Studies

Extractables and leachables studies usually follow a two-step program. In the first step, an exaggerated extraction is conducted using simple solvent conditions more aggressive than those anticipated to be realized in a clinical setting in order to determine to determine the complete extraction profile and to identify the potential extraction compounds, desired or undesired. In the second step, a leaching study is conducted that attempts to simulate the clinical environment of the target application. The simulated leaching environment often comprises a more complex biological matrix than those used for extraction, which in turn complicates the chemical analysis assays used to identify and quantify the leaching materials. In this presentation, we show examples of studies that required a more detailed testing assay to identify and quantify compounds coming from implanted medical devices.

Biography

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Adam Kozak specializes in the chemical and mechanical analysis of polymer materials and medical devices. He has substantial experience in the use of gas chromatography-mass spectroscopy (GC-MS) for leachables and extractables analysis, trace impurity/contaminant analysis, residual monomer content, unknown compound identification, migration levels, deformulation, and odor analysis by headspace GC-MS and other chromatographic techniques.

Posted by CatherineCerasuolo
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October 6, 2017

Fatty Acid and Triglyceride Analysis: Linseed Oil

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Figure 1: On left, flax seeds, the source of linseed oil. On right, a representative triglyceride found in a linseed oil.

Linseed oil is derived from flax seeds (Fig 1; typically via pressing and solvent extraction methods). In the presence of oxygen, it polymerizes to form a rigid and hydrophobic solid through a highly exothermic oxidation reaction. This is often misleadingly referred to as “drying”; the process does not depend on evaporation of water but rather on the presence of oxygen to form crosslinks between adjacent triglycerides at points of fatty acid unsaturation (Fig 2). The resulting material is an excellent example of a naturally derived, crosslinked polymer whose properties arise from a complex mixture of its constituents and the processing conditions under which it is formed.

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Figure 2: Polymerized and hydrogenated linseed oil. Crosslinks between triglycerides (formerly double bonds) are indicated with arrows.

Due to its easy workability and advantageous “dry” properties, linseed oil is widely used in applications ranging from nutritional supplements (it is rich in Omega-3 fatty acids), as a binder in paint, and in linoleum. In fact, the name “Linoleum” derives from the Latin words for flax (“linum”) and oil (“oleum”). In its native state, linseed oil is a liquid composed of triglycerides (Fig 1) consisting of various combinations of fatty acids—the most common being linoleic acid, alpha-linoleic acid, palmitic acid, stearic acid, and oleic acid.

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Figure 3: Example separation of 37 fatty acids by gas chromatography for subsequent quantitation.

The fatty acid fingerprint of a triglyceride-based oil (Fig 3) is a valuable analytical tool for material/compositional identification, correlation to functional properties, good/bad analysis, and quantitative analysis. CPG has a variety of methods which may be leveraged for the analysis of oils—this includes techniques such as gas chromatography (which may be coupled to mass spectrometry; GCMS) which can be used to determine the fatty acid distribution for a sample. 

Note that due to the highly exothermic nature of the polymerization process, linseed oil should be handled with care and is often treated as a fire hazard. Over the years many fires have been attributed to the spontaneous combustion of oil soaked rags, often abandoned after a painting job. Such rags are especially dangerous because they present a very high surface area and accelerate the oxidation reaction. If left balled up, temperatures may rise sufficiently high to ignite the entire mass. The Massachusetts Office of Public Safety and Security offers clear guidelines for the safe disposal of such materials.

Working with natural oils? Looking to better understand differences between performance of naturally derived materials? Contact us to see how our team may be able to assist in your project.

 

Posted by CatherineCerasuolo
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October 5, 2017

CPG Awarded Patent for Degradable Hydrogel

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Cambridge Polymer Group has received notification of the award of their patent “Thiolated PEG-PVA Hydrogels” (14/328,176).  This patent describes a new way of creating hydrogels from a conventional biomaterial poly(vinyl alcohol).  The resulting hydrogels cure under physiological conditions with no toxic crosslinkers or bi-products and can be tuned to degrade over periods of weeks. 

They are therefore likely to see value in drug release, temporary tissue bulking or scaffold applications, and although they can be cured in vitro, they appear particularly well suited to in vivo applications.  In fact, we are already working to commercialize this material through the recent award of an NIH Phase 1 SBIR grant in the field of retinal detachment.  

Posted by CatherineCerasuolo
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September 29, 2017

Needle in the Haystack: What’s Buried in Your Polymer LC-MS Data?

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CPG Webinar - Thursday, October 5, 2 p.m. EST 

LC-MS is a widely used analytical technique for characterization of polymer additives, extractables and leachables, degradation products, APIs, drug release studies, and material stability. Typical LC-MS studies however usually focus on small molecules rather than the polymer or excipient components themselves. Structured appropriately, methods for the LC-MS analysis of polymers can yield large, complex datasets that can reveal valuable structural information about polymers and oligomers present in a medical device or pharmaceutical product. Such techniques can help identify the root cause for lot to lot variability or underlying reasons for why polymer blend A is “good” while polymer blend B is “bad.”

Join us for a CPG webinar that will walk through the basic principles and limitations of conducting LC-MS on polymers and oligomers for the purpose of performing structural characterizations, repeat unit analysis, charge state analysis, and molecular weight determination. Key variables such as material ionizability, separation mode, and mobile phase considerations will be discussed, as well as mass spectral data analysis techniques such as two dimensional contour plot visualizations, which can reveal a wealth of data “buried” under the total ion chromatogram. The presentation shall cover specific applications for complex polymer systems such as ethoxylates and hydrogel precursors/degradation products.

Your webinar presenter, Adam Kozak, is a research scientist and biomedical engineer at Cambridge Polymer Group, where he specializes in the chemical analysis of polymer materials. He has substantial experience in chromatography techniques including trace impurity/contaminant analysis, residual monomer/solvent content, extractables/leachables, cleanliness analysis, unknown compound identification, deformulation, migration analysis, molecular weight analysis, and odor analysis. He has managed the development and validation of many custom analytical methods, including extraction and recovery of target analytes from complex polymer and biological matrices.

This 40 minute webinar is targeted towards:

  • Material Engineers
  • Medical Device Engineers
  • Product Designers
  • Pharmaceutical Developers
  • Regulatory Personnel

For more information and to register for the webinar, visit: https://attendee.gotowebinar.com/register/4618685894792158978

Posted by CatherineCerasuolo
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September 28, 2017

Correlating Melt Flow Index to Molecular Weight

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The certificate of analysis for polymer resins often includes a melt flow index (MFI) or melt flow rate (MFR), reported as grams of material/10 min under a specified temperature and load. This testing is normally performed per ASTM D1238 or ISO 1133 using a plastometer. A plastometer consists of a temperature-controlled cylindrical annulus through which a polymer melt is extruded by pressurization with a weight-loaded piston. The amount of material extruded through the die at the bottom of the annulus is measured by weight for a measured period of time. This mass, normalized by time, provides the MFI. It is easy to see that lower viscosity materials will result in a higher MFI, since more material can be extruded for a given amount of time.

How does MFI correlate to the molecular weight of a polymer? At CPG, we often measure molecular weight by gel permeation chromatography or dilute solution viscometry. Both these techniques involve dissolving the polymer in a good solvent to form a dilute solution, so that individual polymer chains can be interrogated directly (in the case of GPC) or indirectly (in the case of viscosity modification in dilute solution viscometry). In MFI testing, the polymer is not dissolved in a solvent, but rather is tested in the melt state. As a result, the MFI has a direct correlation to the polymer's melt viscosity. For polymer melts, the zero-shear viscosity h0 (or the viscosity at very low shear rates) has a relationship to the weight averaged-molecular weight as follows:

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Given the inverse relationship between MFI and viscosity, it is logical to see that the MFI has a relationship to molecular weight as follows, which has been shown empirically for linear polymers:[1]

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Bremner and Rudin found values of LLDPE had G values ranging from 2x10-20 to 1x10-24 (10 min/g(x+1)(molx)), and x ranged from 3.9-4.6. In a later article, Bremner found x values between 3.4 and 3.7.[2] The authors cautioned that this relationship becomes tenuous with polymers having variability in branching and polydispersity index. In order for the equation above to be valid, the authors’ note, the viscosity at the MFI conditions normalized by the zero shear viscosity should be a constant for the polymers in a given family. If not,  gel permeation chromatography is warranted.


[1] Bremner, T.; A. Rudin, Melt Flow Index Values and Molecular Weight Distributions of Commercial Thermoplastics. J. Appl. Polym. Sci. 1990, 41, 1617-1627

[2] Bremner, T., Cook, D.G., Rudin, A. “Further Comments on the Relations between Melt Flow Index Values and Molecular Weight Distributions of Commercial Plastics,” J. Appl. Polym. Sci. 2003, 43, 1773.

Posted by CatherineCerasuolo
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September 22, 2017

The Plastics of Capri

vase.jpgVitrum Flexile, or flexible glass. Although lost in legend, three different authors provided an account of a glass that could be dented and then repaired in Rome’s first century. According to the Corning Museum of Glass, Petronius (who died in 63 A.D.) told of a drinking vessel presented to Emperor Tiberius (reign 14-37 A.D.). The vessel was thrown to the ground, and though dented, the glassmaker was able to remove the dent with a hammer.

Pliny told a similar story in his encyclopedia, completed around 78 A.D., although his story goes on to say that the glassmaker's workshop was destroyed so that the value of copper, silver and gold would not be affected by the vitrum flexile. 

Dio Cassius provides the third story, in which an architect, who fell out of favor with Tiberius, provided the aforementioned demonstration of denting a glass vessel, then repairing it with his hands.

Unfortunately, no other accounts of vitrum flexile exist beyond these stories. As polymer scientists, we naturally assume that the vitrum flexile was not glass, but rather an early form of plastic, given its mechanical behavior and appearance. Perhaps it was formed of a natural resin, or from a crude polymerization. Ethylene gas was known to be in the Mediterranean around this time (the suspected source of the Oracle of Delphi’s visions). Did a resourceful Greek manage to perform some early free radical polymerization?

Posted by CatherineCerasuolo
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September 20, 2017

It's a Plastic Sort of World

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Provocatively Titled Study Explores “All Plastics Ever Made”

A recent study by Geyer et al published in Science Advances takes a wide-ranging look at the production and fate of all plastic produced to date, based on data collated from a range of market research and consulting groups.

Some key observations from the authors’ study are as follows:

The total amount of polymer resin produced from 1950-2015 is approximately 7800 Mt. Production growth has been accelerating with a compound annual growth rate of 8.4%—for perspective, half of the 7800 Mt has been produced in last 13 years!

Assuming an average pellet mass of 25 mg, the total amount of resin produced through 2015 is the equivalent of 3.12 * 1017 pellets.

Plasticizers, fillers, and flame retardants account for approximately 75% of all produced additives between 2000-2014. Antioxidants and heat stabilizers account for approximately 11% of additives produced.

Industrial Use of Plastics 

The largest industrial use sector for plastics is packaging. In fact, 42% of all produced nonfiber plastics are used for packaging purposes. The second largest use sector is construction, which makes use of 69% of all PVC produced.

GlobalPrimaryPlasticsProductionaccordingtoindustrialsectorusecropped.pngfig. S1. Global primary plastics production (in million metric tons) according to industrial use sector from 1950 to 2015.  [1]

The most commonly produced plastics are polyethylene and polypropylene, which make up 57.3% of all polymer resins produced from 2002-2014.

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              fig. S2. Global primary plastics production (in million metric tons) according to polymer type from 1950 to 2015. [2]

Where Is All That Plastic Now? 

It is estimated that 30% of all plastics ever made are currently in use—the rest having been disposed in one way or another. It is estimated that 12% of all plastics disposed of have been incinerated, and only 9% have been recycled. The remainder are in landfills or the natural environment. Note that none of the commonly used plastics are naturally biodegradable; the vast majority are derived from petroleum hydrocarbons.

In addition, there is an increased attention of to the ultimate fate of polymer fibers (such as those used in textile/clothing applications). Environmental accumulation of polymer fibers is in many respects analogous to recent concerns about the deliberate addition of polymer microparticles to consumer products—recall the Microbead-Free Waters Act of 2015 which banned the manufacture and sale of rinse-off cosmetics containing polymer microbeads.

How CPG Can Work With You

At Cambridge Polymer Group, our expertise and analytical capabilities intersect with the topics raised by such studies in multiple ways. We can assist your team in:

  1. Material selection and screening
  2. Resin equivalency studies
  3. Identification of unknown polymers
  4. Characterization of material stability and polymer degradation
  5. Identification/quantitation of chemical degradation products
  6. Impact of additive packages on polymer and device functional properties

CPG is an ISO 9001 certified, 17025 accredited contract R&D and analytical testing lab. Contact us to see how we can work with you.


Posted by CatherineCerasuolo
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