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Residual solvents can sometimes be found in pharmaceuticals after processing. These solvents are sometimes used during manufacturing to synthesize, purify or blend the active pharmaceutical ingredient (API) with excipients, or may be used elsewhere in the manufacturing process, from  solvents to clean equipment or solvents used in the packaging process. Often, these solvents can be hazardous if present in levels above a critical threshold. USP provides three levels of solvent classes based on their potential risk. Class 1 describes solvents to be avoided, which includes known and suspected carcinogens (examples include benzene and 1,2 dichloroethane). Class 2 describes solvents to be limited in their use, and includes nongenotoxic animal carcinogens and other significant but reversible toxicities (examples include chloroform, toluene, ethylene glycol) . Class 3 describes solvents with low toxic potential (examples include acetone, isopropyl alcohol, ethyl acetate).   USP provides permitted daily exposure (PDE) thresholds for the individual solvents in each class.  Other residual solvents, for which no adequate toxicological data is available, are also discussed.

Analysis of pharmaceutical compounds for residual solvents is normally performed by gas chromatography with mass spectroscopy coupled to either a flame ionization detector or a mass spectrometer, often with a head-space system used for sample introduction. This analysis requires the optimization of test conditions to ensure adequate separation of the various compounds in the chromatography column. Limits of detection and quantification, along with linearity, precision, and percent recovery are then determined for the specific solvent and matrix. Depending on the solvent and matrix, limits of detection can be as low as several parts per billion.

CPG regularly performs residual solvent analysis. Contact us for more information, or visit our web page.

Multiple degradable thermoplastics are being used for implant or other in vivo use in the medical industry. Polycaprolactone, polylactic acid, poly lactic-co-glycolic acid and polydioxanone are just four examples of polymers that will biodegrade when placed in the body through a hydrolysis reaction. The benefits of these polymers for biomedical applications depend on their degradation rates, properties during degradation, and the degradation compounds. Whereas there are fairly well established methods for assessing degradation rates and the resulting properties of the degrading polymer, determination of the degradation products can be more challenging. Often, researchers will perform in situ degradation studies, using a simulated environment such as phosphate buffered saline, enzymatic solutions, or similar, with the assumption that these in situ environments will result in the same degradation pathway as an in vivo environment.

CPG has developed assays that allow the identification and quantification of degradation products of biodegradable polymers from animal studies. En bloc tissue samples containing the device and surrounding tissue are analyzed for degradation products amongst the biological tissue. The results can then be compared to in vitro degradation samples to assess if the in vitro assay is faithfully generating the same degradation products as the in vivo test.

Contact us for more information.

CPG researcher Adam Kozak was a co-author on a recently published article in the Journal of the Mechanical Behavior of Biomedical Materials. Along with co-authors from UC-Berkeley (Ansari, Gludovatz, Ritchie, and Pruitt), these researchers investigated the sensitivity of ultra high molecular weight polyethylene (UHMWPE) to fatigue when stress concentration sites are present in the form of notches. The authors investigated 3 formulations of UHMWPE commonly used in hip or knee implants today, and found that the sensitivity to crack propagation resulting from fatigue was more sensitive to microstructure, such as crosslink density, rather than specifics of the notch geometry.

Link to Article

Formaldehyde, or CH2O, is commonly used in producing resins for coatings and adhesives, automotive materials, as well as materials for the textile industry. In these applications, the formaldehyde is normally incorporated into the material through a chemical reaction, and hence loses its chemical identity. Formaldehyde is also a by-product of some chemical reactions.

Aqueous solutions of formaldehyde, also known as formalin, are used as disinfecting agent for biological tissues, in that it is effective in killing bacteria and fungi. This toxicity to bacteria applies to humans as well, prompting manufacturers to reduce residual formaldehyde to safe levels in manufactured products.

CPG has developed sensitive techniques to measure trace levels of formaldehyde in a variety of matrices. This approach allows manufacturers to determine whether their formaldehyde levels have been reduced below threshold levels.

Ever wonder what those little blue particles are in some toothpastes? One of our scientists did, and started to investigate their effects on teeth brushing. Known as microbeads or microplastics, these blue particles are usually polyethylene or polypropylene. They are commonly included as exfoliants in face cleansers, and may be added to toothpaste for visual effects.

CPG researcher Lucas Rossier performed a bench top study comparing enamel wear using toothpastes with and without microbeads. A model enamel substrate was used in place of an actual tooth surface. Through optical and electron microscopy, Rossier showed greater scratching and abrasive wear in the toothpaste containing microbeads. Although the results may not be directly comparable to actual tooth enamel wear, they do demonstrate that the microparticles have an abrasive effect that is greater than the toothpaste alone.


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