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•Improved identification tests for guar gum were developed.•Raman identification tests can distinguish between guar gum and other gums.•Spectral-based tests can be implemented in ...field on portable spectrometers.•Field tests developed will enhance the security of raw material supply chain.
Guar gum is a well-known inactive ingredient (excipient) used in a variety of oral pharmaceutical dosage forms as a thickener and stabilizer of suspensions and as a binder of powders. It is also widely used as a food ingredient in which case alternatives with similar properties, including chemically similar gums, are readily available. Recent supply shortages and price fluctuations have caused guar gum to come under increasing scrutiny for possible adulteration by substitution of cheaper alternatives. One way that the U.S. FDA is attempting to screen pharmaceutical ingredients at risk for adulteration or substitution is through field-deployable spectroscopic screening. Here we report a comprehensive approach to evaluate two field-deployable Raman methods—spectral correlation and principal component analysis—to differentiate guar gum from other gums. We report a comparison of the sensitivity of the spectroscopic screening methods with current compendial identification tests. The ability of the spectroscopic methods to perform unambiguous identification of guar gum compared to other gums makes them an enhanced surveillance alternative to the current compendial identification tests, which are largely subjective in nature. Our findings indicate that Raman spectral identification methods perform better than compendial identification methods and are able to distinguish guar gum from other gums with 100% accuracy for samples tested by spectral correlation and principal component analysis.
A new spectral library-based approach that is capable of screening a diverse set of finished drug products using only an active pharmaceutical ingredient spectral library is described in this paper. ...This approach obviates the need for a comprehensive drug product library, thereby streamlining the use of spectral library-based tests for anti-counterfeiting efforts, specifically to target finished drug products containing the wrong active ingredient or no active ingredient at all. Both laboratory-based and portable spectrometers are used in the study to demonstrate the usefulness and transferability of the spectral correlation method for field screening. The spectral correlation between the active pharmaceutical ingredient and finished drug product spectra is calculated using both full spectral analysis and targeted spectral regions analysis of six types of antimalarial, antibiotic and antiviral products. The spectral regions were determined using a moving window spectral correlation algorithm, and the use of specific spectral regions is shown to be crucial in screening finished drug products using only the active pharmaceutical ingredient spectrum. This comprehensive screening spectral correlation method is tested on seven different validation samples from different manufacturers as those used to develop the method, as well as simulated counterfeits which were prepared to mimic falsified drugs containing no active ingredient. The spectral correlation method is successful in correctly identifying 100% of the authentic products and simulated counterfeit samples tested.
A new spectral library-based approach that is capable of screening a diverse set of finished drug products using only an active pharmaceutical ingredient spectral library is described in this paper.
We report our efforts to study host−guest complexes in the gas phase using a combination of cluster spectroscopy and density functional theory. Mass-selected M+(18-crown-6 ether)(H2O)1−4 complexes ...for the alkali metal ion series were probed using infrared predissociation (IRPD) spectroscopy in the OH stretching region. As the degree of hydration is increased, the IRPD spectra undergo significant changes as the strong 18c6···M+ interaction weakens and allows H2O···H2O hydrogen-bonding interactions to compete. The size of the ion is important in determining when this transition occurs. For the smaller ions, Li+ and Na+, the 18c6···M+ interaction proves to be more resilient and is still dominant with two and three waters present. The potassium cation, with its optimum size match with the 18-cown-6 ether cavity, serves as a bridge between the larger and smaller alkali metal ions. In particular, we found a structure for K+(18-crown-6 ether)(H2O)2 that appears to be a building block for K+(18-crown-6 ether)(H2O)3 complexes and is also believed to be present in Rb+(18-crown-6 ether)(H2O)2,3 and Cs+(18-crown-6 ether)(H2O)2,3. With four waters present, we were unable to spectrally resolve features associated with individual water molecules due to broad hydrogen bonding. However, results for Cs+(18-crown-6 ether)(H2O)4 suggest that H2O···H2O hydrogen bonding has become the dominant interaction present at this size.
From the beginning of the COVID-19 pandemic, researchers assessed the impact of the disease in terms of loss of life, medical load, economic damage, and other key metrics of resiliency and ...consequence mitigation; these studies sought to parametrize the critical components of a disease transmission model and the resulting analyses were informative but often lacked critical parameters or a discussion of parameter sensitivities. Using SARS-CoV-2 as a case study, we present a robust modeling framework that considers disease transmissibility from the source through transport and dispersion and infectivity. The framework is designed to work across a range of particle sizes and estimate the generation rate, environmental fate, deposited dose, and infection, allowing for end-to-end analysis that can be transitioned to individual and population health models. In this paper, we perform sensitivity analysis on the model framework to demonstrate how it can be used to advance and prioritize research efforts by highlighting critical parameters for further analyses.
Library-based Raman spectral correlation methods are widely used in surveillance applications in multiple areas including the pharmaceutical industry, where Raman spectroscopy is commonly used in ...verification screening of incoming raw materials. While these spectral correlation methods are rapid and require little or no sample preparation, their sensitivity to the presence of contaminants has not been adequately evaluated. This is particularly important when dealing with pharmaceutical excipients, which are susceptible to economically motivated adulteration by substances having similar physical/chemical/spectroscopic properties. We report a novel approach to evaluating the sensitivity of library-based Raman spectral correlation methods to contaminants in binary systems using a hit-quality index model. We examine three excipient/contaminant systems, glycerin/diethylene glycol, propylene glycol/diethylene glycol, and lactose/melamine and find that the sensitivity to contaminant for each system is 18%, 32%, and 4%, respectively. These levels are well-correlated to the minimum contaminant composition that can be detected by both verification and identification methods. Our studies indicate that the most important factor that determines the sensitivity of a spectral correlation measurement to the presence of contaminant is the relative Raman scattering cross section of the contaminant.
The paclitaxel protein-bound particles for injectable suspension (marketed under the brand name Abraxane®) contains nanosized complexes of paclitaxel and albumin. The molecular interaction between ...paclitaxel and albumin within the higher-order nanostructure is analytically challenging to assess, as is any correlation of differences to differences in therapeutic effect. However, because the higher-order nanostructures may affect the paclitaxel release, a suitable
in vitro
assay to detect potential differences in paclitaxel release between comparator lots and products is desirable. Herein, solution NMR spectroscopy with a T
2
-filtering technique was developed to detect paclitaxel signal while suppressing albumin signals to follow the released paclitaxel in the NMR tube upon dilution. The non-invasive nature of NMR allows for precise measurement of a full range of dilution-induced drug release percentage from 14 to 92% without any sample extraction. The critical concentration of the drug product (DP) at 50% of release was 0.63 ± 0.04 mg/mL in PBS buffer. In addition, 2D diffusion ordered NMR spectroscopy (DOSY) results revealed that the released paclitaxel experiencing slightly slowed diffusion rates than free paclitaxel, which was attributed to paclitaxel in equilibrium with albumin-bound states. Collectively, the dilution-based NMR method offered an analytical approach to investigate physicochemical attributes of complex injectable products with minimal needed sample preparation and perturbation to nanoparticle formulation.
Argon-tagged alkali metal ion-crown ether complexes were generated in the gas phase and investigated using a combination of infrared predissociation (IRPD) spectroscopy, density functional, and ...symmetry-adapted perturbation theory (SAPT). The IRPD spectra of M+(12-crown-4 ether)Ar and M+(18-crown-6 ether)Ar, where M = Li, Na, K, Rb, and Cs, were collected in the CH stretching region, using the argon-messenger technique. The gas-phase neutral vibrations for each crown ether shift to higher frequency when complexed to an alkali metal ion. Similarities in the experimental IRPD spectra of Li+(12-crown-4 ether)Ar and Li+(18-crown-6 ether)Ar indicate that the binding of Li+ is similar for both crown ethers. In the 12-crown-4 ether systems, there are trackable changes with ion size in the IRPD spectra until the point is reached where the ion is too large to bind to the interior of the macrocycle. Starting with Na+, the 18-crown-6 spectra vary only slightly as the ion size is increased. The overall profiles of the IRPD spectra indicate that a similar configuration of the complexes is adopted for the ions larger than Na+. The calculated SAPT interaction energies mirror the trends exhibited by the IRPD spectra and provide interesting insights on the roles of the different interaction energy components in binding the cation to the crown-ether.
Extreme Rightwing Organizations (EROs) routinely use media outlets to harass professors and students. Simultaneously, EROs fund speakers and campus organizations that have a history of intimidating ...members of academic communities. Debates about how and whether to respond to ERO tactics that are framed in terms of balancing 'freedom of speech' against 'inclusion' engage in a variety of color-evasive racism that sustains white supremacist ideology and protects white privilege. This framing legitimizes tactics that empower EROs with the right to silence their critics and foster a climate of oppression. Through an autoethnographic case study of struggles at a small liberal arts college with how to respond to ERO tactics, this article argues that rejecting the 'freedom of speech' versus 'inclusion' framing that so often characterizes the debates can help us to move beyond the paralysis that EROs have manufactured and rally against their tactics of intimidation and harassment.
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