Pseudo-3D Subsurface Imaging of Pharmaceutical Solid Dosage Forms Using Micro-spatially Offset Low-Frequency Raman Spectroscopy.

A new combinatory Raman subtechnique of low-frequency and micro-spatially offset Raman spectroscopy (denoted micro-SOLFRS) is demonstrated via analysis of pharmaceutical solid dosage forms. A variety of different (multilayer/multicomponent) model systems comprising celecoxib, α-lactose (the anhydrous and monohydrate form), and polyvinylpyrrolidone (PVP) were probed to test the potency of this newly developed technique to, for example, provide qualitative and quantitative information on surface and subsurface layer characteristics, including their thicknesses as well as enable monitoring of surface-driven solid-state form transformations. A simultaneous collection of low- and, the more commonly used, mid-frequency data enabled a direct comparison between these spectral regions, where the low-frequency domain (hence, micro-SOLFRS) proved superior for every respective analysis carried out herein.

A New Frontier for Nondestructive Spatial Analysis of Pharmaceutical Solid Dosage Forms: Spatially Offset Low-Frequency Raman Spectroscopy.

A new Raman subtechnique, spatially offset low-frequency Raman spectroscopy (SOLFRS), is demonstrated via an analysis of pharmaceutical solid dosage forms. Several different model systems comprised of celecoxib (a popular anti-inflammatory drug), α-lactose anhydrous stable form, α-lactose monohydrate, and polyvinylpyrrolidone (PVP) were used to represent tangible scenarios for the application of SOLFRS. Additionally, the challenges and limitations were highlighted in relation to its real-time use, and potential solutions to address them were also provided. Lastly, the future directions for this new variation of Raman spectroscopic technique were briefly discussed, including its potential for broader application in pharmaceutical analysis and other research fields.

Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions.

Compression-induced destabilization was investigated in various celecoxib amorphous solid dispersions containing hydroxypropyl methylcellulose (HPMC), poly(vinylpyrrolidone)/vinyl acetate copolymer (PVP/VA), or poly(vinylpyrrolidone) (PVP) at a concentration range of 1-10% w/w. Pharmaceutically relevant (125 MPa pressure with a minimal dwell time) and extreme (500 MPa pressure with a 60 s dwell time) compression conditions were applied to these systems, and the changes in their physical stability were monitored retrospectively (i.e., in the supercooled state) using dynamic differential scanning calorimetry (DSC) and low-frequency Raman (LFR) measurements over a broad temperature range (-90 to 200 and -150 to 140 °C, respectively). Both techniques revealed similar changes in the crystallization behavior between samples, where the application of a higher compression force of 500 MPa resulted in a more pronounced destabilization effect that was progressively mitigated with increasing polymer content. However, other aspects such as more favorable intermolecular interactions did not appear to have any effect on reducing this undesirable effect. Additionally, for the first time, LFR spectroscopy was used as a viable technique to determine the secondary or local glass-transition temperature, Tg,ß, a major indicator of the physical stability of neat amorphous pharmaceutical systems.

Surface Stabilization and Dissolution Rate Improvement of Amorphous Compacts with Thin Polymer Coatings: Can We Have It All?

The distinction between surface and bulk crystallization of amorphous pharmaceuticals, as well as the importance of surface crystallization for pharmaceutical performance, is becoming increasingly evident. An emerging strategy in stabilizing the amorphous drug form is to utilize thin coatings at the surface. While the physical stability of systems coated with pharmaceutical polymers has recently been studied, the effect on dissolution performance as a function of storage time, as a further necessary step toward the success of these formulations, has not been previously studied. Furthermore, the effect of coating thickness has not been elucidated. This study investigated the effect of these polymer-coating parameters on the interplay between amorphous surface crystallization and drug dissolution for the first time. The study utilized simple tablet-like coated dosage forms, comprising a continuous amorphous drug core and thin polymer coating (hundreds of nanometers to a micrometer thick). Monitoring included analysis of both the solid-state of the model drug (with SEM, XRD, and ATR FTIR spectroscopy) and dissolution performance (and associated morphology and solid-state changes) after different storage times. Stabilization of the amorphous form (dependent on the coating thickness) and maintenance of early-stage intrinsic dissolution rates characteristic for the unaged amorphous drug were achieved. However, dissolution in the latter stages was likely inhibited by the presence of a polymer at the surface. Overall, this study introduced a versatile coated system for studying the dissolution of thin-coated amorphous dosage forms suitable for different drugs and coating agents. It demonstrated the importance of multiple factors that need to be taken into consideration when aiming to achieve both physical stability and improved release during the shelf life of amorphous formulations.

An Exploration of Mineral Density, Elemental and Chemical Composition of Primary Teeth in Relation to Cord-Blood Vitamin D, Using Laboratory Analysis Techniques.

Postnatally, severe vitamin D deficiency commonly results in rickets as well as potential defects in tooth mineralization. The effects of milder deficiency on oral health outcomes later in life are still unclear. This study used micro-computed tomography (µCT), energy dispersive X-ray analysis (EDX), and Raman spectroscopy to investigate mineral density, total density, and elemental composition of enamel and dentine in 63 exfoliated primary incisors from participants with known 25-hydroxyvitamin D levels (25-OHD) at birth. No differences in mineralization and chemical composition using µCT and EDX analysis were observed irrespective of 25-OHD status. Subtle structural differences were observed via Raman spectroscopy, with more crystalline enamel observed in those with sufficient 25-OHD at birth. Although subtle, the differences seen suggest further attention should be given to children with known milder levels of vitamin D deficiency in early life. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Quantification and characterization of microplastics in commercial fish from southern New Zealand.

Plastics are ubiquitous throughout global marine ecosystems. To date, there has been limited research on the prevalence of microplastic ingestion by commercially important marine fish in the southern hemisphere, particularly in the South Pacific. Therefore, this research aimed to quantify ingested microplastics from ten commercially important fish species from southern New Zealand using microscopy and Raman spectroscopy. Overall, we found evidence of microplastic ingestion in 75 % of fish, with an average of 2.5 individual particles per fish. Microplastic fibers were the most commonly ingested. The most common colored microplastics ingested were blue, black and red, and 99.68 % of plastics identified were smaller than 5 mm. Raman spectroscopy of plastics recovered from nine fish species found polyethylene and polypropylene to be the most common plastic polymers ingested. Further research is necessary to ascertain the human ecological and health risks involved when exposed to microplastics through eating plastic contaminated fish.