Optical Coherence Tomography (OCT) has emerged as a powerful non-destructive imaging tool capable of delivering high-resolution cross-sectional images of drug formulations, particularly useful for evaluating coating uniformity, detecting defects and characterizing multi-layered structures in solid dosage forms. Despite OCT potential, its widespread acceptance has been limited due to the lack of pharmacopeial monographs and specific regulatory guidelines. In recent years, growing regulatory interest in advanced analytics has prompted increased attention to method validation, alignment with Quality by Design (QbD) principles and compliance with Good Manufacturing Practices (GMP). This work provides an integrated perspective on the development, implementation and regulatory evaluation of OCT in the pharmaceutical industry. It reviews the implementation process and the evolving regulatory framework surrounding OCT in pharmaceutical applications, along with practical considerations for its adoption. As interest in OCT on the part of regulatory bodies grows, the pharmaceutical industry is moving toward broader engagement, emphasizing the need for standardization and eventual inclusion of OCT methodologies in regulatory frameworks. With continued collaboration between the industry stakeholders, regulatory agencies and standard-setting organizations, OCT is positioned to become an integral component of modern pharmaceutical quality control strategies.
In the present investigation we have reported the impact of different processes, commonly used in the development of formulations, on the generation of free radicals. Polyvinylpyrrolidone (PVP) polymer is used as a model excipient. PVP is commonly used as a carrier in pharmaceutical drug delivery systems. PVP is synthesized via radical polymerization reaction of the N-vinylpyrrolidone monomer using peroxides. The peroxide, as a residual impurity, due to the manufacturing process and storage conditions have the tendency to develop free radicals. The free radicals generated are chemically very active and thus reacts with the API resulting in the formation of degraded products. The free radicals generated via different process were then quantified using spin trapping and electron paramagnetic resonance (EPR). The developed radicals were trapped via 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and transformed into a stable nitroxide radicals. Those persistent nitroxide radicals were then quantified using the calibration curve obtained by the observation of variable concentrations of the reference 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy radicals (TEMPOL). The free radical concentration was found to be significantly higher in case of the samples (with non-zero initial levels of free radicals) exposed under pressurized thermal oxidation as compared to the drying and milling. However, in case of the PVP having zero free radicals content, the free radical concentration was found to be higher in samples treated with milling followed by pressurized thermal oxidation. Thus, the free radical concentration generated was found to be primarily dependent on the initial level of free radicals present in the raw material, independent of PVP chain length. Further, the impact of lot-to-lot variation and storage stability conditions were also investigated, demonstrating changes in free radical concentration on incubating the samples at RT and accelerated stability conditions. There is dearth of research work published in the multifaceted research domain comprising free radical chemistry, polymer science and pharmaceuticals. Thus, the present investigation could act as the pivotal link to establish the relation between the drug product degradation and free radical concentration.
Purpose Optical coherence tomography (OCT) is a fast and robust process analytical technology (PAT) for the in-line monitoring of pharmaceutical coating processes. During early process and formulation development, however, when detection settings, formulations, or process parameters are not yet optimized, a fraction of the acquired B-scans may correspond to misdetections rather than to genuine process outliers. Separating these misdetections from true outliers by manual image inspection is reliable but laborious and time-consuming. The purpose of this work is to automate this task in order to accelerate OCT-based process and formulation development. Methods A ResNet-18 convolutional neural network, pretrained on ImageNet-1K, was fine-tuned to classify OCT B-scans of oral solid dosage forms as correct or incorrect detections. The data were acquired in-line during fluidized-bed and drum coating trials using an ultra-high-resolution OCT (UHR-OCT) unit. The model was validated on 146 previously unseen images, and gradient-weighted class activation mapping (Grad-CAM) was used to confirm that the classification relied on diagnostically meaningful image regions. Results The model reached a validation accuracy of 95.9% with balanced performance across both classes. Applied to full measurement campaigns of several thousand B-scans, it reduced the outlier-review effort from hours or days to minutes and reliably separated true process outliers from misdetections, thereby lowering the scatter of the reported coating-thickness data. Conclusion AI-assisted classification makes OCT data evaluation substantially faster and easier, particularly under the challenging, non-optimized conditions typical of early development. Once a process is established for routine production, such misdetections largely disappear, so the tool primarily serves to de-risk and accelerate process and product development.
A two-step continuous flow synthesis using molecular oxygen to prepare cannabidiol quinone derivative, Etrinabdione, under sustainable conditions is reported.
In response to recent regulatory guidelines, including ICH (International Council for Harmonisation) Q2 (R2) and Q14, we developed a UPLC-ELSD method to quantify Medium-Chain Triglycerides (MCTs) in Labrafac™ WL 1349 for nanoemulsion applications. This procedure, crafted using Analytical Quality by Design (AQbD) principles, addresses not only the validation of the methodology but also the lifecycle management challenges associated with the analysis of lipid-based excipients. Key parameters such as mobile phase composition, organic modifier, column type, flow rate, diluent, and column temperature were optimized to meet regulatory standards and ensure robustness in MCT quantification. Optimal conditions were achieved with a Waters Acquity HSS T3 (100 × 2.1 mm i.d., 1.8 μm) column at 33 °C, using a mixture of methanol (97.5%) and water (2.5%) containing 0.4% of formic acid at a flow rate of 0.41 mL/min. The method demonstrated an excellent fit on a cubic modelization for MCTs over a broad range of concentrations. Forced degradation studies, including hydrolytic (acidic and basic), oxidative, and thermal stress, confirmed the method’s suitability for possible stability scenarios. This validated UPLC method was successfully applied to quantitative analyses of bulk and formulation prototype samples containing MCTs. This AQbD-driven method enhances not only knowledge but also regulatory-compliant and cost-effective excipient control.
