Technical and regulatory perspective on acid stage dissolution assessed via optical coherence tomography (Part 1: Release Scenario).

Enteric coating ensures a targeted release of active pharmaceutical ingredients (APIs) by protecting them from premature dissolution in the stomach. The effectiveness of such coating depends on its thickness and integrity, which are critical for achieving the desired acid protection. This study explores the use of Optical Coherence Tomography (OCT) as an innovative and non-destructive alternative to traditional acid stage dissolution testing performed by directly measuring the coating thickness.

AQbD-based development of a stability-indicating UHPLC-PDA-QDa method for triptorelin in parenteral formulations.

A robust, stability-indicating analytical method for the quantification of triptorelin in suspension formulations was developed using reverse-phase ultra (high)-performance liquid chromatography (RP-UHPLC) under the Analytical Quality by Design (AQbD) framework. This systematic, risk-based approach enabled the efficient identification and optimization of critical method parameters, reducing reliance on traditional trial-and-error procedures. Key variables such as column type, temperature, gradient profile, and organic modifier composition were evaluated.

One-Pot Photoreactions: A Source for Metal-Polymer Nanocomposites.

We have developed a one-step, one-pot photo-induced method for synthesizing metal/polymer nanocomposites. This approach utilizes the photolysis of a bis(acyl)phosphane oxide (BAPO) photoinitiator. Two types of radicals are formed.

Process Analytical Strategies for Size Monitoring: Offline, At-Line, Online, and Inline Methods in a Top-Down Nano-Manufacturing Line.

: Continuous manufacturing is gaining importance in the nanopharmaceutical field, offering improved process efficiency and product consistency. To fully leverage its potential, the integration of Process Analytical Technology (PAT) tools is essential for real-time quality control and robust process monitoring. Among the critical quality attributes (CQAs) of nanosystems, particle size plays a key role in ensuring product consistency and performance.

Evaluation of Analytical Quality by Design Approaches on the Development and Optimization of Size Exclusion Chromatography Analytical Procedures for Bovine Serum Albumin.

The development of analytical procedures, following the International Council of Harmonisation (ICH) regulatory requirements, is crucial for managing the lifecycle of methodologies. This study applies analytical quality by design (AQbD) principles to optimize size exclusion chromatography (SEC) determination for bovine serum albumin (BSA), chosen as a model drug. Key method variables, including mobile phase buffer concentration, flow rate, and column type, were systematically evaluated using risk assessment and design of experiments (DoE).

Quantification of Hydrogen Peroxide in PVP and PVPVA Using H qNMR Spectroscopy.

Objective: Peroxides in pharmaceutical products and excipients pose risks by oxidizing drug molecules, leading to potential toxicity and reduced efficacy. Accurate peroxide quantification is essential to ensure product safety and potency. This study explores the use of quantitative proton nuclear magnetic resonance (H qNMR) spectroscopy as a sensitive and specific method for quantifying peroxide levels in pharmaceutical excipients.

Tailoring the release of highly loaded amorphous solid dispersions via additive manufacturing.

In the last decades, tremendous improvements have been made in enhancing the bioavailability of poorly soluble active pharmaceutical ingredients (APIs). Lately, their customisation potential has become a reality through filament-based 3D-printing (3DP). Highly loaded oral amorphous solid dispersions (ASDs) are of particular interest, since they drastically reduce the pill burden.

Real-time monitoring of multiparticulate coating processes at industrial-scale using ultra-high-resolution optical coherence tomography.

Optical Coherence Tomography (OCT) has been reported as a promising technology for in-line monitoring of pharmaceutical film-coating processes, providing real-time information on actual tablet coating thicknesses and thickness variability, together enabling correlation modeling of the dissolution behavior. However, an increasing interest in the in-line investigation of multiparticulates demands further evolution of the technology and new concepts for process interfacing. To achieve this, we present a novel way to interface OCT to the relevant coating processes using a cutting-edge industry-ready ultra-high-resolution OCT (UHR-OCT) for in-line monitoring.

Light-Driven Photobiocatalytic Oxyfunctionalization in a Continuous Reactor System without External Oxygen Supply.

Oxygenases catalyze C-H oxyfunctionalization under mild reaction conditions and often display outstanding selectivity. However, their utilization is hampered by the difficulty of transporting oxygen across the gas-liquid interface, which is particularly problematic for continuous reactor systems and can only be alleviated by high pressure or the use of complex oxygen-permeable materials. Herein, oxygen is directly released into the medium by the phototrophic cyanobacterium sp.

The uncertainty inherent to DEM simulations of interlocking particles.

In industrial applications, the handling of heterogeneous mixtures of phases and materials poses challenges for direct measurements and experiments, necessitating complementary modeling approaches. The Discrete Element Method (DEM) is commonly used for simulating the flow of granular systems, typically with spherical particles. However, certain applications, such as recycled polymers and batteries, require alternative non-convex particle representations in DEM simulations.

Evaluating the flow-enhancing and antistatic properties of excipients in free and salt forms: A case study on stearic acid and magnesium stearate.

Powder flow characteristics are crucial for efficient processing and manufacturing in the pharmaceutical industry. The occurrence of tribo-charging, a surface phenomenon where particles acquire an electrical charge due to frictional contacts with other particles or surfaces, poses risks for reduced flowability, process inefficiencies, handling difficulties, and ultimately, for the quality of the final products. One strategy to mitigate this effect is the addition of antistatic agents to formulations.

Polystyrene-bound AlCl - a catalyst for the solvent-free synthesis of aryl-substituted tetrazoles.

Tetrazole moieties are components of various pharmacologically active molecules. Several synthetic protocols for the synthesis of tetrazoles have been developed. Among those, the reaction of organic nitriles with azides catalyzed by Lewis acids (LAs) provides a convenient access.

AQbD-Based UPLC-ELSD Method for Quantifying Medium Chain Triglycerides in Labrafac™ WL 1349 for Nanoemulsion Applications.

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.

ESG assessment methodology for emerging technologies: plasma conventional technology for ammonia production.

Environmental, social and governance (ESG) criteria demand that enterprises should not be assessed solely on their financial performance, but also on their environmental, social, and governance performance. This numerical assessment of ESG criteria enables them to be evaluated with the consideration of other financial issues of enterprises' performance and thereby guides financial investments into environmentally and socially responsible firms. ESG, however, solidifies the continuance of conventional technologies but can potentially disadvantage emerging technologies.

Implications of crystal disorder on the solid-state stability of olanzapine.

Mechanical perturbations of drug during solid pharmaceutical processing like milling can often generate crystal disorder posing serious implications to drug's stability. While physical changes like amorphization, recrystallization, polymorphism of the disordered drugs are extensively studied and reported in the literature, the propensities and inter-dependencies of recrystallization and degradation of disordered drugs have seldom received deep attention. Previous investigations from our lab have explored some of these interplays, aiming to develop predictive stability models.

Comparing Low-Dose Carvedilol Continuous Manufacturing by Solid and Liquid Feeding in Self-Emulsifying Delivery Systems via Hot Melt EXtrusion (SEDEX).

This study compared two pilot scale continuous manufacturing methods of solid self-emulsifying drug delivery systems (SEDDSs) via hot melt extrusion (HME). : A model poorly water-soluble drug carvedilol in low dose (0.5-1.

Influence of L-leucine content on the aerosolization stability of spray-dried protein dry powder inhalation (DPI).

Inhalable formulations of medicines intended to act locally in the lung are therapeutically effective at lower doses with targeted delivery, compared to parenteral or oral administration. Meanwhile, different APIs, including biologics, have proven to be challenging regarding formulation and final bioavailability. This study focuses on the production, improved stability performance, and delivery of spray-dried, inhalable protein powders to the lungs.

In-line porosity and hardness monitoring of tablets by means of optical coherence tomography.

In-line monitoring of critical quality attributes (CQAs) during a tableting process is an essential step toward a real-time release strategy. Such CQAs can be the tablet mass, the API content, dissolution, hardness and tensile strength. Since dissolution testing is laborious and time-consuming and cannot be performed in-line, it is desirable to replace dissolution testing with predictive models based on other CQAs that affect the dissolution characteristics, such as the tablet porosity and hardness.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 2. Validation of calibration workflow.

This paper is the second in a series of two that describes the application of discrete element method (DEM) and reduced order modeling to predict the effect of disturbances in the concentration of drug substance at the inlet of a continuous powder mixer on the concentration of the drug substance at the outlet of the mixer. In the companion publication, small-scale material characterization tests, a careful DEM parameter calibration and DEM simulations of the manufacturing process were used to develop a reliable RTD models. In the current work, the same calibration workflow was employed to evaluate the predictive ability of the resulting reduced-order model for an extended design space.

Development of a high-fidelity digital twin using the discrete element method for a continuous direct compression process. Part 1. Calibration workflow.

In this work, a high-fidelity digital twin was developed to support the design and testing of control strategies for drug product manufacturing via direct compression. The high-fidelity digital twin platform was based on typical pharmaceutical equipment, materials, and direct compression continuous processes. The paper describes in detail the material characterization, the Discrete Element Method (DEM) model and the DEM model parameter calibration approach and provides a comparison of the system's response to the experimental results for stepwise changes in the API concentration at the mixer inlet.

Investigation of the Influence of Copovidone Properties and Hot-Melt Extrusion Process on Level of Impurities, In Vitro Release, and Stability of an Amorphous Solid Dispersion Product.

Hot-melt extrusion (HME) is a widely used method for creating amorphous solid dispersions (ASDs) of poorly soluble drug substances, where the drug is molecularly dispersed in a solid polymer matrix. This study examines the impact of three different copovidone excipients, their reactive impurity levels, HME barrel temperature, and the distribution of colloidal silicon dioxide (SiO) on impurity levels, stability, and drug release of ASDs and their tablets. Initial peroxide levels were higher in Kollidon VA 64 (KVA64) and Plasdone S630 (PS630) compared to Plasdone S630 Ultra (PS630U), leading to greater oxidative degradation of the drug in fresh ASD tablets.

Effect of processing and formulation factors on Catalase activity in tablets.

The manufacturing of tablets containing biologics exposes the biologics to thermal and shear stresses, which are likely to induce structural changes (e.g., aggregation and denaturation), leading to the loss of their activity.

Integration of mucus and its impact within in vitro setups for inhaled drugs and formulations: Identifying the limits of simple vs. complex methodologies when studying drug dissolution and permeability.

Traditionally, developing inhaled drug formulations relied on trial and error, yet recent technological advancements have deepened the understanding of 'inhalation biopharmaceutics' i.e. the processes that occur to influence the rate and extent of drug exposure in the lungs.

Process analytical technology in Downstream-Processing of Drug Substances- A review.

Process Analytical Technology (PAT) has revolutionized pharmaceutical manufacturing by providing real-time monitoring and control capabilities throughout the production process. This review paper comprehensively examines the application of PAT methodologies specifically in the production of solid active pharmaceutical ingredients (APIs). Beginning with an overview of PAT principles and objectives, the paper explores the integration of advanced analytical techniques such as spectroscopy, imaging modalities and others into solid API substance production processes.

Archaeosomes for Oral Drug Delivery: From Continuous Microfluidics Production to Powdered Formulations.

Archaeosomes were manufactured from natural archaeal lipids by a microfluidics-assisted single-step production method utilizing a mixture of di- and tetraether lipids extracted from The primary aim of this study was to investigate the exceptional stability of archaeosomes as potential carriers for oral drug delivery, with a focus on powdered formulations. The archaeosomes were negatively charged with a size of approximately 100 nm and a low polydispersity index. To assess their suitability for oral delivery, the archaeosomes were loaded with two model drugs: calcein, a fluorescent compound, and insulin, a peptide hormone.