Novel development of lipid-based formulations: Improved wettability and homogeneous API solid dispersion visualised via near-infrared hyperspectral imaging.

Lipid-based formulations have been successfully applied to improve the aqueous solubility of active pharmaceutical ingredients (APIs), however, with the bottleneck of limited wettability of the system. In this study, a lipid-based system was developed using polyglycerol ester of fatty acids (PGFA) as the main component and hexaglycerol (PG6) as a wetting agent. Felodipine, a BCS class II compound was selected as a model API.

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.

Better GRAS than sorry: Excipient toxicity in pulmonary formulations.

Similar to other routes of administration, pulmonary formulations typically contain excipients. The panel of substances that can be used in pulmonary formulations is limited compared to other routes of administration, and most of them have the generally regarded as safe (GRAS) status. New excipients must undergo in vitro and complete in vivo testing to be approved by regulatory authorities.

Low concentration press cake protein isolates preserve biological activity during lyophilization and spray drying.

A primary challenge in bringing cultivated meat to the market is the high cost of the cell culture media, largely due to their reliance on serum albumins. The production of these albumins is anticipated to become a major bottleneck of this industry. Recently, human serum albumin (HSA) was successfully substituted with seed protein isolates from press cakes enriched with plant albumins.

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.

The Role of Synthetic Organic Electrochemistry in the Technological Revolution of Pharmaceutical Industry.

Electrochemistry is significantly contributing to the technological revolution of organic synthesis, where the implementation of different techniques has garnered innovative and scalable synthetic methodologies. This article explores the impact of synthetic organic electrochemistry in the pharmaceutical and agrochemical industry. Key examples in high throughput experimentation, medicinal chemistry, discovery process chemistry, and process chemistry are presented, highlighting the relevance of electrochemistry in the advancement of organic synthesis, and driving innovation in the fine chemical industry.

Exploring a coating design spacing using experimental and simulated coating techniques.

This study aimed to enhance an understanding of a laboratory-scale tablet coating process using CFD-DEM simulations to model the momentum, heat and mass transfer between the tablets and the fluid phase. Eight process points were selected from an experimental design space study and simulated in silico. The simulations were analyzed regarding the tablet movement, the coating mass distribution, the tablet and air temperatures and the solvent evaporation.

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.

Impact of pharmaceutical tablet properties on optical porosimetry performance.

The porosity of a pharmaceutical tablet influences liquid transport, disintegration and dissolution, rendering its monitoring and control crucial for quality by design. Optical porosimetry, a non-destructive process analytical technology (PAT), combines gas in scattering media absorption spectroscopy (GASMAS), photon time-of-flight spectroscopy (PToFS), tablet thickness measurement and tablet solid refractive index. This article presents a short tutorial on optical porosimetry theory and a performance study of optical porosimetry on pharmaceutical tablets via design of experiments.

A universal digital control concept for end-to-end manufacturing.

With the implementation of advanced manufacturing concepts (e.g., continuous operation, integration of different process routes and modular manufacturing), control of the process and the related product quality becomes more complex.

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.

General and versatile synthesis of highly recyclable chiral phosphoric acid organocatalysts.

The development of recyclable catalysts has gained more attention in recent years in order to minimize the environmental effect and the overall cost of catalytic processes. Some of the most broadly used chiral organocatalysts are BINOL-derived chiral phosphoric acids, making it necessary to develop efficient recycling strategies. While literature reports require up to 13 synthetic steps to access recyclable chiral phosphoric acids, here we report a general and concise 9-step approach to anthracene decorated heterogeneous chiral phosphoric acids (PS-Anth), which have shown high performance either in batch or continuous flow without observing catalyst degradation.

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.

Intraluminal enzymatic hydrolysis of API and lipid or polymeric excipients.

The role of intraluminal enzymes for the hydrolysis of active pharmaceutical ingredients (API), prodrugs and pharmaceutical excipients will be reviewed. Carboxylesterases may hydrolyze ester-based API, prodrugs and ester-bond containing polymer excipients, whereas lipases digest lipid formulation excipients, such as mono-, di- and triglycerides. To clarify the conditions that should be mimicked when designing in vitro studies, we briefly review the upper gastrointestinal physiology and provide new data on the inter-individual variability of enzyme activities in human intestinal fluids.

A modern strategy for digital real-time release testing in continuous tablet manufacturing.

The pharmaceutical industry is currently moving away from traditional approaches to quality control with off-line quality tests, limited in-line process monitoring and minimal control strategies towards more sophisticated methods. This transition addresses several critical aspects, including the reduction of ecological and economic footprints and ensuring the safety for patients and personnel. In that context, the initial step is the application of process monitoring tools, such as process analytical technology (PAT) and soft sensors, for real-time product quality assessment.

Unlocking the Phosphoric Acid Catalyzed Asymmetric Transfer Hydrogenation of 2-Alkenyl Quinolines for Efficient Flow Synthesis of Hancock Alkaloids.

Chiral tetrahydroquinolines are present in several bioactive molecules, such as the Hancock alkaloids. Although the organocatalytic asymmetric transfer hydrogenation of 2-aryl quinolines has emerged as a safer alternative to using hydrogen gas, analogous reactions with 2-alkenyl quinolines remain unexplored. Here we present a protocol to synthesize key enantioenriched intermediates to the Hancock alkaloids, providing a constant outcome for, at least, a 24 h continuous flow operation.

Unraveling the Effects of Filtration, Process Interruptions, and Post-Process Agitation on Protein Aggregation.

Filtration is an essential process step for the manufacturing and filling of biopharmaceuticals. In filling operations, sterile filtration is typically achieved through dead-end filtration using fine membrane filters that completely retain colony-forming units per square centimeter of filter area. According to FDA and USP guidelines, sterilizing filters must be product-compatible and composed of non-fiber releasing materials, typically with a absolute pore size rating of 0.

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.

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.

Electrochemical Fluorination of Organic Compounds Using a Hexafluorosilicate Salt as an Inexpensive and Widely Available Fluorine Source.

The introduction of fluorine into organic molecules is of the utmost importance in the preparation of active pharmaceutical ingredients (APIs). While a wide range of fluorine sources for organic synthesis have been used over the past decades, the associated safety risks, cost, or environmental impact are still serious limitations. Hexafluorosilicate salts are one of the most inexpensive and readily available sources of nucleophilic fluorine, but they have so far not been used in organic synthesis.

A PopPBPK-RL approach for precision dosing of benazepril in renal impaired patients.

Current treatment recommendations mainly rely on rule-based protocols defined from evidence-based clinical guidelines, which are difficult to adapt for high-risk patients such as those with renal impairment. Consequently, unsuccessful therapies and the occurrence of adverse drug reactions are common. Within the context of personalized medicine, that tries to deliver the right treatment dose to maximize efficacy and minimize toxicity, the concept of model-informed precision dosing proposes the use of mechanistic models, like physiologically based pharmacokinetic (PBPK) modeling, to predict drug regimes outcomes.

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.

Exploring pharmaceutical powder behavior in commercial-scale bin blending: A DEM simulation study.

Bin blending is one of the main steps in pharmaceutical production processes. Commercial-scale production of expensive products typically does not allow to perform a large number of experiments in order to optimize the process. Alternatively, Discrete Element Method (DEM) simulations can be used to evaluate the powder behavior (flow and blending pattern) during blending, identify the risks (e.