Marc Suñé-Pou

Hydrophilic matrix tablets based on hydroxypropyl methylcellulose (HPMC) were developed to enable sustained release of non-micronized progesterone, a highly lipophilic and poorly water-soluble steroid. Formulations containing different HPMC concentrations were manufactured at three tablet hardness levels to evaluate the influence of polymer content and matrix compaction on drug release. In vitro dissolution studies showed that HPMC concentration and tablet hardness markedly affected release rate and completeness. Mathematical modeling using nonlinear mixed-effects analysis showed that formulation-related differences were primarily explained by changes in the release-rate constant (k), with HPMC content and tablet hardness retained as covariates, whereas no systematic effects were identified on the release exponent (n). Several formulations exhibited an approximately linear release profile over a substantial portion of the dissolution period, indicating near-constant release rates, an uncommon behavior for hydrophilic HPMC matrices in which hydration, swelling and erosion typically result in time-dependent release rates. Importantly, this quasi-linear behavior does not imply a single underlying release mechanism, as the Korsmeyer–Peppas exponent suggested concurrent contributions from diffusion and polymer relaxation or erosion. Among the formulations evaluated, 18% HPMC K100M compressed at 100 N exhibited the most favorable dissolution performance, achieving complete drug release within 24 h and complying with the pharmacopoeial dissolution criterion. These findings demonstrate the feasibility of directly compressed HPMC matrices for sustained progesterone release and highlight the interplay between formulation variables, release rate and mechanism.

Background and purpose: From the early use of liposomes in the 1960s to modern nucleic acid delivery platforms, nanotechnology has shown its value in drug delivery and diagnostic applications. A wide range of nanostructures has been investigated for drug delivery, including inorganic, polymeric and lipid-based nanomaterials. While some of these nanomaterials have reached more advanced stages of clinical development, some even reaching commercialization, new alternatives are continuously being explored. Approach: This review describes the different categories of nanomaterials being used as nanocarriers and provides concrete representative examples of commercially approved products. Key results: Current trends of nanotechnology developments in the pharmaceutical market largely focus on the treatment of cancer, infectious diseases, central nervous system disorders and cardiovascular diseases. At the same time, lipid nanoparticle platforms are gaining relevance in current development pipelines. However, some of the main challenges limiting clinical translation include manufacturability, scale-up, long-term stability, regulatory uncertainty, intellectual property issues and the lack of representative preclinical study models. Conclusion: Nanotechnology has become a fundamental breakthrough in medicine, especially for advanced therapies such as gene silencing or gene editing alternatives. All things considered, no universal nanocarrier fits all biomedical applications; the evolution of the field depends on several platforms demonstrating their individual potential.

Background/Objectives: In this study, an analytical method by high-performance liquid chromatography (HPLC) that allows the determination of the content of the active ingredient itraconazole (ITZ), as well as the quantification of its degradation products and known impurities, is developed. Some of the existing methods, including the compendial ones, present long run times or different methods for the quantification of ITZ and the quantification of its impurities. Methods: In this article, an initial screening approach, starting on the described compendial methods, was conducted in order to establish the initial working conditions of the chromatographic method parameters. Once these parametric conditions were established, an optimisation was conducted utilising a statistical approach and a Design of Experiments (DoE), with the objective of attaining an optimised method that allows the quantification of ITZ and its related substances in one single injection. The data obtained during the DoE were processed using the Minitab^® statistical programme. Once an optimised method was obtained, a short pre-validation assessment studying the selectivity, linearity and system suitability, among others, was carried out, confirming the suitability of the method for the intended use. Results: The resulting method employs an isocratic mobile phase of acetonitrile (ACN) and buffer (ammonium phosphate 10 mM at pH 4.0), utilising a stationary phase of a Poroshell EC-C18 150 × 3.0 mm, 2.7 µm column. The retention time of itraconazole is 8.5–9.0 min, with a total chromatographic run time of 15 min. Conclusions: The developed method exhibits a shorter run time and greater environmental sustainability compared to compendial methods, underscoring its improved analytical performance.

SeptiLoop® is a novel in vitro diagnostic (IVD) lateral flow test designed to detect ex vivo TNF-α production in whole blood stimulated with LPS, indicating bloodstream infection related to immune dysregulation in early sepsis. This study aims to assess the analytical validity of SeptiLoop® for detecting ex-vivo TNF-α production. The analytical performance of SeptiLoop® was evaluated based on pre-specified criteria, including Limit of Detection (LoD), specimen stability, interference, precision (repeatability and reproducibility), shelf-life, robustness and ruggedness, and hook effect. Stability tests for blood samples, reagents, and the device's shelf-life were also conducted. Whole blood samples from healthy volunteers were used in the assay to measure TNF-α production following LPS stimulation. SeptiLoop® demonstrated a Limit of Detection (LoD) of 250 pg/mL for TNF-α. Interference tests indicated minimal interference from common medications and patient conditions. The device showed high precision, with >95% agreement in repeatability and reproducibility across different test conditions. No hook effect was detected within the assay's measuring range. Sample stability was confirmed for 16 hours post-collection in whole blood, with diluted samples stable for up to 15 minutes after incubation. The device also demonstrated a 3-month shelf-life and maintained operational stability under various conditions. SeptiLoop® met all analytical performance criteria, including accuracy, LoD, and precision, making it a reliable tool for early sepsis detection. These findings highlight the need for further clinical evaluation to establish its role in timely sepsis diagnosis and management.

The pharmaceutical industry’s pursuit of enhanced product quality, regulatory compliance, and operational efficiency has catalyzed the integration of Artificial Intelligence (AI) into Ongoing Process Verification (OPV) frameworks. This comprehensive review examines the synergistic application of Human-in-the-Loop (HITL) AI systems within OPV, contextualized by the evolving regulatory landscape, particularly the newly introduced Annex 22 of the European Union Good Manufacturing Practices (EU-GMP). The review delineates the sector’s strategic shift from traditional validation models toward dynamic, data-driven approaches that leverage AI for real-time monitoring, predictive analytics, and proactive process control. Central to this transformation is the HITL paradigm, which ensures that human expertise remains embedded in critical decision-making loops, thereby safeguarding patient safety, product quality, data integrity, and ethical responsibility. Annex 22 explicitly mandates deterministic behavior, traceability, and explainability for AI models used in GMP-critical applications, excluding adaptive and probabilistic systems from such contexts. The document also reinforces the necessity of multidisciplinary governance, rigorous validation protocols, and risk-based oversight throughout the AI lifecycle. This paper synthesizes current industry practices, regulatory expectations, and technological capabilities, offering a structured framework for compliant AI deployment in OPV. By aligning AI implementation with Annex 22 principles and existing GMP frameworks (e.g., Annex 11 and ICH Q9), the pharmaceutical sector can harness AI’s transformative potential while maintaining robust regulatory compliance. The review concludes with actionable recommendations for integrating HITL AI into OPV strategies, fostering a resilient, transparent, ethical, and future-ready manufacturing ecosystem.

Background and purpose: The delivery of therapeutics to the central nervous system (CNS) remains a major challenge due to the restrictive nature of the blood-brain barrier (BBB), a key evolutionary feature that preserves brain homeostasis. This review seeks to synthesize current knowledge on BBB composition, physiology, and transport mechanisms, and critically analyses drug delivery strategies aimed at overcoming this barrier and enabling effective CNS therapies. Approach: We conducted a comprehensive narrative review integrating evidence on BBB anatomy, transport and permeability mechanisms, drug delivery optimization strategies, with a particular focus on nanotechnology-based systems, and preclinical evaluation models. Key results: We highlight how a deeper understanding of BBB architecture and dynamic regulation can inform rational design of targeted strategies. Drug delivery approaches are summarized and compared, with emphasis on the potential of nanotechnology-based platforms to enhance CNS drug delivery. Translational considerations, including scalability, reproducibility, and regulatory requirements, are critically addressed. Major challenges identified include receptor saturation, competition with endogenous ligands, disease-specific variability in BBB permeability, and the limited predictive value of current preclinical models. Emerging tools, such as organ-on-chip (for evaluation) and microfluidic mixing (for manufacturing nanomaterials), offer promising means to improve physiological relevance and accelerate translation. Conclusion: Progress in BBB research has laid the groundwork for innovative therapies, but significant hurdles remain. Advancing CNS drug delivery will require collaborative work refining transport-targeting mechanisms, developing standardized preclinical models, and integrating fundamental research, applied nanomedicine, and regulatory science to open new opportunities for treating neurological and psychiatric disorders and brain tumours.

This comprehensive review of the synergistic use of Quality by Design (QbD) and the Pi–Buckingham theorem explores an innovative approach to enhancing product development and process optimization within the pharmaceutical industry. QbD is a systematic, proactive methodology that integrates quality considerations throughout the product lifecycle to ensure that pharmaceutical products meet regulatory standards for safety and efficacy from the outset of development. The Pi–Buckingham theorem serves as a foundational principle in dimensional analysis, facilitating the simplification of complex models by transforming physical variables into dimensionless parameters. This synergy enables researchers to better understand and control the factors affecting critical quality attributes (CQAs), thereby improving manufacturing outcomes and minimizing variability.

Background/Objectives: Carbamazepine is widely used as a first-line treatment for pediatric patients with benign epilepsy. However, most commercial formulations have doses of 100 mg or higher, limiting their suitability for pediatric use. The aim of this study was to develop mini orally disintegrating tablets (ODTs) containing 50 mg of carbamazepine, utilizing direct compression technology, specifically tailored to meet the unique needs of pediatric patients. Methods: The development was carried out following a Quality by Design (QbD) approach, beginning with preformulation studies using the SeDeM expert system. Various co-processed excipients (PROSOLV^® ODT and PARTECK^® ODT) and non-co-processed excipients (L-HPC LH11 and L-HPC NBD-022) were evaluated. Additionally, modifications to the radius parameter of the SeDeM expert system were investigated to improve formulation design. Results: Optimized Formulations 13 and 14 achieved disintegration times below 1 min, hardness values between 25 and 60 N, and friability under 1%, fulfilling the predefined Critical Quality Attributes (CQAs). Tablets were successfully produced with a diameter of 5 mm and a weight below 100 mg. Moreover, reducing the SeDeM incidence radius from 5.0 to values between 4.0 and 3.5 proved viable, enabling the inclusion of excipients previously considered unsuitable and broadening formulation options without compromising quality. Conclusions: This study demonstrates the feasibility of producing small, fast-disintegrating, and mechanically robust 50 mg carbamazepine ODTs tailored for pediatric patients. It also validates the adjustment of SeDeM parameters as an effective strategy to expand excipient selection and enhance formulation flexibility in pediatric drug development.