Ronny Vargas

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.

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.

El objetivo del estudio fue desarrollar un procedimiento operativo estandarizado para una empresa farmacéutica de Costa Rica. Para esto, se efectuó una entrevista personal no estructurada con la gerente de Control de Calidad. Posteriormente, se realizó una búsqueda de información en distintas bases de datos, para conocer sobre el análisis y el manejo de riesgos, y la utilización del Análisis Modal de Fallos y Efectos. Se desarrolló el documento relacionado con su uso, a través de la generación y la revisión de seis versiones distintas. Para finalizar, se brindó una capacitación a 10 personas de la empresa. Como resultado se obtuvo que uno de los elementos que exige mayor trabajo para la implementación del procedimiento es la definición adecuada de los parámetros de severidad, probabilidad de ocurrencia y probabilidad de detección. Además, la presencia de personas de distintos departamentos es necesaria, dado que aportan una perspectiva distinta a partir de la cual se puede abordar un riesgo dado.

Research on alternatives to the use of animal models and cell cultures has led to the creation of organ-on-a-chip systems, in which organs and their physiological reactions to the presence of external stimuli are simulated. These systems could even replace the use of human beings as subjects for the study of drugs in clinical phases and have an impact on personalized therapies. Organ-on-a-chip technology present higher potential than traditional cell cultures for an appropriate prediction of functional impairments, appearance of adverse effects, the pharmacokinetic and toxicological profile and the efficacy of a drug. This potential is given by the possibility of placing different cell lines in a three-dimensional-arranged polymer piece and simulating and controlling specific conditions. Thus, the normal functioning of an organ, tissue, barrier, or physiological phenomenon can be simulated, as well as the interrelation between different systems. Furthermore, this alternative allows the study of physiological and pathophysiological processes. Its design combines different disciplines such as materials engineering, cell cultures, microfluidics and physiology, among others. This work presents the main considerations of OoC systems, the materials, methods and cell lines used for their design, and the conditions required for their proper functioning. Examples of applications and main challenges for the development of more robust systems are shown. This non-systematic review is intended to be a reference framework that facilitates research focused on the development of new OoC systems, as well as their use as alternatives in pharmacological, pharmacokinetic and toxicological studies.

Objective: This study aimed to develop a microstructured lipid carrier that improves the rate of dissolution of the active pharmaceutical ingredient (API) Albendazole. Methods: A solvent diffusion method was used for the development of microstructured lipid carriers. The developed carriers were characterized by optical microscopy, infrared spectroscopy, differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and dissolution testing. Results: The morphology of the carriers was irregular, and their size tends to decrease with the addition of modifiers. Furthermore, the diffractograms and the thermograms indicated a loss of crystallinity. The thermograms and infrared spectra showed that there are not chemical incompatibilities between the API and the excipients. When the lipid carrier particles were modified with Aerosil® 200 (specifically when using this excipient at a level of 6% w/w), dissolution was increased up to 85.96±1.17 % of the drug content as per USP test for Albendazole tablets in comparison with 36.13±0.52 % for a lipid carrier formulation without modifiers. Conclusion: It was demonstrated that it is possible to develop a modified lipid carrier that improves the dissolution rate of an API with a low solubility, which was related to the amorphization of the API crystalline structure.

Este proyecto de investigación busca contribuir con el desarrollo de una metodología pionera para la caracterización de tabletas farmacéuticas durante el proceso de recubrimiento por el método de aspersión aleatoria, utilizando diferentes técnicas. Se procura apoyar el desarrollo de una opción viable para sistemas de mayor complejidad, alto volumen de producción y gran procesamiento de información. Los resultados parciales obtenidos, permiten identificar patrones de comportamiento que pueden ser utilizados para facilitar el desarrollo de dispositivos y metodologías automatizables, aplicables a procesos similares, que puedan impactar en los procesos de recubrimiento como factores clave de la calidad y de la gestión productiva.