Carvedilol (CARV) is a blocker of α- and β- adrenergic receptors, used as an “off-label” treatment for cardiovascular diseases in pediatrics. Currently, there is no marketed pediatric-appropriate CARV liquid formulation, so its development is necessary. Palatability (appreciation of smell, taste, and aftertaste) is a key aspect to be considered during the development of pediatric formulations since only formulations with good palatability also have adequate acceptability in this population. Consequently, the aim of this research was to assess the palatability and acceptability of different CARV formulations using an in vivo taste assessment (ID Number PR103/22) in order to select the highest palatability-rated CARV formulation. The preparation of CARV formulations was based on a reference 1 mg/mL CARV solution, which contains malic acid as a solubilizing agent. Subsequently, sucralose and flavoring agents were added and mixed until complete dissolution to the corresponding formulations. Adult volunteers participated in this study and evaluated the taste and odor of various CARV formulations through a questionnaire and a sensory test. The mean palatability score, measured on a 10-point scale, increased from 1.60 for the unflavored control to 7.65 for the highest-rated flavored formulation. Moreover, the bitterness of the optimized CARV formulation was reduced from 66.67% to 17.86%, and the taste pleasantness was increased from 25/100 to 73/100. This optimized CARV formulation contains a sweetening agent, sucralose, in addition to two flavoring agents at appropriate concentrations for pediatrics. Furthermore, the physicochemical and microbiological stability of the optimized CARV formulation were evaluated for 6 months at 25, 30, and 40 °C, in addition to in-use stability for 15 days at 25 °C, whose results were confirmed. Thus, we successfully developed a palatable CARV liquid solution that contains excipients appropriate for pediatrics and is stable under the studied conditions.

The pharmaceutical industry is facing significant economic challenges due to measures aimed at containing healthcare costs and evolving healthcare regulations. In this context, pharmaceutical laboratories seek to extend the lifespan of their machinery, particularly fluid bed dryers, which play a crucial role in the drug production process. Older fluid bed dryers, lacking advanced sensors for real-time temperature optimization, rely on fixed-time deterministic approaches controlled by operators. To address these limitations, a groundbreaking approach taking into account Exploration Data Analysis (EDA) and a Catboost machine-learning model is presented. This research aims to analyze and enhance a drug production process on a large scale, showcasing how AI algorithms can revolutionize the manufacturing industry. The Catboost model effectively reduces preheating phase time, resulting in significant energy savings. By continuously monitoring critical parameters, a paradigm shift from the conventional fixed-time models is achieved. It has been shown that the model is able to predict on average a reduction of 50.45% of the preheating process duration and up to 59.68% in some cases. Likewise, the energy consumption of the fluid bed dryer for the preheating process could be reduced on average by 50.48% and up to 59.76%, which would result on average in around 3.120 kWh energy consumption savings per year.

Carvedilol (CARV) is an ‘off-label’ β-blocker drug to treat cardiovascular diseases in children. Since CARV is nearly insoluble in water, only CARV solid forms are commercialized. Usually, CARV tablets are manipulated to prepare an extemporaneous liquid formulation for children in hospitals. We studied CARV to improve its aqueous solubility and develop an oral solution. In this study, we assessed the solubility and preliminary stability of CARV in different pH media. Using malic acid as a solubility enhancer had satisfactory results. We studied the chemical, physical, and microbiological stability of 1 mg/mL CARV–malic acid solution. A design of experiment (DoE) was used to optimize the CARV solution’s preparation parameters. A 1 mg/mL CARV solution containing malic acid was stable for up to 12 months at 25 °C and 30 °C and 6 months at 40 °C. An equation associating malic acid with CARV concentrations was obtained using DoE. Microbiological data showed that the use of methylparaben was not necessary for this period of time. We successfully developed an aqueous CARV solution suitable for paediatrics and proven to be stable over a 12-month period.

In this paper, a data preprocessing methodology, EDA (Exploratory Data Analysis), is used for performing an exploration of the data captured from the sensors of a fluid bed dryer to reduce the energy consumption during the preheating phase. The objective of this process is the extraction of liquids such as water through the injection of dry and hot air. The time taken to dry a pharmaceutical product is typically uniform, independent of the product weight (Kg) or the type of product. However, the time it takes to heat up the equipment before drying can vary depending on different factors, such as the skill level of the person operating the machine. EDA (Exploratory Data Analysis) is a method of evaluating or comprehending sensor data to derive insights and key characteristics. EDA is a critical component of any data science or machine learning process. The exploration and analysis of the sensor data from experimental trials has facilitated the identification of an optimal configuration, with an average reduction in preheating time of one hour. For each processed batch of 150 kg in the fluid bed dryer, this translates into an energy saving of around 18.5 kWh, giving an annual energy saving of over 3.700 kWh.

Liquid formulations are mostly used in the paediatric population. However, with certain active pharmaceutical ingredients (APIs), it is very difficult to guarantee quality and stability; this is the case, for example, with omeprazole. Omeprazole is used as a model drug due to the lack of a paediatric formulation meeting gastro-resistance requirements, which remains a challenge today. In this experimental study, the development of enteric polymer-coated pellets is proposed. It is proposed to use aqueous coating dispersions without the use of organic solvents, which are commonly used in fluidised bed coatings. To do this, the design of experiments method is used as a statistical tool for experiment creation and the subsequent analysis of the responses. In particular, this study uses a randomised full factorial design. The mean weight increases of the protective layer and the enteric coating are chosen as factors. Each factor is assigned two levels. Therefore, the design of the used experiments is a 2² + 1 central point. Overall, the obtained pellets can be an alternative to the compounding formulas of omeprazole that are currently used in the paediatric population, which do not meet the gastro-resistance specifications necessary to guarantee the therapeutic efficacy of this active ingredient.

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.