Current Issue : July-September Volume : 2025 Issue Number : 3 Articles : 5 Articles
Introduction: The preservation of mesenchymal stem cell (MSC) viability and biological activity is a key aspect in optimizing advanced therapy medicinal products (ATMPs). Evaluating various excipients to optimize MSC conservation and functionality is essential. Methods: Five excipients with different proportions of human platelet lysate (hPL) and Hypothermosol were evaluated at two different cell concentrations (0.1 × 106 MSC/μL and 0.008 × 106 MSC/μL). Cell viability, adhesion, and proliferation capacity were assessed at 24 and 48 h under hypothermic conditions (2–8 ◦C). Results: A significant interaction was observed between cell concentration and excipient, where the 0.008 × 106 MSC/μL concentration showed better viability results. Excipients with a combination of 50–75% Hypothermosol improved cell viability and adhesion. No significant differences were found in cell proliferation among the excipients studied. Viability, adhesion, and proliferation decreased significantly at 48 h for all excipients and concentrations evaluated. Conclusions: The combination of hPL and Hypothermosol enhances MSC stability and preserves their functionality, suggesting its potential as an optimized storage solution for cell-based therapies. Additionally, the impact of cell concentration on viability underscores the importance of selecting appropriate dosing. Future studies should further investigate how these findings translate into clinical outcomes, particularly in terms of therapeutic efficacy and patient safety....
Background: The bioavailability of a drug depends, among other parameters, on solubility. One of the strategies used to enhance the solubility of sparingly soluble drugs is the use of excipients. Excipients can interact with the drug by increasing its solubility and/or stabilizing supersaturated solutions. Some of the most common excipients are cyclodextrins and hydrophilic polymers. Objectives: The effect of two cyclodextrins (captisol and cavasol) and three hydrophilic polymers (klucel, kollidon and plasdone S630) on the solubility of three ionizable drugs (benzthiazide, isoxicam, and piroxicam) is evaluated at biorelevant pH values, using two complementary techniques. Methods: The solubility enhancement was evaluated by the comparison of the solubility with and without the presence of excipients through the shake-flask and CheqSol methodology. Results: Captisol and cavasol slightly increase the concentration of the neutral species of the drugs in the solution before precipitation begins, although they do not enhance the supersaturation duration nor the thermodynamic solubility of the drugs. The increase in solubility in the presence of cyclodextrins is mainly caused by the ionization state of the drug. Hydrophilic polymers not only improve thermodynamic solubility but also the extent and the duration of the supersaturation. Some metastable forms are observed for benzthiazide and isoxicam in the presence of kollidon and plasdone S630. Conclusions: The shake-flask method enabled the evaluation of thermodynamic solubility both in the absence and presence of excipients. Meanwhile, the CheqSol method provided insights into the presence of supersaturated solutions. Different behavior is observed depending on the nature of the excipient....
Gluten and soy allergies are significant health concerns, particularly in individuals with celiac disease or soy sensitivity. While dietary sources of these allergens are well-studied, their presence in medicinal products remains under-explored. This study assessed the prevalence of gluten and soy-derived excipients in 308 medicinal products authorized for marketing in Portugal. A systematic search of the Summary of Product Characteristics (SmPC) database was conducted for 108 analgesics and antipyretics containing paracetamol, 85 NSAIDs containing ibuprofen, and 115 antiasthmatic and bronchodilator medicinal products. The study found significant associations between pharmacotherapeutic groups and the presence of these allergens (p < 0.001). Gluten was more prevalent in the group of analgesics and antipyretics (44.4%) than in NSAIDs (8.2%), whereas soy-derived excipients were more frequent in NSAIDs (14%) than in analgesics and antipyretics (6.5%). No excipients containing gluten or soy were identified in antiasthmatic and bronchodilator medicinal products. In analgesics and antipyretics, 51.2% of solid oral dosage forms and 40% of liquid oral formulations contained gluten. Within the NSAIDs group, gluten was mainly present in liquid oral dosage forms (26.7%). Soy-derived excipients were found in 30% of liquid oral formulations and in 33.3% of rectal dosage forms of analgesics and antipyretics. In the NSAIDs group, soy was more prevalent in liquid oral formulations (26.7%). These findings highlight the need for clearer labeling of allergens in medicinal products and underscore the importance of vigilance for patients with gluten or soy allergies. Further research is required to address gaps in allergen disclosure by pharmaceutical manufacturers and to promote safer medicinal product use for sensitive populations. Enhanced awareness among healthcare providers and patients is essential to mitigate the risk of allergic reactions associated with hidden excipients in medicinal products....
Pharmaceutical excipients such as P-glycoprotein inhibitors can also increase the solubility and affinity of drugs to the intestinal membrane, enhance paracellular pathways and endocyte uptake, and activate lymph transport pathways, thereby increasing the bioavailability of oral drugs. This review aims to review and assess the performance of pharmaceutical excipients as P-glycoprotein permeability inhibitors in improving oral drug bioavailability in drug formulations by evaluating meta data from P-glycoprotein efflux in permeability and pharmacokinetics studies. The review results are pharmaceutical excipients that have proven effective as P-glycoprotein inhibitors from the surfactant and polymer groups, namely TPGS and Poloxamer 188, respectively. All nanosystems incorporating pharmaceutical excipients as P-gp inhibitors show potential in enhancing the permeability and bioavailability of oral drugs when compared to conventional formulations. The effectiveness of these systems has been evaluated through in vitro (Caco-2 cells), ex vivo (everted gut sac), in situ (SPIP), and in vivo (AUC) methods....
Most novel active pharmaceutical ingredients have low water solubility; therefore, solubility-enhancing methods are applied. The aim of the present investigation is to study the impact of nine commonly used pharmaceutical excipients (fillers, surfactants, cyclodextrins, polymers) on solubility, permeability and their relationship. This is crucial for ensuring optimal bioavailability. Carbamazepine, naproxen and pimobendan were chosen as model compounds due to their different acid–base properties. Equilibrium solubility was measured by the traditional shake flask method. Effective permeability was determined by the PAMPA model. Measurements of ionizable compounds were carried out at three pH values. The pH-dependent change in the investigated parameters is maintained even in the presence of excipients. Fillers resulted in a slight or no effect, while the impact of other excipients showed a significant concentration dependence. The impact of excipients was influenced by the structure and ionization state of the molecules. The dominance of the ionized form moderates the impact of excipients. The changes in solubility were more pronounced than in the case of permeability. By examining the effect of the ionization state and interactions with excipients, this work supports the development of formulations that enhance solubility with minimal impacts on permeability. Additionally, it can serve as good basis for preformulation studies and design optimization....
Loading....