Search Results (168)

Background/Objectives: The major limitations of self-nanoemulsifying systems include complex processing and expensive instrumentation required for solidification approaches. In this study, smart poloxamer-based solidification strategies were used to develop and optimize febuxostat-loaded formulations. Methods: A self-nanoemulsifying drug delivery system (SNEDDS) component was selected based on solubility and emulsification tests. The influence of poloxamer molecular weight (low or high) and its concentration (2–10% w/w) on formulation performance was assessed through the design of experiments. Finally, in-vitro melting assessment and a comparative dissolution test were performed on the optimized SNEDDS formulation. Results: Imwitor 988 and Tween 20 were selected to prepare the formulations. Increasing the molecular weight and concentration of the poloxamer significantly increased the temperature and time required for the melting of the SNEDDS formulation. The optimized SNEDDS formulation comprised 3.98% w/w poloxamer 188, which melts at 36 °C within 111 s. In-vitro melting showed that the formulation completely converted to a liquid state upon exposure to body temperature. Finally, the optimized SNEDDS formulation exhibited superior dissolution efficiency (96.66 ± 0.28%) compared to raw febuxostat (72.09 ± 4.33%) and marketed tablets (82.23 ± 3.10%). Conclusions: The poloxamer-based approach successfully addressed the limitations associated with conventional solidification while maintaining superior dissolution performance. Therefore, it emerges as a promising alternative approach for enhancing the bioavailability of poorly water-soluble drugs. Full article

Manual assembly remains essential in modern manufacturing, yet the increasing complexity of customised production imposes significant cognitive burdens and error rates on workers. Existing Spatial Augmented Reality (SAR) systems often operate passively, lacking adaptive interaction, real-time feedback and a control system with gesture. In response, we present Gest-SAR, a SAR framework that integrates a custom MediaPipe-based gesture classification model to deliver adaptive light-guided pick-to-place assembly instructions and real-time error feedback within a closed-loop interaction instance. In a within-subject study, ten participants completed standardised Duplo-based assembly tasks using Gest-SAR, paper-based manuals, and tablet-based instructions; performance was evaluated via assembly cycle time, selection and placement error rates, cognitive workload assessed by NASA-TLX, and usability test by post-experimental questionnaires. Quantitative results demonstrate that Gest-SAR significantly reduces cycle times with an average of 3.95 min compared to Paper (Mean = 7.89 min, p < 0.01) and Tablet (Mean = 6.99 min, p < 0.01). It also achieved 7 times less average error rates while lowering perceived cognitive workload (p < 0.05 for mental demand) compared to conventional modalities. In total, 90% of the users agreed to prefer SAR over paper and tablet modalities. These outcomes indicate that natural hand-gesture interaction coupled with real-time visual feedback enhances both the efficiency and accuracy of manual assembly. By embedding AI-driven gesture recognition and AR projection into a human-centric assistance system, Gest-SAR advances the collaborative interplay between humans and machines, aligning with Industry 5.0 objectives of resilient, sustainable, and intelligent manufacturing. Full article

Background/Objectives: Hot-melt extrusion (HME) has gained prominence for the manufacture of sustained-release oral dosage forms, yet the application of wax-based matrices and their resilience to alcohol-induced dose dumping (AIDD) remains underexplored. This study aimed to develop and characterise wax-based sustained-release felodipine formulations, with a particular focus on excipient functionality and robustness against AIDD. Methods: Felodipine sustained-release formulations were prepared via HME using Syncrowax HGLC as a thermally processable wax matrix. Microcrystalline cellulose (MCC) and lactose monohydrate were incorporated as functional fillers and processing aids. The influence of wax content and filler type on mechanical properties, wettability, and drug release behaviour was systematically evaluated. Ethanol susceptibility testing was conducted under simulated co-ingestion conditions (4%, 20%, and 40% v/v ethanol) to assess AIDD risk. Results: MCC-containing tablets demonstrated superior sustained-release characteristics over 24 h, showing better wettability and disintegration. In contrast, tablets formulated with lactose monohydrate remained structurally intact during dissolution, overly restricting drug release. This limitation was effectively addressed through granulation, where reduced particle size significantly improved surface accessibility, with 0.5–1 mm granules achieving a satisfactory release profile. Ethanol susceptibility testing revealed divergent behaviours between the two filler systems. Unexpectedly, MCC-containing tablets showed suppressed drug release in ethanolic media, likely resulting from inhibitory effect of ethanol on filler swelling and disintegration. Conversely, formulations containing lactose monohydrate retained their release performance in up to 20% v/v ethanol, with only high concentrations (40% v/v) compromising matrix drug-retaining functionality and leading to remarkably increased drug release. Conclusions: This study highlights the pivotal role of excipient type and constitutional ratios in engineering wax-based sustained-release formulations. It further contributes to the understanding of AIDD risk through in vitro assessment and offers a rational design strategy for robust, alcohol-resistant oral delivery systems for felodipine. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that impairs motor function, including the fine motor control required for handwriting. Traditional diagnostic methods often lack sensitivity and objectivity in the early stages, limiting opportunities for timely intervention. There is a growing need for non-invasive, accessible tools capable of capturing subtle motor changes that precede overt clinical symptoms. Among early PD manifestations, handwriting impairments such as micrographia have shown potential as digital biomarkers. However, conventional handwriting analysis remains subjective and limited in scope. Recent advances in artificial intelligence (AI) and machine learning (ML) enable automated analysis of handwriting dynamics, such as pressure, velocity, and fluency, collected via digital tablets and smartpens. These tools support the detection of early-stage PD, monitoring of disease progression, and assessment of therapeutic response. This paper highlights how AI-enhanced handwriting analysis provides a scalable, non-invasive method to support diagnosis, enable remote symptom tracking, and personalize treatment strategies in PD. This approach integrates clinical neurology with computer science and rehabilitation, offering practical applications in telemedicine, digital health, and personalized medicine. By capturing dynamic features often missed by traditional assessments, AI-based handwriting analysis contributes to a paradigm shift in the early detection and long-term management of PD, with broad relevance across neurology, digital diagnostics, and public health innovation. Full article

Background/Objectives: This study focused on developing an organic solvent-free formulation of phytantriol-based cubosomes for nifedipine delivery. It assessed the physicochemical properties and in vitro administration performance in pediatric nasogastric tubes and preliminarily evaluated toxicity in a brine shrimp lethality model. Methods: The nanocarrier formulation was characterized in terms of the particle size and drug release properties and was compared with extemporaneous formulations prepared using nifedipine tablets in flow rate tests through pediatric feeding tubes. The recovery efficiency was evaluated across different tube sizes and rinsing volumes. A preliminary toxicity study was conducted using a brine shrimp lethality model. Results: Compared with nifedipine tablets, the nanocarrier formulation demonstrated favorable physicochemical properties, including controlled release and superior flow rates, in the pediatric tubes. Full recovery of the nifedipine content was achieved with the nanocarrier formulation, whereas extemporaneous formulation of the nifedipine recovery depended on the tube dimensions and rinsing protocols. Conclusions: Compared with the traditional formulations, the nanocarrier formulation represents a promising alternative for administering nifedipine via pediatric feeding tubes, offering an enhanced administration recovery. Full article

This study presents a mobile-based sperm analysis system featuring a user-friendly, droplet-loaded microfluidic chip that enables non-specialist users to perform the rapid and accurate quantitative evaluation of boar semen directly on the farm. The iSperm system integrates a tablet, optical module, heater, and real-time image analysis app to deliver automated measurements of sperm concentration, motility, and progressive motility in under one minute. Precision and user variability tests demonstrated high concordance with CASA and the hemocytometer, with minimal differences between trained and untrained users. A method comparison using 77 farm-collected samples confirmed agreement through Passing–Bablok regression and Bland–Altman analysis. ROC curve analyses further validated diagnostic accuracy for all parameters, with AUC values exceeding 0.95. The iSperm platform offers a reliable, user-friendly, and field-deployable solution for on-site semen quality assessment, improving decision-making in swine artificial insemination. Full article

Background/Objectives: The growing interest in personalized medicine has accelerated the exploration of three-dimensional (3D) printing technologies in pharmaceutical applications. This study investigates the potential of selective laser sintering (SLS) as a flexible, small-scale manufacturing method for atomoxetine tablets tailored for individualized therapy, comparing it with conventional direct compression. Methods: Atomoxetine tablets were produced using SLS 3D printing with varying laser scanning speeds and compared to tablets made via a compaction simulator. Formulations were based on hydroxypropyl methylcellulose (HPMC) as the primary matrix former. The physical properties, drug content, disintegration time, and dissolution profiles were evaluated. The structural and chemical integrity were assessed using SEM, FTIR, DSC, and XRPD. Results: The SLS tablets exhibited comparable mechanical properties and drug content to those made by compaction. Lower laser speeds produced harder tablets with slower disintegration, while higher speeds yielded more porous tablets with ultra-rapid drug release (>85% in 15 min). All tablets met the European Pharmacopoeia dissolution criteria. No significant drug–excipient interactions or changes in crystallinity were detected. Conclusions: SLS printing is a viable alternative to traditional tablet manufacturing, offering control over drug release profiles through parameter adjustment. The technique supports the development of high-quality, patient-specific dosage forms and shows promise for broader implementation in personalized pharmaceutical therapy. Full article

Background: The increasing prevalence of dementia and mild cognitive impairment (MCI) among the elderly population is a global health issue. Information and Communication Technology (ICT)-based interventions hold promises for maintaining cognition, but their viability is affected by several challenges. Objectives: This study aimed to significantly assess the effectiveness of ICT-based cognitive and memory aid technology for individuals with MCI or dementia, identify adoption drivers, and develop an implementation model to inform practice. Methods: A PRISMA-based systematic literature review, with the protocol registered in PROSPERO (CRD420251051515), was conducted using seven electronic databases published between January 2015 and January 2025 following the PECOS framework. Random effects models were used for meta-analysis, and risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists. Results: A total of ten forms of ICT interventions that had proved effective to support older adults with MCI and dementia. Barriers to adoption included digital literacy differences, usability issues, privacy concerns, and the lack of caregiver support. Facilitators were individualized design, caregiver involvement, and culturally appropriate implementation. ICT-based interventions showed moderate improvements in cognitive outcomes (pooled Cohen’s d = 0.49, 95% CI: 0.14–1.03). A sensitivity analysis excluding high-risk studies yielded a comparable effect size (Cohen’s d = 0.50), indicating robust findings. However, trim-and-fill analysis suggested a slightly reduced corrected effect (Cohen’s d = 0.39, 95% CI: 0.28–0.49), reflecting potential small-study bias. Heterogeneity was moderate (I² = 46%) and increased to 55% after excluding high-risk studies. Subgroup analysis showed that tablet-based interventions tended to produce higher effect sizes. Conclusions: ICT-based interventions considerably enhance cognition status, autonomy, and social interaction in older adults with MCI and dementia. To ensure long-term scalability, future initiatives must prioritize user-centered design, caregiver education, equitable access to technology, accessible infrastructure and supportive policy frameworks. Full article

Maintaining the cleanliness of orthodontic aligners is crucial for oral hygiene and preserving the optical properties of aligners. In this randomized clinical trial, we compared the effectiveness of different cleaning methods for the maintenance of Invisalign clear aligners. Twelve adult patients received five aligners, each worn for 10 days. The aligners were divided based on the cleaning method: tooth brushing with whitening toothpaste, vinegar, Fittydent Super Cleansing Tablets, Invisalign cleaning crystals, and only water. Scanning electron microscopy (SEM) was used to detect surface morphology changes; color changes (ΔE) were evaluated using a spectrophotometer. Fourier transform infrared spectroscopy (FTIR) with a diamond hemisphere was used to study the aligners’ chemical compositions. Nanoindentation testing was used to assess changes in the elastic modulus. SEM confirmed the effectiveness of Invisalign cleaning crystals in maintaining cleanliness, revealing a surface similar to that of the control group with no adverse effects. Color stability analysis revealed significant ΔE value differences; whitening toothpaste had significantly lower ΔE values than water and Invisalign cleaning crystals. The elastic modulus and FTIR analyses indicated no significant differences between the cleaning methods. Therefore, Invisalign cleaning crystals and whitening toothpaste are safe for aligner maintenance, showing successful and aesthetically pleasing results. Full article

Background: Fexofenadine hydrochloride (FEX) is widely used to treat allergic rhinitis. However, poor solubility, high cohesiveness, and risk of polymorphic transformation present significant formulation challenges. Conventional FEX tablet formulations are large and may pose swallowing difficulties for patients with dysphagia. Therefore, a miniaturized FEX tablet that maintained bioequivalence with the marketed product was developed. Methods: An organic solvent-based binder and porous carrier enhanced solubility, flowability, and process efficiency. The formulation was optimized using a design of experiments approach to assess the effects of tablet size and porous carrier incorporation on dissolution and residual solvent content. Scale-up feasibility was evaluated using Froude number-based process optimization, and stability studies were conducted under accelerated conditions (40 °C and 75% relative humidity) to ensure long-term formulation robustness. Results: The miniaturized tablet exhibited dissolution at pH 4.0 and pH 6.8 equivalent to that of the reference product, whereas a faster dissolution rate was observed at pH 1.2. No significant changes were observed in the dissolution rate, crystalline structure, or impurity levels over six months. An in vivo bioequivalence study demonstrated that the test formulation met the bioequivalence criteria, with 90% confidence intervals for the area under the curve and the C_max falling within the regulatory acceptance range. Conclusions: A miniaturized and commercially viable fexofenadine hydrochloride tablet was developed (44% weight reduction and 50% volume reduction compared to the marketed product). The organic solvent-based binder and porous carrier system improved manufacturing efficiency, stability, and solubility, thereby ensuring compliance with regulatory standards. These findings provide valuable insights into size reduction, solubility enhancement, and large-scale production strategies for the development of future pharmaceutical formulations. Full article

Background: Feeding and Eating Disorders (FEDs) are severe mental health conditions often emerging during childhood or adolescence, with rising prevalence. They are frequently associated with psychiatric and organic comorbidities, including anxiety symptoms and insomnia. Phytotherapy, particularly Passiflora incarnata L. Herba, has been suggested as a potential treatment option for anxiety and insomnia in youth. Methods: this is an observational and retrospective study that includes patients assessed in a third-level Italian Regional Centre for Feeding and Eating Disorders in Children and Adolescents between 1 January 2020 and 31 December 2023. Eligible patients had a confirmed diagnosis of a FED, along with either an anxiety or a sleep disorder. During follow-up, the clinical efficacy of Passiflora incarnata L. Herba was assessed using the Clinical Global Impression–Improvement scale (CGI-I). Comparative analyses were conducted by stratifying the sample based on the target symptoms (sleep disorders/insomnia and anxiety), FED subtype, and whether polytherapy was used. Results: this study includes 94 patients, with most diagnosed with anorexia nervosa (71.3%). Passiflora incarnata L. Herba was administered at a dosage of 200 mg (1–2 tablets for day). It was often combined with selective serotonin reuptake inhibitors (SSRIs) (56.5%), atypical antipsychotics (27.7%), or benzodiazepines (7.4%). Treatment was initiated for anxiety symptoms (75.5%) or insomnia (28.7%). No side effects were reported. Among patients with specific outcome data, 53.3% reported improvements in anxiety symptoms, and 45.4% reported improvements in insomnia. Conclusions: this is the first study to evaluate the use of Passiflora incarnata L. Herba for anxiety and insomnia in children and adolescents with FEDs. Our findings suggest that Passiflora incarnata L. Herba may serve as a well-tolerated adjunctive treatment, showing symptomatic improvement in up to 53% of the patients with data on treatment outcomes. Notably, 53.3% and 45.4% of participants, with specific outcome data, reported reduced anxiety and insomnia symptoms, respectively. Given its excellent safety profile and preliminary efficacy, Passiflora incarnata L. Herba may represent a promising alternative for patients with mild symptoms or for caregivers hesitant about conventional pharmacotherapy. Full article

Background/Objectives: Traditional Quality by Testing (QbT) strategies rely heavily on end-product testing and offer limited insight into how critical process parameters (CPPs) influence product quality. This increases the risk of variability and inconsistent outcomes. To overcome these limitations, this study aimed to implement a Quality by Design (QbD) approach to optimize the manufacturing process of clopidogrel tablets. Methods: A science- and risk-based QbD framework was applied to identify and prioritize key CPPs, intermediate critical quality attributes (iCQAs), and final product CQAs across key unit operations—pre-blending, dry granulation, post-blending, lubrication, and compression. Risk assessment tools and statistical design of experiments (DoE) were used to define proven acceptable ranges (PARs). Results: The study revealed strong correlations between CPPs and CQAs, allowing the definition of PARs and development of a robust control strategy. This led to improved manufacturing consistency, reduced variability, and enhanced process understanding. Conclusions: The QbD approach minimized reliance on end-product testing while ensuring high-quality outcomes. This study offers a novel QbD implementation tailored to the manufacturing challenges of clopidogrel tablets, providing a validated approach that integrates dry granulation CPPs with process-specific CQAs. These results demonstrate the value of QbD in achieving robust pharmaceutical manufacturing and meeting regulatory expectations. Full article

Background/Objectives: Dentifrice tablets are a new over-the-counter dentifrice form that are gaining global interest. The aim of this microbial study was to investigate the effectiveness of a dentifrice tablet (DT) containing nanohydroxyapatite (nHAP) to prevent tooth demineralization. Methods: 120 bovine tooth blocks were randomly assigned to four treatment groups (30/group): Nanohydroxyapatite DT (5% nHAP), placebo DT (Placebo), NaF toothpaste (1100 ppm Fluoride) and no-treatment (Control). Blocks were subjected to 7-day demineralization by plaque growth in a mixed-organism Microbial Caries Model. Toothpaste was made into slurry (1 toothpaste:3 water), while DT was thoroughly crushed and homogenized with water (1 tablet:3 water) to slurry. Both slurries were applied twice daily for 2 min on each occasion. Demineralization was assessed using Surface Microhardness (SMH) testing before and after plaque exposure. Change (ΔSMH) and percentage change (%∆SMH) in SMH (percentage demineralization [%Dem]), and % demineralization inhibition (%Dem-Inhibition) in each group were calculated. Intra-group (SMH) comparison (paired t-test) and intergroup (%∆SMH) comparison (ANOVA/Tukey’s test) were conducted (α = 0.05). Results: The paired t-test indicated a significant difference (p < 0.001) between pre-treatment and post-treatment SMH in all groups. The intergroup comparison based on their %Dem using ANOVA/Tukey’s test showed that Control (29.93 ± 5.58) had significantly (p < 0.05) higher %Dem than Placebo (22.81 ± 7.47, p < 0.05), nHAP (13.93 ± 11.31, p < 0.001) and Fluoride (14.44 ± 10.65, p < 0.001). The Placebo had significantly (p < 0.01) higher %Dem than nHAP and Fluoride. No significant difference between nHAP and Fluoride. Intergroup comparison based on their %Dem-Inhibition (calculated relative to the control) using ANOVA/Tukey’s test, nHAP (51.74 ± 40.05, p < 0.01) and Fluoride (50.56 ± 37.21, p < 0.05) had significantly higher %Dem-Inhibition than Placebo tablet (21.86 ± 5.55). No significant difference in %Dem-Inhibition between nHAP and Fluoride. Conclusions: The present study demonstrated that dentifrice tablets containing 5% nanohydroxyapatite are as effective as NaF toothpastes containing 1100 ppm fluoride in preventing tooth demineralization. Full article

(1) Background: Immersive virtual reality (IVR) has emerged as a promising non-pharmacological intervention to promote relaxation and improve emotional well-being in this population. (2) Methods: This crossover study evaluated the effects of IVR on anxiety and psychological well-being in a sample of eight participants with mild dementia attending a day-care center. Participants underwent two conditions: an experimental condition involving relaxing nature-based VR scenarios (Nature Treks VR) and a control condition using personalized YouTube videos on a tablet. Each condition lasted 12 sessions. Assessments included heart rate (HR), the I-PANAS-SF, the reduced State–Trait Anxiety Inventory (STAI-r), behavioral observations, and a subjective response questionnaire. (3) Results: A significant reduction in HR over time was found during IVR exposure, suggesting a calming physiological effect not observed in the control condition. While changes in PANAS and STAI-r scores were not statistically significant, the PANAS score improvement in the experimental condition approached statistical significance (p = 0.054) and was just below the minimal clinically important difference (MCID), suggesting a potentially meaningful trend. Behavioral responses were higher during YouTube sessions, likely due to personalized content. All participants rated the IVR experience positively on the subjective questionnaire, indicating high acceptability, though social desirability bias cannot be excluded. (4) Conclusions: IVR appears to be a feasible and acceptable intervention for individuals with dementia, warranting further investigation. Full article

Background/Objective: Cabotegravir (CAB), available as an oral tablet and as a long-acting (LA) nanosuspension for intramuscular injection, is approved as a combination therapy for the treatment, and as a monotherapy for the prevention, of HIV-1 infection. People living with HIV may receive multiple concomitant medications, with the associated risk of drug–drug interactions (DDIs). CAB is an inhibitor of OAT1/OAT3 renal transporters and a substrate of the UDP-glucuronosyltransferase enzymes UGT1A1 and 1A9, in vitro. While the effect of induction of UGT1A1/UGT1A9 on CAB exposure had been investigated in the clinic, the effect of the risk of DDIs with CAB via inhibition of these enzymes, or as an inhibitor of OAT1/OAT3 transporters, had not been evaluated. Methods: A physiologically-based pharmacokinetic (PBPK) model was developed and verified for orally dosed CAB to investigate the DDI risks associated with CAB, using a matrix approach to extensively qualify the PBPK platform and the substrates and/or inhibitors of either OAT1/OAT3 or UGT1A1/UGT1A9. The effect of uncertainties in in vitro inhibition values for OAT1/OAT3 was assessed via sensitivity analysis. Results: A mean increase of less than 25% in systemic exposure for OAT1/OAT3 substrates was predicted, with the potential for an increase of up to 80% based on the sensitivity analysis. On co-dosing with UGT1A1/UGT1A9 inhibitors, the predicted mean increase in CAB exposure was within 11%. Conclusions: PBPK modelling indicated that clinically relevant DDIs are not anticipated with OAT1/3 substrates or UGT1A1/1A9 inhibitors and CAB. With maximal exposure of the LA formulation of CAB being lower than the oral, the results of these simulations can be extrapolated to LA injectable dosing. Full article