Search Results (49)

Background: The well-established biopharmaceutical advantages provided by nanosuspensions (NSs) make their conversion into solid oral dosage forms particularly appealing for improving both patients’ compliance and product stability. However, such a transformation continues to represent a significant challenge. Aim: This study explored manual wet granulation (WG) as a laboratory-scale strategy to transform an NS containing cinnarizine (CN) into granules, which were intended for direct administration or to be further processed. Methods: A range of polymers, characterized by different interaction mechanisms with aqueous fluids, were employed as carriers to incorporate the CN-containing NS during manual WG. The resulting granules were thoroughly characterized before tableting. Results: The NS-loaded products exhibited satisfactory physio-technological properties, effective nanocrystal redispersibility, high drug load efficiency, and expected in vitro performance. Moreover, they turned out to be suitable intermediates for mini-tablet production. Conclusions: Based on the data collected, WG turned out to be an effective lab-scale method for transforming an aqueous CN-containing NS into solid products (i.e., granules and mini-tablets), while preserving the starting properties of the drug nanocrystals. By adjusting formulation and process parameters, a variety of release kinetics were achieved, highlighting the value of the pursued approach, especially for early-stage screening of new drug candidates belonging to class II of the biopharmaceutical classification system. Full article

Background: Pantoprazole is a widely used proton pump inhibitor that is highly unstable under acidic conditions. This limits the performance of conventional formulations and typically requires enteric-coated dosage forms or alternative modified-release approaches. This study reports the development of polymeric matrix mini-tablets designed to protect pantoprazole during gastric exposure and to enable pH-dependent release under intestinal conditions. The formulations combine Eudragit^® S 100, a pH-dependent polymer, with HPMC, a hydrophilic matrix former that modulates drug release through hydration and swelling. Methods: Matrix mini-tablets were prepared by blending pantoprazole with selected excipients at optimised proportions and compressing the blends by direct compression using an eccentric tablet press. Powder blends and mini-tablets were characterised according to pharmacopoeial specifications. Analytical techniques—including High-Performance Liquid Chromatography (HPLC), Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Absorption Spectroscopy (FT-IR), Powder X-Ray Diffraction (PXRD), and Scanning Electron Microscopy (SEM)—were employed to evaluate drug content uniformity, thermal behaviour, and potential drug–excipient interactions. In vitro dissolution studies were performed under sequential pH conditions, and the release kinetics were analysed using mathematical models. Results: Dissolution testing identified formulations F2 and F6 as providing the most suitable gastro-resistant performance in the acidic stage, together with sustained release up to 24 h. Kinetic modelling supported formulation-dependent release mechanisms, and multivariate analysis (PCA) highlighted relationships between physico-mechanical attributes and drug-release behaviour. Conclusions: The proposed matrix system shows potential as a robust, coating-free platform for the modified delivery of acid-labile drugs using direct compression, simplifying manufacturing. These findings support the rational design of oral modified-release formulations based on polymeric matrices. Full article

With the rapid advancement of technology in recent years, signatures on contracts and documents have increasingly shifted from traditional handwritten forms on paper to digital handwritten signatures executed on devices (hereafter referred to as digital tablets). This transition introduces new challenges for forensic document examination due to the differences in writing instruments. According to the European Network of Forensic Science Institutes (ENFSI), a Digital Capture Signature (DCS) refers to data points captured during the writing process on digital devices such as tablets, smartphones, or signature pads. In addition to retaining the visual image of the signature, DCS provides more information previously unavailable, including pen pressure, stroke order, and writing speed. These features possess potential forensic value and warrant further study and evaluation. This study employs three devices—Samsung Galaxy Tab S10, Apple iPad Pro, and Apple iPad Mini—together with their respective styluses as experimental tools. Using custom-developed handwriting capture software for both Android and iOS platforms, we simulated signature-writing scenarios common in the financial and insurance industries. Thirty participants were asked to provide samples of horizontal Chinese, English, and number writings (FUJ-IRB NO: C113187), which were subsequently normalized and segmented into characters. For analysis, we adopted distance-based time-series alignment algorithms (FastDTW and SC-DTW) to match writing data across different instances (intra- and inter-writer). The accumulated distances between corresponding data points, such as coordinates and pressure, were used to assess handwriting stability and to study the differences between same-writer and different-writer samples. The findings indicate that preprocessing through character centroid alignment, followed by the analysis, substantially reduces the average accumulated distance of handwriting. This procedure quantifies the stability of an individual’s handwriting and enables differentiation between same-writer and different-writer scenarios based on the distribution of DCS distances. Furthermore, the use of styluses provides more precise distinctions between same- and different-writer samples compared with direct finger-based writing. In the context of rapid advancements in artificial intelligence and emerging technologies, this preliminary study aims to contribute foundational insights into the forensic application of digital signature examination. Full article

Background/Objectives: Mini-tablets have gained popularity as a pediatric dosage form owing to their high acceptability. Since 2022, the Showa University Hospital has prescribed acetylsalicylic acid (ASA) mini-tablets to pediatric patients with Kawasaki disease (KD). In this study, we investigated the real-world, at-home administration status of ASA mini-tablets in pediatric patients with KD. Methods: This retrospective study included 14 pediatric patients with KD on ASA mini-tablet therapy between November 2022 and October 2024. Medication administration completeness, mood changes during administration, administration patterns, beverages consumed, and swallowing-related events were analyzed. Associations between changes in the administration pattern or beverage consumption and swallowing events or mood changes were evaluated. Serious adverse events and coronary artery aneurysms were assessed using medical records. Results: Patients were prescribed ASA mini-tablets for a mean duration of 60.9 days. No serious adverse events or coronary aneurysms were observed. Among the 679 medication records, 5 swallowing-related events were identified. No mood changes following administration were observed in >90% of cases. The mood worsened to “Bad” once, with no further deterioration. The “All at once” administration pattern occurred in 64% of occasions across 12 patients (age: 9–79 months). Patients aged <3 years used medication-assisted jelly, whereas older patients mostly used water. Conclusions: ASA mini-tablets can be safely administered at home with minimal swallowing problems. Patients completed full doses irrespective of tablet number, age, administration pattern, or beverage, supporting ASA mini-tablets as an acceptable dosage form option for ASA in KD. Full article

Background/Objectives: The COVID-19 pandemic limited access to in-person physiotherapy, raising concerns about post-operative rehabilitation outcomes. This prospective observational study, without a control group, evaluated whether a self-rehabilitation protocol following a mini-open Learjet procedure influenced short-term clinical outcomes in active military personnel. Materials and Methods: We prospectively enrolled 18 patients (19 shoulders) undergoing mini-open Latarjet between May and October 2020. Patients performed a standardized self-rehabilitation protocol starting on the first post-operative day, with progressive range-of-motion (ROM) exercises added at two weeks. Pain was assessed using the Visual Analog Scale (VAS), ROM was recorded at each follow-up, complications were noted, and patient satisfaction was evaluated at 12 weeks. Results: A total of eighteen patients were prospectively enrolled in the study. At 12 weeks, mean VAS decreased from 1.2 ± 0.6 at week 1 to 0 at week 4 onward. The mean drug consumption was 2.5 ± 0.7 tablets/day only for the first week. Mean assisted forward flexion improved from 155° ± 10° at week 1 to 180° in all patients by week 4. External rotation reached 60° ± 5°at 4 weeks, 75° ± 4° at 8 weeks, and 80° ± 3°at 12 weeks, with no deficits compared to the contralateral side. Internal rotation improved to the T7 level by week 8 and remained stable in week 12. No complications, recurrent instability, or graft displacements were reported. Patient satisfaction at 12 weeks was assessed using a 0–10 numeric rating scale, with a mean score of 9.5 ± 0.4. Conclusions: Implementation of a self-rehabilitation protocol after mini-open Latarjet surgery was associated with favorable short-term outcomes in young military patients, including early recovery, high satisfaction, and absence of complications. Further validation of these findings will require larger, rigorously controlled studies. Full article

Pediatric drug delivery presents unique challenges due to physiological and pharmacological differences across age groups, requiring specialized formulation approaches beyond simple dose adjustments of adult medications. This review synthesizes recent advances in polysaccharide-based pediatric drug delivery and highlights novel findings that may accelerate clinical translation. It summarizes how chitosan, alginate, hyaluronic acid, dextran, modified starches, and other polysaccharides are engineered into nanoparticles, hydrogels, films, and orodispersible/mini-tablet formulations to improve stability, bioavailability, taste masking, and controlled release across neonates to adolescents. These systems can accommodate developmental variations in absorption, distribution, metabolism, and excretion processes across pediatric subpopulations, with particular emphasis on oral and alternative administration routes. Evidence supporting unexpectedly high acceptability of mini-tablets, successful integration of modified polysaccharides in 3D-printed personalized low-dose therapies, and the emergence of blood–brain barrier-penetrating and RGD-functionalized polysaccharide nanocarriers for pediatric oncology are emphasized as novel, clinically relevant trends. This review also addresses regulatory considerations, safety profiles, and future perspectives. By integrating developmental insights with innovative formulation strategies, polysaccharide polymers offer promising solutions to improve medication adherence, safety, and efficacy across the pediatric age spectrum. Full article

Background: The increasing prevalence of dementia and mild cognitive impairment (MCI) underscores the need for reliable and scalable digital cognitive screening tools. Although several studies have validated smartphone- or tablet-based assessments in community-dwelling older adults, few have examined their reliability in clinical populations with neurological disorders. This study aimed to evaluate the intra- and inter-rater reliability and agreement between the traditional paper-based Mini-Mental State Examination-Korean version (MMSE-K) and a tablet PC-based MMSE-K kit in patients with neurologic diseases undergoing rehabilitation. Methods: A total of 32 patients with neurological conditions—including stroke-related, encephalitic, and myelopathic disorders—participated in this study. Two occupational therapists (OT-A and OT-B) independently administered both the paper- and tablet-based MMSE-K versions following standardized digital instructions and fixed response rules. The intra- and inter-rater reliabilities of the tablet version were analyzed using intraclass correlation coefficients (ICCs) with a two-week retest interval, while Bland–Altman plots were used to assess agreement between the paper and tablet scores. Results: The tablet-based MMSE-K showed strong agreement with the paper-based version (r = 0.969, 95% CI 0.936–0.985, p = 1.05 × 10⁻¹⁹). Intra- and inter-rater reliabilities were excellent, with ICCs ranging from 0.89 to 0.98 for domain scores and 0.98 for the total score, and the Bland–Altman plots showing acceptable agreement without systematic bias. Minor variability was observed in the Attention/Calculation and Comprehension/Judgment domains. Conclusions: The tablet PC-based MMSE-K kit provides a standardized, examiner-independent, and reliable alternative to the traditional paper version for assessing cognitive function in patients with neurologic diseases. These findings highlight the tool’s potential for clinical deployment in hospital and rehabilitation settings, bridging the gap between traditional paper assessments and automated digital screening. Future multicenter studies with larger, disease-diverse cohorts are warranted to establish normative data and validate its diagnostic precision for broader clinical use. Full article

Background/Aims: This preference study aimed to identify the maximum number of mini-tablets of two different sizes that children and adolescents would be willing to take, and parents, nurses, and pediatricians would be willing to administer to children and adolescents. Methods: A total of 336 participants (24 per cohort) were stratified into 14 cohorts: Acutely and chronically sick children/adolescents aged 6–<12 years (y) and 12–<18 y, parents of acutely and chronically sick children/adolescents aged 0–<2 y, 2–<6 y, 6–<12 y, and 12–<18 y, nurses, and pediatricians. After participants were shown seven different numbers of 2 and 3 mm mini-tablets, they were asked to assess the maximum number acceptable for short-, middle-, and long-term treatment using cohort-specific questionnaires. Results: Within all groups and treatment durations, the specified maximum accepted number of 2 mm mini-tablets was higher than the number of 3 mm mini-tablets. The maximum number of mini-tablets acceptable to the participants increased with increasing age of the children and ranged from 40–500 (30–400) for the 2 mm (3 mm) mini-tablets. With increasing duration of treatment, a lower maximum number of mini-tablets was considered tolerable. Chronically sick children were willing to take higher numbers of mini-tablets than acutely sick children. The maximum accepted numbers of mini-tablets specified by pediatric patients, parents, and healthcare professionals were similar for each age group; however, pediatricians consistently specified slightly higher numbers of mini-tablets than parents and nurses. Conclusions: The study demonstrated that even a high number of mini-tablets would be well-accepted by children during middle- or long-term treatment. Full article

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. Full article

Background/Objectives: Mini-tablets are a novel pediatric dosage form designed to mask drug taste and facilitate easier administration. This study aimed to assess the feasibility and acceptability of uncoated acetylsalicylic acid (ASA) mini-tablets in Japanese children with Kawasaki disease (KD) aged 1 to 4 years. Methods: A retrospective case series study of three pediatric patients with KD treated with ASA mini-tablets (3 mm diameter, 10 mg) was conducted at Showa University Hospital. ASA mini-tablets were administered for up to 68 days. Caregivers recorded daily medication intake and any issues in medication logbooks. Results: All three patients successfully took 100% of the prescribed doses. No adverse events related to mini-tablet ingestion were reported. Patients could take the mini-tablets for extended periods (63–68 days) as part of their KD treatment. Conclusions: ASA mini-tablets showed potential acceptability in this small cohort of pediatric patients with KD. This study represents the first investigation into the acceptability of mini-tablets containing active ingredients in Japanese pediatric patients. Larger studies are needed to confirm these findings and evaluate long-term safety and efficacy. Full article

Upper-limb paresis is one of the main complications after stroke. It is commonly associated with impaired wrist-extension function. Upper-limb paresis can place a tremendous burden on stroke survivors and their families. A novel soft-actuator device, the Balonikotron, was designed to assist in rehabilitation by utilizing a balloon mechanism to facilitate wrist-extension exercises. This pilot study aimed to observe the functional changes in the paralyzed upper limb and improvements in independent and cognitive functions following a 4-week regimen using the device, which incorporates a multimedia tablet application providing audiovisual feedback. The device features a cardboard construction with a hinge at wrist level and rails that guide hand movement as the balloon inflates, controlled by a microcontroller and a tablet-based application. It operates on the principle of moving the hand at the wrist by pushing the palm upwards through a surface actuated by a balloon. A model was developed to describe the relationship between the force exerted on the hand, the angle on hinge, the pressure within the balloon, and its volume. Experimental validation demonstrated a Pearson correlation of 0.936 between the model’s force predictions and measured forces, supporting its potential for real-time safety monitoring by automatically shutting down when force thresholds are exceeded. A pilot study was conducted with 12 post-stroke patients (six experimental, six control), who participated in a four-week wrist-extension training program. Clinical outcomes were assessed using the Fugl–Meyer Assessment for the Upper Extremity (FMA-UE), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), wrist Range of Motion (ROM), and Barthel Index (BI). Statistically significant results were obtained for the Barthel index (p < 0.05) and FMA-UE, indicating that the experimental use of the device significantly improved functional independence and self-care abilities. The results of our pilot study suggest that the Balonikotron device, which uses the principles of mirror therapy, may serve as a valuable adjunct to conventional rehabilitation for post-stroke patients with hemiparetic hands (BI p = 0.009, MMSE p = 0.151, mRS p = 0.640, FMA-UE p = 0.045, MOCA p = 0.187, ROM p = 0.109). Full article

Background/Objectives: Following tooth extraction, resveratrol (RSV) can support healing by reducing inflammation and microbial risks, though its poor solubility limits its effectiveness. This study aims to develop a solid nanocomposite by embedding RSV in lipid nanoparticles (mLNP) within a hydrophilic matrix, to the scope of improving local delivery and enhancing healing. Hydroxyapatite (HXA), often used as a bone substitute, was added to prevent post-extraction alveolus volume reduction. Methods: The mLNP-RSV dispersion was mixed with seven different polymers in various mLNP/polymer ratios. Following freeze-drying, the powders were redispersed, and the resulting dispersions were tested by DLS experiments. Then, the best two nanocomposites underwent extensive characterization by SEM, XRD, FTIR, Raman spectroscopy, and thermal analysis as well as in vitro partitioning studies aimed at verifying their ability to yield the mLNP-RSV from the hydrophilic matrix to a lipophilic tissue. The characterizations led to identify the best nanocomposite, which was further combined with HXA to obtain hybrid nanocomposites, further evaluated as pharmaceutical powders or in form of mini-tablets. Results: PEG-based nanocomposites emerged as optimal and, following HXA insertion, the resulting powders revealed adequate bulk properties, making them useful as a pharmaceutical intermediate to produce ≈59 mm³ mini-tablets, compliant with the post-extraction socket. Moreover, they were proven ex vivo to be able to promote RSV and GA accumulation into the buccal tissue over time. Conclusions: The here-proposed mini-tablet offers an innovative therapeutic approach for alveolar wound healing promotion as they led to a standardized dose administration, while being handy and stable in terms of physical solid identity as long as it takes to suture the wound. Full article

Introduction: In recent years, the integration of robotic systems into various aspects of daily life has become increasingly common. As these technologies continue to advance, ensuring user-friendly interfaces and seamless interactions becomes more essential. For social robots to genuinely provide lasting value to humans, a favourable user experience (UX) emerges as an essential prerequisite. This article aimed to evaluate the usability of the MINI robot, highlighting its strengths and areas for improvement based on user feedback and performance. Materials and Methods: In a controlled lab setting, a mixed-method qualitative study was conducted with ten individuals aged 65 and above diagnosed with mild dementia (MD) and mild cognitive impairment (MCI). Participants engaged in individual MINI robot interaction sessions, completing cognitive tasks as per written instructions. Video and audio recordings documented interactions, while post-session System Usability Scale (SUS) questionnaires quantified usability perception. Ethical guidelines were followed, ensuring informed consent, and the data underwent qualitative and quantitative analyses, contributing insights into the MINI robot’s usability for this demographic. Results: The study addresses the ongoing challenges that tasks present, especially for MD individuals, emphasizing the importance of user support. Most tasks require both verbal and physical interactions, indicating that MD individuals face challenges when switching response methods within subtasks. These complexities originate from the selection and use of response methods, including difficulties with voice recognition, tablet touch, and tactile sensors. These challenges persist across tasks, with individuals with MD struggling to comprehend task instructions and provide correct answers and individuals with MCI struggling to use response devices, often due to the limitations of the robot’s speech recognition. Technical shortcomings have been identified. The results of the SUS indicate positive perceptions, although there are lower ratings for instructor assistance and pre-use learning. The average SUS score of 68.3 places device usability in the “good” category. Conclusions: Our study examines the usability of the MINI robot, revealing strengths in quick learning, simple system and operation, and integration of features, while also highlighting areas for improvement. Careful design and modifications are essential for meaningful engagement with people with dementia. The robot could better benefit people with MD and MCI if clear, detailed instructions and instructor assistance were available. Full article

Various rapid propagation strategies have been discovered, which has facilitated large-scale plant reproduction and cultivar development. These methods, in many plant species, are used to rapidly generate large quantities (900 mini-tubers/m²) of high-quality propagule (free from contamination) at a relatively low cost in a small space. They are also used for plant preservation. This review article aims to provide potential applications for regeneration and clonal propagation. Plant propagation using advanced agrotechnology, such as aeroponics, is becoming increasingly popular among academics and industrialists. The advancement of asexual aeroponic propagation has been achieved through advancements in monitoring and control systems using IoT and smart sensor technology. New sensor technology systems have gained substantial interest in agriculture in recent years. It is used in agriculture to precisely arrange various operations and objectives while harnessing limited resources with minimal human intervention. Modern intelligent technologies and control systems simplify sensor data collection, making it more efficient than manual data collection, which can be slow and prone to errors. Specific ambient variables like temperature, humidity, light intensity, stock solution concentrations (nutrient water), EC (electrical conductivity), pH values, CO₂ content, and atomization parameters (frequency and interval) are collected more effectively through these systems. The use of intelligent technologies provides complete control over the system. When combined with IoT, it aids in boosting crop quality and yield while also lowering production costs and providing data directly to tablets and smartphones in aeroponic propagation systems. It can potentially increase the system’s productivity and usefulness compared to the older manual monitoring and operating methods. Full article

Terahertz spectroscopy systems, which integrate terahertz sources and detectors, have important applications in many fields such as materials science and security checking. Based on highly sensitive frequency up-conversion detection, large dynamic range spectral measurements in a terahertz region are reported. Our system realized the detection sensitivity at a 10 aJ level with a 2-(3-(4-hydroxystyryl)-5,5-dime-thylcyclohex-2-enylidene) malononitrile (OH1) crystal and a dynamic range up to seven orders. Based on this system, we verified the validity of the spectral measurement with tests which were conducted on monohydrate glucose, anhydrous glucose and mixed tablet samples with a thickness of 0.8 mm in 1~3 THz, respectively. Also, a mini coppery elbow tube with an inner diameter of 1 mm was used for the transmission of a terahertz wave to simulate some strip biological tissue samples. By allowing terahertz to transmit through this tube filled with 0.5 g glucose powder, we successfully obtained the absorption spectrum with a minimum transmittance at the absorption peak in the order of 10⁻⁴. Full article