Hedan tablet ameliorated non-alcoholic steatohepatitis by moderating NF-κB and lipid metabolism-related pathways via regulating hepatic metabolites.

Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease. If not treated, it can lead to liver damage, cirrhosis and even liver cancer. However, advances in treatment have remained relatively slow, and there is thus an urgent need to develop appropriate treatments. Hedan tablet (HDP) is used to treat metabolic syndrome. However, scientific understanding of the therapeutic effect of HDP on NASH remains limited. We used HDP to treat a methionine/choline-deficient diet-induced model of NASH in rats to elucidate the therapeutic effects of HDP on liver injury. In addition, we used untargeted metabolomics to investigate the effects of HDP on metabolites in liver of NASH rats, and further validated its effects on inflammation and lipid metabolism following screening for potential target pathways. HDP had considerable therapeutic, anti-oxidant, and anti-inflammatory effects on NASH. HDP could also alter the hepatic metabolites changed by NASH. Moreover, HDP considerable moderated NF-κB and lipid metabolism-related pathways. The present study found that HDP had remarkable therapeutic effects in NASH rats. The therapeutic efficacy of HDP in NASH mainly associated with regulation of NF-κB and lipid metabolism-related pathways via arachidonic acid metabolism, glycine-serine-threonine metabolism, as well as steroid hormone biosynthesis.

Tolerability of sublingual versus vestibular allergy immunotherapy tablet administration: A randomized pilot study.

BACKGROUND: Local application site reactions are common with sublingual allergy immunotherapy (AIT)-tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT-tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT-tablets compared with the sublingual route in adult subjects with AR/C. METHODS: Adults (n = 164) aged 18-65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment-related adverse events (TRAEs) during the first 28 days of treatment. RESULTS: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p = .16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p = .01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%). CONCLUSION: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT-tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT-tablets for AR/C.

An easy and green assay to determine albendazole and ivermectin in veterinary preparations by micellar liquid chromatography.

A procedure to determine albendazole and ivermectin in veterinary formulations, like tablet, bolus, oral suspensions, and injections by micellar liquid chromatography, has been developed. Sample preparation was a batch solid-to-liquid extraction in mobile phase, consisting of a stirring step (15 min), followed by ultrasonication (15 min) and filtration of the obtained supernatant, to reach a target concentration of 2 mg/L for both analytes. Using a mobile phase of 0.15 M sodium dodecyl sulfate-6% 1-pentanol buffered at pH 3 with a 0.01 M phosphate salt, running at 1 mL/min through a C18 column, both drugs were resolved in less than 10 min. Absorbance detection wavelength was 292 nm. Procedure was validated by the guidelines of the International Council on Harmonization in terms of specificity, calibration range (0.025-5 mg/L), trueness (97.8%-102.6%), precision (<2.2%), and system suitability. The method was found easy-to-handle, low cost, safe, green, and with high sample-throughput, thus useful for routine analysis. Therefore, it represents a valuable alternative for quality control of veterinary formulations. It was applied to samples of veterinary formulations purchased from local chemists and veterinarians, and label claims were inside the acceptance criteria (95%-105%).

Mechanism of Xing 9 ling tablet candy for alcoholic liver disease based on network pharmacology.

Xing 9 Ling tablet candy (X9LTC) effectively treats alcoholic liver disease (ALD), but its potential mechanism and molecular targets remain unstudied. We aimed to address this gap using network pharmacology. Furthermore, high-performance liquid chromatography (HPLC) and database analysis revealed a total of 35 active ingredients and 311 corresponding potential targets of X9LTC. Protein interaction analysis revealed PTGS2, JUN, and FOS as its core targets. Enrichment analysis indicated that chemical carcinogenesis-receptor activation, IL-17 and TNF signaling pathway were enriched by multiple core targets, which might be the main pathway of action. Further molecular docking validation showed that the core targets had good binding activities with the identified compounds. Animal experiments showed that X9LTC could reduce the high expression of ALT, AST and TG in the serum of ALD mice, alleviate the lesions in liver tissues, and reverse the high expression of PTGS2, JUN, and FOS proteins in the liver tissues. In this study, we established a method for the determination of X9LTC content for the first time, and predicted its active ingredient and mechanism of action in treating ALD, providing theoretical basis for further research.

Transdermal Delivery of Pramipexole Using Microneedle Technology for the Potential Treatment of Parkinson's Disease.

Parkinson's disease (PD) is a debilitating neurodegenerative disease primarily impacting neurons responsible for dopamine production within the brain. Pramipexole (PRA) is a dopamine agonist that is currently available in tablet form. However, individuals with PD commonly encounter difficulties with swallowing and gastrointestinal motility, making oral formulations less preferable. Microneedle (MN) patches represent innovative transdermal drug delivery devices capable of enhancing skin permeability through the creation of microconduits on the surface of the skin. MNs effectively reduce the barrier function of skin and facilitate the permeation of drugs. The work described here focuses on the development of polymeric MN systems designed to enhance the transdermal delivery of PRA. PRA was formulated into both dissolving MNs (DMNs) and directly compressed tablets (DCTs) to be used in conjunction with hydrogel-forming MNs (HFMNs). In vivo investigations using a Sprague-Dawley rat model examined, for the first time, if it was beneficial to prolong the application of DMNs and HFMNs beyond 24 h. Half of the patches in the MN cohorts were left in place for 24 h, whereas the other half remained in place for 5 days. Throughout the entire 5 day study, PRA plasma levels were monitored for all cohorts. This study confirmed the successful delivery of PRA from DMNs (Cmax = 511.00 ± 277.24 ng/mL, Tmax = 4 h) and HFMNs (Cmax = 328.30 ± 98.04 ng/mL, Tmax = 24 h). Notably, both types of MNs achieved sustained PRA plasma levels over a 5 day period. In contrast, following oral administration, PRA remained detectable in plasma for only 48 h, achieving a Cmax of 159.32 ± 113.43 ng/mL at 2 h. The HFMN that remained in place for 5 days demonstrated the most promising performance among all investigated formulations. Although in the early stages of development, the findings reported here offer a hopeful alternative to orally administered PRA. The sustained plasma profile observed here has the potential to reduce the frequency of PRA administration, potentially enhancing patient compliance and ultimately improving their quality of life. This work provides substantial evidence advocating the development of polymeric MN-mediated drug delivery systems to include sustained plasma levels of hydrophilic pharmaceuticals.

Visuomotor tracking strategies in children: associations with neurodevelopmental symptoms.

Children with neurodevelopmental disorders (NDDs) often display motor problems that may impact their daily lives. Studying specific motor characteristics related to spatiotemporal control may inform us about the mechanisms underlying their challenges. Fifty-eight children with varying neurodevelopmental symptoms load (median age: 5.6 years, range: 2.7-12.5 years) performed an interactive tablet-based tracking task. By investigating digit touch errors relative to the target's movement direction, we found that a load of neurodevelopmental symptoms was associated with reduced performance in the tracking of abrupt alternating directions (zigzag) and overshooting the target. In contrast, reduced performance in children without neurodevelopmental symptoms was associated with lagging behind the target. Neurodevelopmental symptom load was also associated with reduced flexibility in correcting for lateral deviations in smooth tracking (spiral). Our findings suggest that neurodevelopmental symptoms are associated with difficulties in motor regulation related to inhibitory control and reduced flexibility, impacting motor control in NDDs.

Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study.

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

Fine-tuning Fluorescence of Amlodipine Adopting on Blocking of Photoinduced Electron Transfer (PET): Application in Human Plasma.

Assessing medication adherence through the determination of antihypertensive drugs in biological matrices holds significant importance. Amlodipine (AP), a potent antihypertensive medication extensively prescribed for hypertensive patients, is particularly noteworthy in this context. This article aims to introduce a rapid, simple, improved sensitivity, and reproducibility in detecting AP in its pure form, tablet formulation, and spiked human plasma than the other reported methods. The proposed method utilizes a fluorescence approach, relying on the inhibition of the intramolecular photoinduced electron transfer (PET) effect of the lone pair of the N-atom in the primary amino moiety of AP. This inhibition is achieved by acidifying the surrounding medium using 0.2 M acetic acid. By blocking PET, the target AP drug is sensitively detected, at [Formula: see text] 423 nm over a concentration range 25-500 ng mL- 1 showcasing an exceptionally low quantitation limit of 1.41 ng mL- 1. Notably, this innovative technique was successfully applied to detect AP in its solid dosage form and spiked human plasma. Remarkably, matrix interference was found to be insignificant, underscoring the robustness and applicability of the established approach. The combination of speed, sensitivity, and reproducibility makes this method particularly suitable for assessing medication adherence in patients prescribed AP for hypertension.

Touch-screen automatisms in the digital age.

OBJECTIVE: To describe a novel set of gestural automatisms related to the use of digital screens on smartphones and tablets in patients with epilepsy. METHODS: Representative patients were selected from among those admitted to the Epilepsy Monitoring Unit at the Toronto Western Hospital between April 2016 and January 2020, and included if they exhibited automatisms clearly related to or mimicking digital device use. RESULTS: In total 5 patients were included, 4 female. All had temporal lobe epilepsy: 2 had left mesial temporal sclerosis and 3 had normal imaging. Nearly equal numbers of seizures began with right (5/9) and left (4/9) temporal onsets, with most automatisms occurring after seizure propagation to bilateral temporal involvement (6/9). Left-handed automatisms were most common (8/9). The majority of the automatisms (7/9) were perseverative on device usage prior to the seizure. CONCLUSION: Gestural automatisms appear related to the contemporary lived experience, culture, and habitual behaviour of patients with epilepsy. In the modern era, the use of smartphones and tablets are both common and habitual for many, and this case series shows that touch-screen automatisms may be added to the semiological panoply of temporal lobe seizures.

Rehabilitation activities with tablet (REACT) in Parkinson's disease.

INTRODUCTION: There is evidence to demonstrate that plasticity is "use-dependent" and that intensive practice may be necessary to modify neural organization. PURPOSE: The main aim of this work is to investigate the REACT usability, an innovative app, to assist People with Parkinson Disease (PwPD) at home. METHODS: A pilot study has been conducted enrolling 20 consecutive PwPD. Before home rehabilitation activities started, each patient received training on the REACT app and how to use the device and the services in daily practice. Motor and cognitive evaluations were administered to assign personalized exercises, tailored to patients' needs and potential. PwPD carried out REACT home program for 1 month, four times a week. The app included motor exercise and tutorial of activities of daily living (ADL) and functional cognitive stimulation. REACT-app usability was evaluated with the System Usability Scale (SUS). RESULTS: The results from SUS questionnaire were, on average, above the threshold of "good usability" (SUS score > 68), as reported in the literature. The 47% of PwPD that used the app rated the usability of the solution as "excellent." Almost all SUS items reached the reference benchmark (except items 4, 5, and 7). No adverse events occurred. CONCLUSIONS: REACT can be considered a useful and safe tool to support the continuity of care and treatment at home, in PwPD. Larger-scale trials are needed to validate the good acceptance and efficacy of home rehabilitation through technology applications.

Rapid analysis of the chemical constituents in Qiangli Dingxuan tablets using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Qiangli Dingxuan (QLDX) tablet is a widely recognized traditional Chinese medicine formula that has been extensively used in China for decades to treat vertigo, tinnitus, and dizziness owing to its outstanding therapeutic outcomes. However, the complexity of the chemical components in this tablet makes it challenging to separate and identify these components. This study presented an effective and sensitive strategy for the rapid separation and simultaneous structural identification of QLDX tablet components using ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry and the UNIFI platform. Based on retention times, accurate masses, fragment ions, related literature, and authentic standards, 119 compounds were identified or tentatively characterized; these included 9 iridoids, 12 lignans, 21 phenylpropanoids, 27 flavonoids, 7 phthalides, and 43 others. Among them, 36 were confirmed using reference standards. The representative compounds with various chemical structures were studied by analyzing their fragmentation patterns and characteristic ions. In conclusion, this study established a rapid approach for characterizing the chemical constituents in QLDX tablet. The proposed approach provides a basis for qualitative analysis and quality control in the manufacturing process and is beneficial for advancing investigations into the efficacy and mechanism of action of this tablet.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Multimodal home-based rehabilitation intervention after discharge from inpatient geriatric rehabilitation (GeRas): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Geriatric rehabilitation aims to maintain the functional reserves of older adults in order to optimize social participation and prevent disability. After discharge from inpatient geriatric rehabilitation, patients are at high risk for decreased physical capacity, increased vulnerability, and limitations in mobility. As a result, ageing in place becomes uncertain for a plethora of patients after discharge from geriatric rehabilitation and effective strategies to prevent physical decline are required. Collaboration between different health-care providers is essential to improve continuity of care after discharge from inpatient geriatric rehabilitation. The aim of this study is to evaluate the effectiveness of a multi-professional home-based intervention program (GeRas) to improve functional capacity and social participation in older persons after discharge from inpatient geriatric rehabilitation. METHODS: The study is a multicenter, three-arm, randomized controlled trial with a three-month intervention period. Two hundred and seventy community-dwelling older people receiving inpatient geriatric rehabilitation will be randomized with a 1:1:1 ratio to one of the parallel intervention groups (conventional IG or tablet IG) or the control group (CG). The participants of both IGs will receive a home-based physical exercise program supervised by physical therapists, a nutritional recommendation by a physician, and social counseling by social workers of the health insurance company. The collaboration between the health-care providers and management of participants will be realized within a cloud environment based on a telemedicine platform and supported by multi-professional case conferences. The CG will receive usual care, two short handouts on general health-related topics, and facultative lifestyle counseling with general recommendations for a healthy diet and active ageing. The primary outcomes will be the physical capacity measured by the Short Physical Performance Battery and social participation assessed by the modified Reintegration to Normal Living Index, three months after discharge. DISCUSSION: The GeRas program is designed to improve the collaboration between health-care providers in the transition from inpatient geriatric rehabilitation to outpatient settings. Compared to usual care, it is expected to improve physical capacity and participation in geriatric patients after discharge from inpatient geriatric rehabilitation. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00029559). Registered on October 05, 2022.

Associations between problem technology use, life stress, and self-esteem among high school students.

BACKGROUND: Adolescence is a critical period for development, with many risk factors resulting in long-term health consequences, particularly regarding mental health. The purpose of this study was to examine the associations between problem technology use, life stress, and self-esteem in a representative sample of adolescents residing in Ontario, Canada. METHODS: Self-reported data were obtained from a cross-sectional sample of 4,748 students (57.9% females) in grades 9 to 12 (mean age: 15.9 ± 1.3 years) who participated in the 2019 Ontario Student Drug Use and Health Survey. Problem technology use was measured using the 6-item Short Problem Internet Use Test, life stress was assessed using an item from the British Columbia Adolescent Health Survey and self-esteem was assessed using a global measure from the Rosenberg Self-Esteem Scale. Ordinal logistic regression models were adjusted for age, sex, ethnoracial background, subjective socioeconomic status, body mass index z-score, tobacco cigarette smoking, alcohol consumption and cannabis use. RESULTS: We found that 18.3% of participants reported symptoms of moderate-to-high problem technology use, although symptoms were more common in females than males (22% vs. 14.7%, respectively). Moderate-to-high problem technology use was associated with 2.04 (95% CI: 1.77-2.35) times higher odds of reporting high life stress and 2.08 (95% CI: 1.76-2.45) times higher odds of reporting low self-esteem compared to all other response options. CONCLUSIONS: Findings from this study show that problem technology use is strongly associated with higher life stress and lower self-esteem in adolescents. This study supports the importance of developing and implementing effective strategies that help to mitigate the adverse effects of problem technology use on adolescent mental health.

TECH preserves global cognition of older adults with MCI compared with a control group: a randomized controlled trial.

BACKGROUND: Cognitive training using touchscreen tablet casual game applications (apps) has potential to be an effective treatment method for people with mild cognitive impairment (MCI). AIMS: This study aimed to establish the effectiveness of 'Tablet Enhancement of Cognition and Health' (TECH), a novel cognitive intervention for improving/preserving cognition in older adults with MCI. METHODS: A single-blind randomized controlled trial with assessments pre-, post-, and at 6-month follow-up was conducted. TECH entailed 5 weeks of daily self-training utilizing tablet apps, facilitated by weekly group sessions. Global cognition was assessed by the Montreal Cognitive Assessment (MoCA), and specific cognitive components were assessed using WebNeuro computerized battery. Short Form Health Survey (SF-12) assessed health-related quality of life (HRQoL). Intention-to-treat analysis was conducted and the %change was calculated between pre-post and between pre-follow-up. Cohen's d effect size was also calculated. RESULTS: Sixty-one participants aged 65-89 years were randomly allocated to TECH (N = 31, 14 women) or to standard care (N = 30, 14 women). Pre-post and pre-follow-up MoCA %change scores were significantly higher in TECH than control (U = 329.5, p < .05; U = 294.5, p < .05) with intermediate effect size values (Cohen's d = .52, Cohen's d = .66). Forty percent of TECH participants versus 6.5% of control participants achieved a minimal clinical important difference in MoCA. Pre-post between-group differences for specific cognitive components were not found and HRQoL did not change. DISCUSSION AND CONCLUSIONS: TECH encouraged daily self-training and showed to preserve global cognition of older adults with MCI. The implementation of TECH is recommended for older adults with MCI, who are at risk for further cognitive decline.

Pharmacokinetic study of five components of Fuzheng Huayu tablets in healthy human plasma.

Natural medicines play a crucial role in clinical drug applications, serving as a primary traditional Chinese medicine for the clinical treatment of liver fibrosis. Understanding the in vivo metabolic process of the Fuzheng Huayu (FZHY) formula is essential for delving into its material basis and mechanism. In recent years, there has been a growing body of research focused on the mechanisms and component analysis of FZHY. This study aimed to examine the pharmacokinetics of FZHY in healthy volunteers following oral administration. Blood samples were collected at designated time intervals after the oral intake of 9.6-g FZHY tablets. A UHPLC-Q/Exactive method was developed to assess the plasma concentrations of five components post-FZHY ingestion. The peak time for all components occurred within 10 min. The peak concentration (Cmax ) values for amygdalin, schisandrin, and schisandrin A ranged from 3.47 to 28.80 ng/mL, with corresponding AUC(0-t) values ranging from 10.63 to 103.20 ng h/mL. For schisandrin B and prunasin, Cmax values were in the range of 86.52 to 229.10 ng/mL, and their AUC(0-t) values ranged from 375.26 to 1875.54 ng h/mL, indicating significant exposure within the body. These findings demonstrate that the developed method enables rapid and accurate detection and quantification of the five components in FZHY, offering a valuable reference for its clinical study.

Online preconcentration and determination of five alkaloids in Yangxinshi tablet by large-volume sample stacking and micelle to solvent stacking in cyclodextrin-modified electrokinetic chromatography.

The two-step preconcentration technique consisting of large-volume sample stacking (LVSS) and micelle to solvent stacking (MSS) in cyclodextrin-modified electrokinetic chromatography (CDEKC) was developed for the analysis of five cationic alkaloids in complex Chinese herbal prescriptions. Relevant parameters affecting separation and stacking performance were optimized separately. Under the optimal LVSS-MSS-CDEKC conditions, less analysis time and organic solvent were required, and the enhancement factors of analytes ranged from 12 to 15 compared with the normal CDEKC separation mode. Further, all validation results demonstrated good applicability and multiple alkaloids (epiberberine, dehydrocorydaline, jatrorrhizine, coptisine and berberine) in Yangxinshi tablet (YXST) have been simultaneously determined. This approach presents powerful potential for the determination of multiple components in complex preparations of Chinese medicine.

Pharmacokinetic study of multicomponent in Hong-Hua-Xiao-Yao tablet.

Hong-Hua-Xiao-Yao tablet (HHXYT) is attracting attention increasingly because of its use in treatment of mammary gland hyperplasia (MGH) and menopausal syndrome. However, its pharmacokinetics remains unclear. This study developed a sensitive and rapid method for simultaneous determination of 10 compounds of HHXYT in rat plasma by liquid chromatography-tandem mass spectrometry and to compare the pharmacokinetics of these compounds in MGH rats and sham operated rats. The linearity, accuracy, precision, stability and matrix effect were within acceptable ranges. This established method was successfully applied to a pharmacokinetics study of 10 compounds in sham operated and MGH rats. According to the results, the bioavailability of glycyrrhetinic acid was highest in MGH rats and sham operated rats. The mean residence times of glycyrrhetinic acid and glycyrrhetinic acid 3-O-glucuronide were higher than those of the other compounds while the mean residence time and half-life of liquiritin, isoliquiritin and paeoniflorin were lower. Some pharmacokinetic parameters of ormononetin, liquiritigenin, isoliquiritigenin, liquiritin, isoliquiritin, paeoniflorin, protocatechuic acid and senkyunolide I were significantly different between MGH rats and sham operated rats. This study elucidated the dynamic changes of multiple components in rats after oral administration of HHXYT systematically and comprehensively, which provided guidance for clinical application.

Factor Analysis of Patients Who Find Tablets or Capsules Difficult to Swallow Due to Their Large Size: Using the Personal Health Record Infrastructure of Electronic Medication Notebooks.

BACKGROUND: Understanding patient preference regarding taking tablet or capsule formulations plays a pivotal role in treatment efficacy and adherence. Therefore, these preferences should be taken into account when designing formulations and prescriptions. OBJECTIVE: This study investigates the factors affecting patient preference in patients who have difficulties swallowing large tablets or capsules and aims to identify appropriate sizes for tablets and capsules. METHODS: A robust data set was developed based on a questionnaire survey conducted from December 1, 2022, to December 7, 2022, using the harmo smartphone app operated by harmo Co, Ltd. The data set included patient input regarding their tablet and capsule preferences, personal health records (including dispensing history), and drug formulation information (available from package inserts). Based on the medication formulation information, 6 indices were set for each of the tablets or capsules that were considered difficult to swallow owing to their large size and concomitant tablets or capsules (used as controls). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of each index. The index demonstrating the highest area under the curve of the ROC was selected as the best index to determine the tablet or capsule size that leads to swallowing difficulties. From the generated ROCs, the point with the highest discriminative performance that maximized the Youden index was identified, and the optimal threshold for each index was calculated. Multivariate logistic regression analysis was performed to identify the risk factors contributing to difficulty in swallowing oversized tablets or capsules. Additionally, decision tree analysis was performed to estimate the combined risk from several factors, using risk factors that were significant in the multivariate logistic regression analysis. RESULTS: This study analyzed 147 large tablets or capsules and 624 control tablets or capsules. The "long diameter + short diameter + thickness" index (with a 21.5 mm threshold) was identified as the best indicator for causing swallowing difficulties in patients. The multivariate logistic regression analysis (including 132 patients with swallowing difficulties and 1283 patients without) results identified the following contributory risk factors: aged <50 years (odds ratio [OR] 1.59, 95% CI 1.03-2.44), female (OR 2.54, 95% CI 1.70-3.78), dysphagia (OR 3.54, 95% CI 2.22-5.65), and taking large tablets or capsules (OR 9.74, 95% CI 5.19-18.29). The decision tree analysis results suggested an elevated risk of swallowing difficulties for patients with taking large tablets or capsules. CONCLUSIONS: This study identified the most appropriate index and threshold for indicating that a given tablet or capsule size will cause swallowing difficulties, as well as the contributory risk factors. Although some sampling biases (eg, only including smartphone users) may exist, our results can guide the design of patient-friendly formulations and prescriptions, promoting better medication adherence.

A prediction model based on artificial intelligence techniques for disintegration time and hardness of fast disintegrating tablets in pre-formulation tests.

BACKGROUND: The pharmaceutical industry is continually striving to innovate drug development and formulation processes. Orally disintegrating tablets (ODTs) have gained popularity due to their quick release and patient-friendly characteristics. The choice of excipients in tablet formulations plays a critical role in ensuring product quality, highlighting its importance in tablet creation. The traditional trial-and-error approach to this process is both expensive and time-intensive. To tackle these obstacles, we introduce a fresh approach leveraging machine learning and deep learning methods to automate and enhance pre-formulation drug design. METHODS: We collected a comprehensive dataset of 1983 formulations, including excipient names, quantities, active ingredient details, and various physicochemical attributes. Our study focused on predicting two critical control test parameters: tablet disintegration time and hardness. We compared a range of models like deep learning, artificial neural networks, support vector machines, decision trees, multiple linear regression, and random forests. RESULTS: A 12-layer deep neural network, as a form of deep learning, surpassed alternative techniques by achieving 73% accuracy for disintegration time and 99% for tablet hardness. This success underscores its efficacy in predicting complex pharmaceutical factors. Such an approach streamlines the drug formulation process, reducing iterations and material consumption. CONCLUSIONS: Our findings highlight the deep learning potential in pharmaceutical formulations, particularly for tablet hardness prediction. Future work should focus on enlarging the dataset to improve model effectiveness and extend its application in pharmaceutical product development and assessment.