Tablet weight variability is a critical quality attribute in solid oral dosage manufacturing. Despite its practical importance, existing approaches for relating tablet weight variability to formulation and tooling parameters remain largely empirical. In this work, we develop a first-principles statistical model that predicts tablet weight variability as a function of tablet weight, punch diameter, and blend particle size distribution. The model builds on particle-sampling theory used in content uniformity analysis and explicitly incorporates tooling geometry and particle size distribution to describe the statistical origins of weight variability. Experimental data spanning multiple punch diameters, tablet weights, and particle sizes were generated using Suglets® spheres to validate the model. The predicted scaling relationships with tablet mass, punch diameter, and particle size were independently confirmed, and a single scaling factor was sufficient to capture the full dataset with high accuracy (R² ≈ 0.93, normalized RMSE ≈ 0.05). Model robustness was demonstrated using bootstrap resampling and a leave-one-out cross-validation scheme. The framework was further applied to quantitatively assess commonly used empirical relationships between particle size and tooling dimensions and to construct design maps illustrating their combined effects on tablet weight variability. This work provides a predictive framework for understanding and controlling tablet weight variability.
Oral hygiene is a crucial aspect of children's healthcare, and the effectiveness of plaque removal is one of the key indicators of good oral health. Traditional toothpaste and toothbrushes have been the cornerstone of oral hygiene practices; however, recent innovations like chewable toothpaste tablets offer a promising alternative. This study aims to compare the plaque removal efficacy and acceptance of a chewable toothpaste tablet with conventional toothpaste using both conventional and powered toothbrushes in children aged 8-12 years. By investigating the effectiveness, acceptability, and user experience of these different oral hygiene methods, the current research seeks to provide valuable insights for parents, caregivers, and healthcare professionals looking to promote optimal oral health in children. The study included 100 participants divided into four groups as follows-group A: conventional toothpaste (Dentoshine) and conventional toothbrush (Oral-B Kids Soft Manual Toothbrush), group B: conventional toothpaste (Dentoshine) and powered toothbrush (Oral-B Pro-Health Jr Battery Powered Kids Automatic Toothbrush), group C: chewable toothpaste tablet (Teeth-a-bit) and conventional toothbrush (Oral-B Kids Soft Manual Toothbrush), and group D: chewable toothpaste tablet (Teeth-a-bit) and powered toothbrush (Oral-B Pro-Health Jr Battery Powered Kids Automatic Toothbrush).The participants of these four groups were advised to use the respective oral hygiene aids for 4 weeks. The oral hygiene index-simplified (OHI-S) and gingival index (GI) scores were recorded before and after 4 weeks, and the results were evaluated and analyzed using SPSS software 22.0. Within the limitation of the study, it was seen that the chewable toothpaste tablet and conventional toothpaste using conventional toothbrush and powered toothbrush were equally effective in plaque removal. The findings suggest that the conventional and electric toothbrush with conventional toothpaste and chewable toothpaste tablet both have similar plaque removal efficiency. However, further comprehensive research is warranted to validate these results, as this study was conducted with a limited sample size. Introducing innovative oral care methods at a young age can foster a lifelong commitment to excellent oral hygiene, leading to improved overall health and well-being. Desai SS, Reddy GR, Varma SA, et al. A Comparative Evaluation of Plaque Removal Efficacy of a Chewable Toothpaste Tablet with Conventional Toothpaste Using Conventional Toothbrush and Powered Toothbrush in Children of Age-group 8-12 Years. Int J Clin Pediatr Dent 2026;19(4):464-469.
Albendazole is a broad-spectrum anthelminthic extensively used in clinical settings and national deworming programs. It is the cornerstone of the preventive chemotherapy for soil-transmitted helminthiases prevalent in low-resource settings. The high proliferation of albendazole generic products, with poor post-market surveillance capacity in the low- and middle-income countries, poses dire risk of substandard and falsified medicines, which may predispose patients to treatment failures, adverse drug reactions, morbidity, and mortality, with consequent loss of public confidence in healthcare systems. This study aimed to determine the quality and pharmaceutical equivalence of albendazole 400 mg tablet brands marketed in Nairobi, Kenya. A cross-sectional analytical study was conducted on seven albendazole 400 mg tablet brands purchased from pharmacy outlets in Nairobi. Tests for identity, friability, hardness, disintegration, assay, uniformity of weight, and dissolution were conducted as specified in the United States, British and International Pharmacopoeias. Dissolution profiles of generic albendazole tablet brands and the innovator brand (Zentel) were compared using model independent fit factors f1 and f2, and the dissolution efficiency (DE). Data was captured and analyzed using Microsoft Excel 2021, and reported as means, relative standard deviations, and percentages. All the seven albendazole 400 mg tablet brands complied with compendial specifications for identity, friability, hardness, assay, and uniformity of weight. However, two brands (EK5 and EK6) did not comply with the disintegration test and consequently demonstrated extremely poor dissolution, having released <6% of labelled albendazole content at 60 minutes with DE < 5%. Only two brands (EK4 and EK2) exhibited dissolution profiles that approximated the innovator brand (f2 > 50, f1 < 10) and could be used interchangeably, while the other two (EK3 and EK7) had intermediate drug release. While all tested albendazole 400 mg tablet brands complied with basic pharmacopoeial specifications for quality, dissolution testing revealed significant nonequivalence, with only three (42.86%) of the seven brands being pharmaceutically equivalent. Poor dissolution of majority (57.14%) of albendazole tablet brands portends therapeutic insufficiency and development of drug resistance, reinforcing the need for stringent post-market surveillance to safeguard public health.
Brigatinib is an ALK tyrosine kinase inhibitor approved for the treatment of adults with ALK+ non-small cell lung cancer. The commercial formulation of brigatinib is an immediate-release (IR) tablet; however, an oral solution was developed for use in pediatric studies for patients unable to swallow solid oral dosage forms. This randomized, two-period, two-sequence crossover study assessed the relative bioavailability of the oral solution versus the IR tablet in healthy adults. Twelve participants received a single 90-mg brigatinib dose as the oral solution or IR tablet on Day 1 of the first study period, followed by the alternate formulation on Day 1 of the second study period. Brigatinib pharmacokinetic parameters were similar following administration of the oral solution and IR tablet. The geometric least-square mean ratios (oral solution vs IR tablet) for Cmax (0.92), AUClast (0.96), and AUCinf (0.96) were close to 1.00 with 90% confidence intervals within the bioequivalence range of 0.80-1.25 (Cmax, 0.87-0.98; AUClast, 0.88-1.04; AUCinf, 0.89-1.03). Treatment-emergent adverse events were reported in three participants (25%), with the most frequent being cough (17%). These results indicate that the oral solution and IR tablet can be used interchangeably without dose adjustment in pediatric studies.
The New World screwworm (NWS), Cochliomyia hominivorax, is an obligate ectoparasite whose larvae cause severe myiasis, leading to extensive tissue damage and potentially fatal outcomes in dogs if not promptly treated. Dogs play an important epidemiological role in maintaining and disseminating infestations, requiring rapid and effective therapeutic options. Fipronil (FIP) is an insecticide widely used for ectoparasite control with systemic efficacy after oral administration to different species, representing a promising alternative for treating canine myiasis. This study describes the development of molded FIP chewable tablets, the evaluation of its pharmacokinetics, and its clinical efficacy in dogs naturally infested by NWS larvae. For pharmacokinetic assessment, eight healthy dogs received a single dose (6 mg/kg) chewable tablet, and blood samples were collected at selected time points to determine plasma concentrations. To assess efficacy, eight dogs naturally infested with NWS larvae received the same dosage. Larvae expelled from hosts were collected over 24 h, after which remaining larvae were mechanically removed. The tablets met established quality control criteria. Following oral administration, FIP was rapidly absorbed, being detectable 30 min after treatment and reaching a maximum plasma concentration (Cmax) of 3126.5 ± 1269.5 ng/mL at 2.2 ± 0.94 h (Tmax). Clinically, larval expulsion increased progressively from 2 h onward, reaching 97.8% effectiveness within 24 h. No live larvae were observed in the lesions at the end of evaluation, resulting in 100% overall effectiveness. These findings demonstrate that the FIP chewable tablet is a viable alternative option for treating canine myiasis from NWS larval infestation.
Apremilast is a pioneering oral selective phosphodiesterase-4 inhibitor for the treatment of psoriasis. To evaluate and compare the pharmacokinetic properties and bioavailability of apremilast tablets manufactured by Nanjing Haijing Pharmaceutical Company (Nanjing, China) with apremilast tablets certified by Celgene Europe B.V. (Utrecht, The Netherlands), we conducted a randomized, open-label, single-dose, two-period, crossover study in healthy Chinese subjects under fasted and fed conditions. Eligible subjects were randomly assigned to receive reference or test apremilast tablets in the first treatment period and the other formulation in the second period. Serial blood samples were collected for pharmacokinetic analysis. Adverse events were recorded. A total of 28 healthy subjects were enrolled in the fasting cohort and 36 subjects in the fed cohort. The 90% confidence intervals of the geometric mean ratios of the test to reference formulations were 91.56 - 106.18% for Cmax, 96.08 - 108.18% for AUC0-t, and 96.02 - 107.67% for AUC0-∞ in the fasting cohort, and 95.15 - 107.05% for Cmax, 105.13 - 113.45% for AUC0-t, and 104.80 - 111.91% for AUC0-∞in the fed cohort, all of which were within the bioequivalence range of 80.00 - 125.00%. There were no serious adverse events. The results showed that the test and reference apremilast tablets were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions.
Deutetrabenazine is approved as a treatment in adults for tardive dyskinesia and chorea associated with Huntington's disease. A once-daily tablet (Austedo XR® Teva) was recently approved in addition to the twice-daily tablet (Austedo®), and studies were conducted to evaluate dosage strength proportionality and food effect of the once-daily formulation. In a randomized cross-over study of dosage strength proportionality, healthy participants (n = 116) received single doses of the once-daily deutetrabenazine formulation and a power model was fitted to describe the relationship between dose and pharmacokinetic parameters (maximum observed plasma drug concentration [Cmax], area under the plasma concentration-time curve from time 0 to 36 h [AUC0-36h], and area under the plasma concentration-time curve from time 0 extrapolated to infinity [AUC0-∞]). In the second cross-over study, a single 24-mg dose of the once-daily formulation was given in fasted and fed conditions to healthy participants (n = 84) and the effect of food was evaluated by constructing 90% confidence intervals of the geometric mean ratios for Cmax, AUC0-t, and AUC0-∞. RESULTS: Dosage strength proportionality for the once-daily formulation was demonstrated for the dosage strengths 6 mg, 12 mg, and 24 mg; and across the approved dose range up to 48 mg for the pharmacokinetic parameters of all analytes (deutetrabenazine, and metabolites; deuterated alpha-dihydrotetrabenazine and beta-dihydrotetrabenazine), individually and as a sum). In the food effect study, the Cmax, AUC0-t, and AUC0-∞ geometric mean ratios for deutetrabenazine and deuterated metabolites all fell within the 90% confidence interval of 80-125. The once-daily formulation of deutetrabenazine exhibited dosage strength proportional pharmacokinetics for doses up to 48 mg and there was no observed effect of food.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, often associated with significant disability. As treatment options increase, comparative effectiveness data for disease-modifying therapies (DMTs) are essential. This study evaluated treatment switching, healthcare resource utilization, and cost outcomes among US patients with MS (PwMS) treated with cladribine tablets (CladT) vs. fingolimod (FTY), dimethyl fumarate (DMF), and teriflunomide (TER) during a 4-year follow-up period. This retrospective study used claims data from the Komodo Healthcare Map (4/1/2018-3/31/2024). Adult PwMS with ≥ 1 claim for CladT, FTY, DMF, and TER were included. Index date was the first claim date for the respective DMT. Continuous enrollment for 12 months pre-index and 48 months post-index was required. Cohorts were balanced using propensity score weighting and 4-year outcomes were assessed using generalized linear and Cox proportional hazards models. Overall, 3038 PwMS were included: CladT (n = 140), FTY (n = 454), DMF (n = 1465), and TER (n = 979). In the weighted cohorts, mean age was 48 years, and 74-77% were female. Treatment switching during a 4-year follow-up period was lower for CladT (11%), vs. FTY (42%), DMF (57%), and TER (42%) cohorts. CladT showed lower all-cause medical costs per patient per year (PPPY): $13,377 vs. FTY (adjusted mean difference [AMD] $10,073; 95% confidence interval (CI) $5006-15,148), DMF (AMD $12,013; 95% CI $7490-16,706), and TER (AMD $9917; 95% CI $6558-13,997) cohorts. All-cause total costs PPPY were lower with CladT ($53,007) vs. FTY (AMD $14,140; 95% CI $7181-22,021) and TER (AMD $6652; 95% CI $567-12,395) cohorts, but similar to DMF cohort (AMD $4472; 95% CI - $2011, $11,111). PwMS treated with CladT had significantly fewer treatment switches and lower all-cause medical costs vs. FTY, DMF, and TER. Total healthcare costs were lower vs. FTY and TER but similar to DMF.
High-altitude polycythemia (HAPC) and its associated cardiac complications, induced by hypobaric hypoxia (HH), pose significant clinical challenges. Xinnaoxin (XNX) tablets are clinically utilized for these conditions; however, their integrated multi-target mechanisms remain poorly understood. This study aims to elucidate the novel mechanisms and therapeutic potential of XNX against HAPC and HH-induced cardiac injury. For the first time, we employed a combined strategy of systems pharmacology and multi-level analysis to comprehensively investigate how XNX confers synergistic protection by modulating both the hematopoietic microenvironment and myocardial signaling networks. The metabolites of XNX were systematically identified, and its chemical profile was established using UPLC-Q-TOF-MS. An HH mouse model was generated by simulating a high-altitude hypoxic environment. Comprehensive assessments included complete blood parameters, hemorheology, the proportion and apoptosis of CD71+ bone marrow cells, and serum levels of erythropoietin (EPO) and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Cardiac injury was evaluated through histopathology, echocardiography, oxidative stress indicators (MDA, T-AOC, CAT, SOD), and Western blot analyses of key signaling pathways, including phosphorylation status of MAPK, JNK, ERK, IκBα, NF-κB, and Akt, as well as the expression of apoptosis-related proteins Bax and Bcl-2. XNX significantly reversed HH-induced elevations in red blood cell count, hemoglobin, hematocrit, white blood cell count, and plasma viscosity, while reducing serum EPO levels. Notably, XNX decreased the bone marrow population of CD71+ cells, indicating inhibition of "ineffective erythropoiesis." Regarding cardioprotection, XNX markedly alleviated myocardial injury, reduced oxidative stress (MDA), enhanced antioxidant enzyme activities, and suppressed pro-inflammatory cytokine release. Mechanistically, XNX coordinately modulated the phosphorylation levels of multiple signaling pathways (MAPK, JNK, IκBα, NF-κB, Akt) and regulated the Bax/Bcl-2 balance, thereby creating a signaling environment favorable for cardiomyocyte survival and repair. XNX exerts its therapeutic effects through a dual mechanism: (1) ameliorating HAPC at its source by regulating EPO expression and enhancing bone marrow erythropoietic efficiency, and (2) counteracting HH-induced cardiac injury via multi-target modulation of the MAPK-related signaling network. These findings clarify the pharmacological basis of XNX and provide a theoretical foundation for developing multi-pathway synergistic therapies for high-altitude hypoxia-related cardiovascular diseases.
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The purpose of this study was to investigate how powder fill weight, particle size, and particle size distribution influence force transmission and compaction behavior of powders during compaction within narrow die cavities. Discrete element method simulations were used to model confined powder compaction. Monodisperse and polydisperse systems were analyzed by varying particle size, size distribution breadth, and fill weight. Compaction force-displacement behavior was examined together with particle-level normal, tangential, and cohesive forces, including their axial and radial spatial distributions. Particle size had a stronger influence on force heterogeneity than fill weight within the range examined, with larger particles generating higher and more heterogeneous contact forces. Force distributions were positively skewed, indicating load localization within force chains. Normal and tangential forces were highest near the die wall, reflecting strong confinement effects. While individual particle forces followed similar size-dependent trends across different size distributions, narrow distributions required higher compaction forces due to localized load-bearing structures, whereas wider distributions promoted more uniform force sharing and lower resistance to compaction. The results demonstrated that macroscopic compaction behavior was governed by the organization of force networks rather than particle-scale force magnitudes alone, highlighting the critical roles of particle size, polydispersity, and confinement effects in powder compaction.
HDM1002 is a potent, orally active, and highly selective small-molecule full agonist of the glucagon-like peptide-1 receptor (GLP-1R), independently developed by Hangzhou Sino-American Huadong Pharmaceutical Co. Ltd. Our aim was to evaluate the pharmacokinetics, relative bioavailability, and food effects of two tablet strengths (100 and 200 mg) of HDM1002 in Chinese health volunteers (HVs). This single-centre, randomised, open-label, single-dose, two-formulation, three-period, double-crossover phase I study enrolled 33 HVs. All subjects received each of the following three treatments in different periods: (A) two 100-mg tablets under fasting conditions; (B) a single 200-mg tablet under fasting conditions; and (C) a single 200-mg tablet following a high-fat meal. A washout period of 7 days was implemented. The plasma concentrations of HDM1002 were measured using HPLC-MS/MS method, and PK parameters were determined by non-compartmental analysis. Under fasting conditions, the 90% confidence intervals (CI) for the geometric mean ratios (two 100-mg tablets vs. one 200-mg tablet) of Cmax, AUC0-t, AUC0-∞ were 106.87% (91.42%, 124.92%), 99.64% (95.32%, 104.15%), and 99.55% (95.20%, 104.09%), respectively, all within the 80.00%-125.00% bioequivalence range. For the food effect on the 200-mg tablet, the 90% CI of Cmax (fed vs. fasted) was 87.53% (76.88%, 99.66%), with its lower limit slightly below 80.00%; AUC0-t and AUC0-∞ were 105.90% (99.80%, 112.37%) and 106.01% (99.92%, 112.47%), both within the range. And there were no serious adverse events (AEs) occurred. HDM1002 was well-tolerated and safe. The two tablet strengths (100 and 200 mg) were bioequivalent under fasting conditions. A high-fat meal modestly reduced the Cmax of the 200-mg tablet but did not significantly affect its overall exposure (AUC). ClinicalTrials.gov identifier: ChiCTR2500111569.
Pain is a complex and unpleasant phenomenon, particularly in children, wherein frequent use of needle procedures during the process of hospitalisation significantly increases somatic and emotional distress in children. This randomised clinical trial was conducted among children aged 4-12 years admitted to a paediatric ward in Karnataka, India. Participants were randomly allocated to one of three arms: a Buzzy device intervention arm, a computer tablet distraction arm, or a control arm receiving routine care. Pain during venipuncture was assessed using the Faces Pain Scale-Revised (FPS-R), scored on a 0-10 scale. A total of 96 children were randomised, with 32 allocated to each of the Buzzy device, computer tablet distraction, and control arms. Both distraction interventions significantly reduced the FPR-R pain score compared with the control arm. The mean FPS-R score was 0.31 ± 0.74 in the Buzzy device arm and 3.25 ± 1.95 in the computer tablet arm. The between-group differences in pain scores were statistically significant (p < 0.001), with the Buzzy device demonstrating greater effectiveness than the computer tablet distraction. The Buzzy device and distraction techniques significantly minimised FPS-R pain scores in children, with the Buzzy device being the most effective. These findings support the incorporation of such interventions into paediatric clinical practice to enhance patient comfort.Trial Registration: Clinical Trials Registry of India (CTRI/2023/04/051864 registered on 21/04/2023).
Isodon rubescens is a widely used traditional folk medicine in China. In this study, 13 natural products were isolated using a two-step ethanol extraction. Notably, flavonoid glycosides 2 and 4, and polymeric caffeic acids 7 and 8, were identified for the first time from the secondary extraction residues, highlighting the continued presence of bioactive compounds with potential for further development. Oridonin (9), the major active compound, was quantified in nine commercial preparations using quantitative NMR (qNMR). Its concentration in the drop pill (0.92 mg/g) was comparable to that in the raw extract (0.90 mg/g). The three tablet samples showed varying levels: Tablet 3 (2.66 mg/g) > Tablet 1 (1.22 mg/g) > Tablet 2 (1.09 mg/g). Capsule, tea bag, and syrup samples could not be quantified due to low concentrations.
We aimed to examine the effect of vitamin E on preinvasive cervical squamous epithelium lesions on a microfluidic chip model. The research was conducted on 60 women, previously determined for a biopsy of the cervix due to an abnormal screening cytological test. The control group consisted of patients who were not treated with vaginal tablets Ialuna® or pure vitamin E. Samples were cultivated on a microfluidic chip, treated with Ialuna® vaginal tablets containing vitamin E combined with other ingredients or pure vitamin E, and then relative gene expression of BAX and BCL2 genes was measured. In tissues from women with chronic cervicitis, treatment with Ialuna® vaginal tablets induced a significant increase in BAX expression and the BAX/BCL2 ratio, while no significant changes were observed in BCL2 expression. In LSIL tissues, Ialuna® treatment resulted in a significant decrease in BCL2 expression, accompanied by increased BAX expression and an elevated BAX/BCL2 ratio. Conversely, pure vitamin E treatment did not produce significant changes in apoptotic markers in either group. This study has shown that conservative therapy is an important part of the treatment of cervical precancerous lesions and can potentially lead to diminishing radical interventions.
We investigated the microenvironmental pH (pHM)-modulating mechanism and intermolecular interaction of alkalizers and their impact on the aqueous stability, release profiles of drugs and alkalizers, pharmacokinetics, and intragastric pH variability in 46 healthy human subjects of lansoprazole (LAN), an acid-labile model drug. Preliminary screening of five alkalizers (CaCO3, MgO, NaHCO3, meglumine, and L-arginine) in LAN-loaded wet granules under simulated gastric fluid demonstrated that calcium carbonate (CaCO3) appeared to be the best stabilizing agent for LAN in a dose-dependent manner according to solution pH changes and drug contents. Immediate-release fixed-dose combination tablets (IFT) containing LAN and CaCO3 were prepared via a dual granulation process using a fluidized bed dryer (FBD) and/or a high shear mixer (HSM). Unlike the commercial enteric-coated granule-loaded Lanston® capsule, IFT released LAN and CaCO3 simultaneously, achieving over 90% drug release within 30 min while maintaining its aqueous stability in pH 1.2 gastric fluid via the acid-neutralizing capacity of simultaneously released CaCO3. The increased modulation of pHM and the intermolecular complex of LAN with calcium ions are crucial for stabilizing LAN under low pH conditions. The optimal IFT formulation demonstrated long-term stability for 3 years, maintaining drug content and dissolution rates while liberating impurities (<0.2%) within regulatory guidelines. IFT demonstrated bioequivalence with the commercial enteric-coated Lanston® capsule with decreased "time to reach the maximum plasma concentration" and displayed superior intragastric pH control, maintaining pH above 4 for a longer duration over 24 h in a cross-over design in 46 healthy human subjects. The current novel IFT containing acid-labile LAN and CaCO3 can be used to substitute current enteric-coated LAN tablets for the immediate release and rapid onset of LAN without chemical degradation in the gastric fluid.
Gut health and brain activity are closely linked, and the gut-brain axis plays a crucial role in regulating mental health. Interventions using beneficial microbes, such as probiotics and postbiotics, are gaining attention as promising approaches to support mental health. This study aimed to evaluate the effects of postbiotic heat-treated Lactobacillus gasseri CP2305 (CP2305) on mental stress and alpha oscillatory activity in the brain. This double-blind, randomized, crossover, placebo-controlled study included 28 healthy participants aged 20-44 years. The participants underwent two trial sessions and consumed a single dose of tablets containing heat-treated CP2305 (postbiotic; 1 × 1010 cells) or matching placebo tablets. In each session, electroencephalography (EEG) at eight positions was recorded from before to 60 min after ingestion to measure the alpha power. Heart rate variability was also recorded to calculate the root mean square of successive differences (RMSSD), an indicator of parasympathetic activity. The effects on mental state were evaluated using the visual analog scale (VAS) and Profile of Mood States, 2nd edition (POMS2). An in vitro study was conducted using the enterochromaffin cell line RIN14B to measure serotonin (5-HT) secretion levels following the heat-treated CP2305 administration. The alpha power showed a significantly greater increase from baseline following consumption of heat-treated CP2305 compared with the placebo. The change in the RMSSD from baseline was significantly greater following consumption of heat-treated CP2305 than following the placebo. Both the mental stress VAS and POMS2 tension-anxiety scores showed significantly greater improvements following consumption of heat-treated CP2305 compared with the placebo. In the in vitro 5-HT assay, extracellular 5-HT levels were significantly higher under the heat-treated CP2305 condition than under the control condition. This is the first clinical study to examine the effects of postbiotics on alpha oscillatory activity in the brain. Heat-treated CP2305 consumption was associated with modulation of brain activity, enhancement of parasympathetic activity, and alleviation of stress, indicating its potential as a functional food ingredient for mental health support. These beneficial effects may be partly associated with alterations in gut-derived 5-HT signaling induced by heat-treated CP2305. However, further studies are required to elucidate the underlying mechanisms. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000064175, Identifier UMIN000056164.
Tirabrutinib, an oral Bruton's tyrosine kinase inhibitor, is used in the treatment of relapsed or refractory primary central nervous system lymphoma (PCNSL) and other B cell malignancies. Although this medication is also administered to older patients, those experiencing dysphagia may require nasogastric administration via a tube. The impact of different administration routes on pharmacokinetics remains a pertinent clinical concern. An 82-year-old male patient with relapsed PCNSL initiated tirabrutinib at 320 mg/day under fasting conditions. While the patient was initially able to swallow tablets, progression of dysphagia necessitated a switch to nasogastric administration using the simple suspension method. Serum tirabrutinib concentrations were determined 11 hours after administration by each route using liquid chromatography followed by tandem mass spectrometry and compared. The serum concentration increased from 83.2 ng/mL with oral administration to 191 ng/mL with nasogastric administration, representing an increase of more than 2-fold. The dose, concomitant medications, and sampling conditions were consistent. On day 19, a rash developed that was suspected to be drug induced, prompting discontinuation of tirabrutinib; however, the serum concentration with nasogastric administration was not markedly higher than the previously reported mean 12-hour concentration of around 120 ng/mL. The observed increase in tirabrutinib concentration may primarily reflect enhanced dispersion with the simple suspension method, leading to improved absorption. Potential auxiliary factors, such as changes in absorption rate or inter-individual variability, cannot be excluded. Although a rash occurred, it is unlikely to represent an adverse event due to excessive exposure. Tirabrutinib concentrations may increase with nasogastric administration using the simple suspension method. In patients unable to ingest tablets orally, careful clinical monitoring is warranted, and therapeutic drug monitoring may be considered in select cases. The accumulation of further cases and pharmacokinetic investigations are warranted.
Direct compression is a generally preferred for tablet manufacturing method. However, it demands excipients with balanced flowability, compressibility, and packing properties. Microcrystalline cellulose (MCC) and calcium sulphate (CaSO₄) have balancing functionalities but individual limitations. To develop and optimize a novel MCC-CaSO₄ co-processed excipient (MCCASUL) for direct compression application using the SeDeM Expert System. To determine critical material attributes (CMA),12 SeDeM parameters were used to categorised MCC and CaSO₄. Functional indices, Parametric Profile Index (IPP), and Good Compression Index (IGC) were also calculated. To overcome the compressibility deficiency of CaSO₄ the required proportion of MCC was determined using SeDeM dilution potential equation. Co-dispersion method was used to prepare 9 MCCASUL batch with varying MCC:CaSO₄ ratios and further evaluated using SeDeM indices. Further characterization by FTIR, DSC, SEM, Heckel, and Kawakita analyses were performed for the optimised batch. MCC was more compressible (ѱc = 7.00) than CaSO₄ (ѱc = 4.67). The theoretical amount of correction for MCC was 14.16% among the batch preparation made, MCCASUL 4 exhibited the best results (IPP = 6.50, ѱf = 7.46, ѱc = 6.31). FTIR analysis proved the compatibility between the materials, DSC analysis revealed that modified thermal characteristics were stable, and SEM revealed improved morphology. With SeDeM expert System, co-processing yielded MCCASUL a highly versatile excipient that exhibited superior flowability, compressibility and stability and showed immense potential for direct compression tablet production.
Dissolution testing is performed to understand the rate and extent of drug release for assurance of in vivo bioavailability. In this case study, an immediate-release tablet of an investigational BCS Class II compound exhibited slow and incomplete dissolution at pH 4.5 and 6.8, indicating a risk of reduced exposure in patients with elevated gastric pH. To diagnose and remediate the issue, we evaluated three factors: (1) drug substance particle size (milled versus unmilled), (2) formulation wettability via incorporation of a surfactant alongside water-soluble versus insoluble fillers, and (3) shear mixing of the powder blend. Dissolution profiles for tablets containing milled and unmilled drug were comparable, and the addition of a surfactant did not improve performance. Subsequent investigation identified presence of drug agglomerates as the root cause of slow dissolution. Introducing a simple shear deagglomeration step as a pre-blend step markedly enhanced dissolution, allowing the clinical formulation composition to be retained and avoiding re-formulation and associated timeline impacts.