Lyophilised reservoirs in combination with hydrogel-forming microarray patches for transdermal delivery of isoniazid and pyridoxine hydrochloride.

Protein-based APIs represent a big group of modern therapeutics. Their characterization involves complex analytical protocols which require special methods, especially in the case when the protein drug is included into tablet dosage forms. Although the fluorescence polarization assay (FPA) is not currently regulated by many national Pharmacopeias, it represents a promising approach for protein drug standardization, considering their rapid, sensitive, and automatable detection suitable for high-throughput analysis and real-time quality control. To evaluate the applicability of FPA for the analysis of protein drugs in tablets, the quantifying of lysozyme in tablet dosage forms was studied by this method with the use of a fluorescently labeled synthetic chitooligosaccharide tracer. It was shown that this approach overcomes the limitations of the conventional turbidimetric assay of lysozyme determination, which is labor-intensive and relies on unstable reagents. Measurements were performed with both portable and stationary fluorescence polarization readers. Commercial tablets from five manufacturers containing lysozyme (20 mg) and pyridoxine hydrochloride (10 mg) together with other excipients were analyzed. The FPIA method showed a linear range of 5.0–70 µg/mL, with specificity confirmed by the absence of interference from excipients. Accuracy, evaluated by standard addition (10–20 mg), yielded recoveries of 100.2–106.0%. Placebo spiked with lysozyme at 80–120% of nominal content demonstrated recoveries of 98.0–100.1%, with RSD (n = 6) not exceeding 13.7%, indicating good precision. The developed method enables reliable lysozyme quantification in tablets, offering speed, simplicity, and robustness, and shows its suitability for the routine quality control of protein-containing dosage forms including the enzyme ones.

Serum Vitamin A Is Associated with Variations in the Relationship between Plasma B6 Vitamers and Cardiovascular Disease Risk.

This study provides an informative thermo-kinetic comparison of vitamin B6 (pyridoxine hydrochloride) formulations produced by British and Emirati pharmaceutical companies. The experiment, designed as an instructive model in pharmaceutical chemistry, illustrates the correlation between temperature and the rate of chemical decomposition through UV–Vis spectrophotometric analysis at 290 nm. Using the Arrhenius and Eyring models, we found kinetic and thermodynamic parameters such as activation energy (Ea), enthalpy (ΔH), entropy (ΔS), and Gibbs free energy (ΔG). The Emirati formulation had a melting point of 210 °C and higher ΔH‡ and ΔG‡ values. This means that it was more thermally and molecularly stable, which means that it had stronger internal bonds and was less likely to break down when heated. The British formulation, however, had a lower melting point (184 °C) and broke down more quickly, which suggests that it was less crystalline. This study provides a replicable laboratory framework for imparting pharmaceutical stability and quality assessment from both scientific and pedagogical perspectives, emphasizing the integration of kinetic and thermodynamic analysis into chemistry education.

Scavenging methylglyoxal improves bone quality and defect healing in diabetic mice

ATP acting on P2X3R within carotid bodies (CBs) underpins chemoreflex-mediated sympathetic overactivity in Spontaneously Hypertensive rats (SHR). Pyridoxal 5'phosphate (PLP), the active form of vitamin B6, is reported as being a non-selective P2X receptor blocker. Hence, we hypothesized that PLP antagonism of P2X3R in the CB would treat hypertension. Herein, we employed a multipronged approach to investigate PLP's capability to attenuate CB hyperexcitability in hypertension.First, PLP inhibited Ca2+ responses evoked by α, β-methylene ATP in cells lines expressing human (h) P2X3R with IC50 of 8.7µM. Next, in-silico data predicted that PLP binds to the same site of Gefapixant, supporting an allosteric antagonism. Using an isolated perfused carotid artery bifurcation-CB preparation, arterial infusion of PLP (50 µM; 15 min) attenuated CBs sensory firing in SHR (P=0.012). Using the in situ working-heart brainstem preparation, carotid artery injections of PLP (1-5mM) attenuated the chemoreflex-evoked sympathetic (P=0.023) but not phrenic (P=0.62) responses; the CB was stimulated with potassium cyanide (KCN,50 µL; 0.04%). In awake telemetered SHR (n=6), intravenous infusion of PLP (48 mg/Kg/h; 30 min) attenuated KCN-evoked chemoreflex responses and reduced systolic, diastolic, and mean blood pressures (ΔMBP = -15.6 mmHg; P=0.025). Translating our results, we performed a small double-blind randomized clinical trial. In volunteers with hypertension (n=14), oral supplementation with pyridoxine hydrochloride (600 mg) attenuated the hypoxic ventilatory response only in patients with high peripheral chemoreflex sensitivity (P=0.021). Our findings suggest that PLP binds to and antagonizes P2X3R and is a viable candidate for larger clinical trials to treat CB dysregulation in cardiovascular diseases.

Thermophysical and UV spectral insights of uracil/uridine with pyridoxine hydrochloride in aqueous media at varied temperatures and compositions

Enhanced microbial production of pyridoxine (Vitamin B6) in Bacillus subtilis via pathway and process optimization

Growing demand for plant-based nutraceuticals drives the need for innovative bioprocessing strategies. This study developed an integrated approach combining germination and Lactobacillus-mediated fermentation to produce a γ-aminobutyric acid (GABA)-enriched functional beverage from brown rice. Systematic screening identified an optimal rice cultivar for germination. Sequential enzymatic liquefaction and saccharification were optimized to generate a suitable hydrolysate. Screening of 13 probiotic strains revealed that a 10-strain Lactobacillus–Bifidobacterium consortium maximized GABA synthesis (12.2 mg/100 g). Fermentation parameters were optimized to 0.25% monosodium glutamate, 4% inoculum, 10 μmol/L pyridoxine hydrochloride, 37 °C, and 24 h. The resulting beverage achieved significantly elevated GABA concentrations while exhibiting low fat (0.2 g/100 g), reduced caloric content (233.6 kJ/100 g), and high viable probiotic counts (2 × 108 CFU/g). This strategy demonstrates significant potential for the scalable production of multifunctional, plant-based nutraceuticals with targeted bioactive components.

Suppression of stress granule assembly by pyridoxal hydrochloride attenuates oxidative damage in skin fibroblasts.

Inhibition of DNA glycoxidation by mannitol and Pyridoxamine: Implications for DNA-antibody development in diabetes and diabetic retinopathy.

The interactions of vitamin B6 (pyridoxine hydrochloride) with different concentrations of cationic compounds (cocarboxylase or thiamine pyrophosphate chloride) were investigated in an aqueous solution using UV-VIS absorption spectroscopy. The results depict a hyperchromic shift at 300 ± 1 nm, a hypochromic shift at 330 ± 1 nm with increasing concentration of carboxylase, and an isosbestic point at 312 nm. Hydrophilic-hydrophilic (hydrogen bonding) interaction is the dominating force for the association of two compounds. The binding constant (Kb) value has been determined by two cases of the Benesi-Hildbrand equation and the concept developed by Hashemi and Sun. The values of Kb calculated from all three methods were in close agreement. Furthermore, the standard free energy change, ΔGo was detected from the computed values of Kb.

This study aimed to assess the extent of vitamin B1 and B6 vitamer loss during a single peritoneal dialysis (PD) session using a combination of chromatographic techniques and chemometric analysis. Dialysis effluent samples were collected from 41 PD patients (22 on continuous ambulatory peritoneal dialysis (CAPD) and 19 on automated peritoneal dialysis (APD)) during a standardised peritoneal equilibration test. Concentrations of thiamine monophosphate, thiamine diphosphate (ThDP), pyridoxine, pyridoxal (PL), and pyridoxamine were determined using high-performance liquid chromatography with a fluorescence detector. The analytical method was validated in terms of sensitivity, linearity, accuracy, and recovery. Multiple regression analysis was employed to identify potential clinical and demographic predictors of vitamin washout. All vitamers except pyridoxal 5-phosphate (PLP) were detectable in dialysis effluents. ThDP exhibited the greatest loss among the B1 forms (ca. 0.05-0.57 mg/24 h), while PL exhibited the most significant loss among the B6 forms (ca. 0.01-0.19 mg/24 h). Vitamin losses varied depending on the dialysis modality (continuous ambulatory peritoneal dialysis, or CAPD, versus automated peritoneal dialysis, or APD) and the peritoneal transport category. Regression analysis identified body weight, haemoglobin, and haematocrit as independent predictors of ThDP washout (R2 = 0.58). No statistically robust models were established for the other vitamers. Even short medical procedures (such as single PD) can result in measurable losses of water-soluble vitamins, particularly ThDP and PL. The results emphasise the importance of personalised vitamin supplementation for PD patients and suggest that body composition and haematological parameters significantly influence the loss of thiamine.

The synthesis and structural characterization of three new triple-stranded helical complexes ([Dy2(L2)3]2Cl∙15H2O (C1), [Y2(L2)3]3(NO3)Cl∙14H2O∙DMSO (C2), and [Eu2(L4)3]∙12H2O (C3), where L2 and L4 are ligands derived from pyridoxal hydrochloride and succinic or adipic acid dihydrazides, respectively, were described. The X-ray data, combined with spectroscopic measurements, indicated that L2 and L4 act as bis-tridentate ligands, presenting two tridentate chelating cavities O,N,O to obtain the dinuclear complexes C1–C3. Their antiviral profile was predicted via in silico calculations in terms of interaction with the structural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein in the down- and up-states and complexed with the cellular receptor angiotensin-converting enzyme 2 (ACE2). The best affinity energy values (−9.506, −9.348, and −9.170 kJ/mol for C1, C2, and C3, respectively) were obtained for the inorganic complexes docked in the model spike-ACE2, with C1 being suggested as the most promising candidate for a future in vitro validation. The obtained in silico antiviral trend was supported by the prediction of the electronic and physical–chemical properties of the inorganic complexes via the density functional theory (DFT) approach, representing an original and relevant contribution to the bioinorganic and medicinal chemistry fields.

Pyridoxine exerts antioxidant effects on kidney injury manifestations in high-fat diet-induced obese rats.

Vitamin B6 (VB6), a metabolic cofactor, is essential for plants, animals, and microorganisms. VB6 has emerged as an important regulator of plant immunity, modulating various immune responses, including basal immunity, stomatal defence, and induced systemic resistance. However, the role of VB6 in systemic acquired resistance (SAR) and the active VB6 vitamers involved in modulating plant immunity remain unclear. A recent study reveals that Δ1-piperideine-6-carboxylic acid (P6C), a metabolite from lysine catabolism, sequesters VB6 vitamers, such as pyridoxal (PL) and pyridoxal 5'-phosphate (PLP), into inert complexes. This depletion of active VB6 vitamers disrupts VB6 homeostasis, impairing SAR, while exogenous application of VB6 restores resistance. Interestingly, the resemblance of this mechanism to pyridoxine-dependent epilepsy in humans suggests evolutionary conservation of these metabolic processes. This article explores the multifaceted roles of VB6 in different aspects of plant immunity. We emphasise the need for further research to decode the complex interplay between VB6 homeostasis and defence hormone pathways to deepen our understanding of immune signalling and develop new strategies to enhance stress resilience in plants.

Objective Vitamin B6 (VB6) deficiency leads to microcytichypochromic anemia with ringed sideroblasts. Sideroblastic anemia due to VB6 deficiency is an important differential diagnosis to consider in cases with sideroblastic anemia associated with myelodysplastic syndrome (MDS). However, VB6 screening is underutilized in Japan as it is not covered by the national health insurance system, potentially leading to low screening rates. Methods This study retrospectively evaluated the relationships between VB6 (pyridoxal (PAL)) and other clinical parameters, including anemia, with univariate and multivariate regression analysis. Among 43 patients, we excluded one case where vitamin B6 supplementation had already started before blood sampling. We enrolled 42 patients who had undergone measurement of VB6 level (PAL) at Toho University Sakura Medical Center (Sakura, JPN) between September 2010 and October 2023. Results The PAL levels were significantly correlated with mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Mean corpuscular hemoglobin concentration (MCHC) and vitamin B12 (VB12) also tended to correlate positively with PAL; however, no correlation was observed between PAL levels and other parameters. The PAL was positively correlated only with MCV and MCH in the subgroup analysis of hematological disorders alone. Only alkaline phosphatase (ALP) showed a significant decrease in the PAL <6 ng/mL group compared with the PAL ≥6 ng/mL groups; no significant differences were observed in RBCs, hemoglobin (Hgb), MCV, MCH, or MCHC between the PAL <6 and ≥6 ng/mL groups in both the overall cohort of 42 patients and the subset of 12 patients with hematological disease. Multivariate regression analysis revealed that only RBC and MCV levels independently and significantly affected Hgb levels. Conclusions These findings suggest that anemia due to VB6 deficiency may not always present as microcytichypochromic anemia. Thus,VB6 deficiency must be included in the differential diagnosis of anemia, especially when there's suspicion for MDS.

Pyridoxine (PN) is the most important commercial form of vitamin B6. Currently, PN is chemically synthesized using toxic chemicals, causing environmental pollution. Microbial production of vitamin B6 offers a more sustainable alternative, but its low productivity makes it difficult to meet commercialization demands. Here, metabolic engineering strategies were used to efficiently improve the PN production. Directed evolution of 4-phosphoerythronate dehydrogenase led to a 4-fold increase in PN production. In addition, the pdxK and pdxH genes were then knocked out to redirect the metabolic flux from pyridoxine 5'-phosphate to PN, and genes involved in glycerol-to-pentose phosphate metabolism were overexpressed to increase precursors for PN synthesis. Finally, the recombinant strain produced 2120.1 ± 7.8 mg/L PN with a productivity of 32.1 mg/L/h by batch fermentation. The strategies reported here will be useful for the efficient and sustainable biobased production of PN.

The current study included the preparation of azo compound (A4) from the aromatic amine reactant (2-aminobenzoate methyl) by the nitrification method and conjugation with pharmaceutical phenolic compounds (pyridoxine hydrochloride, ortho-vanillin, para-vanillin, and kojic acid). Then, the compound (A4) was converted into new ester polymers. By reacting it with succinic acid and apic acid. All compounds and polymers were then characterized by IR, UV-Vis, mass spectrometry and 1H NMR spectroscopy. The effect of pH was studied in the electronic absorption spectra of azo compounds (A4) in the visible region, in a range of wavelengths (470) nm, using different buffer solutions with different pH values.

The treatment of several pediatric metabolic diseases involves vitamins supplementation. Among these, thiamine, riboflavin, pyridoxine and biotin can be prescribed and compounded as hard gelatin capsules. In compounding practice, a medication can be done extemporaneously, leading to a risk of error. However, a medication can also be done in advance, analytically controlled and stored. Such practice reduce the risk of error and decrease the cost, but also imposes the realization of stability studies to establish beyond-use-dates. Thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, and biotin hard gelatin capsules chromatographic and microbiological methods were both validated and used to perform stability studies. Thiamine hydrochloride 50 mg hard gelatin capsules with microcrystalline cellulose and silica as excipients are stable for 6 months when stored at 25 °C/ 60% RH protected from light. Riboflavin 50 mg with microcrystalline cellulose, pyridoxine hydrochloride 50 mg with microcrystalline cellulose and biotin 40 mg with microcrystalline cellulose/silica are stable for one year when stored at 25 °C/ 60% RH protected from light. These results allow the compounding in advance of batches of 300 capsules controlled, stored, and quickly dispensed in case of an emergency, such decreasing the risk of error and/or iatrogenic event.