Suspension Formulation Research Articles

First-in-human safety, tolerability, and pharmacokinetic results of DFV890, an oral low-molecular-weight NLRP3 inhibitor.

This first-in-human study evaluated the safety, tolerability, single- and multiple-dose pharmacokinetic profiles with dietary influence, and pharmacodynamics (PD) of DFV890, an oral NLRP3 inhibitor, in healthy participants. In total, 122 participants were enrolled into a three-part trial including single and 2-week multiple ascending oral doses (SAD and MAD, respectively) of DFV890, and were randomized (3:1) to DFV890 or placebo (SAD [3-600 mg] and MAD [fasted: 10-200 mg, once-daily or fed: 25 and 50 mg, twice-daily]). DFV890 was generally well-tolerated. Neither deaths nor serious adverse events were reported. A less than dose-proportional increase in exposure was observed with the initially used crystalline suspension (3-300 mg); however, an adjusted suspension formulation using spray-dried dispersion (SDD; 100-600 mg) confirmed dose-proportional increase in exposure. Relative bioavailability between crystalline suspension and tablets, and food effect were evaluated at 100 mg. Under fasting conditions, Cmax of the tablet yielded 78% compared with the crystalline suspension, and both formulations showed comparable AUC. The fed condition led to a 2.05- and 1.49-fold increase in Cmax and AUC0-last compared with the fasting condition. The median IC50 and IC90 for ex-vivo lipopolysaccharide-stimulated interleukin IL-1β release inhibition (PD) were 61 (90% CI: 50, 70) and 1340 ng/mL (90% CI: 1190, 1490). Crystalline tablets of 100 mg once-daily or 25 mg twice-daily were sufficient to maintain ~90% of the IL-1β release inhibition over 24 h at steady state. Data support dose and formulation selection for further development in diseases, in which an overactivated NLRP3 represents the underlying pathophysiology.

Effectiveness of Bacillus genus application in the treatment of osteoarthritis by bioactive fish concentrate

Background. Understanding the impact of gut microbiota on the development of osteoarthritis (OA) and investigating the potential of probiotics as a treatment remain crucial areas of research. The study aimed to evaluate the efficacy of a Bacillus-based probiotic in combination with a bioactive marine fish concentrate for the OA treatment. Materials and methods. This study included 38 patients diagnosed with grade II knee OA. A structural-modifying drug containing 0.2 ml of bioactive concentrate derived from small marine fish, was administered every other day in a dose of 2.0 ml (10 intramuscular injections in total) for 21 days. Twenty patients (main group) additionally received a probiotic containing bacteria of the genus Bacillus (B.subtilis, B.licheniformis, B.amyloliquefaciens, B.megaterium, B.pumilus) in the dosage form of oral suspension daily for the entire treatment period of 21 days. Clinical efficacy was assessed by the Western Ontario McMaster Osteoarthritis Index (WOMAC), the questionnaire was comple­ted by all patients before the study and after 3, 7, 14 and 21 days of the therapy. Results. The findings showed a significant reduction in pain by 40.6 % (p < 0.001), stiffness by 36.8 % (p < 0.001), and improvement in knee function by 26.6 % (p < 0.05) in the main group (undergoing combined therapy with bioactive fish concentrate and the probiotic) on the 7th day of treatment. In the comparison group, a decrease in pain by 27.4 % (p < 0.05), stiffness by 25.0 % (p < 0.05), and improvement in joint function by 28.9 % (p < 0.05) were observed only on the 14th day of therapy. Conclusions. It was demonstrated that administering a probiotic composition containing bacteria from the genus Bacillus enhances the efficacy of bioactive sea fish concentrate in treating OA. Reduction in pain, stiffness, and improvement in joint function can be observed as early as the 7th day after initiating their combined use. In contrast, when using the bioactive concentrate of marine fish alone, the clinical effect is typically observed by the 14th day of treatment.

Study on the preparation of high-concentration ammonium phosphate suspension fertilizer from wet-process phosphoric acid and its rheological properties

BackgroundNew water-soluble fertilizer can be applied to modern irrigation systems and has significant advantages. This study uses wet-process phosphoric acid as raw material and chelation and suspension technology to prepare water-soluble fertilizer containing high-concentration ammonium phosphate. MethodsFirst, the composition and viscosity of the wet-process phosphoric acid was analyzed, and the ammoniation and chelation processes were explored. Subsequently, four suspension formulations were compared and selected after product analysis. The final process conditions are: 42 wt % (P2O5 %) phosphoric acid, 20 wt % chelating agent, pH = 4.5, 0.03 wt % xanthan gum or 0.02 wt % carboxymethyl cellulose of respectively, and obtain suspension fertilizer by high-speed shearing. Significant FindsThe Bingham model and Casson model were used to fit the rheological data of the two, and R2 values were greater than 0.94. The thixotropic loops of the two were measured using the triangular shear rate variation method mode, and the Huang equation and MBM models were used to fit the thixotropic loop data of the two respectively. In addition, at different pH and temperature, the suspended fertilizer performed well.

Modified powder suspensions for fingermark detection on adhesive tapes in austere or contested environments

ABSTRACT Pressure-sensitive adhesive tapes may be associated with a wide range of criminal and terrorist activity as physical evidence. In this study, a carbon powder suspension formulation for the detection of latent fingermarks on the adhesive side of tapes was modified by using consumer products as alternative surfactant sources. The modified formulations were used to successfully develop latent fingermarks deposited on transparent adhesive tape. This project ultimately intends to establish the performance windows of the modified techniques to allow evidence-based decision-making during technical exploitation in contested and austere environments.

An eco-friendly spectrophotometric analysis tool with whiteness assessment to assay erythromycin in pharmaceutical formulation through metal complexation with Ni2+: application to the microbiological activity using agar diffusion method

A new, facile and eco-friendly spectrophotometric method for estimating erythromycin (ERY) in its dosage form has been proposed and validated. It depends on the formation of a complex between the drug and nickel at pH 7, using distilled water as a diluent, where the absorbance of the generated complex was measured at 228.5 nm. The formed complex followed a linear response over the concentration range of 80.0 to 300.0 µg/mL of ERY. The proposed method was fully validated according to international conference of harmonization (ICH) and was used to estimate the relevant concentration of the drug in its oral suspension formulation providing mean percentage recovery of 100.0±1.08 with a limit of detection and limit of quantification of 60 µg/mL and 80 µg/mL, respectively. the reaction stoichiometry was investigated and a reaction mechanism proposal was offered. Eventually, the antimicrobial effect of ERY and its metal complex with Ni2+ were compared using agar diffusion method, where no significant difference in their activities was observed.

Enabling superior drug loading in lipid-based formulations with lipophilic salts for a brick dust molecule: Exploration of lipophilic counterions and in vitro-in vivo evaluation

Lipid-based formulations (LbFs) are an extensively used approach for oral delivery of poorly soluble drug compounds in the form of lipid suspension and lipid solution. However, the high target dose and inadequate lipid solubility limit the potential of brick dust molecules to be formulated as LbFs. Thus, the complexation of such molecules with a lipophilic counterion can be a plausible approach to improve the solubility in lipid-based solutions via reducing drug crystallinity and polar surface area. The study aimed to enhance drug loading in lipid solution for Nilotinib (Nil) through complexation or salt formation with different lipophilic counterions. We synthesized different lipophilic salts/ complexes via metathesis reactions and confirmed their formation by 1H NMR and FTIR. Docusate-based lipophilic salt showed improved solubility in medium-chain triglycerides (∼7 to 7.5-fold) and long-chain triglycerides (∼30 to 35-fold) based lipids compared to unformulated crystalline Nil. The increased lipid solubility could be attributed to the reduction in drug crystallinity which was further confirmed by the PXRD and DSC. Prototype LbFs were prepared to evaluate drug loading and their physicochemical characteristics. The findings suggested that structural features of counterion including chain length and lipophilicity affect the drug loading in LbF. In addition, physical stability testing of formulations was performed, inferring that aliphatic sulfate-based LbFs were stable with no sign of drug precipitation or salt disproportionation. An in vitro lipolysis-permeation study revealed that the primary driver of absorptive flux is the solubilization of the drug and reduced amount of lipid. Further, the in vivo characterization was conducted to measure the influence of increased drug load on oral bioavailability. Overall, the results revealed enhanced absorption of lipophilic salt-based LbF over unformulated crystalline Nil and conventional LbF (drug load equivalent to equilibrium solubility) which supports the idea that lipophilic salt-based LbF enhances drug loading, and supersaturation-mediated drug solubilization, unlocking the full potential of LbF.

Pharmacokinetics of Dihydroquercetin after Single and Repeated Administration to Rats.

The pharmacokinetic properties of dihydroquercetin (DHQ) were studied after single and repeated (for 3 days) administration to rats in the form of a starch suspension at a dose of 25 mg/kg. Blood samples were collected using a permanent catheter in the jugular vein in 2, 5, 10, 20, and 30 min and in 1, 2, 4, and 6 h after administration. Before the repeated administration (5 min), blood sample was collected to assess the concentration of DHQ at the zero time point. Quantitative analysis was carried out by HPLC-tandem mass spectrometry. DHQ was very quickly absorbed by the gastrointestinal tract and quickly eliminated from the body. Repeated administration of DHQ did not lead to its accumulation in the body but had an effect on the enzymatic system with a subsequent increase in DHQ exposure (accumulation factor >1 by AUC after repeated administration).

Improving Oral Bioavailability of Meloxicam: Development and Characterization of Solid Dispersions

This study investigated the development of a solid dispersion to improve the solubility and dissolution of meloxicam, a poorly water-soluble drug. Meloxicam is used to treat pain and inflammation in various conditions. The challenge was to enhance the drug's oral bioavailability by overcoming its low solubility. Two approaches were explored:
 
 1. Kneading method with Poloxamer 407: This method resulted in a formulation with significantly improved solubility compared to the pure drug.
 Solvent evaporation method with PVP K-30: While this method offered satisfactory solubility enhancement, it was not as effective as the kneading method with Poloxamer 407.Following the development of the optimized solid dispersion, a suspension formulation was prepared using various suspending agents. The optimized drug formula was then incorporated into the suspension mix. Characterization studies confirmed compatibility between the drug and excipients. FT-IR analysis showed no interaction between the drug and the carriers. Scanning electron microscopy (SEM) revealed a change in meloxicam particle morphology from crystalline to a more amorphous form, indicating a reduction in particle size and a potential explanation for the improved dissolution profile. The dissolution profile of the solid dispersion suspension prepared by the kneading method with Poloxamer 407 outperformed the one prepared with the solvent evaporation method and PVP K-30.This study demonstrates the effectiveness of the kneading method with Poloxamer 407 in developing a solid dispersion of meloxicam with enhanced solubility and dissolution. The optimized formulation exhibited good stability, acceptable drug content and release, and satisfactory rheological properties. This approach has the potential to improve the bioavailability of meloxicam and lead to a more effective oral dosage form.
 
 Keywords: Oral Bioavailability, Meloxicam:, Solid Dispersions , FT-IR analysis, SEM

Research of the Process of Electrochemical Deposition of Chromium in the Presence of a Composite Compound Based on Detonation Diamond-Containing Carbon

The purpose of the study is to develop a method for obtaining high-quality electrochemical chromium coating using a new type of diamond-containing additive that has significant advantages over traditionally used detonation nanodiamonds (DNA) in the form of aqueous suspensions. Detonation diamond-containing carbon (DDC) obtained by detonation of charges from tetryl was used as an additive. DDC contains 63,0 wt. % DNA and 4.4 wt. % non-combustible impurities. We used standard chromium electrolyte: CrO3 - 250 g/l, H2SO4 – 2,5 g/l, DNA – from 0,2 to 5 g/l, traditional methodologies and algorithm of experimentation. The scope of the study is limited to the creation and application of a specific, easy to handle and prepare formulation with DDC. DDC can be added to the standard chromium electrolyte directly or in the form of freshly prepared aqueous suspension, it is environmentally safe. The originality of the work lies in the application of a cheap diamond-containing product obtained directly after the explosion of an individual explosive (tetryl) and providing stability of DDC suspensions. An increase in microhardness of wear-resistant chrome coating by 1,5 times (up to 11 GPa) and hard chrome coating by 1,7 times (up to 13,3 GPa) was achieved. The wear resistance of the obtained coatings increased by 1,9 times. Concentration (per pure detonation nanodiamond (DNA)) from 0,63 to 3,15 g/l in the electrolyte (very low).

Abstract 7185: Long acting injectable FHD-609 micro-suspension: A potent BRD9 degrader with comparable efficacy, reduced frequency of dosing in preclinical models

Abstract Bromodomain-containing protein 9 (BRD9) is a unique component of the non-canonical Brahma-associated factor (ncBAF) complex, essential for cancer cells relying on this complex for survival. This makes it an attractive target for cancer treatment. In synovial sarcoma (SS), SS18-SSX fusion protein drives disease progression and integrates into BAF complexes, promoting tumor growth. Targeting BRD9 degradation is a potential therapeutic approach for SS tumors, as it depletes the essential SS18-SSX fusion protein upon which cancer cells depend for survival within the BAF complex. FHD-609, a potent heterobifunctional degrader of BRD9, has been administered intravenously (IV) in medical facilities twice weekly during clinical trials. In order to facilitate less frequent and more convenient patient-centric dosing, a long acting injectable formulation was developed that allows subcutaneous (SC) or intramuscular (IM) dosing every 4 weeks in preclinical studies. The formulation is an aqueous microsuspension containing the drug along with a polymer and surfactant which provides sustained release of FHD-609 upon injection. We compared the long acting injectable formulation dosed once every 4 weeks to the IV formulation dosed twice a week for the pharmacokinetic and pharmacodynamic properties, as well as the efficacy of the long in xenograft models of different sensitivities, including cell line-derived xenografts (CDX) and patient-derived xenografts (PDX). Our results showed that a single dose of the injectable suspension formulation was well-tolerated in mice and exhibited a significantly flatter PK profile than IV injection with a lower peak to trough ratio and detectable compound concentrations 4 weeks post dose. Moreover, it demonstrated comparable in vivo efficacy and BRD9 protein degradation to the standard intravenous (IV) administration. The long acting FHD-609 injectable formulation has the potential to offer better patient compliance and acceptance in clinical settings than IV dosing. The long acting injectable formulation provides a promising and effective drug delivery option for various protein degraders that are not orally bioavailable. Citation Format: Meiyun Lin, Ammar Adam, Abira Pyne Ramakrishnan, Hafiz Ahmad, Xiaohuan Wu, Brandon Antonakos, Chong-Hui Gu, Ashish Ramani, Victoria Amaral, Claudia Dominici, Qianhe Zhou, Mike Collins, Jessica Piel, Sal Topal, Brian Ethell, Kelly McKiernan, Scott Innis. Long acting injectable FHD-609 micro-suspension: A potent BRD9 degrader with comparable efficacy, reduced frequency of dosing in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7185.

Evaluation of the Antifungal Activity of Fluconazole Nanovesicles Against Aspergillus fumigatus

Fluconazole is potent triazole drug used as effectively anti-fungal for treating a variety of local and systemic fungal infections. This drug is sparingly soluble in water. The objective of this research was to statistically optimize nanovesicular formulations contain fluconazole to improve its antifungal effect. The nanovesicular formulations were composed of Tween® 80, cetyl alcohol, and chitosan. The prepared nanovesicular formulations were investigated for their zeta potential, polydispersity index, particle size, and encapsulation efficiency. The nanovesicular that has been optimized formulation was consist of tween/cetyl alcohol ratio of 15:1 and 0.1% chitosan. Additionally, the optimized formulation increased significantly in fluconazole release ratio and extent in comparison to the suspension form of the drug. The find that fluconazole nanovesicles had a better effect and lower MIC when compared to the aqueous fluconazole suspension. Finally, the optimized nanovesicles can be considered a promising nanocarrier for delivery of fluconazole to increase its systemic antifungal efficacy.

High porosity hafnia ceramics by freeze casting

Highly porous hafnia ceramics are prepared by freeze casting. The major challenge resides in the high density of the hafnia particles typically leading to settling in the slurry. To address this, we optimized the suspension formulation to achieve structures with porosities of 68–74 %. Our approach includes a reduction in additive quantities and an adjustment of the pH value for suspension stabilization and prevention of particle settling. The use of PVA and PEG ensures a green body strength during the process yielding in cellular microstructure with pore channels aligned in the freezing direction throughout the sample. With increasing solid loading, the scaffolds become denser and the pore wall thickness increases. Compressive strength tests confirm the enhanced stiffness of the samples with 15 vol% hafnia. Samples with 10 vol% hafnia show a buckling-dominated failure behavior. Our results provide valuable insights to the preparation of suspensions containing high density materials.

Nanocrystalline cellulose from Arctic brown algae Laminaria digitata and Saccharina latissima

Nanocrystalline cellulose (NCC) was successfully obtained from two Arctic brown algae species, Laminaria digitata and Saccharina latissima. The production process involved a sequential extraction of non-cellulosic compounds, an environmentally friendly bleaching process with hydrogen peroxide, and subsequent acidic hydrolysis, resulting in the formation of nanosized rod-like particles. Comprehensive assessments were conducted to evaluate the influence of hydrolysis conditions, specifically using hydrochloric and sulfuric acids, on the key characteristics of the nanocellulose. The resulting NCC was characterized using various techniques including Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA, DTG), scanning electron microscopy (SEM), laser diffraction, and low-temperature nitrogen sorption. The obtained algal NCC demonstrated a yield of 76–91%, a degree of polymerization of 150–230 units, and a crystallinity index of 69–80%. The choice of acid during the production significantly influenced the thermal stability, particle size distribution, and porous properties of the samples. Remarkably, the algal NCC, acquired in the form of stable gel-like suspensions, exhibited robust stability during extended storage. These materials showcase promising potential for applications in biomedicine, serving as versatile components for hydro/aerogels, matrices, and fillers in the development of advanced medical dressings.

Simplex Lattice Design and Machine Learning Methods for the Optimization of Novel Microemulsion Systems to Enhance p-Coumaric Acid Oral Bioavailability: In Vitro and In Vivo Studies

Novel p-coumaric acid microemulsion systems were developed to circumvent its absorption and bioavailability challenges. Simplex-lattice mixture design and machine learning methods were employed for optimization. Two optimized formulations were characterized using in vitro re-dispersibility and cytotoxicity on various tumor cell lines (MCF-7, CaCO2, and HepG2). The in vivo bioavailability profiles of the drug loaded in the two microemulsion systems and in the suspension form were compared. The optimized microemulsions composed of Labrafil M1944 CS (5.67%)/Tween 80 (38.71%)/Labrasol (38.71%)/water (16.92%) and Capryol 90 (0.50%)/Transcutol P (26.67%)/Tween 80 (26.67%)/Labrasol (26.67%)/water (19.50%), respectively. They revealed uniform and stable p-coumaric acid-loaded microemulsion systems with a droplet size diameter of about 10 nm. The loaded microemulsion formulations enhanced the drug re-dispersibility in contrast to the drug suspension which exhibited 5 min lag time. The loaded formulae were significantly more cytotoxic on all cell lines by 11.98–16.56 folds on MCF-7 and CaCo2 cells and 47.82–98.79 folds on HepG2 cells higher than the pure drug. The optimized microemulsions were 1.5–1.8 times more bioavailable than the drug suspension. The developed p-coumaric acid microemulsion systems could be considered a successful remedy for diverse types of cancer.Graphical

Common Oral Manifestations in a Denture Wearer Patients with Suspected Diabetes Mellitus

Background. Acute pseudomembranous candidiasis or often called oral thrush is a disease in the oral cavity caused by the overgrowth of Candida albicans. Angular cheilitis is an inflammatory lesion on the corners of the mouth. The purpose of this case report is to document the oral manifestations in patients with suspected diabetes mellitus. Case Report. A 57-year-old woman came with complaints of a burning sensation throughout the mouth and lips and presented a white spot on her tongue with soreness in the past year. The patient has diabetes mellitus and regularly takes medication. Despite this, the patient still has experienced classical signs of diabetes mellitus which are polyphagia, polydipsia, and polyuria. Intraorally the burning sensations were related to the full denture continuous wearness and were diagnosed as acute pseudomembranous candidiasis and angular cheilitis. The treatment given to this patient was symptomatic therapy in the form of Aloclair Plus mouthwash, causative therapy in the form of Nystatin oral suspension and referral to an internist to further examine the condition of diabetes mellitus, and supportive therapy in the form of lanolin and vaseline. Treatment ends with the provision of communication, instruction, and education.

Formulation and Evaluation of Extended Release Oral Suspension of Metformin Hydrochloride

The research scheme of formulation and evaluation of extended-release oral suspension of metformin hydrochloride with the objective to develop a stable, redispersible oral liquid suspension based on extended-release pellets to facilitate swallowing in patients with diabetes. Pellets were prepared by using Bed Coating During Sliding method with the Metformin hydrochloride used as antidiabetic drug and various polymers. Extended release was affected by the ethylcellulose coating of drug formulation used as coating agent, MCC, Lactose, PVP K-30 Prepared metformin hydrochloride pellets putted in to prepared sugar free syrup vehicle using polymers like Xanthan Gum as a suspending agent for uniform drug distribution, Sorbitol solution, Aspartame are artificial sweeteners, Sodium Citrate, Potassium sorbate, Methyl paraben. The formulation was optimized based on Design expert software and Central Composite Design was used for study. Drug and polymers were studied for compatibility and interaction study, carried out by FTIR and DSC and found to be compatible to each other. The Redispersibility, Sedimentation volume, Sedimentation rate, Rheological Study, Viscosity, Specific gravity, Particle Size, dissolution study and %Drug content of formulated batches was evaluated. All the results were within the acceptable pharmacopeial limits and were evaluated statistically by using one way ANOVA test for quadratic model. From the result, MET6 batch was observed optimized formulation because up to 8 hrs 85.25% drug was released. kinetic studies of the drug release for optimized formulation follows zero order kinetics.

Laser Processing of Liquid Feedstock Plasma-Sprayed Lithium Titanium Oxide Solid-State-Battery Electrode

The astonishing safety and capacity characteristics of solid-state-batteries are encouraging researchers and companies to work on the manufacturing, development, and characterization of battery materials. In the present work, the effects of laser beam interaction with a liquid feedstock plasma-sprayed ceramic solid-state-battery (SSB) material coating were studied. Lithium Titanium Oxide (LTO) in the form of an aqueous suspension consisting of submicron powder particles was plasma-sprayed for the first time using a high-power axial III plasma torch on an aluminum substrate. The plasma-sprayed LTO coating suspension was subsequently post-processed using a fiber laser. The energy input of the laser beam on the surface of the deposited layer was the main variable. By varying the laser power and laser processing speed, the energy input values were varied, with values of 3.8 J/mm2, 9.6 J/mm2, 765.9 J/mm2, and 1914.6 J/mm2, and their effects on some key characteristics such as laser-processed zone dimensions and chemical composition were investigated. The results indicated that changing the laser beam parameter values has appreciable effects on the geometry, surface morphology, and elemental distribution of laser-processed zones; for instance, the highest energy inputs were 33% and 152%, respectively, higher than the lowest energy input.

Development of an extemporaneous preparation formulation using a simple and non-solubilizing matrix for first in human clinical study

Extemporaneous preparation (EP) formulation is an attractive strategy to accelerate the formulation development of new chemical entities for first entry into human study. In this work, an EP suspension formulation for a development drug candidate GDC-6599 was successfully developed. The formulation spanned a wide concentration range from 0.1 to 2.0 mg/mL. A non-solubilizing vehicle, 0.6 % (w/v) methylcellulose solution was used to suspend GDC-6599. An aversive agent denatonium benzoate at an extremely low level (6 ppm) was applied as a taste masking agent. This enabled a simple matrix for the analysis of related substances from GDC-6599 during all stability studies. Microcrystalline cellulose at 10 mg/mL concentration was added to the EP formulation to generate a suspension appearance, leading to the success of using a single placebo for matching active formulation at all concentrations. The developed formulation demonstrated excellent homogeneity, sufficient stability and passed microbiological enumeration test. Rinsing performance test demonstrated that greater than 99.8 % amount of drug was successfully recovered by rinsing with water twice, providing guidance for clinical dosing. Biopharmaceutical assessment was conducted by both in silico simulation and in vitro tests. Greater than 90 % bioaccessibility of the EP suspension formulation was obtained via an in vitro system mimicking the human gastrointestinal absorption, consistent with the result from the in silico modeling. The developed EP formulation was successfully used to support the early single ascending dose (SAD) cohorts of GDC-6599 Phase I clinical study. The formulation matrix and assessment workflow developed in this work are generalizable as a platform for EP formulation development of new chemical entities for early phase clinical studies.

Technological process for treating radioactive TBP/OK spent solvents

Tributyl phosphate (TBP) and kerosene (OK) spent radioactive organic solvents will be produced during the nuclear fuel reprocessing process, which may cause equipment corrosion by direct incineration. Therefore, additives need to be added to prepare a uniformly stable suspension. The amount of each raw material added during the preparation process and the stirring operation can have a significant effect on the performance of the suspension. In this paper, the influence of the amount of each raw material and the stirring rate on the emulsion formation, stabilization time, and fluidity of suspension is studied through different experiments to optimize the suspension formulation of the pyrolysis/incineration processes. The experimental results show that when the volume content of TBP was 30%~60%, the prepared suspension had excellent performance and could be used as the basic solution for suspension formulation. In contrast, when the volume content of TBP was more than 80%, the prepared suspension became less stable, the emulsion phase broke and settled, and the performance of the suspension was poor. When the volume contents of TBP were 30% and 60%, respectively, the DBP content was less than 0.26% and 0.6%, respectively, the Ca-P ratio was 1.25~1.75. Water content was 8~12%. The prepared suspension had great emulsion formation and fluidity. The viscosity and stability time meet the requirements with little secondary waste. The suspension can be applied in TBP/OK spent radioactive organic solvents pyrolysis/incineration reprocessing project.

Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.