Dosing Frequency Research Articles

Vaccine enhancement and improved immunogenicity using erythrocytes as carriers

Achieving optimal immunogenicity and efficacy in vaccination presents significant challenges, including the need for multiple doses and the limited immunogenicity observed with certain vaccine formulations. To overcome these obstacles, researchers are exploring supplementary components and innovative delivery strategies. The development of an effective vaccine delivery technology is crucial for achieving sufficient protective immunity and disease prevention. This article focuses on the potential of erythrocytes as vaccine carriers to enhance vaccine effectiveness, particularly in the context of whole particle vaccines. The extended lifespan of erythrocytes enables sustained antigen exposure, resulting in continuous antigen presentation to immune cells. Moreover, erythrocytes exhibit biocompatibility, a well-established safety profile, and the capacity to modulate immune responses through interactions with complement receptors. These characteristics position erythrocytes as an appealing platform for targeted vaccine delivery. The hypothesis suggests utilizing bispecific monoclonal antibodies to complement receptor 1 and specific pathogen proteins to hitchhike inactivated pathogens onto erythrocytes. These modified erythrocytes can then serve as carriers to deliver the whole particle vaccine to antigen-presenting cells (APCs) or function as APCs themselves in the spleen. This article puts forward treatment protocols aimed at improving accessibility of vaccinations at the appropriate location, reducing the frequency of vaccine doses, and stimulating sufficient protective immunity.

Development of Albendazole Nanodispersion for the Effective Treatment of Helminthiasis

Albendazole is a drug used to treat parasitic worm infections. ALB results in the tegument and intestinal cells of the worm undergoing degenerative changes, which ultimately lead the parasite to become immobile and die. The purpose of the study was to improve the solubility and effectiveness of an ALB-loaded solid nano dispersion for the effective treatment of helminthiasis.ALBFs were generated by a solvent evaporation procedure involving PVPK30 and carbopol, which may improve the stability of controlled drug release rates. The newly found ALBFs are more soluble than pure albendazole and have a better bioavailability. ALBFs allow for the optimization of therapeutic efficacy while lowering potential side effects and modulating enzymatic resistance, degradation, and drug release rate. Thus, the created ALBFs demonstrated successful helminthiasis treatment with lower dose frequency.

Patient preferences for preventive migraine treatments among Canadian adults: A discrete choice experiment.

To evaluate preferences for key attributes of injected or infused preventive migraine treatments and assess heterogeneity in preferences among Canadian participants with migraine. Current treatment options for migraine prevention differ in their attributes, including mode of administration, efficacy, and dosing frequency; preferences for such attributes can vary among patients. With the advent of new therapies, evidence demonstrating patient preferences for injected or infused preventive migraine treatments is necessary. Canadian adults self-reporting a diagnosis of migraine completed a cross-sectional, internet-based survey that included a discrete choice experiment. Participants were presented with attributes of preventive migraine treatments, including speed of onset, durability of efficacy, mode of administration, administration setting, and dosing frequency. Latent class analysis (LCA) was used to identify subgroups of patients who differed in their treatment preferences. In total, 200 participants completed the survey. Participants' treatment preferences were most sensitive to improvements in the durability of effectiveness from "wears off 2 weeks before next dose" to "does not wear off before the next dose" (absolute difference in weights = |-0.95 to 1.07| = 2.02) and improvements from "cranial injections" to "intravenous infusions" (|-1.04 to 0.58| = 1.62); participants equally preferred self-injection and intravenous infusion from a health-care provider (mean weight = 0.58 and 0.47, respectively) as a route of administration over cranial injections (mean weight = -1.04). Three subgroups were identified with LCA: group one (n = 103) prioritized fast-acting and durable therapies, group two (n = 54) expressed aversion to cranial injections, and group three (n = 43) favored treatments administered in a health-care provider setting. In this sample of Canadian adults with migraine, we showed that durability of effectiveness and mode of administration are key attributes influencing patient preferences for preventive migraine treatments; however, certain groups of patients may differ in their treatment priorities. Our results highlight the need for patient-provider discussions regarding treatment attributes and consideration of patients' preferences when selecting a preventive migraine treatment.

Unravelling the potential of hydrogen in biological systems

Molecular hydrogen (H2) and oxyhydrogen (66% H2/ 33% O2) gases have been demonstrated to remediate the effects of numerous diseases in adults[1-4]. By acting as an anti-inflammatory and antioxidative agent, it is reported that H2 can improve recovery through mitigating hyperinflammatory responses and reducing oxidative stress[5-7]. As the precise mechanisms of H2 activity are currently undefined, the lack of primary target identification, coupled with difficulties regarding administration methods (e.g., dosage and dosage frequencies, and long-term effects of treatments), there is a requirement for H2 research to evidence how it can reasonably and effectively, be incorporated into healthcare.

Deposition, dissipation, metabolism, and dietary risk assessment of chlorothalonil on pakchoi

For the scientific application of chlorothalonil, a thorough understanding of chlorothalonil deposition, distribution, and dissipation on pakchoi is required so as to reduce its application dosage. In this study, the effects of the application dosage, application season, planting environment, initial deposition, field dissipation and metabolism of pakchoi were investigated. The chlorothalonil deposition amount gradually increased with increasing dosage and application frequency. The deposition law in each application strategy was leaf > edible parts > petiole > planting soil. The half-lives of chlorothalonil in pakchoi in May, October, and December were 2.86–5.79, 3.08–5.87, and 6.41–11.32 days, respectively. The deposition concentration and dissipation half-life of chlorothalonil in different parts of pakchoi and the planting soil in greenhouse environments were higher than those in open-field environments. The initial deposition concentration and half-life of chlorothalonil in pakchoi gradually decreased from north to south: Beijing >Hefei >Changsha in April and Hefei >Sanya in December. Chlorothalonil can be converted to metabolite I (C8HCl3N2O) in pakchoi plants, which can gradually dechlorinate to produce metabolite II (C8HCl3N2), metabolite III (C8H2Cl2N2), and metabolite IV (C8H3ClN2). Within an application interval of 7 days, the long-term consumption of pakchoi leaves and edible parts poses unacceptable dietary risks. This study improves chlorothalonil utilization rates and provides technical guidance for its scientific application in the pakchoi planting ecosystem.

Dexamethasone-loaded ROS stimuli-responsive nanogels for topical ocular therapy of corneal neovascularization

Dexamethasone (DEX) has been demonstrated to inhibit the inflammatory corneal neovascularization (CNV). However, the therapeutic efficacy of DEX is limited by the poor bioavailability of conventional eye drops and the increased risk of hormonal glaucoma and cataract associated with prolonged and frequent usage. To address these limitations, we have developed a novel DEX-loaded, reactive oxygen species (ROS)-responsive, controlled-release nanogel, termed DEX@INHANGs. This advanced nanogel system is constructed by the formation of supramolecular host-guest complexes by cyclodextrin (CD) and adamantane (ADA) as a cross-linking force. The introduction of the ROS-responsive material, thioketal (TK), ensures the controlled release of DEX in response to oxidative stress, a characteristic of CNV. Furthermore, the nanogel's prolonged retention on the corneal surface for over 8 h is achieved through covalent binding of the integrin β1 fusion protein, which enhances its bioavailability. Cytotoxicity assays demonstrated that DEX@INHANGs was not notably toxic to human corneal epithelial cells (HCECs). Furthermore, DEX@INHANGs has been demonstrated to effectively inhibit angiogenesis in vitro. In a rabbit model with chemically burned eyes, the once-daily topical application of DEX@INHANGs was observed to effectively suppress CNV. These results collectively indicate that the nanomedicine formulation of DEX@INHANGs may offer a promising treatment option for CNV, offering significant advantages such as reduced dosing frequency and enhanced patient compliance.

Dose-exposure-efficacy response of intravenous immunoglobulin G 10% in multifocal motor neuropathy.

Multifocal motor neuropathy is a rare chronic immune-mediated neuropathy with impaired grip strength representing a common symptom. While intravenous immunoglobulin G is an effective treatment for the disease, significant variation in treatment response has been observed but not well understood. This analysis characterized dose-exposure-response relationships in multifocal motor neuropathy, using grip strength as a clinical efficacy measure. Serum immunoglobulin G trough concentrations and grip strength data for the more affected hand from a Phase 3, randomized, double-blind, placebo-controlled, crossover trial of intravenous immunoglobulin 10% in 44 patients with multifocal motor neuropathy (NCT00666263) were used to develop a population pharmacokinetic-pharmacodynamic model. The model adequately described the observed pharmacokinetic and pharmacodynamic data and relationships between intravenous immunoglobulin 10% dose, serum immunoglobulin G trough levels, grip strength, and inter-patient variabilities in multifocal motor neuropathy. Model-based simulations for various dosing regimens (0.4-2.0 g/kg every 2-4 weeks) indicated that ≥1.6 g/kg/month would achieve clinically meaningful improvements in grip strength (≥4 kg) in ≥70% of patients. More frequent dosing at an equivalent monthly dose led to a more consistent response in grip strength. Furthermore, splitting the dose over multiple days for high doses (>1 g/kg) did not impact grip strength. These findings suggest that the majority of patients with multifocal motor neuropathy would respond rapidly to intravenous immunoglobulin 10% with a range of dosing regimens. Shorter dosing intervals may avoid the diminishing response seen with longer dosing intervals. Dose-splitting provided similar outcomes while offering flexibility and convenience.

Quality-by-Design-Driven Nanostructured Lipid Scaffold of Apixaban: Optimization, Characterization, and Pharmacokinetic Evaluation.

Apixaban, an anticoagulant, is limited in its efficacy due to poor solubility, low bioavailability, and extensive metabolism. This study investigates the application of nanostructured lipid carriers (NLCs) to enhance the bioavailability of Apixaban. NLCs were prepared using the high-pressure homogenization method. The influence of independent variables, viz., the amount of Tween 80, HPH pressure, and the number of HPH cycles, were studied using a 23 factorial design. The average particle size, PDI, zeta potential, and entrapment efficiency of the optimized NLCs were found to be 232 ± 23 nm, with 0.514 ± 0.13 PDI and zeta potential of about -21.9 ± 2.1 mV, respectively. Additionally, concerning the thermal and crystallographic properties of the drug, the NLCs showed drug entrapment without altering its potency. The in-vitro drug release studies revealed an immediate release pattern, followed by sustained release for up to 48 h. In-vivo pharmacokinetic experiments demonstrated that Apixaban-loaded NLCs exhibited higher values of t1/2 (27.76 ± 1.18 h), AUC0-∞ (19,568.7 ± 1067.6 ng·h/mL), and Cmax (585.3 ± 87.6 ng/mL) compared to free drugs, indicating improved bioavailability. Moreover, a decrease in the elimination rate constant (Kel) reflected the sustained effect of Apixaban with NLCs. NLCs offer improved oral absorption rates and enhanced therapeutic impact compared to free drugs, potentially reducing dose frequency and improving patient outcomes.

Effects of differences in dose and frequency of teriparatide on bone structure in Proximal Femur. - Analysis by DXA-based 3D-modeling (3D-SHAPER Software) -TRIPLE-BONE study (The effects of TeRIParatide preparation on bone mineraL density increase and BONE structure).

To examine the effects of differences in the amount of teriparatide (TPTD) per administration and its dosing frequency on the bone structure in the proximal femur by dual-energy X-ray absorptiometry (DXA)-based 3D-modeling (3D-SHAPER software). This was a multicenter retrospective study. Patients aged 50 years or older with primary osteoporosis who continuously received once-/twice-weekly (1・2/W, n= 60) or 1/D TPTD (n= 14) administration for at least one year were included in the study. Measurement regions included the femoral neck (FN), trochanter (TR), femoral shaft (FS), and total proximal hip (TH). Concurrently, the bone mineral density (BMD) and Trabecular Bone Score (TBS) were measured. The cross-sectional area, cross-sectional moment of inertia, and section modulus in the FS were significantly improved in the 1・2/W TPTD group, as compared to the 1/D TPTD group. However, significant improvement of the cortical thickness and buckling ratio in the FN was observed in the 1/D TPTD group, as compared to the 1・2/W TPTD group. Trabecular BMD values in the FS and TH were significantly increased in the 1/D TPTD group, as compared to the 1・2/W TPTD group, while the cortical BMD values in the TR, FS, and TH were significantly increased in the 1・2/W TPTD group, as compared to the 1/D TPTD group. Trends toward more favorable improvement of the cortical bone by 1・2/W TPTD and that of the trabecular bones by 1/D TPTD were observed.

Huntington Disease Treated with Austedo (Deutetrabenazine)

Huntington's disease (HD) is a neurodegenerative disorder characterized by chorea, cognitive decline, and psychiatric symptoms. Austedo (deutetrabenazine) represents a significant advancement in the treatment of chorea associated with HD, being the first deuterated drug approved by the US Food and Drug Administration (FDA) for this purpose. Deutetrabenazine, a modified form of tetrabenazine, acts by inhibiting vesicular monoamine transporter 2 (VMAT2), thereby reducing dopamine levels. Its unique structure, incorporating deuterium instead of hydrogen, prolongs its half-life and allows for less frequent dosing. Clinical trials, such as Phase III First HD, have demonstrated deutetrabenazine's efficacy in improving chorea symptoms in HD patients, with favorable tolerability reported. Despite similarities in effectiveness with tetrabenazine, deutetrabenazine offers a potentially better-tolerated option for chorea treatment in HD. However, further research, including direct comparative studies and long-term data, is necessary to fully elucidate its advantages over existing therapies.

Preference for a Novel Oral Alternative to Parenterally Administered Medications.

Rani Therapeutics is developing a robotic pill (RP), an oral drug delivery platform called RaniPill™ that can deliver a number of biotherapeutics with high bioavailability; eliminating the need for injections. While patients in general prefer oral to injectable therapies, preference for a more frequent oral regimen compared to a less frequent injectable regimen is unknown. Two marketing surveys were conducted to gather data on preference for oral versus injectable therapies. A clinical study gathered data on participant preference for oral pills vs injections before and after swallowing a Mock-RP capsule. A total of 1689 adults taking injections (mean duration 3-7 years) to treat endocrine or inflammatory conditions were anonymously surveyed online for their preference to administer/prescribe medications orally via the RP. In the clinical study, 150 participants currently taking injections for chronic conditions evaluated the swallowability of a Mock-RP and completed a questionnaire regarding their preferences. Majority of respondents surveyed stated they would be willing to convert to an oral alternative over their current parenteral therapy regardless of drug or disease. In the clinical study, all participants were able to swallow the Mock-RP and 91% indicated their preference for the oral route versus their current parenteral route of drug administration. Survey respondents and those in the clinical study using frequent injections were more willing to select a once-daily capsule compared to those injecting infrequently. Even study participants who inject infrequently (≥monthly: 80%) would prefer a once-daily pill over their injection regimen. Patients taking injections and prescribing physicians strongly prefer oral dosing to parenteral administration of biologics even if dosing frequency with the oral option, such as the RP, is increased.

Antitubercular nanocarrier monotherapy: study of in-silico molecular docking and in-vitro efficacy of repurposed antiviral drug

Abstract There has to be a breakthrough in tuberculosis (TB) treatment to address issues with drug resistance, patient noncompliance, and dosage frequency. We produced durable therapeutic nanocarriers (NCs) and tested their efficiency in-vitro in macrophages infected with Mycobacterium tuberculosis. Our goal was to decrease adverse effects linked to systemic drug distribution and improve drug concentration at the target site. There are multiple pathways by which antiviral medications induce renal failure. Several novel drugs have been shown to cause direct renal tubular toxicity through their distinct impacts on kidney epithelial cells. In this present study the in-silico docking studies were performed and the silver nanoparticles of the antiviral drug Entecavir was prepared and characterized by using SEM and HR-TEM studies. The prepared nanoparticles were evaluated for its anti-tubercular activity by in-vitro and the results showed the repurposed antiviral drug showed remarkable anti-tubercular activity. There is mounting evidence that the repurposed antitubercular drug Entecavir is a viable new option for treating tuberculosis.

Plasma Venetoclax Concentrations in Patients with Acute Myeloid Leukemia Treated with CYP3A4 Inhibitors.

Venetoclax (VEN) is used in patients with acute myeloid leukemia (AML) and is primarily metabolized by CYP3A4, a major drug-metabolizing enzyme. Patients with AML simultaneously administered VEN and CYP3A4 inhibitors require a more appropriate management of drug-drug interactions (DDIs). Here, we report two cases of patients with AML (54-year-old man and 22-year-old woman) administrated VEN and CYP3A4 inhibitors, such as posaconazole, cyclosporine, or danazol. In the first case, we evaluated the appropriateness of timing for adjusting VEN dosage subsequent to the cessation of posaconazole. Consequently, modifying the VEN dosage in conjunction with the cessation of Posaconazole simultaneously may result in elevated plasma VEN levels. In the second case, plasma VEN concentrations were markedly elevated when co-administered with several CYP3A4 inhibitors. Additionally, in vitro assays were conducted for reverse translational studies to analyze CYP3A4 inhibition. CYP3A4 inhibition by combinatorial administration of cyclosporine A and danazol was demonstrated in vitro, which potentially explains the increasing plasma VEN concentrations observed in clinical settings. Although the acquisition of therapeutic effects is a major priority for patients, frequent therapeutic drug monitoring and dosage adjustments considering DDIs would be important factors in chemotherapy.

Bioadhesive polymer in antifungal drug delivery for therapeutic treatment of candidiasis.

Candida species are the primary cause of candidiasis, a common yeast infection, with Candida albicans being the most prevalent pathogen. These infections often infiltrate the body through cutaneous and vaginal routes. Given the potential severity of some Candida infections, particularly invasive cases, there is a critical need for effective antifungal treatments. Controlled drug delivery strategies have been developed to achieve optimal release kinetics and precise targeting of active agents, especially in fungal infection therapeutics. Consequently, significant attention has been focused on exploring and utilizing bioadhesive polymers to enhance the performance of drug delivery systems for antifungal medications. Bioadhesive drug delivery systems aim to sustain the release of therapeutic agents, reducing the need for frequent dosing. This article provides a comprehensive review of scientific investigations into the use of antifungal drugs within bioadhesive drug delivery systems for treating candidiasis, locally and systemically. The evaluation covers the efficacy of these systems against candidiasis, factors affecting prolonged contact at the application site, and the underlying mechanisms of drug delivery.

Development and Characterization of Lipid Nanoparticles Loaded with Antipsychotic Drugs using Central Composite Design

Background: Fluoxetine and olanzapine combination tablets are available in the market for oral administration in the treatment of depression, but fluoxetine has been shown to have a dose-related side effect due to its high oral dose and ability to undergo excessive first-pass metabolism. Olanzapine has low solubility and low bioavailability. Objective: The objective of this study was to prepare lipid nanoparticles containing fluoxetine and olanzapine to enhance the solubility and dissolution profile of the drugs. Methods: Lipid nanoparticles (LNs) were prepared by high-speed homogenization using the ultrasonication method. Different lipids and surfactants were used to screen out the best lipids, surfactants, and their ratio in the preparation of lipid nanoparticles. Drug and polymer compatibil-ity was examined using FTIR and DSC studies. The formulation was optimized using the central composite design to establish functional relationship between independent variables and respons-es. Optimized batch was characterized using particle size, PDI, zeta potential, % EE, % CDR, and stability. Results: Phase solubility study revealed FLX to have highest solubility in stearic acid and oleic acid, whereas OLZ showed highest solubility in Precirol ATO 5 and oleic acid. Poloxamer 188 was selected on the basis of high entrapment efficiency of the drug. In LNs, no significant interaction between drug and polymer was confirmed by DSC and FTIR. The particle size of optimized batch was found to be 411.5 nm with 0.532 PDI and - 9.24 mV zeta potential. For FLX and OLZ, the %EE and %CDR after 8h were found to be more than 90%. No significant change in %EE and %CDR of the formulation was observed after 4 weeks of storage. Conclusion: Experimental results demonstrated excellent drug entrapment as well as controlled release behavior from optimized LNs of FLX and OLZ at reduced dosage frequency.

Exploring the potential of carbocisteine loaded microparticulate system by using ccd model for the treatment of respiratory infections

Background: Multi-particulate drug delivery systems (microbeads) deliver drugs over an extended period, distributing them evenly throughout the gastrointestinal tract and minimizing local irritation. Microbeads are small, solid, free-flowing particulate carriers that contain drug particles that have been dispersed and are either crystalline in solution. Aim: The present work explores the potential of the carbocisteine-loaded floating microparticulate drug delivery system. Methodology: Floating microbeads were prepared using the ionotropic gelation method and optimized using Central Composite Design. Result and discussion: Floating microbeads of prepared carbocisteine were evaluated for the FTIR study, which reveals no interaction between the drug and other excipients. Buoyancy time, drug content, particle size, and % drug release were also characterized; it found that drug release was 90.24 %, up to 17 hours, 250 to 220 µm, and drug content 96.67%, respectively, for the optimized batch. An accelerated stability study was performed, showing that the formulation was stable. Floating microparticulate drugs were prepared, and batch B-3 was optimized based on in-vitro buoyancy and release patterns. The floating ability of the beads was observed visually for 10 to 17 hr, and an increase in polymer concentration decreased the swelling of the beads. Conclusion: The results obtained from the formulation batch B-3 show good results for all the parameters tested. Floating microbeads could be the best possible approach to deliver drugs with the benefit of reduced dosing frequency

A unifying model to explain frequent SARS-CoV-2 rebound after nirmatrelvir treatment and limited prophylactic efficacy

In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals. Yet, nirmatrelvir/ritonavir failed as post-exposure prophylaxis in a trial, and frequent viral rebound has been observed in subsequent cohorts. We develop a mathematical model capturing viral-immune dynamics and nirmatrelvir pharmacokinetics that recapitulates viral loads from this and another clinical trial (PLATCOV). Our results suggest that nirmatrelvir’s in vivo potency is significantly lower than in vitro assays predict. According to our model, a maximally potent agent would reduce the viral load by approximately 3.5 logs relative to placebo at 5 days. The model identifies that earlier initiation and shorter treatment duration are key predictors of post-treatment rebound. Extension of treatment to 10 days for Omicron variant infection in vaccinated individuals, rather than increasing dose or dosing frequency, is predicted to lower the incidence of viral rebound significantly.

Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn’s disease patients over three years

Long-term data on ustekinumab in real-life Crohn’s disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn’s disease patient cohort with a three-year follow-up. Crohn’s disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn’s Disease (SES-CD)) were collected for three-years’ time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn’s disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn’s disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.

Mimosa/quince seed mucilage–co-poly (methacrylate) hydrogels for controlled delivery of capecitabine: Simulation studies, characterization and toxicological evaluation

This research focused on developing pH-regulated intelligent networks using quince and mimosa seed mucilage through aqueous polymerization to sustain Capecitabine release while overcoming issues like short half-life, high dosing frequency, and low bioavailability. The resulting MSM/QSM-co-poly(MAA) hydrogel was evaluated for several parameters, including complex structure formation, stability, pH sensitivity, morphology, and elemental composition.FTIR, DSC, and TGA analyses confirmed the formation of a stable, complex cross-linked network, demonstrating excellent stability at elevated temperatures. SEM analysis revealed the hydrogels' smooth, fine texture with porous surfaces. PXRD and EDX results indicated the amorphous dispersion of Capecitabine within the network.The QMM9 formulation achieved an optimal Capecitabine loading of 87.17 %. The gel content of the developed formulations ranged from 65.21 % to 90.23 %. All formulations exhibited excellent swelling behavior, with ratios between 65.91 % and 91.93 % at alkaline pH. In vitro dissolution studies indicated that up to 98 % of Capecitabine was released after 24 h at pH 7.4, demonstrating the potential for sustained release.Furthermore, toxicological evaluation in healthy rabbits confirmed the system's safety, non-toxicity, and biocompatibility.

Efficacy and tolerability of Brivaracetam in people with intellectual disability compared to those without intellectual disability

IntroductionIn England, nearly a quarter of people with intellectual disability (PwID) have epilepsy. Though 70 % of PwID have pharmaco-resistant seizures only 10 % are prescribed anti-seizure medication (ASMs) licenced for pharmaco-resistance. Brivaracetam (BRV) licenced in 2016 has had nine post-marketing studies involving PwID. These studies are limited either by lack of controls or not looking at outcomes based on differing levels of ID severity. This study looks at evidence comparing effectiveness and side-effects in PwID to those without ID prescribed Brivaracetam (BRV). MethodsPooled case note data for patients prescribed BRV (2016–2022) at 12 UK NHS Trusts were analysed. Demographics, starting and maximum dose, side-effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher’s exact and logistic regression methods were employed. Results37 PwID (mild 17 M/P 20) were compared to 102 without ID. Mean start and maximum dose was lower for PwID than non-ID. Mean maximum dose reduced slightly with ID severity. No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in BRV’s efficacy i.e. >50 % seizure reduction or tolerability. Mental and behavioural side-effects were more prevalent for PwID (27.0 % ID, 17.6 % no ID) but not significantly higher (P = 0.441) or associated with ID severity (p = 0.255). ConclusionThis is the first study on BRV, which compares ID cohorts with differing severity and non-ID. Efficacy, tolerability and side-effects reported are similar across differing ID severity to those with no ID.