Suspension Formulation Research Articles

The influence of spatial dispersion on the steady-state characteristics and thermodynamic instability fluctuations of one-dimensional iron particle flames

This study utilizes a simplified one-dimensional discrete model to analyze the characteristic parameters involved in the flame propagation of iron particles. It focuses on the influence of dispersive "micro flames" within these flames on propagation dynamics, investigating stable and unstable scenarios. The model adopts the form of particle suspension delineating alternant reaction intervals and inert intervals. The spatial dispersion rate (Γ) which describes the spatial extent of the "micro flames" is introduced, with Γ=1 for the continuum model and Γ>1 for the discrete model. Theoretical equations, combining kinetic and diffusion equations, are solved with the finite difference method. The solution is evaluated preliminarily to distinguish numerical instability and thermodynamic instability. Additionally, in the preset time and space range, conditions for different equivalence ratios, particle radius and spatial dispersion rates are analyzed emphatically, with a comparison of typical simulation results and experimental data. As shown in the numerical simulation, the flame maintains stable propagation when ϕ≥0.7. The flame front, where the particle temperature rises above the gas temperature, extends backward with the increase of particle radius. The increase of Γ tends to extend the flame front of the fuel-lean flame and constringe that of the fuel-rich flame. Thermodynamic instability occurs in fuel-lean suspension with its manifestation preliminarily classified to distinct fluctuation, faint fluctuation and the final cessation. The increase of Γ also extends the flame propagation time under the dominance of thermodynamic instability, indicating different temperature structure evolution from the continuum model.

Effectiveness and patient satisfaction with the new sildenafil oral suspension formulation compared to sildenafil oro-dispersible film: a real-life study.

Sildenafil is one of the most used phosphodiesterase type 5 inhibitor (PDE5i) for the treatment of erectile dysfunction (ED) in clinical practice. A new oral suspension formulation (OSF) of sildenafil has been introduced to overcome the drawbacks of previous formulations. We assess the efficacy and patients' experience with sildenafil 50 mg OSF in men with ED who were taking the sildenafil oro-dispersible film (ODF). Demographics and clinical data from 70 consecutive men with mild-moderate ED were analysed. Patients were treated with sildenafil 50 mg ODF for 12 weeks (follow-up 1), then, after 2-week washout, were administered sildenafil 50 mg OSF for 12 weeks (follow-up 2). At each follow-up, patients completed the International Index of Erectile Function (IIEF), the Patient Global Impression of Improvement (PGI-I), and the Psychological and Interpersonal Relationship Scales-Short Form (PAIRS-SF) questionnaires. Descriptive statistics described the whole cohort. The Wilcoxon Signed Rank Test assessed potential differences in psychometric scores at different follow-up assessments. Logistic regression analyses tested the associations between study variables and satisfaction after sildenafil OSF treatment. Overall, median age was 56 (51-62) years, and median IIEF-EF score was 14 (12-17). Compared to baseline, IIEF-EF scores significantly improved after sildenafil ODF and OSF treatment (all p < 0.01) with no differences between the two formulations. IIEF-overall satisfaction (OS) was higher after sildenafil OSF than ODF (p < 0.001). Similarly, median PGI-I score were better after sildenafil OSF than ODF (p < 0.001). The PAIRS-SF spontaneity scores were significantly higher after OSF than ODF (p < 0.01). At multivariable logistic regression analysis, younger age (p = 0.02) and lower baseline IIEF-EF scores (p = 0.01) were independent predictors of improved satisfaction with OSF compared to ODF. The sildenafil OSF and ODF had similar efficacy, however the new OSF provides higher satisfaction and spontaneity scores compared to the oro-dispersible film.

223. PIDS FEATURED ORAL ABSTRACT: Assessment of Bacterial Pathogens in Young Children with Acute Otitis Media: A Prospective Cohort Study in the United States (US)

Abstract Background Despite the success of pediatric pneumococcal conjugate vaccine (PCV) programs in the US, acute respiratory illness, including acute otitis media (AOM) due to Streptococcus pneumoniae (SPN) persists. PCV13 has been recommended for pediatric routine use since 2010. With recent adoption of higher-valency PCVs, there is a continued need to survey pathogens causing AOM in children.Table 1:Bacterial Results of Nasal Specimens in Children 6-35 Months Diagnosed with Acute Otitis Media (Cohorts 1&amp;2) or Upper Respiratory Infection (Cohort 3) Methods Children aged 6 to 35 months diagnosed with AOM (Cohort 1 &amp; 2) and upper respiratory infection (URI, Cohort 3) were enrolled from primary care and ENT practices in Pittsburgh, PA. Nasal specimens (nasopharyngeal or mid-turbinate) were collected for all children. Middle ear fluid (MEF) specimens were collected by tympanocentesis for children enrolled in Cohort 1. MEF and nasal specimens were cultured for SPN, Hemophilus influenzae (Hflu), and Moraxella catarrhalis (Mcat). Serotypes (ST) and susceptibility testing were determined for SPN isolates.Table 2:Correlation of Bacterial Cultures of Nasal and Middle Ear Fluid (MEF) Specimens (n=72 pairs) in Children 6-35 Months Diagnosed with Acute Otitis Media (Cohort 1) Results From October 2019 to January 2024, 545 children were enrolled (Cohort 1: n=72; Cohort 2: n=322; Cohort 3: n=151). Among nasal specimens from children with AOM (n=394), SPN, Hflu and Mcat were detected in 47%, 44% and 70%, respectively. In MEF specimens from children with AOM (n=72), SPN, Hflu and Mcat were detected in 15%, 54% and 17% respectively. Nasal-MEF pairs were concordant for 79% (57/72). Children with Hflu had higher rates of nasal-MEF concordance than children with SPN or Mcat. In nasal specimens from children with URI (n=151), SPN, Hflu and Mcat were detected in 36%, 18% and 54%, respectively. In nasal specimens, co-detection of bacterial pathogens occurred more often in those with AOM (220/394, 56%) than URI (49/151, 32%). Of the SPN ST results available (nasal: n=174; MEF: n=8), 35B, 15B, 3, and 15C were most frequent; 8% of nasal and 50% of MEF were PCV13 STs. SPN was found simultaneously in the nasal-MEF pairs of 10/72 children, of which STs are available for 7 pairs; 6/7 pairs agreed, 1 disagreed (nasal:35B and MEF:3). SPN nonsusceptible to penicillin were uncommon (2% of nasal and 9% of MEF isolates).Figure 1:Distribution of S. pneumoniae Serotypes by Isolate Source Conclusion STs 3 and 19A, included in PCV13, were responsible for half of SPN isolates found in MEF of children with AOM. Continued surveillance is still warranted to guide vaccine development and therapeutic decision-making for children. Disclosures Judith M. Martin, MD, Centers for Disease Control and Prevention: funding to the institution to support this work|Centers for Disease Control and Prevention: funding to the institution for unrelated work|Merck, Sharp and Dhome: funding to the institution to support this work|Moderna: funding to the institution for unrelated work|NIH: funding to the institution for unrelated work Matthew C. Lee, BA, Centers for Disease Control and Prevention (CDC): Grant paid to the institution|Merck Sharpe &amp; Dohme: Grant paid to the institution Jessica Weaver, PhD, MPH, Merck &amp; Co. Inc.: Employment|Merck &amp; Co. Inc.: Stocks/Bonds (Public Company) Meghan White, PharmD, Merck Sharp &amp; Dohme, LLC: Employee|Merck Sharp &amp; Dohme, LLC: Stocks/Bonds (Public Company) Alejandro Hoberman, MD, Kaizen Biosciences: Advisor/Consultant|Kaizen Biosciences: Pediatric oral suspension formulation of amoxicillin-clavulanate potassium and the method for use.|Kaizen Biosciences: Ownership Interest|Not licensed: Method and apparatus for aiding diagnosis of otitis media by classifying tympanic membrane images.

Acceptability and Implementation Challenges of Benzathine Penicillin G Secondary Prophylaxis for Rheumatic Heart Disease in Ethiopia: A Qualitative Study

Background: Monthly intramuscular injections of benzathine penicillin G (BPG) remain the cornerstone of secondary prophylaxis for acute rheumatic fever and rheumatic heart disease (RHD). The barriers to successful delivery of BPG may be patient- or service-delivery-dependent. Objective: The aim of the present study was to explore the perceived acceptability and implementation challenges of BPG treatment for RHD, from the perspective of healthcare providers (HCPs). Methodology: A descriptive qualitative study using semi-structured interview guides was conducted in four public hospitals in Ethiopia. Physicians and nurses who had at least 1 year of experience in delivering RHD secondary prophylaxis were recruited. The interviews were audio recorded, transcribed verbatim, and translated into English for analysis using framework method thematic analysis. Identified behavioral factors were mapped onto a theoretical framework of acceptability (TFA), and the Capability, Opportunity, Motivation-Behavior (COM-B) model. Result: Twenty-two interviews were conducted with HCPs (mean age 39 years, 55% nurses). Insights into BPG use and acceptability were categorized into four major themes related to: (1) individual factors (e.g., fear of anaphylactic reaction), (2) health system barriers (e.g., BPG shortage), (3) patient/caregiver perceptions (e.g., reliance on injectables, over expectation of treatment outcomes), and (4) product (e.g., injection pain, needle blockage). Conclusions: HCPs identified facilitators and barriers which highlight the complexities associated with BPG as secondary prophylaxis for RHD in Ethiopia. Based on these data, we suggest RHD control programs should (1) provide cross-disciplinary training and education programs to support safe and context-appropriate delivery of BPG (2) improve resourcing of health facilities to facilitate safe drug delivery, (3) establish a comprehensive system for auditing severe adverse reactions post-BPG injection to generate robust pharmacovigilance data, and consider alternative approaches to BPG delivery including access to improved formulations (e.g., BPG suspension formulations in pre-filled syringes). Highlights: Key barriers included (a) resistance from healthcare providers to administer benzathine penicillin G (BPG) due to their concerns about injection-related severe adverse events, and potential repercussions should an event occur, (b) poor community and healthcare provider awareness of the disease and its treatment, (c) lack of resources to manage adverse events, and (d) injection pain. Key enablers included (a) perceived superior treatment benefits of BPG and (b) co-administration of lidocaine/analgesics to reduce injection pain. Recommendations to address identified challenges include (a) improved training/education on RHD diagnosis, disease progression, and treatment, (b) improved access to supportive resources, (c) active adverse reaction monitoring and reporting, and (d) encouraging the provision/access of globally subsidized BPG suspension formulations in pre-filled syringes.

“Timing” Transitions or “Times” in Transition? Revisiting the Value of Time Suspension for Young People in Italy After the COVID-19 Pandemic

Much has been written to address the increasing complexity of youth temporalities, especially through a focus on when adulthood is reached, an approach that informs the tradition of youth studies called “youth transitions.” This article discusses some of the shortcomings of this approach that were revealed during the global pandemic, through the social distancing measures that were put in place in response to it and how young people reacted to new imposed rhythms. The pandemic has predominantly been seen as a “suspension,” with implications in particular on two different temporal dimensions: on the one hand, young people have experienced profound changes in their everyday lives due to lockdown restrictions; and, on the other hand, at the biographical level, a search for alternative lifestyles has emerged, impacting on mid-term perspectives. These changes urge us to reconsider various phenomena of time suspension associated with youth, such as moratorium and waithood, paying attention to the value that young people attribute them. Borrowing from Flaherty’s work on time work, this article discusses various nuances of time suspensions that allow us to examine agency transformations during the pandemic. It does so by looking at a case study of young people in Italy, and how a disregard for the temporalities that are typical of value to youth appears to have taken place, based on documentary sources and qualitative material analyzed for a project called IANG. By reflecting on the changes in the ways of looking at young people during the pandemic, and zooming in on some rituals that were reworked due to lockdown restrictions such as the final school exam, I conclude that we should shift attention from “timing transitions,” to “times” in transition, and look more attentively at the meanings attributed to various forms of time suspension that make up youth through specific youth temporalities.

Preparation and characterization of andrographolide nano-cocrystals using hummer acoustic resonance technology.

Andrographolide (AG) is a diterpene lactone with significant anti-inflammatory and antitumor activities. However, the poor water solubility limits its clinical application. An andrographolide-salicylic acid (AG-SLA) nano-cocrystal delivery system was rapidly developed using hummer acoustic resonance (HAR) technology in this research. The formulation of the AG-SLA nano-cocrystal suspension and the process parameters for HAR technology were optimized in a high-throughput manner, with SDS-Tween 80 as the optimal composite stabilizer. Nano-cocrystal suspension of AG-SLA with an average particle size of 190 nm were successfully prepared, and then the optimal formulation were tenfold scaled up. Freeze-drying was adopted to solidify the nano-cocrystal and improve its stability. Various analytical techniques were used to characterize the particle size and solid state of the nano-cocrystals. The high-energy input from the HAR instrument induced partial amorphization of the nano-cocrystals, as confirmed by PXRD and DSC analyses. Saturation solubility experiments demonstrated that the solubility in pH 1.2 hydrochloric acid buffer and pH 6.8 phosphate buffer increased by 5.74 times and 6.82 times, respectively, compared to raw AG. In vitro dissolution tests indicated that the cumulative release over 120min in pH 1.2 hydrochloric acid buffer and pH 6.8 phosphate buffer increased by 1.60 times and 1.88 times, respectively, compared to raw AG.

Photodegradation reveals that singlet energy transfer impedes energy-gradient-driven singlet fission in polyacene blends.

Singlet fission (SF) is a process that is potentially beneficial for photovoltaics by producing two triplet excitons from a single photon, but its application is often hindered by the inability to effectively separate the resultant triplet excitons. It has been proposed that an energy gradient can assist in separating triplet excitons through triplet energy transfer between chromophores of different triplet energies, but this approach has only been studied in solution and the efficacy of this strategy in the solid state is under explored. Here, we investigate energy-gradient-driven SF in a disordered solid state, in the form of suspensions of 5,12-bis(triisopropylsilylethnyl)tetracene:6,13-bis(triisopropylsilylethnyl)pentance (TIPS-Tn:TIPS-Pn) blend nanoparticles (NPs). Rather than using more conventional techniques such as ultrafast (sub-nanosecond) spectroscopy, we study the photophysics in these NPs through monitoring their photodegradation. TIPS-Tn photodegrades rapidly in neat NPs, but this photodegradation is suppressed upon the addition of TIPS-Pn, indicating a decrease in the TIPS-Tn triplet population. By modeling the photodegradation over a timescale of minutes to hours, we are able to reveal details of processes on the ultrafast timescale. We show that triplet energy transfer occurs from TIPS-Tn to TIPS-Pn, leading to slower photodegradation for TIPS-Tn, and faster photodegradation for TIPS-Pn. However, modeling additionally indicates that singlet energy transfer from TIPS-Tn to TIPS-Pn also occurs, and in fact acts to reduce the efficiency of TIPS-Tn SF. Hence, in this particular system, the energy gradient impedes SF, rather than assisting it. These findings indicate that chromophore pairs must be carefully selected to switch off singlet energy transfer for the energy-gradient approach to be effective in enhancing SF.

A retrospective descriptive cross-sectional study of Oral Dosage Form Administered in The Form of Suspension to ICU Patients at Hospital X

Patients in the intensive care unit were often very sick and had lost consciousness. Because they had trouble swallowing, individuals with reduced awareness frequently depended on enteral tubes (NGT) for their daily medical and nutritional requirements. Since not all medications were accessible in parenteral forms, patients who relied on enteral tubes often had issues, including drug stability. Many problems arose in clinical usage when the medication was crushed or suspended and put into the NGT, including drug obstruction in the enteral tube and a reduction in drug stability as a result of the dose form being altered, making the drug unstable. Thus, this study aimed to ascertain the stability of oral suspension medications given to intensive care unit patients. The medical records of intensive care unit patients who had received oral medication therapy at X Hospital in Jakarta were examined retrospectively using a cross-sectional, descriptive approach. According to the statistics, coated tablets accounted for 68% of the most frequently used oral medication preparations. It was highly likely that crushing the coated tablets and administering them via NGT had resulted in tube obstruction. Additionally, 59.26% of the medications used had exhibited hygroscopic qualities, and several had been readily hydrolyzed. Based on these findings, it was concluded that oral medications, particularly crushed-coated tablets, could negatively affect drug stability. Active substances with hygroscopic properties and those prone to hydrolysis were also identified as potential contributors to instability.

The puzzle of defeated suspension

Abstract As scholars have commonly observed, a central difference between epistemic and practical normativity is the fact that the reasons of the former kind balance prohibitively, while reasons of the latter kind do so permissively. To explain the prohibition to believe or disbelieve in the face of tied evidence, several scholars have appealed to normative reasons in favour of a third doxastic option, the suspension of judgement. However, the question remains as to what happens if these latter reasons are defeated. In such cases, one seems to be stuck in an impasse: either one is forced into an epistemic dilemma– where neither of one’s doxastic options seems permissible– or one must relax the prohibitive balancing principle– where there might be, after all, situations in which believing in the face of tied evidence is rationally permissible. In this paper, I discuss different ways to derive this puzzle of defeated suspension, as well as the most common strategy in responding to it. I argue that an appeal to undefeated reasons to suspend judgement comes with significant downsides and, thus, one should seek a different response: in extreme forms of the puzzle of defeated suspension, a form of higher-order suspension becomes rational. If one treats higher-order suspension as an additional doxastic option, one can avoid the puzzle in its entirety. Furthermore, an analogue puzzle of higher-order doubt merits the same treatment.

Clonidine Oral Suspension (Onyda XR) for ADHD

The FDA has approved Onyda XR (Tris), an extended-release (ER) oral suspension formulation of the alpha2-adrenergic agonist clonidine, for use as monotherapy or as an adjunct to stimulant therapy for treatment of attention-deficit/hyperactivity disorder (ADHD) in children ≥6 years old. Clonidine ER tablets have been available for years for treatment of ADHD in children 6-17 years old.

Overview of suspension systems for mobile wheeled robots

A common type of transport system used in robotics is a wheeled platform with at least one drive axle and some form of suspension for each wheel. Autonomous navigation at high speed over rough terrain is a challenging and relevant task for wheeled robots. To achieve mobility on terrain, a wheeled robot must adapt and respond quickly. The suspension systems of mobile wheeled robots play a key role in ensuring their stability, maneuverability, and overall efficiency. This article presents a comprehensive overview of the different types of suspensions used in modern mobile wheeled robots. The main designs of passive and active, rigid and elastic suspensions are considered, as well as their features, advantages and disadvantages. As a result of the analysis, it was found that the optimal choice of suspension system depends on the specific operating conditions of the robot and the tasks set. For example, for robots operating in difficult terrain, suspensions with high damping are more suitable, while for robots performing precise maneuvers on a flat surface, suspension stiffness is more important. The article may be useful for engineers, researchers, and developers of robotic systems who seek to improve the designs of mobile wheeled robots and increase their efficiency and reliability. The conclusions and recommendations presented in the article can contribute to the development of new approaches to suspension design and optimization of existing solutions in the field of mobile robotics.

Oral Suspension as Versatile Galenic Formulation in Pediatry

In the last years increased the prescription of drugs in pediatry as pharmaceutical form of oral suspension. The same in commerce there are various producer that provide specific ready for use excipeints to make more easy to prepare OS in the galenic laboratory. Aim of this work is to verify the advantages of this pharmaceutical form to cover pediatrics dosages and also shortcomings of registered drugs. In this work are reported also scientific literature relates same ready for use product as bases-veicle for suspension and some formulations of interest.

Use of a capsule suspension formulation of S-metolachlor in fenclorim-treated rice

Abstract As herbicide resistance continues to render commonly used rice herbicides ineffective, alternative sites of action are paramount to maintaining yield and producer profitability. Combining a slow-release formulation and a fenclorim seed treatment might allow the safe use of S-metolachlor in rice. Experiments were initiated in 2022 and 2023 near Colt, AR, on a silt loam soil to evaluate crop safety using a capsule suspension (CS) formulation of S-metolachlor and a fenclorim seed treatment in rice. The first experiment assessed the tolerance of two cultivars (‘Diamond’ and ‘DG263L’) to three rates (0.42, 0.84, and 1.68 kg ai ha−1) of a CS S-metolachlor at a delayed preemergence (DPRE) application timing in conjunction with a fenclorim seed treatment. The second experiment evaluated a 1- to 2-leaf (EPOST) application of a CS S-metolachlor at 0.56 and 1.12 kg ai ha−1 to fenclorim-treated rice. Fenclorim reduced injury and partially protected rice yield when S-metolachlor was applied DPRE at 1.68 kg ai ha−1 in both years. However, in one year, under adverse conditions, rice yields were only 65% and 66% of the nontreated control for fenclorim-treated ‘Diamond’ and ‘DG263L’, respectively. An EPOST application of S-metolachlor at 1.12 kg ai ha−1 resulted in 44% to 51% visible injury 35 d after treatment. Relative rice yields were 88% and 89% of the nontreated weed-free treatment in 2022 and 2023, respectively. Fenclorim provided enhanced crop safety at both the 0.84 and 1.68 kg ai ha−1 rates of S-metolachlor. However, the potential for reduced yield can arise when unfavorable conditions occur soon after application. An EPOST application timing of CS S-metolachlor at 0.56 kg ai ha−1 may be a viable option in rice, but 1.12 kg ai ha−1 is too high on a silt loam soil, resulting in significant rice injury.

Effectiveness of combined proton pump inhibitors and posaconazole prophylaxis against invasive fungal infections in patients with hematologic malignancies: a retrospective study.

Posaconazole is widely recommended for preventing and treating invasive fungal infections (IFIs) in immunocompromised patients, especially those with prolonged neutropenia. However, the concentration of the oral suspension formulation can be affected by factors such as co-administration with acid-suppressing medications, influencing its efficacy and safety. This study examined the impact of proton pump inhibitors (PPIs) and other factors on posaconazole concentrations and the concentration-to-dose ratio (C/D) while also evaluating adverse drug reactions in patients with hematologic malignancies. We conducted a retrospective analysis of patients who received posaconazole for IFI prophylaxis or treatment, assessing demographic and clinical data, adverse reactions, treatment outcomes, and drug concentration assays. The study focused on the effects of PPIs on Cmin and C/D. Data from 283 posaconazole Cmin measurements in 86 patients were analyzed. The incidence of probable or proven IFIs was 6.4% (5/78). PPI use reduced posaconazole Cmin levels but did not significantly impact prophylactic efficacy. Esomeprazole and rabeprazole were explicitly associated with decreased Cmin. Hepatotoxicity was linked to the co-administration of hepatotoxic drugs, indicating that posaconazole was not the sole contributor. Co-administration of esomeprazole or rabeprazole lowers posaconazole plasma concentrations without compromising prophylactic efficacy against IFIs. Nonetheless, caution is advised when combining these drugs in high-risk immunocompromised patients.

Long-acting injectable in situ forming implants: Impact of polymer attributes and API.

Poly(DL-lactide-co-glycolide) (PLGA) and N-methyl-2-pyrrolidone (NMP)-based in situ forming implants are liquid formulations that solidify through phase separation following injection into the body. Drug is dissolved or suspended in the final formulation liquid prior to injection. Depending on the polymers used, the depots formed can deliver drug over different periods of time. Accordingly, it is important to understand the impact of PLGA properties on implant drug release. However, currently available publications only investigate such impacts based on a single drug, which is insufficient to determine the potential interplay between drug and PLGA properties affecting drug release, or to draw any solid conclusions concerning the general impact of PLGA on drug release. The current work explores in situ forming implants with different active pharmaceutical ingredients (APIs) to determine whether any interplay between the APIs and the polymer attributes might affect drug release. In particular, the drug state (solution or suspension form) may impact polymer interaction and drug release. Naproxen and meloxicam were chosen as model drugs and were loaded into in situ forming implants. The final implants of naproxen and meloxicam were solutions and suspensions, respectively. The impact of PLGA properties (slight changes in molecular weight (MW), slight/major changes in lactic/glycolic acid (L/G) ratio, as well as changes in polymer blockiness in end-cap (acid vs ester)) on drug release was investigated. The slight changes in PLGA MW (18-31 KDa), L/G ratio (75/15-85/15) and blockiness had similar impacts on the release of naproxen and meloxicam from the formulations. These impacts were consistent with a previous report on risperidone implants. However, the impact of end-cap and significant change in the L/G ratio (from 75/15-85/15 to 50/50) was determined to be drug dependent. For meloxicam and for risperidone (previous report), the ester end-cap (compared to the acid end-cap) and much higher L/G ratio (75/15-85/15 versus 50/50) resulted in significantly longer overall drug release durations. In contrast, the naproxen implants had shorter release durations when prepared with the ester end-caped polymer (compared to acid end-cap), and when prepared with significantly higher L/G ratio polymers (75/15-85/15 versus 50/50). In addition, using the same PLGA polymer, implants loading different APIs demonstrated different release durations. This work highlights the complexity of PLGA attributes in determining the performance of implant drug formulations and the critical role of the interplay with the API properties. This study provides valuable knowledge for the future development of in situ forming implant drug products.

Advantages of the refined Developability Classification System (rDCS) in early discovery.

Rat pharmacokinetic studies are commonly utilized in early discovery to support absorption, distribution, metabolism, and excretion optimization of active pharmaceutical ingredients (APIs). The aim of this work was to compare exposures from fit-for-purpose oral suspension and solution formulations in rats to guidance provided by the refined Developability Classification System (rDCS) with respect to identifying potential limits to oral absorption, formulation strategy selection, and to optimize oral bioavailability (BA). This investigation utilized six diverse APIs covering a large range of biorelevant solubility, metabolic stability, and oral BA in rats. While results for our model compounds acetaminophen, voriconazole, fedratinib, lemborexant, and istradefylline indicated oral BA in rats was limited by first-pass metabolism, only the results for voxelotor indicated an oral absorption limitation by intestinal dissolution/solubility. The in vivo studies highlighted challenges and limitations often encountered in early discovery. The rDCS analysis provided a more differentiated assessment of developability risks associated with oral solid dosage form development, incorporating compound-specific physicochemical attributes and human physiology without the need of preclinical data. The rDCS results were shown to align well with the clinical/marketed formulation strategies for the investigated APIs.

Antidiabetic Effectiveness Test of Bitter melon (Momordica charantia L) Extract Suspension in Male White Mice (Mus musculus)

Diabetes mellitus is a metabolic disorder characterised by the inability of the pancreas to produce the hormone insulin in accordance with the body's requirements. Diabetes mellitus is a lifelong disease and, as yet, there is no cure. The costs associated with diabetes mellitus drugs are currently quite expensive. The utilisation of traditional medicinal practices involving the use of medicinal plants represents an alternative treatment option that employs natural ingredients with minimal side effects. One such example is the use of bitter melon (Momordica charantia L.), which has been demonstrated to possess antidiabetic properties. The objective of this study was to ascertain the antidiabetic efficacy of a bitter melon fruit extract suspension formula. This study employed an experimental methodology, whereby a suspension formulation of bitter melon fruit extract was prepared with three distinct doses. A total of 25 male white mice, induced with alloxan, were selected as test animals and divided into five treatment groups. Group X1 received a dose of 150 mg/kg b.w., Group X2 received a dose of 300 mg/kg b.w., Group X3 received a dose of 450 mg/kg b.w., while the negative control and positive control groups were also included. The data were subsequently analysed using the statistical software package SPSS (version 27), which included tests for normality, homogeneity, one-way ANOVA and the T-test. The findings of this study indicate that the treatment group, which received a suspension of bitter melon fruit extract at a dose of 450 mg/kg bw, exhibited a superior efficacy in reducing blood glucose levels, approaching the level observed in the positive control group.

Machine learning strengthened formulation design of pharmaceutical suspensions

Many different formulation strategies have been investigated to oppose suboptimal treatment of long-term or chronic conditions, one of which are the nano- and microsuspensions prepared as long-acting injectables to prolong the release of an active pharmaceutical compound for a defined period of time by regulating the size of particles by milling. Typically, surfactant and/or polymers are added in the dispersion medium of the suspension during processing for stabilization purposes. However, current formulation investigations with milling are heavily based on prior expertise and trial-and-error approaches. Various interacting parameters such as the milling bead size, stabilizer type and concentration have confounded the investigation of milling process. The present study systematically exploited statistical and machine learning (ML) strategies to understand the relationship between suspension characteristics and formulation parameters under full-factorial milling experiments. Stabilizer concentration was identified as a significant factor (p < 0.001) for median suspension diameter (D50). A formulation stability classification ML model with high prediction accuracy (0.91) and F1-score (0.91) under 10-fold cross-validation was constructed based on 72 formulation datapoints. Model interpretation through Shapley additive explanations (SHAP) revealed the prominent impact of stabilizer concentration and milling bead size on formulation stability. The present work demonstrated the potential to achieve a deeper understanding of the design and optimization of nano- and microsuspensions through explainable ML modelling on formulation screening data.

Italian Ryegrass Control Using a Capsule Suspension Formulation of S-metolachlor in Fenclorim-treated Wheat

Abstract Italian ryegrass control is one of the most significant limitations in wheat production in the U.S. today. Resistance to Herbicide Resistance Action Committee (HRAC)/Weed Science Society of America (WSSA) Groups 1, 2, and 9 in Arkansas have further complicated postemergence control, while residual herbicides still show effective weed control. One problem is the potential of HRAC/WSSA Group 15 herbicides to injure wheat when applied preemergence, indicating the need for a herbicide safener. A series of experiments were conducted in Fayetteville, AR, to evaluate crop tolerance and Italian ryegrass control using a capsule suspension formulation of S-metolachlor in conjunction with fenclorim-treated wheat. Experiments were conducted as a two-factor factorial with S-metolachlor applied at three rates (0.37, 0.74, and 1.12 kg ai ha-1) and a microencapsulated formulation of acetochlor at 1.05 kg ai ha-1, and three rates of a fenclorim seed treatment at 0, 0.5, and 2.0 g ai kg-1 of seed. Separate experiments utilized either a preemergence (PRE) or a delayed-preemergence (DPRE) application timing. In both experiments, S-metolachlor at 0.74 and 1.12 kg ai ha-1 provided 77 to 96% control of Italian ryegrass by preharvest, whereas acetochlor only provided 49 to 72% control. Visible wheat injury from PRE applications ranged from 7 to 49% for all treatments 21 d after treatment (DAT), with a reduction in injury when fenclorim-treated wheat was used for both the 0.74 and 1.12 kg ai ha-1 rate of S-metolachlor. In the DPRE experiments, wheat injury ranged from 5 to 16% 21 DAT with no noticeable safening from the presence of fenclorim at any herbicide rate. The results of these experiments indicate that a DPRE application using a CS formulation of S-metolachlor would be more favorable for producers to mitigate the potential for injury to wheat while providing Italian ryegrass control. Additionally, at the DPRE application timing, fenclorim is unnecessary for S-metolachlor to be safely applied at the rates evaluated.

Evaluating pediatric antimicrobial dosing of β-lactam antibiotics for upper respiratory tract infections in emergency and primary care settings.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Pediatric prescribing is often weight and indication specific and has been associated with high rates of error. The aim of this study was to evaluate outpatient β-lactam suspension dosing practices for pediatric upper respiratory tract infections (URIs), to characterize the rate of error and to describe common error types. This retrospective cohort study was conducted at a community health system with 2 emergency departments and 20 outpatient family medicine practices. Pediatric patients treated from these settings with oral suspension formulations of amoxicillin, amoxicillin/clavulanate, cefdinir, or cephalexin for streptococcal pharyngitis or otitis media between June 1, 2020, and May 31, 2023, were eligible for inclusion. Doses were evaluated against indication-specific best-practice guidelines and assessed for guideline concordance. Of the 200 patients evaluated, 100 were treated for streptococcal pharyngitis and 100 were treated for otitis media. Of the prescribed β-lactam doses, 32% were discordant with best-practice guideline recommendations. Dosing errors were more common for pharyngitis than for otitis media (47% vs 17%; P < 0.001). Overdosing was the most frequently observed error in pharyngitis prescriptions (93.6% of errors) and most commonly occurred in patients weighing more than the 20-kg weight associated with the dosing maximum (80.9% of overdosing errors). All patients receiving an inappropriate dose for otitis media were underdosed. Outpatient pediatric dosing errors for URI indications are common among both emergency medicine and family medicine prescribers. Patients weighing over the weight corresponding to the dosing maximum are at highest risk for error. Antimicrobial stewardship interventions targeting the point of prescribing are urgently needed to provide safe dosing practices for pediatric patients.