Antimicrobial resistance in Acinetobacter baumannii poses a significant global health challenge. Phage therapy, particularly through phage-antibiotic synergy (PAS), offers a promising strategy to combat this pathogen. This study demonstrated significant PAS, where the combination of phage Indie and ceftazidime achieved a bacterial reduction of more than 85% of A. baumannii strain AbAK03 at 17 h using low doses. Notably, this combination overcame phage resistance observed at 4 h when the phage was used alone, extending bacterial eradication by 13 h. Furthermore, phage Indie restored bacterial susceptibility to ceftazidime, supporting its role in improving interventional treatments against multidrug-resistant A. baumannii. To explore this interaction, phage Indie was isolated and characterized from multidrug-resistant clinical strains. An in vitro PAS experiment was performed using ceftazidime and piperacillin-tazobactam. The combination of phage Indie with ceftazidime consistently showed superior bactericidal effects compared to either agent alone, while the combination of phage Indie with piperacillin-tazobactam exhibited an antagonistic effect. These findings provide clear evidence supporting the application of phage-antibiotic combinations as an effective intervention strategy and lay the groundwork for future in vivo trials in a mouse model to combat antimicrobial resistance.
The majority of indie game development teams are driven by the desire to produce a blockbuster game. But there are many obstacles on the way to realizing this desire, especially in the beginning. It is possible to create a game alone, but more often than not, something genuinely amazing involves a group of talented people working together toward a similar objective. Finding the correct stakeholders is one of the biggest problems with starting an independent game development team. People with the required technical talents, such as programmers and artists, as well as those with business acumen, like marketing and finance experts, are included in this. Success depends on being able to locate these people and manage them. But after the correct individuals have been identified, it is crucial to develop open lines of communication and a common comprehension of the project's objectives and expectations. Finding the perfect people to join their team is a problem that independent game development teams frequently encounter. Attracting talented individuals to a brand-new, unproven initiative might be difficult. The attention of skilled people interested in working on cutting-edge and intriguing initiatives might be attracted through networking. There are other things to consider as well since forming a team comes with the type of game one is making, finding skilled teammates, team chemistry, conflict resolution, communication, long-term relation maintenance and leadership aspects. In general, creating and leading an independent game team is a difficult process. There is no specific method for doing this, but with a little help from others' expertise, it is possible to assemble a team of creative people who can collaborate to produce a game that is genuinely enjoyable.
Commercial game makers at all scales of production have increasingly come to incorporate livestreaming into every stage of the game development cycle. Mainstream hits like Fortnite and League of Legends owe their ongoing success in no small part to their massive uptake by streamers, and triple-A releases from major publishers can reliably expect significant attention on streaming platforms. But what about smaller, lower budget games? For independent game developers, the costs and benefits of streaming are less clear. Based on interviews with small commercial indie developers in Toronto and Montréal, this article critically examines different discourses around streaming and commercial indie games, focusing on developer perceptions of the benefits and risks of streaming and its impacts on indie game-making practices, including production, promotion, and community-building. Contrary to persistent popular myths about streaming as the key to 'discoverability', commercial indie game development remains a precarious form of cultural work, and indie games collectively attract only a tiny fraction of the overall audience on streaming platforms. There is a high level of uncertainty about the factors that led to a given game's success, leaving many indie developers ambivalent about leveraging influencer attention and even as they commit significant time and energy trying to doing so.
This article describes the design and evaluation of a virtual field trip on the topic of radioactive waste management research for university education. We created an interactive virtual tour through the Mont Terri underground research laboratory by enhancing the virtual experiment information system, designed for domain experts, with background information, illustrations, tasks, tests, and an improved user interface. To put the tour's content into context, a conventional introductory presentation on the final disposal of radioactive waste was added. A user study with 22 participants proved a good perceived usability of the virtual tour and the virtual field trip's ability to transfer knowledge. These results suggest a benefit of employing virtual field trips in geoscientific university courses. In addition, it is conceivable to use the virtual field trip as a tool for science communication in the context of participatory processes during nuclear waste disposal site selection processes.
Seasonal malaria chemoprevention (SMC) involves repeated administrations of sulfadoxine-pyrimethamine plus amodiaquine to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. While highly impactful in reducing Plasmodium falciparum malaria burden in controlled research settings, the impact of SMC on infection prevalence is moderate in real-life settings. It remains unclear what drives this efficacy decay. Recently, the WHO widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to children below 10 years old. We aim to assess the impact of SMC on clinical incidence and parasite prevalence and quantify the human infectious reservoir for malaria in this population. We will perform a cluster randomised trial in Saponé Health District, Burkina Faso, with three study arms comprising 62 clusters of three compounds: arm 1 (control): SMC in under 5-year-old children, implemented by the MoH without directly observed treatment (DOT) for the full course of SMC; arm 2 (intervention): SMC in under 5-year-old children, with DOT for the full course of SMC; arm 3 (intervention): SMC in under 10-year-old children, with DOT for the full course of SMC. The primary endpoint is parasite prevalence at the end of the malaria transmission season. Secondary endpoints include the impact of SMC on clinical incidence. Factors affecting SMC uptake, treatment adherence, drug concentrations, parasite resistance markers and transmission of parasites will be determined. The London School of Hygiene & Tropical Medicine's Ethics Committee (29193) and the Burkina Faso National Medical Ethics Committee (Deliberation No 2023-05-104) approved this study. The findings will be presented to the community; disease occurrence data and study outcomes will also be shared with the Burkina Faso MoH. Findings will be published irrespective of their results. NCT05878366.
This article draws on over 60 interviews and 120 surveys with indie game developers to illustrate relational labour and entrepreneurship practices in cultural industries and their relationship to 'good work'. We first outline the changing organization of games work, the shift towards so-called indie production, and the associated rejection of creatively constrained, hierarchically managed production models. In the move towards small-scale games making, indies jettisoned producers because producers represented industry modes of work, values and creative constraints. But indies are now struggling to manage production processes without producers. We use developer narratives to highlight how this 'missing producer' work is redistributed in the form of cultural entrepreneurship, cultural intermediation and relational labour. This relational labour simultaneously supports and undermines sustainable production practices, as developers take on impossible workloads associated with networking and connecting with others. We next illustrate how the inherent valorization of growth and expansion in cultural entrepreneurship discourses may force developers to mimic industry practices and organization in order to find funding, but these practices inherently conflict with their desire to focus on making games as small, sustainable and creatively autonomous teams. Ultimately, we want to demonstrate how interviews and time spent with indie developers help us account for otherwise invisible and ambiguous cultural labour practices and discourses, thus allowing us to make sense of the larger context of cultural production and its possible futures.
Just mere brushing of teeth is not enough for maintaining good oral health. Regular cleaning of tongue is equally important for maintaining good oral hygiene and to escape social embarrassment and personal discomfort, which could arise as a result of halitosis. To test the variables of Theory of Reasoned Action to explain the behavior of tongue cleaning among college going students of Udaipur city, Rajasthan, India. A descriptive cross-sectional survey was conducted amongst 756 college going students of Udaipur city, India using an online self-administered structured questionnaire which was designed based on our study objectives. Logistic regression analysis and structural equation modelling (SEM) were employed for statistical analysis. Confidence level and level of significance were set at 95% and 5% respectively. Logistic regression analysis showed that with one unit increase in subjective norm, the tongue cleaning behavior odds increased significantly by 1.124. Also, the tongue cleaning behavior odds was 1.77 times significantly greater among those brushing their teeth twice a day than those brushing once a day. Structural Equation modelling also evidenced the significant direct effect of subjective norm on tongue cleaning behavior (β = 0.2, p≤0.05). Our results highlighted the importance of subjective norms in espousing tongue cleaning preventive behaviour habit. It is thus recommended to highpoint the role of significant others in changing tongue cleaning behaviour.
Correlation of genes within tissues has attracted much attention. In contrast, genes that are INDependent In Expression (INDIE) remain poorly understood, even though they may represent tissue admixtures, reflect new regulatory mechanisms, either transcriptional or post-transcriptional, and contribute to biomarkers or machine learning algorithms. We hypothesised that INDIE genes can be found, may remain uncorrelated across tissues, and replicate within tissues in external datasets. Biweight midcorrelation was calculated for each gene against all other genes with sufficiently high expression in the given tissue from the GTEx dataset v8, along with the means of absolute values of obtained correlation coefficients. The threshold for gene designation as INDIE was both absolute (r) and relative (Z-score), while the threshold for external validation in the whole blood (four datasets) and the ileum (two datasets) was relative. Only one gene, RPL13P12, was INDIE in all the analysed GTEx tissues, but it did not replicate in the external datasets. In contrast, HIST1H2AD and TMEM176B were not only INDIE in GTEx whole blood but also replicated in all four external datasets, despite their heterogeneity. Moreover, ACAT2 replicated in both external ileal datasets. The haemoglobin gene HBB belonged to most widespread INDIE genes in various GTEx tissues and was validated in an external ileal dataset, pointing towards the importance of tissue heterogeneity in bulk samples. A set of genes exhibiting independent expression patterns across various tissues of GTEx was described. Results for each tissue are made available. Even though many findings can be explained by tissue heterogeneity, some results point towards interesting mechanisms of gene expression regulation.
This article presents a situational analysis of the expert advice offered by Independent SAGE, a group of scientists that formed in May 2020 in the UK to provide advice on the Covid response. Based on interviews with the group's members and partners, we argue that through its interventions Indie SAGE demonstrated an important alternative approach to linking science and politics in a time of emergency. They showed that the only way to ensure that policy and decision-making on Covid-19 was grounded in knowledge was by making expert advice public. Indie SAGE's decision to 'go public' was a response to the political situation in the UK, one in which scientific advice, in particular public health expertise, was being ignored, sidelined and contested as such. We identify four rationales for making expert advice public: openness, calling out, translation, and responsive engagement. We describe associated modes of intervention that Indie SAGE adopted in relation to different critical situations of Covid-19. Distinctive about their advice, we argue, is its prioritization of situational adequacy. Much of it was explicitly oriented towards addressing practical and existential challenges experienced by particular social groups, professions and everyday publics. We argue that this way of making science public in an 'ontological' register acquires critical importance in a political situation like the UK Covid response, which was marked not just by disagreements about science but growing contestation of science as such. In this respect, our study holds a wider lesson for the understanding of the role of evidence in public politics. To advocate for evidence-based governance, as Indie SAGE did, is not necessarily to endorse a post-political vision of government. When science is contested in a time of emergency, making evidence public becomes a key means for responding to the demands of situations. It is not only pragmatic but a critical accomplishment.
Tensile strength loss during scale-up is commonly attributed to strain rate sensitivity, where shorter dwell times are assumed to weaken tablets. Since compression speed and feed frame paddle speed are typically increased together in rotary presses, decoupling their individual impact on tensile strength remains challenging. This study decoupled their impact using a compaction simulator. Materials with different deformation behaviours were studied. Tablets for each material were compressed at two dwell times (lab- and industrial-scale) across different feed frame speeds. Matched in-die porosity was maintained for each material across all conditions to ensure similar in-die densification, and a machine-independent porosity-tensile strength approach was used for analysis. In unlubricated excipients (with and without die-wall lubrication), reducing dwell time from 150 to 15ms showed no reduction in tensile strength; however, hard-brittle dibasic calcium phosphate showed a slight increase. Upon internal lubrication with different magnesium stearate loads, only starch showed a reduction in tensile strength, driven by lubrication and increased elastic recovery at shorter dwell time. Unexpectedly, feed-frame shear at a fixed 1% lubrication load resulted in greater strength loss than increasing lubrication loads for viscoelastic, plastic, and brittle materials. This study reveals that dwell time effects were limited, with only lubricated starch showing a reduction, whereas feed frame shear induced lubrication plays a major role in tensile strength loss during scale-up. These findings enable formulators to implement feed frame focused strategies that maintain tensile strength and support reliable scale-up.
Tablet mechanical strength is governed by both the intrinsic mechanical properties of the constituent materials and the applied compaction conditions. In this work, we investigated the relationships among tablet tensile strength, tablet brittleness, quantified by the tablet brittleness index, and powder plasticity, quantified by in-die mean yield pressure. Seven common excipients and twelve binary mixtures were selected to represent materials spanning a wide range of mechanical behaviors. For a given material, tablets become more brittle and weaker as porosity increases, following an exponential decay relationship. At a fixed tablet porosity, in-die mean yield pressure shows a positive correlation with tablet brittleness index that follows a power-law function. This relationship enables prediction of tablet brittleness index at a specified porosity directly from in-die mean yield pressure. Because in-die mean yield pressure can be readily obtained from in-die compression data using only small quantities of material, it offers an efficient means to estimate tablet brittleness early in development and provides valuable guidance for designing robust tablets.
HIV-1 enters the central nervous system (CNS) early in infection, and a significant proportion of people with HIV experience CNS complications despite anti-retroviral therapy. Chronic immune dysfunction, inflammatory cytokines and chemokines, and viral proteins like Tat and gp120 released by HIV-1-infected immune cells are implicated in the pathogenesis of HIV-1-associated neurocognitive disorders (HAND). To elucidate the contribution of non-viral factors to CNS complications in people with HIV-1, a comparative analysis of neurovirulent subtype B (HIV-1ADA) and non-neurovirulent subtype C (HIV-1Indie-C1) isolates was performed. Culture supernatants from HIV-1-infected PBMCs, either with or without immunodepletion of Tat and gp120, were used to treat SH-SY5Y neuroblastoma cells. HIV-1ADA-infected PBMC media showed significantly higher neurotoxicity than HIV-1IndieC1-infected PBMC media, notwithstanding the depletion of Tat and gp120, highlighting the role of non-viral factors (e.g., cytokines) contributing to neurotoxicity. A comparison of inflammatory profiles revealed that HIV-1ADA media contained elevated levels of cytokines (IL-1α, IL-1β, IL-6 and TNFα) and chemokines (CCL2, CCL3, CCL4 and IP-10). Given the involvement of Tat in upregulating immune mediators, we tested the role of purified Tat proteins from HIV-1 subtypes B and C in inducing an inflammatory phenotype in PBMCs. PBMCs from healthy subjects were treated with recombinant purified Tat from subtype B or C. Subtype B Tat induced a stronger inflammatory response than subtype C Tat. These results confirm that both viral and non-viral immune factors mediate neuronal damage in people with HIV.
Equimolar griseofulvin (GRI) co-amorphous systems (CAMS) with amino-acids (AAs) were prepared by hot-melt-extrusion and evaluated for compactibility and "in-tablet" stability at ambient (21-23°C), intermediate (43-46°C), and high temperature [87-92°C, near CAMS' glass transition (Tg)]. Compression was studied by "in-die" measurements. Tablet strength and morphology were evaluated by diametrical compression and electron microscopy, moisture uptake by dynamic sorption, and solid-state stability by X-ray powder diffraction and micro-spatially offset low-frequency Raman spectroscopy. CAMS powders exhibited lower Heckel yield pressure (Py) and compaction work (Wc) but higher elastic recovery than crystalline physical mixtures (PMs). However, the strength of PM and CAMS tablets prepared at low or intermediate temperatures were comparable, due to balancing the effects of deformability (Py) and surface interaction (Wc). Compression near CAMS' Tg gave weak tablets. CAMS tablets exhibited low moisture sorption and remained amorphous after 90 days at 45°C/75% relative humidity, confirming excellent stability, whereas tablets of amorphous drug recrystallized after 30 days. Low-frequency Raman spectroscopy revealed details that escaped crystallography. Isolated residual drug crystals were detected, suggesting further finer-tuning for optimal GRI/AA ratio. These findings indicate the potential of GRI/AA CAMS for direct compression providing that adequate flowability is assured.
For women in the United States desiring implant-based breast reconstruction, the maximum volume of commercially available silicone breast implants has, to date, been 800cc. We evaluated the safety of MENTOR® larger-size MemoryGel® Ultra-High Profile breast implants (≥930cc) in women undergoing postmastectomy breast reconstruction. This 10-year, multicenter, open-label, prospective, investigational study assessed the safety and effectiveness of larger-volume implants in women undergoing postmastectomy 2-stage primary or revision reconstruction. Three-year Kaplan-Meier curves and multivariable Cox regression analyzed the association between patient and treatment characteristics and surgical outcomes. Breast-Q was used to assess effectiveness at 3 years. Four hundred women were enrolled (225 primary, 175 revision reconstruction). Mean body mass index (BMI) was 35.8 kg/m2; 81% had a BMI ≥30 kg/m2. At 3 years, the cumulative incidence of postoperative complications (excluding rupture) was 63.0% (95% confidence interval [CI], 58.1-67.9). The reoperation rate was 24.5% (95% CI, 20.4-29.1), and the explantation rate was 15.8% (95% CI, 23.5-19.9). Independent predictors of complications included radiation and a history of smoking. There were no significant associations between postoperative complications and implant volume ≥1135cc or <1135cc. Breast-Q scores at Year 3 showed significant improvements from baseline in satisfaction with breasts, psychosocial well-being, sexual well-being, and physical well-being (all P<0.0001). The mean score for satisfaction with outcome was 79.9. These 3-year results demonstrate that larger-volume silicone breast implants represent a safe and effective option for patients with larger breasts who are requesting postmastectomy implant-based reconstruction.ClinicalTrials.gov Identifier: NCT02724371.
Exploratory listening encompasses the various ways, contexts, and levels of attention with which listeners engage with their sonic environment. This paper presents findings from qualitative research conducted with audience members during the Stardew Valley: Festival of Seasons concert tour. During these events, attendees encountered music from the widely successful indie video game, reorchestrated in a new context. Just as the game encourages exploration through open-ended gameplay, the concerts prompt listeners to explore how the rearranged music refers to and diverges from its use in the game. Findings suggest that attendees deployed their attention to divergent aspects of the music. While some attendees focused on specific musical aspects like recognizable melodies and instrumentation, others focused on the broader audiovisual and community aspects of the performance. Results also indicate that highly immersed listeners experience diverse thoughts, including those not directly about the immediate musical content. Positioning music-evoked imaginings as a way listeners become immersed in musical experiences, we report on how exploratory listening shapes the dynamics of attention, immersion, and enjoyment within musical and audiovisual contexts.
A series of novel potent HIV-1 protease inhibitors featuring diverse hydroxyaromatic acetanilide derivatives as P2 ligands and 4-substituted phenyl sulfonamides as P2' ligands were designed, synthesized, and biologically evaluated. The majority of the target compounds demonstrated potent enzyme inhibitory activity with IC50 values below100 nM. Notably, compound 18h, incorporating a 2-(4-hydroxypyrimidin-5-yl) acetamide P2 ligand and a 4-methoxybenzenesulfonamide as the P2' ligand, exhibited exceptional potency with an enzyme IC50 of 0.46 nM and antiviral EC50 of 0.26 μM against HIV-1NL4-3 strain. In addition, 18h displayed activity with EC50 value of 0.25 μM against the subtype C HIV-1 Indie strain. The extensive hydrogen-bonding interactions with the protease active site revealed in the molecular docking analysis of 18h-bound HIV-1 protease provided valuable structural insights for the rational design of next-generation HIV-1 protease inhibitors.
Background: The compaction of formulation blends is a critical stage in pharmaceutical tablet manufacturing, particularly when drug substances or functional excipients exhibit limited flowability and tabletability. Objectives: This study systematically examined the mechanical behaviour of viscoelastic microcrystalline cellulose (MCC) and brittle anhydrous dibasic calcium phosphate (DCPA), as well as their mixtures, to check how deformation mechanisms influence powder handling and tablet performance. Methods: A compaction simulator, mimicking a small rotary tablet press, was used to evaluate tablet weight variability, densification profiles, die-filling height, force-displacement behaviour, and in-die Heckel analysis. Additional assessments included compression times, breaking force, tensile strength, elastic recovery, as well as in-die and out-of-die tablet thickness across various compositions and compaction pressures. Results/Conclusions: Bulk density values from the simulator showed strong correlation with pharmacopeial measurements (R2 ≥ 0.997). Measurable differences in true density and cohesiveness led to poor flowability for MCC and good flow for DCPA, with mixtures containing higher DCPA concentration displaying markedly improved flow characteristic. Compaction analyses confirmed extensive plastic deformation for MCC and fragmentation for DCPA. Increasing MCC content elevated die-fill height, compaction energy, and tablet weight variability, whereas higher DCPA fractions decreased apparent density of tablets and reduced energy demand. Tabletability and compressibility profiles reflected that MCC generated hard tablets but exhibited higher elastic recovery, while DCPA formed softer tablets with closer to linear strength-pressure relationships. Energy profiling demonstrated that MCC stored more elastic energy and required higher overall compression work, whereas DCPA reduced elastic accumulation. Overall, blending viscoelastic and brittle excipients offers a robust strategy for optimizing manufacturability, mechanical strength, and energy efficiency in tablet production.
The elastic strain limit, which quantifies the elastic flexibility of a material, is critical for technological applications of functional materials in a number of fields. Although the elastic flexibility of molecular crystals has been recognized, the extent of elastic flexibility of such materials remains to be defined. Here, we report a molecular crystal, i.e., form I polymorph of celecoxib (CEL), exhibiting exceptional elastic flexibility with an elastic strain of at least 8.70%. The record high elastic strain is accompanied by low Young's modulus (E = 3.18 ± 1.01 GPa) and hardness (H = 39.8 ± 15.6 MPa), as determined by single crystal nanoindentation, along with the high plasticity of the bulk powder observed in in-die Heckel analysis.
This short communication aims to assess the associations of body mass index (BMI) with key functional parameters, including exercise tolerance and functional status, among individuals with chronic heart failure. From four chronic heart failure studies ( HF-ACTION [Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training], NEAT-HFpEF [Nitrate's Effect on Activity Tolerance in Heart Failure With Preserved Ejection Fraction (HFpEF)], INDIE-HFpEF [Inorganic Nitrite Delivery to Improve Exercise Capacity in HFpEF], and RELAX-HFpEF [Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction]), we studied 2,546 participants (mean age: 60.2 ± 12.8 years, 67.8% men, 43.7% non-Whites individuals, 83% with heart failure with reduced ejection fraction (HFrEF), 17% with heart failure with preserved ejection fraction [HFpEF]). Among them, 52.8% had obesity [n = 1344], 29.8% were overweight [n = 758], and 17.4% had a normal body mass index [n = 444]). One-unit increment in BMI (kg/m2) was associated with a lower 6MWT-D (β: -2.78, 95% CI: -3.54, -2.02), a lower VO2max (β: -0.18, 95% CI: -0.21, -0.15), a lower VO2AT (β: -0.10, 95% CI: -0.12, -0.08), a lower RERpeak (β: -0.003, 95% CI: -0.004, -0.002), a lower QoL (β for ln [KCCQ score]: -0.005, 95% CI: -0.008, -0.002), but not with HRpeak (β: β: -0.04, 95% CI: -0.20, 0.11). After adjustment for confounders, individuals with obesity (BMI ≥ 30 kg/m2) compared to those with a normal BMI had lower 6MWT-D (beta coefficient [β]: -21.02, 95% CI: -34.27, -7.77), VO2max (β: -1.90, 95% CI: -2.42, -1.38), VO2AT (β: -1.16, 95% CI: -1.53, -0.80), RERpeak (β: -0.03, 95% CI: -0.05, -0.02), and QoL (β for ln [KCCQ score]: -0.05, 95% CI: -0.10, -0.0006) levels. However, the obesity and normal BMI groups were not significantly different in terms of HRpeak (β: 1.07, 95% CI: -1.71, 3.85). Our study found that in patients with chronic heart failure, increasing body mass index is associated with poor exercise capacity and functional status. Our findings underscore the potential importance of optimizing weight management among individuals with chronic heart failure to improve functional status.
Diclofenac (DIC) is a nonsteroidal anti-inflammatory drug with poor tabletability and water solubility. In the present study, a new diclofenac-picolinamide cocrystal (DIC-PIC) was prepared to simultaneously improve its tabletability and solubility. The cocrystal was characterized using multiple techniques, such as X-ray diffraction, thermal methods and spectral analyses. The tabletability of DIC-PIC was significantly improved over DIC, which is attributed to the larger bonding area between crystals due to the higher plasticity of DIC-PIC, demonstrated by the lower in-die mean yield pressure, Py,i, of DIC-PIC (59.5 ± 0.6 MPa) than DIC (86.6 ± 1.4 MPa). The higher plasticity of DIC-PIC is consistent with the existence of a slip plane (001) in its crystal structure. The solubility of DIC-PIC is significantly higher than that of DIC (112 times higher in water and 22 times higher in pH = 6.8 buffer solution). Hence, the simultaneous improvement in tabletability and solubility of DIC-PIC overcomes two main barriers in developing DIC tablets, which makes it a promising candidate for developing a DIC tablet with improved performance.