Solid Lipid Nanoparticles Incorporated with Retinol and Pentapeptide-18-Optimization, Characterization, and Cosmetic Application.

Solid lipid nanoparticles (SLNs) incorporated with retinol and oligopeptide can have a full spectrum of effects on the skin as a compatible combination of ingredients with broad anti-aging properties. The research's main objective was to ensure the stability of lipid nanocarriers containing retinol and peptide due to the planned use of this dispersion as a cosmetic raw material. To confirm the effectiveness of method optimization (high shear homogenization, HSH) and proper selection of substrates, SLN dispersions were obtained in three combinations: 1-non-incorporated SLNs; 2-SLNs containing only retinol; 3-SLNs containing retinol and pentapeptide-18; these were then stored at different temperatures (4, 25, 45 °C) for 4 weeks. The desired values of the physicochemical parameters of the optimized dispersion of lipid nanoparticles incorporated with retinol and oligopeptide over the required storage period were confirmed: mean particle size (Z-Ave) = 134.7 ± 0.3 nm; polydispersity index (PDI) = 0.269 ± 0.017 [-]; zeta potential (ZP) = 42.7 ± 1.2 mV (after 4 weeks at 25 °C). The results confirmed the proper selection of the SLN production method and the effectiveness of the optimization performed. The possibility of using the obtained raw material as an ingredient in cosmetic products with anti-aging properties was indicated.

Composite Material Based on Polypropylene and Modified Natural Fillers.

The work presents the results of a comprehensive study on obtaining compositions based on polypropylene and natural fillers modified by enzymatic preparations under high-shear forces. The experiment protocol includes determining the modification time and the ratio of water volume to the mass of natural filler (hydro modulus) during modification, which turned out to be different for each type of filler. Physical and mechanical analyses were conducted to evaluate the operational characteristics of the obtained composites, with particular attention given to comparing the modified compositions with their unmodified counterparts. The time and hydro module of the enzymatic modification of the natural fillers under consideration were investigated, which turned out to be different for each type of filler. It was found that surface modification of natural fillers improves mechanical properties; namely, the tensile strength of composites with wood and sunflower fillers increases by 10%, and the impact viscosity of composites also increases by 12% with wood and sunflower fillers. Water absorption decreases in composites, after 2 h boiling, with wood flour by 30% and with rice husk by 10%. After a 14-day test at room temperature, water absorption decreases by more than 30% in composites with rice husk. When determining the free surface energy of composites, it was found that the modification of the filler reduces the polarity of the composites in all samples, which can be interpreted as an improvement in the interaction between the filler and the polymer matrix. The findings of this research have important implications for the development of advanced polymeric materials that can be used in a wide range of applications, including automotive, aerospace, and construction industries. The results underscore the importance of surface modifications to optimize the properties of polymeric composites and provide valuable insights into the role of natural fillers in enhancing the performance of these materials.

A novel haemodilution chip mounted on the total thrombus-formation analysis system, a flow chamber system, enables stable analysis of platelet products under low platelet concentration/high shear conditions.

BACKGROUND AND OBJECTIVES: The total thrombus-formation analysis system (T-TAS) can quantitatively analyse the contribution of platelets to haemostasis using reconstituted blood samples. However, it is unsuitable in cases with low platelet counts. We introduced a haemodilution (HD) chip with a shallow chamber depth, adapted to low platelet counts and high shear conditions (1500 s-1). MATERIALS AND METHODS: Blood samples were prepared by mixing red blood cell products, standard human plasma and platelet products; the final platelet count was 50 × 103/µL. Aggregation tests were performed by using the aggregation inducers collagen, adenosine diphosphate (ADP) and ristocetin. Samples with 2-, 4- and 9-day-old platelet products (N = 10) were evaluated. RESULTS: The HD chip enabled the stable analysis of the haemostatic function of all samples at a platelet count of 50 × 103/µL. Haemostatic function was correlated with ADP aggregation (time to 10 kPa [T10]: r = -0.53; area under the curve for 30 min: r = 0.40) and storage period (T10: r = 0.44). CONCLUSION: The HD chip-mounted T-TAS can stably analyse haemostatic function under low platelet counts and high shear conditions; this approach is expected to serve as a bridge to in vivo haemostatic tests with experimental animals.

Green production of functionalized few-layer borophene decorated with cerium-doped iron oxide nanoparticles for repeatable hydrogen peroxide detection.

Functionalized few-layer borophene (FFB) was prepared using gallnut extract and coffee waste extract as natural exfoliating and stabilizing agents in an environmentally friendly ultrasonic and high shear exfoliation. Here, a facile precipitation method was employed to grow iron oxide nanoparticles doped with cerium (Ce-FeONPs) onto the surface of FFB. This intriguing combination of materials yielded Ce-FeONPs nanoparticles that exhibited exceptional peroxidase-like activity, efficiently catalyzing the conversion of 3,3',5,5'-tetramethylbenzidine (TMB) to a blue oxidized TMB (oxTMB) in the presence of hydrogen peroxide (H2O2). Additionally, the introduction of FFB contributes a reducibility effect to the catalytic oxidation of TMB, facilitating the restoration of the oxTMB to TMB. Thus, FFB-Ce-FeONPs showcase intriguing properties encompassing both oxidative and reductive characteristics, suggesting their potential as a reagent for repeated detection of H2O2. Moreover, a colorimetric sensing system enabled the liner detection of H2O2 spanning a concentration range from 0.08 to 1 mM, with a detection limit of 0.03 mM. Noteworthily, FFB-Ce-FeONPs demonstrated sustained efficacy over ten successive recycling cycles, as indicated by consistent slopes and observable color changes. In summary, this work reports the first application of nanoenzymes in repetitive H2O2 detection. Even after ten multiple cycles, the detection limit remains virtually unaltered, underscoring the robustness and enduring effectiveness of the engineered nanomaterial. The proposed simultaneous oxidation and reduction strategies for detecting H2O2 showed a commendable capability in ten cycles of H2O2 detection, thus providing a promising approach in the field of H2O2 detection.

Cultivating High-Performance Flexible All-in-One Supercapacitors With 3D Network Through Continuous Biosynthesis.

Flexible supercapacitors can potentially power next-generation flexible electronics. However, the mechanical and electrochemical stability of flexible supercapacitors under different flexible conditions is limited by the weak bonding between adjacent layers, posing a significant hindrance to their practical applicability. Herein, based on the uninterrupted 3D network during the growth of bacterial cellulose (BC), a flexible all-in-one supercapacitor is cultivated through a continuous biosynthesis process. This strategy ensures the continuity of the 3D network of BC throughout the material, thereby forming a continuous electrode-separator-electrode structure. Benefitting from this bioinspired structure, the all-in-one supercapacitor not only achieves a high areal capacitance (3.79 F cm-2) of electrodes but also demonstrates the integration of high tensile strength (2.15 MPa), high shear strength (more than 54.6 kPa), and high bending resistance, indicating a novel pathway toward high-performance flexible power sources.

Activation of heme oxygenase-1 by laminar shear stress ameliorates high glucose-induced endothelial cell and smooth muscle cell dysfunction.

High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.

Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity.

PURPOSE: Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid. METHODS: RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size. RESULTS: Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (-16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug's characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid's ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 µM for free RES to 0.5 ± 0.033 µM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 µMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 µM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension. CONCLUSION: Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.

Taste Masking of Dexketoprofen Trometamol Orally Disintegrating Granules by High-Shear Coating with Glyceryl Distearate.

Orally disintegrating granules (ODGs) are a pharmaceutical form commonly used for the administration of NSAIDs because of their easy assumption and fast dispersion. The development of ODGs is not easy for drugs like dexketoprofen trometamol (DXKT), which have a bitter and burning taste. In this work, high-shear coating (HSC) was used as an innovative technique for DKXT taste masking. This study focused on coating DXKT granules using the HSC technique with a low-melting lipid excipient, glyceryl distearate (GDS). The HSC technique allowed for the coating to be developed through the thermal rise resulting from the friction generated by the granules movement inside the equipment, causing the coating excipient to soften. The design of the experiment was used to find the best experimental coating conditions in order to gain effective taste masking by suitably reducing the amount of drug released in the oral cavity. The influence of the granule dimensions was also investigated. Coating effectiveness was evaluated using a simulated saliva dissolution test. It was found that low impeller speed (300 rpm) and a 20% coating excipient were effective in suitably reducing the drug dissolution rate and then in taste masking. The coated granules were characterized for their morphology and solid-state properties by SEM, BET, XRPD, DSC, and NIR analyses. A human taste panel test confirmed the masking of DXKT taste in the selected batch granules.

Enhancing the Techno-Functional Properties of Lentil Protein Isolate Dispersions Using In-Line High-Shear Rotor-Stator Mixing.

In response to global challenges such as climate change and food insecurity, plant proteins have gained interest. Among these, lentils have emerged as a promising source of proteins due to their good nutritional profile and sustainability considerations. However, their widespread use in food products has been impeded by limited solubility. This study aimed to investigate the potential of high-shear mixing, a resource-efficient technique, to enhance lentil protein solubility and its functional properties. Red lentil protein isolate powders were rehydrated and subjected to a semi-continuous in-line high-shear treatment at 10,200 rpm for a timespan ranging from 0 to 15 min. The results highlighted a significant (p < 0.05) increase in solubility from 46.87 to 68.42% after 15 min of shearing and a reduction in particle size as a result of the intense shearing and disruption provided by the rotor and forced passage through the perforations of the stator. The volume-weighted mean diameter decreased from 5.13 to 1.72 µm after 15 min of shearing, also highlighted by the confocal micrographs which confirmed the breakdown of larger particles into smaller and more uniform particles. Rheological analysis indicated consistent Newtonian behaviour across all dispersions, with apparent viscosities ranging from 1.69 to 1.78 mPa.s. Surface hydrophobicity increased significantly (p < 0.05), from 830 to 1245, indicating exposure of otherwise buried hydrophobic groups. Furthermore, colloidal stability of the dispersion was improved, with separation rates decreasing from 71.23 to 24.16%·h-1. The significant enhancements in solubility, particle size reduction, and colloidal stability, highlight the potential of in-line high-shear mixing in improving the functional properties of lentil protein isolates for formulating sustainable food products with enhanced techno-functional properties.

A computational investigation of occlusive arterial thrombosis.

The generation of occlusive thrombi in stenotic arteries involves the rapid deposition of millions of circulating platelets under high shear flow. The process is mediated by the formation of molecular bonds of several distinct types between platelets; the bonds capture the moving platelets and stabilize the growing thrombi under flow. We investigated the mechanisms behind occlusive thrombosis in arteries with a two-phase continuum model. The model explicitly tracks the formation and rupture of the two types of interplatelet bonds, the rates of which are coupled with the local flow conditions. The motion of platelets in the thrombi results from competition between the viscoelastic forces generated by the interplatelet bonds and the fluid drag. Our simulation results indicate that stable occlusive thrombi form only under specific combinations for the ranges of model parameters such as rates of bond formation and rupture, platelet activation time, and number of bonds required for platelet attachment.

The effect of polymeric binder type and concentration on flow and dissolution properties of SMEDDS loaded mesoporous silica-based granules.

Self-microemulsifying drug delivery systems (SMEDDS) are lipid-based formulations, designed to improve the solubility of poorly-water soluble drugs. Mesoporous silica is frequently used for SMEDDS solidification by various techniques. One of them is wet granulation, which enables achieving both high SMEDDS load and good flow properties. This study investigated the effect of six polymeric binders' addition to granulation dispersion (GD) (povidone K30, povidone K90, copovidone, Pharmacoat® 603, Pharmacoat® 615 and Methocel™ K100 Premium LV) on characteristics of produced SMEDDS granules, prepared by wet granulation. By incorporation of polymer in GD, it was possible to produce mesoporous silica-based free-flowing granules, with preserved self-microemulsifying properties, responsible for improved in vitro release of carvedilol. The incorporation of higher molecular weight binders resulted in slower in vitro release, while high binder concentration was related to faster drug release. The highest release rate was achieved with povidone K30 at 7.45 % binder concentration, as corresponding granules exhibited complete drug release already in 5 min. Granulation method (manual vs. high-shear) influenced the release rate of carvedilol as it was released slower from SMEDDS granules prepared using the granulator. Finally, SMEDDS tablet formulation was optimized to achieve maximum granule content and adequate tablet hardness. Increased granule content found to negatively influence tablet hardness, as maximum granule content of 25 % was needed to obtain appropriate hardness. Such tablets exhibited short disintegration time, so this final prototype can be considered as orodispersible tablet.

Evaluating the impact of transient shear stress on platelet activation, adhesion, and aggregation with microfluidic chip technique.

BACKGROUND: When nonphysiological stenosis occurs, the transient high shear stress formed in vessels increases the risk of thrombosis and is a potential factor for cardiovascular diseases. But the platelet adhesion and aggregation behavior at nonphysiological post-stenosis and its affecting factors are not fully understood yet. METHODS: In this experiment, platelet aggregation on collagen and fibrinogen at different shear stresses and different hematocrits were observed by microfluidic technology. Platelet activation (P-selectin, glycoprotein IIb/IIIa) and monocyte-platelet aggregate (MPA) levels under different shear stresses were analyzed by flow cytometry. RESULTS: On fibrinogen, platelets aggregate more at higher shear stress conditions. While on collagen, it becomes more difficult for platelets to form stable aggregation at higher shear stress conditions. If platelets adhere initially at low shear stress, stable platelet aggregation can be formed at subsequent high shear stress. Moreover, when the shear stress increases, platelet activity markers (P-selectin, glycoprotein IIb/IIIa and MPAs) increase significantly. Hematocrit affects the degree of platelet aggregation, and the influence of hematocrit is obvious at high shear stress. CONCLUSION: Transient high shear stress (46 ms) can effectively activate platelets. Platelet aggregation behavior was different for coated fibrinogen and collagen protein. Stable platelet adhesion at post-stenosis is more dependent on fibrinogen and platelet aggregation is stable on both fibrinogen and collagen. Hematocrit can significantly affect the formation of platelet aggregation.

Computational fluid dynamics for predicting the growth of small unruptured cerebral aneurysms.

OBJECTIVE: Larger cerebral aneurysms are more likely to enlarge, but even small aneurysms can grow. The aim of this study was to investigate the hemodynamic characteristics regarding the growth of small aneurysms using computational fluid dynamics (CFD). METHODS: The authors analyzed 185 patients with 215 unruptured cerebral aneurysms with a maximum diameter of 3-5 mm, registered in a multicenter prospective observational study of unruptured aneurysms (Systematic Multicenter Study of Unruptured Cerebral Aneurysms Based on Rheological Technique at Mie) from January 2013 to February 2022. Based on findings on repeated images, aneurysms were divided into a stable group (182 aneurysms) and a growth group (33 aneurysms). The authors developed the high shear concentration ratio (HSCR), in which high wall shear stress (HWSS) was defined as a value of 110% of the time-averaged wall shear stress of the dome. High shear area (HSA) was defined as the area with values above HWSS, and the ratio of the HSA to the surface area of the dome was defined as the HSA ratio (HSAR). They also created the flow concentration ratio (FCR) to measure the concentration of the inflow jet. Multivariate logistic regression analysis was performed to determine morphological variables and hemodynamic parameters that independently characterized the risk of growth. RESULTS: The growth group had a significantly higher projection ratio (0.74 vs 0.67, p = 0.04) and volume-to-ostium area ratio (1.72 vs 1.44, p = 0.02). Regarding the hemodynamic parameters, the growth group had significantly higher HSCR (6.39 vs 4.98, p < 0.001), lower HSAR (0.28 vs 0.33, p < 0.001), and lower FCR (0.61 vs 0.67, p = 0.005). In multivariate analyses, higher HSCR was significantly associated with growth (OR 0.81, 95% CI 7.06 e-1 to 9.36 e-1; p = 0.004). CONCLUSIONS: HSCR may be a useful hemodynamic parameter to predict the growth of small unruptured cerebral aneurysms.

The effect of mixing on the dispersibility of adhesive mixtures for inhalation. Comparison of high shear and Turbula mixers.

This study investigates the effect of different mixers and the applicability of the mixing energy (ME) concept to dry powder formulations for inhalation. With the aim to step-wise build and expand this concept, adhesive mixtures of 2 % budesonide and lactose carrier were investigated, both with 1 % magnesium stearate (MgSt) added in a 'coating' step, and without, the latter referred to as 'naked' formulations. For high shear mixed formulations, the fine particle fraction (FPF) was found to increase with increasing ME up to 60 % and thereafter decreased, using the Novolizer device. The data could be well fitted to the modeling equation, thus confirming the validity of the ME concept. The naked formulations displayed a linear decrease in FPF with increasing ME, again showing the validity of the ME concept. For Turbula mixed formulations, FPF increased with increased mixing time (and mixing energy) for all batches. The naked (binary) composition reached to higher FPF values than for high shear mixing and the formulation with MgSt reached to FPF values around 60 %, demonstrating that it is possible to achieve the same high drug dispersibility with the Turbula mixer as for high shear mixer. An equation for calculation of mixing energy in Turbula mixing was set up in an analogous way to the equation for high shear mixing, which enabled direct comparison between the two mixers.

Mechanical Exfoliation of Expanded Graphite to Graphene-Based Materials and Modification with Palladium Nanoparticles for Hydrogen Storage.

Hydrogen is a promising green fuel carrier that can replace fossil fuels; however, its storage is still a challenge. Carbon-based materials with metal catalysts have recently been the focus of research for solid-state hydrogen storage due to their efficacy and low cost. Here, we report on the exfoliation of expanded graphite (EG) through high shear mixing and probe tip sonication methods to form graphene-based nanomaterial ShEG and sEG, respectively. The exfoliation processes were optimized based on electrochemical capacitance measurements. The exfoliated EG was further functionalized with palladium nanoparticles (Pd-NP) for solid-state hydrogen storage. The prepared graphene-based nanomaterials (ShEG and sEG) and the nanocomposites (Pd-ShEG and Pd-sEG) were characterized with various traditional techniques (e.g., SEM, TEM, EDX, XPS, Raman, XRD) and the advanced high-resolution pair distribution function (HRPDF) analysis. Electrochemical hydrogen uptake and release (QH) were measured, showing that the sEG decorated with Pd-NP (Pd-sEG, 31.05 mC cm-2) and ShEG with Pd-NP (Pd-ShEG, 24.54 mC cm-2) had a notable improvement over Pd-NP (9.87 mC cm-2) and the composite of Pd-EG (14.7 mC cm-2). QH showed a strong linear relationship with an effective surface area to volume ratio, indicating nanoparticle size as a determining factor for hydrogen uptake and release. This work is a promising step toward the design of the high-performance solid-state hydrogen storage devices through mechanical exfoliation of the substrate EG to control nanoparticle size and dispersion.

Flow induced attrition of cellulose nanocrystals.

To study the potential impacts of shear stress on cellulose nanocrystals (CNCs), a microcapillary rheometer was employed to repeatedly shear approximately 10 mL of 6 wt% aqueous CNC suspension at 25 °C and rates ranging from 1,000 s-1 to 501,000 s-1. A 9 wt% CNC suspension was also tested at 316,000 s-1 for comparison of concentration effects on the behavior of the suspensions. After monitoring viscosity for 25 steady shear measurements, the suspensions processed at 1,000 s-1 decreased in viscosity by approximately 20 %. Higher shear rates produced smaller changes in viscosity, while increasing the concentration produced higher general viscosities. Atomic force microscopy (AFM) and X-ray diffraction (XRD) probed physical changes between the neat and sheared CNC samples. AFM images showed up to a 24 % reduction in length after shearing, but an insignificant reduction in cross-section. XRD showed a slight increase in the ratio of amorphous to crystalline fractions of the CNCs. Additionally, conductometric titration showed insignificant differences between neat and sheared samples. These findings suggest that viscosity changes in CNC suspensions during steady shear flow arise from physical fracturing of the CNCs perpendicular to their length, and not significantly from chemical degradation or reduction in residual amorphous content.

The Influence of Wet Granulation Parameters on the Compaction Behavior and Tablet Strength of a Hydralazine Powder Mixture.

The aim of this paper was to describe the influence of high-shear wet granulation process parameters on tablet tensile strength and compaction behavior of a powder mixture and granules containing hydralazine. The hydralazine powder mixture and eight types of granules were compacted into tablets and evaluated using the Heckel, Kawakita and Adams analyses. The granules were created using two types of granulation liquid (distilled water and aqueous solution of polyvinylpyrrolidone), at different impeller speeds (500 and 700 rpm) and with different wet massing times (without wet massing and for 2 min). Granulation resulted in improved compressibility, reduced dustiness and narrower particle-size distribution. A significant influence of wet massing time on parameters from the Kawakita and Adams analysis was found. Wet massing time had an equally significant effect on tablet tensile strength, regardless of the granulation liquid used. Granules formed with the same wet massing time showed the same trends in tabletability graphs. Tablets created using a single-tablet press (batch compaction) and an eccentric tablet press showed opposite values of tensile strength. Tablets from granules with a higher bulk density showed lower strength during batch compaction and, conversely, higher strength during eccentric tableting.

Effect of process parameters in high shear granulation on characteristics of a novel co-processed mesoporous silica material.

In this study, insights into the development and optimization of a co-processed excipient based on mesoporous silica are presented. The main advantage of such a material is that it is appropriate for direct tablet compression and has a sufficiently large specific surface area to be suitable for potential subsequent drug loading and formulation of (amorphous) solid dispersions. Our aim was to use a Design of Experiments approach to investigate which process parameters in high shear granulation affect the characteristics of such a co-processed material. The parameters included were the amount of binder (isomalt), the amount of water (granulation liquid), the water addition rate and the speed of the impeller. The responses evaluated and modelled were particle size and its distribution, specific surface area, bulk density, flowability, compressibility and compactibility. The models obtained showed good quality in terms of goodness of fit and predictive power. Active effects were identified for all responses, giving a thorough insight into factors affecting the material characteristics. Optimization experiments resulted in products with the desired characteristics (high specific surface area, large particle size, good flow and compression properties) and confirmed the validity of the generated models.

Attribute transmission and effects of diluents and granulation liquids on granule properties and tablet quality for high shear wet granulation and tableting process.

This study aims to examine (i) the effect of diluent types (lactose monohydrate, corn starch, and microcrystalline cellulose) and granulation liquids (20% polyvinylpyrrolidone K30, 65% alcohol, and dispersion containing 40% model drug- Pithecellobium clypearia Benth extracted powder) on granule properties and tablet quality for high shear wet granulation and tableting (HSWG-T) and, more importantly, (ii) the attribute transmission in the process. In general, the impact of diluents on granule properties and tablet quality was more dominant than that of granulation liquids. Attribute transmission patterns were revealed as follows. The granules' ISO. Roundness and density correlated with raw material (i.e., model drug, diluent, and/or granulation liquid) properties such as density and viscosity. The granules' compressibility parameter a correlated with the granules' Span, and parameter y0 correlated with the granules' flowability and friability. Compactibility parameters ka and kb correlated mainly with granules' flowability and density, and parameter b correlated significantly and positively with tablet tensile strength. The compressibility correlated negatively with tablet solid fraction (SF) and friability, while the compactibility correlated positively with tablet disintegration time. Moreover, the rearrangement and elasticity of granules correlated positively with SF and friability, respectively. Overall, this study provides some guides for achieving high-quality tablets via HSWG-T.

High-Shear Granulation of Hygroscopic Probiotic-Encapsulated Skim Milk Powder: Effects of Moisture-Activation and Resistant Maltodextrin.

A fine, hygroscopic, and poorly flowable probiotic powder encapsulating Lactobacillus rhamnosus GG (LGG) was granulated using a high-shear granulation process, wherein a small amount of water (4%, w/w) was used for moisture-activation with or without 10% (w/w) resistant maltodextrin (RM). The process consisted of four steps; premixing, agglomeration, moisture absorption, and drying steps. The moisture content, water activity, and viable cell count were monitored during the granulation. The size, morphology, and flowability of the granules were determined. The powder was successfully converted to about 10-times-larger granules (mass mean diameter = 162-204 µm) by this process, and the granules had a 'snowball' morphology. The LGG cells were well preserved under the high-shear granulation conditions, and the viable cell count of the granules greatly exceeded the minimum therapeutic level recommended for probiotic powders. The addition of RM decreased the moisture content of the granules; improved cell resistance to drying stress; narrowed the particle size distribution, with reductions seen in both very fine and very large particles; and produced more flowable granules. Moisture sorption analysis and differential scanning calorimetry demonstrated that these positive effects of RM on granulation were primarily attributed to its water distribution ability rather than its glass transition-related binding ability.