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Plastic production has experienced a significant increase in the last sixty years due to its cost-efficiency and adaptable characteristics, leading to the extensive use of additives to improve its performance and longevity. Due to the high demand for plastic, plastic waste production has increased, contaminating the environment and living beings by leaching additives, among other substances. Pyrolysis stands out among recycling techniques because it can handle mixed polymer waste feedstock. However, understanding the pyrolyzates distribution of additives is fundamental to assessing pyrolysis process of plastic waste. This study investigated the pyrolysis product distributions of two commonly used antioxidants, namely, Irgafos 168 and zinc stearate (ZnSt), using one-dimensional gas chromatography equipped with a quadruple mass spectrometer (GC-MS) and two-dimensional gas chromatography coupled to flame ionization detector and time-of-flight mass spectrometer (GC×GC-FID/TOF-MS). While GC separation technique provided limited information on product distribution, GC×GC offered enhanced resolution and identification of the decomposition products. In the pyrolysis of Irgafos 168 at 550 °C, GC identified 18 products, while GC×GC identified 198 products, representing an increase of approximately 11-fold. Similarly, for ZnSt, GC identified 67 products, while GC×GC identified 434 products, representing a 6-fold increase. GC×GC identified decomposition products from 15 different chemical classes for Irgafos 168 and 16 chemical classes for ZnSt, compared to 4 and 11 chemical classes identified by GC, respectively. Phenols and their derivatives were the major chemical class in the decomposition products of Irgafos 168 with a yield of 9.51 wt.%. In contrast, olefinic products were the dominant ones for ZnSt, with a yield of 9.73 wt.%. The major decomposition product of Irgafos 168 and ZnSt was 2‑tert‑butyl‑methylphenol (C 11 H 16 O) and C6 olefin (C 6 H 12 ) with yields of 3.88 wt.%, and 1.13 wt.%, respectively. Utilizing the GC×GC separation method improved the ability to identify decomposition products, which can ultimately lead to a better understanding of antioxidant degradation that occurs during the pyrolysis process. GC×GC also provided thorough characterization of minor and co-eluted products along with major antioxidant degradation products. Additionally, the decomposition product distribution of Irgafos 168 and ZnSt was also compared with the primary antioxidants, Irganox 1010, Irganox 1076, and BHT, studied in part 1. The analysis indicated that the olefinic chemical class was the predominant one in Irganox 1010, Irganox 1076, and ZnSt, while ketones were the major chemical class in the decomposition of BHT and phenolics had the highest yield in Irgafos 168., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hilal Ezgi Toraman reports a relationship with American Chemical Society that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Genistein (Gen); a naturally occurring isoflavone, acts as a tyrosine kinase inhibitor and efficiently downregulates inflammatory cytokines, which are pivotal in eye inflammation. Also, Gen suffers from sparse ocular bioavailability due to poor solubility. In this work, nanostructured lipid carriers (NLCs) were successfully fabricated by using solid (stearic acid and compritol) and liquid (oleic acid) lipids. The optimized Gen-loaded NLCs showed a nanosize range of 140-246 nm, ≥ 98 % entrapment efficiency, and controlled release over 48 h. The ζ-potential of NLCs was increased from -27.3 mV to 25-27.4 mV due to surface modification with chitosan (CS) or eudragit RS100 (ERS 100). All NLCs showed prominent biocompatibility with enhanced cellular uptake on corneal stromal fibroblasts. Moreover, the different NLCs were incorporated into a mucoadhesive in situ gel. The optimized in situ gel (G9), containing 20 % poloxamers and 0.5 % hydroxyethyl cellulose, exhibited excellent gelling ability within 10.5 s, gelling temperature at 33.1 ± 0.6 ℃, spreadability diameter of 4.73 ± 0.12 cm, shear-thinning behavior, and 20 min ex vivo mucoadhesion time with drug release for 120 h. The in vivo results showed distinguished permeation and distribution potential for ocular delivery. In vivo anti-inflammatory effects after 3 days of treatment with CS-Gen-NLCs/G9 and ERS-Gen-NLCs/G9 revealed a downregulation of interleukin-6 levels in the cornea and retina compared to the untreated group. Our research highlights the promising anti-inflammatory potential of ERS-Gen-NLCs/G9 as an efficient, non-irritant Gen nanodelivery system for managing anterior and posterior ocular inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Over the past decade, continuous manufacturing has garnered significant attention in the pharmaceutical industry. Still, numerous continuous unit operations need developments, such as powder blending and feeding at low and high throughputs. Especially the continuous and consistent feeding of solid drug substances and excipients at low feed rates remains challenging. This study demonstrates a micro-feeder capable of feeding poorly-flowing pharmaceutical powders at low feed rates. The system performance was investigated using three grades of pharmaceutical powder: croscarmellose sodium (cohesive), magnesium stearate (very cohesive), and an active ingredient, paracetamol (non-flowing). The results show that the micro-feeder can continuously and consistently feed powders at low flow rates (<20 g/h) with low variability (<10 % for non-flowing materials and < 5 % for cohesive materials). Notably, the micro-feeder achieves these results without any feedback control and remains unaffected by refilling, making it a truly versatile and industry-relevant solution. The study's results demonstrate that this micro-feeder system effectively tackles the challenge of consistent and accurate powder feeding at low rates., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Hou, Gavin Halbert and Daniel Markl have patent #PCT/GB2023/051291 pending to Assignee. Daniel Markl recently accepted to serve on the Editorial Board of IJP and IJP:X in 2024. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This study aimed to explore the effects of various lipids on the structure, cooking quality, and in vitro starch digestibility of extruded buckwheat noodles (EBNs) with and without 20% high-amylose corn starch (HACS). Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction revealed that lauric acid bound more strongly to starch than did stearic acid and oleic acid, and the binding capacity of fatty acids with starch was stronger than that of glycerides. The presence of HACS during extrusion facilitated increased formation of starch-lipid complexes. Evaluations of cooking quality and digestion characteristics showed that EBNs containing 20% HACS and 0.5% glycerol monooleate demonstrated the lowest cooking loss (7.28%), and that with 20% HACS and 0.5% oleic acid displayed the lowest predicted glycemic index (pGI) (63.54) and highest resistant starch (RS) content (51.64%). However, excessive starch-lipid complexes were detrimental to EBNs cooking quality and the resistance of starch to digestive enzymes because of the damage to the continuity of the starch gel network. This study establishes a fundamental basis for the development of EBNs with superior cooking quality and a relatively lower GI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Major depression is a prevalent disorder characterized by sadness, lack of interest or pleasure, interrupted sleep or food, and impaired concentration. Mirtazapine (MTZ), a tetracyclic antidepressant drug, is commonly used to treat moderate to severe depression. MTZ is classified as a BCS class II drug that has shown bioavailability of 50% due to extensive first-pass metabolism. The aim of this research is to develop a delivery platform with enhanced solubility and oral bioavailability of MTZ through formulating polymeric micelles modeled in a rapid release tablet. Mirtazapine loaded polymeric micelles (MTZ-PMs) were formulated to enhance the solubility. Solutol ® HS 15 and Brij 58 were used as combined surfactants in a ratio of (20:1) to MTZ in addition to Transcutol ® P as a penetration enhancer. The following in vitro tests were performed: particle size, PDI, zeta potential, solubility factor, stability index, and transmission electron microscopes. Afterward, MTZ-PMs were converted to dry free flowable powder through loading on the adsorptive surface of Aerosil 200; then, the powder mixture was directly compressed (MTZ-PMs-RRT) into 13 mm tablets. MTZ-PMs-RRT was further investigated using in vitro evaluation tests of the tablets, namely, weight variation, thickness, diameter, hardness, friability, disintegration time, drug content, and in vitro dissolution test, which complied with the pharmacopeial limits. The pharmacokinetic parameters of MTZ-PMs-RRT compared to Remeron ® tablet were further investigated in rabbits. The results showed enhanced solubility of MTZ with improved percentage relative bioavailability to 153%. The formulation of MTZ in the form of MTZ-PMs-RRT successfully improved the solubility, stability, and bioavailability of MTZ using a simple and scalable manufacturing process., (© 2024. The Author(s).)

The goal of this research was to analyse the synergistic effect between selected plant extracts with zinc oxide particles, and zinc stearate. The influence of ZnO on the antimicrobial effectiveness of the selected extracts was confirmed in previous research carried out by the authors. However, the impact of zinc stearate on extract activity has yet to be analysed. The aim was to cover PLA films with active coatings based on hydroxy-propyl-methyl-cellulose (HPMC), or/and ethyl cellulose (EC) containing plant extracts and ZnO which has a synergistic effect. An additional aim was to use a CO 2 extract of raspberry seed (RSE) with zinc stearate as active additives within the coatings. An examination of the antimicrobial properties (against Staphylococcus aureus , Escherichia coli , Bacillus subtilis , Pseudomonas syringae and Φ6 bacteriophage) of the covered films, as well as an investigation of layer presence with regards to PLA morphology (SEM, ATR-FTIR analysis) was carried out. The research work that was performed indicated that black chokeberry extract (ChE) and zinc oxide particles were effective against S. aureus , P. syringae and B. subtilis strains. In addition, the ChE with zinc stearate (ZnSt) was active against all analysed strains. The HPMC with ChE and ZnO as additives had antimicrobial properties against S. aureus , P. syringae and E. coli strains. The ChE was found to inhibit the growth of all of the analysed bacterial strains. When considering the coatings based on EC with the CO 2 extract of raspberry seed (RSE) and ZnO, it was noted that they were only active against Gram-negative bacteria. The results of the experiments confirmed that AC1 (EC with RSE with ZnO) and AC2 (EC with RSE with ZnSt) coatings were not active against a phi6 bacteriophage. The HPMC coating containing the AC3 layer (ChE and ZnO) eliminated Φ6 particles, confirming its antiviral properties. In addition, the presence of the active (AC1, AC2 and AC3) coatings was confirmed by SEM and FTIR analysis.

Limited attempts have been made previously to develop high-loading CBD inhalable powders, which are essential for high dose delivery. Therefore, this study aimed to develop and characterise inhalable powders with ≥ 95 % w/w CBD by wet ball milling. The effects of magnesium stearate (2 % and 5 %) and inhaler resistance (low-resistance and high-resistance RS01 inhalers) on aerosol performance were also compared. Wet ball milling produced CBD powders with > 50 % production yield. The milled particles showed irregular shapes. The powders were crystalline with minimal amorphous content, low residual solvent level (<1%), and low moisture sorption (<4%). Magnesium stearate improved both the emitted and fine particle fractions. The aerodynamic particle size distribution of the formulations differed between the low-resistance and high-resistance RS01 inhalers. The latter decreased throat deposition but increased inhaler retention. The dissolution profiles showed that all three formulations released CBD steadily and plateaued at 30 min. The best scenario was CBD with 5 % magnesium stearate dispersed from the high resistance RS01 inhaler, showing the highest FPF with the lowest throat deposition. This combination may be tested in vivo in the future to investigate its pharmacokinetic profile., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The compendial USP〈701〉 disintegration test method offers a crucial pass/fail assessment for immediate release tablet disintegration. However, its single end-point approach provides limited insight into underlying mechanisms. This study introduces a novel calorimetric approach, aimed at providing comprehensive process profiles beyond binary outcomes. We developed a novel disintegration reaction calorimeter to monitor the heat release throughout the disintegration process and successfully obtained enthalpy change profiles of placebo tablets with various porosities. The formulation comprised microcrystalline cellulose (MCC), anhydrous lactose, croscarmellose sodium (CCS), and magnesium stearate (MgSt). An abrupt temperature rise was observed after introducing the disintegration medium to tablets, and the relationship between the heat rise time and the tablet's porosity was investigated. The calorimeter's sensitivity was sufficient to discern distinct heat changes among individual tablets, and the analysis revealed a direct correlation between the two. Higher porosity corresponded to shorter heat rise time, indicating faster disintegration rates. Additionally, the analysis identified a concurrent endothermic process alongside the anticipated exothermic phenomenon, potentially associated with the dissolution of anhydrous lactose. Since lactose is the only soluble excipient within the blend composition, the endothermic process can be attributed to the absorption of heat as lactose molecules dissolve in water. The findings from this study underscore the potential of utilising calorimetric methods to quantify the wettability of complex compounds and, ultimately, optimise tablet formulations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: JAZ is a member of the editorial board of the International Journal of Pharmaceutics. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Previous RS5 (type 5 resistant starch) research has significantly broadened starch use and benefited society, yet the effects of the molecular weight of amylose on RS5 remain underexplored. In this study, amyloses with different molecular weights were complexed with caproic acid (C6), lauric acid (C12), and stearic acid (C18) to observe the effects of the molecular weight of amylose on the structure and in vitro digestive properties of RS5. Gel permeation chromatography revealed that the peak average molecular weight (Mp) values of high-amylose cornstarch NF-CGK (CGK), high-amylose cornstarch obtained via cornstarch via autoclave (high temperature and high pressure)-cooling combined pullulanase enzymatic hydrolysis (CTE), and high-amylose cornstarch NF-G370 (HCK) were 21,282, 171,537, and 188,084 before fatty acid complexation, respectively. Additionally, their weight average molecular weight (Mw) values of 32,429, 327,344, and 410,610 and hydrolysis rates of 58.12 %, 86.77 %, and 64.58 %, respectively. The hydrolysis rate of low-Mw amylose (GCK) complexes with fatty acids was lower than that of HCK and CTE starch-lipid complexes. However, HCK and CTE having similar molecular weights, there was no significant difference in the hydrolysis rate of starch-lipid complexes. X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy and complexing index analyses confirmed the formation of these complexes. This study proposed the mechanism of RS5 formation and provided guidance for its future development., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The effects of common migration substances in milk packaging on digestive protease were studied. We choose the common migrants found in eight types of multi-layer composite milk packaging. Enzyme activity experiments revealed that pepsin activity decreased by approximately 18 % at 500 μg/mL of stearic acid and stearamide treatment, while trypsin activity decreased by approximately 18 % only by stearic acid treatment (500 μg/mL). Subsequently, fluorescence spectroscopy, circular dichroism spectroscopy, and molecular docking technology were employed to investigate the inhibition mechanism of protease activity by migrating substances in three systems: stearic acid-trypsin, stearic acid-pepsin, and stearamide-pepsin. Results showed that the inhibitory effect of stearic acid on trypsin is a reversible mixed inhibition, whereas the inhibitory effects of stearic acid and stearamide on pepsin are non-competitive. In all three systems, ΔH < 0, ΔS < 0, and ΔG < 0, indicating the binding process between the migrant and the protease is a spontaneous exothermic process primarily driven by hydrogen bonding and van der Waals forces. In addition, their binding constants are all around 10 4 L/moL, indicating that there are moderate binding affinities exist between migrants and proteases. The binding process results in the quenching of the protease's endogenous fluorescence and induces alterations in the enzyme's secondary structure. Synchronized fluorescence spectroscopy showed that stearic acid enhanced the hydrophobicity near the Tyr residue of trypsin. The molecular docking results indicated that the binding affinity of stearic acid-trypsin, stearic acid-pepsin, and stearamide-pepsin was -22.51 kJ/mol, -12.35 kJ/mol, -19.28 kJ/mol respectively, which consistent with the trend in the enzyme activity results. This study can provide references for the selection of milk packaging materials and the use of processing additives, ensuring food health and safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Herein, the surface-enhanced Raman scattering (SERS) platform was combined with an azo coupling reaction and an aluminum alloy covered with a hydrophobic layer of praseodymium oxide and stearic acid complexes for the detection of histamine. The praseodymium oxide on aluminum alloy was successfully synthesized by the rare-earth-salt-solution boiling bath method and modified by stearic acid. Its surface exhibits a water contact angle (WCA) of 125.0°. Through the azo derivatization reaction with 3-amino-5-mercapto-1,2,4-triazole (AMTA) diazonium salts, histamine can be converted into the derivatization product with higher Raman activity. The mixture of the derivatization product and β-cyclodextrin-modified Ag nanoparticles (β-CD-AgNPs) were dropped onto the surface of an aluminum alloy covered with a hydrophobic layer of praseodymium oxide and stearic acid complexes, and dried for SERS measurement. The intensity ratio between the SERS peaks at 1246 cm -1 and 1104 cm -1 (I 1246 /I 1104 ) of the derivatization product was used for the quantification of histamine. Under the selected conditions, the limit of detection (LOD) and the limit of quantification (LOQ) for this method were 7.2 nM (S/N = 3) and 24 nM (S/N = 10), respectively. The relative standard deviation (RSD) of this method for the determination of 1 μM histamine was 6.1 % (n = 20). The method was also successfully used for the determination of histamine in fish samples with recoveries ranging from 92 % to 111 %. The present method is simple, sensitive, reliable, and may provide a new approach for preparing the composite hydrophobic layer that can enhance SERS signals through hydrophobic condensation effect. Meanwhile, it may have a promising future in the determination of small molecular compounds containing an imidazole ring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Magnesium alloy is currently regarded as the most favourable biodegradable metal; however, obstacles remain to be overcome in terms of managing its corrosion and ensuring its biocompatibility. In this study, a metal-organic complex comprising Ca ions incorporated in tannic acid (TA) was prepared and used to coat magnesium alloy by chemical conversion and dipping processes, followed by modification with stearic acid (SA). This metal-organic complex coating was demonstrated to be homogeneous and compact, and it significantly improved the electrochemical corrosion resistance and long-term degradation behaviour of the coated samples. Consequently, the well-controlled release of Mg and Ca ions, as well as the osteo-compatible TA and SA molecules, promoted the proliferation of osteoblast cells. This metal-organic complex coating offers a promising modifying strategy for magnesium-based orthopaedic implants.

In this study, five C18 fatty acids (FA) with different numbers of double bonds and configurations including stearic acid (SA), oleic acid (OA), elaidic acid (EA), linoleic acid (LA), and α-linolenic acid (ALA), were selected to prepare highland barely starch (HBS)-FA complexes to modulate digestibility and elaborate the underlying mechanism. The results showed that HBS-SA had the highest complex index (34.18 %), relative crystallinity (17.62 %) and single helix content (25.78 %). Furthermore, the HBS-C18 FA complexes were formed by EA (C18 FA with monounsaturated bonds) that had the highest R1047/1022 (1.0509) and lowest full width at half-maximum (FWHM, 20.85), suggesting good short-range ordered structure. Moreover, all C18 FAs could form two kinds of V-type complexes with HBS, which can be confirmed by the results of CLSM and DSC measurements, and all of them showed significantly lower digestibility. HBS-EA possessed the highest resistant starch content (20.17 %), while HBS-SA had the highest slowly digestible starch content (26.61 %). In addition, the inhibition of HBS retrogradation by fatty acid addition was further proven, where HBS-SA gel firmness (37.80 g) and aging enthalpy value were the lowest, indicating the most effective. Overall, compounding with fatty acids, especially SA, could be used as a novel way to make functional foods based on HBS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lubricants are essential for most tablet formulations as they assist powder flow, prevent adhesion to tableting tools and facilitate tablet ejection. Magnesium stearate (MgSt) is an effective lubricant but may compromise tablet strength and disintegratability. In the design of orodispersible tablets, tablet strength and disintegratability are critical attributes of the dosage form. Hence, this study aimed to conduct an in-depth comparative study of MgSt with alternative lubricants, namely sodium lauryl sulphate (SLS), stearic acid (SA) and hydrogenated castor oil (HCO), for their effects on the tableting process as well as tablet properties. Powder blends were prepared with lactose, sodium starch glycolate or crospovidone as the disintegrant, and a lubricant at different concentrations. Angle of repose was determined for the mixtures. Comparative evaluation was carried out based on the ejection force, tensile strength, liquid penetration and disintegratability of the tablets produced. As the lubricant concentration increased, powder flow and tablet ejection improved. The lubrication efficiency generally decreased as follows: MgSt > HCO > SA > SLS. Despite its superior lubrication efficacy, MgSt is the only lubricant of four evaluated that reduced tablet tensile strength. Tablet disintegration time was strongly determined by tensile strength and liquid penetration, which were in turn affected by the lubricant type and concentration. All the above factors should be taken into consideration when deciding the type and concentration of lubricant for an orodispersible tablet formulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Transport of oral nanocarriers across the GI epithelium necessitates transport across hydrophilic mucus layer and the hydrophobic epithelium. Based on hydrophobic-hydrophilic balance, Curcumin-Lipomer (lipid-polymer hybrid nanoparticles) comprising hydrophobic stearic acid and hydrophilic Gantrez™ AN 119 (Gantrez) were developed, by a radical in-situ approach, to successfully traverse both barriers. A monophasic preconcentrate (Cur-Pre) comprising Cur (Curcumin), stearic acid, Gantrez and stabilizers, prepared by simple solution, was added to an aqueous phase to instantaneously generate Curcumin-Lipomer (Cur-Lipo) of nanosize and high entrapment efficiency (EE). Cur-Lipo size and EE was optimized by Box-Behnken Design. Cur-Lipomers of varying hydrophobic-hydrophilic property obtained by varying the stearic acid: Gantrez ratio exhibited size in the range 200-400 nm, EE > 95% and spherical morphology as seen in the TEM. A decrease in contact angle and in mucus interaction, evident with increase in Gantrez concentration, indicated an inverse corelation with hydrophilicity, while a linear corelation was observed for mucopenetration and hydrophilicity. Cur-SLN (solid lipid nanoparticles) which served as the hydrophobic reference revealed contact angle > 90°, maximum interaction with mucus and minimal mucopenetration. The ex-vivo permeation study through chicken ileum, revealed maximum permeation with Cur-Lipo1 and comparable and significantly lower permeation of Cur-Lipo1-D and Cur-SLN proposing the importance of balancing the hydrophobic-hydrophilic property of the nanoparticles. A 1.78-fold enhancement in flux of hydrophobic Cur-SLN, with no significant change in permeation of the hydrophilic Cur-Lipomers (p > 0.05) following stripping off the mucosal layer was observed. This reiterated the significance of hydrophobic-hydrophilic balance as a promising strategy to design nanoformulations with superior permeation across the GI barrier., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Nanoenabled strategies have recently attracted attention as a sustainable platform for agricultural applications. Here, we present a mechanistic understanding of nanobiointeraction through an orthogonal investigation. Pristine (nS) and stearic acid surface-modified (cS) sulfur nanoparticles (NPs) as a multifunctional nanofertilizer were applied to tomato ( Solanum lycopersicum L.) through soil. Both nS and cS increased root mass by 73% and 81% and increased shoot weight by 35% and 50%, respectively, compared to the untreated controls. Bulk sulfur (bS) and ionic sulfate (iS) had no such stimulatory effect. Notably, surface modification of S NPs had a positive impact, as cS yielded 38% and 51% greater shoot weight compared to nS at 100 and 200 mg/L, respectively. Moreover, nS and cS significantly improved leaf photosynthesis by promoting the linear electron flow, quantum yield of photosystem II, and relative chlorophyll content. The time-dependent gene expression related to two S bioassimilation and signaling pathways showed a specific role of NP surface physicochemical properties. Additionally, a time-dependent Global Test and machine learning strategy applied to understand the NP surface modification domain metabolomic profiling showed that cS increased the contents of IA, tryptophan, tomatidine, and scopoletin in plant leaves compared to the other treatments. These findings provide critical mechanistic insights into the use of nanoscale sulfur as a multifunctional soil amendment to enhance plant performance as part of nanoenabled agriculture.

The majority of tablets manufactured contain lubricants to reduce friction during ejection. However, especially for plastically deforming materials, e.g., microcrystalline cellulose (MCC), the internal addition of lubricants is known to reduce tablet tensile strength. This reduction is caused by the surface coverage by lubricant particles, the extent of which depends on both process and formulation parameters. Previously published models to predict the lubrication effect on mechanical strength do not account for changes in the excipient particle size. In this study, the impact of both lubricant concentration and mixing time on the tensile strength of tablets consisting of three different grades of MCC and four grades of magnesium stearate (MgSt) was evaluated. By taking into account the particle size of the applied excipients, a unifying relationship between the theoretically estimated surface coverage and compactibility reduction was identified. Evaluating the dispersion kinetics of MgSt as a function of time reveals a substantial impact of the initial surface coverage on the dispersion rate, while the minimal tensile strength was found to be comparable for the majority of formulations. In summary, the presented work extends the knowledge of lubricant dispersion and facilitates the reduction of necessary experiments during the development of new tablet formulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

Purpose: The primary objective of this study was to optimize formulation variables and investigate the in vitro characteristics of fluticasone propionate (FP)-loaded mixed polymeric micelles, which were composed of depolymerized chitosan-stearic acid copolymer (DC-SA) in combination with either tocopheryl polyethylene glycol succinate or dipalmitoylphosphatidylcholine for pulmonary drug delivery., Methods: A D-optimal design was employed for the optimization procedure, considering lipid/ polymer ratio, polymer concentration, drug/ polymer ratio, and lipid type as independent variables. Dependent variables included particle size, polydispersion index, zeta potential, drug encapsulation efficiency, and loading efficiency of the polymeric micelles. Additionally, the nebulization efficacy and cell viability of the optimal FP-loaded DC-SA micellar formulations were evaluated., Results: The mixed polymeric micelles were successfully prepared with properties falling within the desired ranges, resulting in four optimized formulations. The release of FP from the optimal systems exhibited a sustained release profile over 72 hours, with 70% of the drug still retained within the core of the micelles. The nebulization efficiency of these optimal formulations reached up to 63%, and the fine particle fraction (FPF) ranged from 41% to 48%. Cellular viability assays demonstrated that FP-loaded DC-SA polymeric micelles exhibited lower cytotoxicity than the free drug but were slightly more cytotoxic than empty mixed micelles., Conclusion: In conclusion, this study suggests that DC-SA/ lipid mixed micelles have the potential to serve as effective carriers for nebulizing poorly soluble FP., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study discusses the lubricant properties of magnesium stearate solid lipid nanoparticles (MgSt-SLN) and their effect on the tabletability, mechanical properties, disintegration, and acetaminophen-model dissolution time of microcrystalline cellulose (MCC) tablets prepared by direct compression. The behavior of MgSt-SLN was compared to reference material (RM) to identify advantages and drawbacks. The nanoprecipitation/ion exchange method was employed to prepare the MgSt-SLN. Particle size, zeta potential, specific surface area, morphology, and true density were measured to characterize the nanosystem. The MgSt-SLN particle sizes obtained were 240 ± 5 nm with a specific surface area of 12.2 m 2 /g. The MCC tablets with MgSt-SLN presented a reduction greater than 20 % in their ejection force, good tabletability, higher tensile strength, lower disintegration delay, and marked differences in acetaminophen dissolution when compared to the RM. The reduced particle size of the magnesium stearate seems to offer a promising technological advantage as an efficient lubricant process that does not affect the properties of tablets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Punch sticking is a recurrent problem during the pharmaceutical tableting process. Powder moisture content plays a key role in the buildup of sticking; it evaporates due to increased tablet temperature, accumulates at the punch-tablet interface, and causes sticking through capillary force. This study investigated the effects of compaction pressure (CP), compaction speed (CS), and lubrication level (magnesium stearate (MgSt) ratio) on tablet surface temperature (TST) and tablet surface moisture content (TSMC). TST and TSMC were measured with an infrared thermal camera and near-infrared sensor, respectively. Microcrystalline cellulose was used as the tableting powder and MgSt as the lubricant. The low range of CS values (16-32 mm/s) considered in this study did not have significant effects on TST and TSMC. MgSt ratio had a significant positive effect on TST; this may be explained by the increase in powder blend effusivity with the addition of MgSt. However, MgSt ratio did not have a significant effect on TSMC. CP had a significant positive effect on both TST and TSMC. Increased CP induced higher heat generation through particle deformation and friction during the compaction phase, leading to increased TST. Furthermore, the water vapor diffusion rate through the powder bed might have increased due to the rise in thermal energy and led to further moisture accumulation at the tablet-punch interface, causing the significant positive effect of CP on TSMC. This result may explain the occurrence of sticking regardless of the CP applied during the tableting process.

Lubricants are excipients used in tablet formulations to reduce friction and adhesion forces within the die or on the punches surface during the manufacturing process. Despite these excipients are always required for the tablets production, their amount must be carefully evaluated since lubricants can negatively impact on mechanical strength, disintegration and dissolution behavior of solid dosage forms. Alternative compounds have been suggested to overcome the issues of conventional lubricants and sodium lauryl sulfate (SDS) is one of the most promising one. Despite SDS has been object of several investigations, a definitive conclusion on its effectiveness cannot still be drawn. Particularly, its efficacy on tablets disaggregation and API dissolution is still unclear. Here, the effect of SDS on all the relevant features of tablets and tableting process has been evaluated on immediate release hydrophobic tablets formulations in comparison with conventional lubricants. The results of this investigation are quite outspoken: SDS has a low lubricant power while it determines only a limited improvement on tablets hardness. It greatly improves the tablets wettability but only on model formulations, the presence of superdisintegrants resets its effectiveness and any possible effect on tablets disaggregation. None of the tested formulations showed improvement on the API dissolution rate., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Lycopene is a natural bioactive compound possessing higher antioxidant and anti-inflammatory properties, which are known to efficiently eliminate the risk of cancer, cardiac complications, and oxidative stress. Food manufacturers are keen on producing lycopene-fortified food products owing to their numerous health benefits and higher nutritional value. The incorporation of lycopene is limited to food products due to its hydrophobic nature and low chemical stability. This study aims to understand the incorporation of lycopene in Oleogel as a new delivery system. Briefly, lycopene and stearic acid (gelator) were combined at ratios of 0, 25, 50, 75, and 100% (w/w) and added to coconut oil (20 g (w/w) ) for the preparation of edible oleogel combinations. These combinations were characterized for oil binding capacity, swelling capacity, color analysis, and texture profile analysis. Further, the formulations were characterized by FTIR (Fourier Transform Infrared Spectroscopy) and DSC (Differential scanning calorimetry). It was observed that samples prepared with a combination of 50% lycopene and stearic acid were found to possess a firm texture and good stability. Conversely, samples with no gelator produced oleogels with less stability. Further, the FTIR spectra helped determine the network formation in the oleogels, which was stabilized by the hydrogen bond. Furthermore, the results of DSC exhibited that the oleogel combinations with gelator and lycopene were not in the crystalline state, and the oleogels held superior internal structure till 45°C. Overall, oleogel-based carrier systems can be used as an alternative method to encapsulate various bioactive compounds having possible potential applications in the bakery and confectionery industries.

Here, we describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature as a function of the 12-HSA/SA mole ratio R. The morphologies of the self-assembled aggregates are obtained through a multi-structural approach that combines confocal and cryo-TEM microscopies with small-angle neutron scattering (SANS) and wide-angle X-ray scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multilamellar tubes are formed. The doping via a low amount of SA molecules slightly modifies the dimensions of the tubes and decreases the bilayer rigidity. The solutions have a gel-like behavior. At intermediate R, tubes coexist in solution with helical ribbons. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems: they are faceted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus. The solutions remain, however, viscous fluids in this regime.

To provide a theoretical basis for the quality improvement of plant protein-based meat substitutes with lipids, the interactions between pea protein and fatty acids (stearic, oleic and linoleic acids) and the effect on protein conformational changes during high-moisture extrusion (HME) processing were investigated using a dead-stop operation. The surface hydrophobicity analysis and Fourier transform infrared spectroscopy results revealed that the fatty acids induced the exposure of hydrophobic groups in the pea proteins, weakened hydrogen bonds, affected the aggregation of legumin subunits and promoted the conversion of α-helix and β-sheet structures to β-turn and random coil during HME processing. In the die, unsaturated fatty acids limited the refolding of protein chains and covalent interactions between proteins. Micromorphology analysis indicated that the coalescence of oleic and linoleic acids in the cooling zone hindered the formation of anisotropic structures while stearic acid promoted the formation of fibrous structures by enhanced disulfide bonds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Scanning electron microscopy-based energy dispersive X-ray spectroscopy (SEM-EDS) is proposed as a versatile tool for quantifying surface area coverage (SAC) by magnesium stearate (MgSt) on pharmaceutical tablets and particles. Our approach involved fast elemental mapping and subsequent SAC quantitation by image analysis. The study was conducted using a multi-component system, but the particle-level mapping was limited to active pharmaceutical ingredient (API) crystals. For both tablets and API particles, the calculated SAC against MgSt loading afforded a positive linear correlation over the range of MgSt levels examined in this work. On the tablet surface, MgSt was found to be preferentially concentrated at or in the close vicinity of grain boundaries, supporting the idea of compression-driven migration and relocation of MgSt within the tablet. On the particle surface, only discrete aggregates of MgSt were observed, as opposed to the widely accepted phenomenon of the formation of a thin lubricant film around host particles. The selection of proper SEM-EDS operating conditions and the challenges confronted in particle surface mapping are discussed in detail., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In rotary tablet presses, the powder flow into the dies is typically facilitated by paddle feeder. For internally lubricated formulations, the shear forces exerted by the paddle rotation can result in a considerable decrease in tablet strength due to the dispersion of lubricant agglomerates. Available models to describe the lubricant dispersion in paddle feeder allow only a limited quantitative description and transferability of the process. This study introduces an empirical dispersion kinetic which is able to precisely describe the reduction of compactibility due to the shear stresses inside the paddle feeder, even for inhomogeneously flowing material. Additionally, by blending different grades of magnesium stearate at three levels of lubricant concentration with two different grades of microcrystalline cellulose, the impact of bulk properties on the lubrication dispersion in the feed frame was investigated. It was shown, that for a given formulation, the kinetics of compactibility reduction are comparable for different magnesium stearate concentrations. Additionally, the bulk properties of the applied magnesium stearate grade critically affect the dispersion kinetics as well as the maximum compactibility reduction inside the feed frame. In summary, the developed model represents a meaningful extension of the currently available process models for pharmaceutical tablet lubrication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This experiment involved the chemical conversion of pure stearic acid from buffalo adipose tissue to a waxy stearyl stearate, which was subsequently applied as a coating film to extend the shelf life of recently harvested fruits. Fat was extracted from minced adipose tissue using the dry rendering procedure, and it was then characterized. The extracted fat was hydrolyzed into a mixture of free fatty acids and glycerol. The supercritical CO 2 extractor was used for stearic acid individual extraction in pure form from the free fatty acid mixture, and it was confirmed according to its melting point (69.2-70.0 °C), elemental analysis, GC-MS for esterified fatty acids. The isolated stearic acid was used for the synthesis of a new hydrophobic wax named stearyl stearate. The chemical structure of the prepared compound was established according to its elemental analysis and spectral data. The new hydrophobic wax was used as a coating film to enhance the shelf life of freshly harvested tomato fruits. Therefore, stearyl stearate solution (2.00% w/v diethyl ether) was used for tomato coating and compared to chitosan-coated tomatoes, where weight loss, pH, fruit firmness, ascorbic acid concentration, and total soluble solids were studied for a period of 15 days at 23 ± 1.0 °C and 65 ± 2.0% relative humidity. The results revealed that coating with stearyl stearate solution (2.00% w/v diethyl ether) could delay tomatoes' ripening during the experiment condition. A sensory evaluation of the coated tomatoes was carried out and showed acceptable taste for the tomatoes that were coated with stearyl stearate. On the other hand, the acute oral toxicity of stearyl stearate using albino mice showed complete safety up to 25 g/kg mice weight., (© 2022. The Author(s).)

Internal lubrication with magnesium stearate (MgSt) is associated with a reduced tensile strength and prolonged disintegration and dissolution times. In the current study, alternative lubricants to MgSt were compared with regard to lubrication efficacy and their impact on tablet properties. The lubricants were combined in different concentrations (0.5-5% w/w) with three fillers (lactose, mannitol and microcrystalline cellulose (MCC)). The high lubrication efficiency of MgSt was associated with the highest reduction of tensile strength. The micronized stearic acid (SA) grades proved good alternatives as they showed a good lubrication efficiency in combination with a limited negative effect on tensile strength. The hydrophobic lubricants (e.g., MgSt and SA) did not prolong disintegration. In contrast, delayed disintegration was observed for sucrose monopalmitate combined with all three fillers and for several other hydrophilic lubricants (sodium lauryl sulfate, poloxamers 188 and P407) combined with MCC. These unexpected findings were explained by the competition-for-water hypothesis. The potential of alternative lubricants to MgSt was demonstrated in this study. Nevertheless, the impact of lubricant addition on process and tablet quality depended on lubricant (type and concentration) and formulation (lubrication need, deformation mechanism and disintegration behavior) properties. Therefore, lubricant selection should be carefully considered in formulation development., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Magnesium stearate (MgSt) is perhaps one of the most frequently used lubricants in tablet formulation due to its superior lubrication capacity, yet it could also negatively affect the critical quality attributes of pharmaceutical products. Therefore, we provided a rather comprehensive evaluation of another two FDA-approved metallic stearates, sodium stearate (NaSt) and calcium stearate (CaSt), as alternative tablet lubricants. The primary objective of the present study is to comparatively evaluate the physicochemical properties and lubrication efficiency of the three metallic stearates. In addition, it was also aimed to specify the most influential factor for ranking and differentiating the lubricity of various lubricants using principal component analysis. Unit ejection force could be used herein as a simple and the most powerful parameter to evaluate the lubrication performance instead of the friction coefficient. The results suggested that CaSt, MgSt, and NaSt had similar impacts on the mechanical strength of tablets. However, CaSt exhibited insufficient lubrication effects as the formulations containing CaSt showed low pressure transmission ratios, high unit ejection forces, and high friction coefficients. In contrast, both MgSt and NaSt displayed satisfactory lubrication efficiency without negatively impacting tabletability. Notably, the lubrication performance of the formulation containing 0.5 wt% NaSt was almost identical to that of the formulation with 1 wt% MgSt, indicating that NaSt had a remarkable lubrication capability probably due to its high specific surface area. In summary, the findings of this investigation should provide practical information and feasible methodologies to readily determine the lubricity and to sensibly select alternative lubricants for pharmaceutical tablet formulations., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Spin label electron paramagnetic resonance (EPR) spectroscopy was used to characterize the components of the Mycobacterium abscessus massiliense cell envelope and their interactions with amphotericin B (AmB), miltefosine (MIL), and nerolidol (NER). Spin labels analogous to stearic acid and phosphatidylcholine (PC) were distributed on an envelope layer with fluidity comparable to other biological membranes, probably the mycobacterial cell wall, because after treatment with AmB a highly rigid spectral component was evident in the EPR spectra. Methyl stearate analogue spin labels found a much more fluid membrane and did not detect the presence of AmB, except for at very high drug concentrations. Unlike other spin-labeled PCs, the TEMPO-PC spin probe, with the nitroxide moiety attached to the choline of the PC headgroup, also did not detect the presence of AmB. On the other hand, the steroid spin labels were not distributed across the membranes of M. abscessus and, instead, were concentrated in some other location of the cell envelope. Both MIL and NER compounds at 10 μM caused increased fluidity in the cell wall and plasma membrane. Furthermore, NER was shown to have a remarkable ability to extract lipids from the mycobacterial cell wall. The EPR results suggest that the resistance of mycobacteria to the action of AmB must be related to the fact that this drug does not reach the bacterial plasma membrane., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The tableting of most pharmaceutical formulations requires the addition of lubricants to reduce ejection forces, prevent tooling damage and tablet defects. The internal addition of lubricants is known to reduce tablet tensile strength, especially of mainly plastically deforming materials. To date, available models show only limited quantitative predictive accuracy for the influence of lubricant concentration on the mechanical strength of tablets. This study aims to fill this gap and present a model based on the Ryshkewitch-Duckworth equation that can estimate the compactibility profiles of lubricated formulations. Binary mixtures of different diluents (microcrystalline cellulose and lactose) were prepared with common lubricants (magnesium stearate and sodium stearyl fumarate) and subsequently tableted. The resulting compactibility profiles were fitted using the Ryshkewitch-Duckworth equation and the derived fit parameters (k b and σ 0 ) were correlated with the lubricant concentration. Subsequently, an empirical model was established which requires a minimum of experimental data and is able to predict the tensile strength of lubricated diluent tablets. Consequently, the developed empirical model is an interesting and valuable addition to the existing multi-component compacting models available and offers the opportunity to accelerate experimentation in the development of new tablet formulations., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Internal lubrication can be associated with reduced tabletability. Deformation mechanism, lubricant type, lubricant blending time and paddle speed (PS) of the forced feeder are known to be influenceable factors. This study investigated the effect of lubricant blending time and PS of forced feeders on the tensile strength of lubricated microcrystalline cellulose (MCC) and lactose tablets. Magnesium stearate (MgSt), sodium stearyl fumarate (SSF) and stearic acid (SA) were used as lubricants. Tablets were produced on a compaction simulator and a rotary tablet press to investigate lubricant sensitivity during upscaling. Lubricant sensitivity was found higher for MCC compared to lactose which was attributed to the higher plasticity of MCC. The reduction in tensile strength upon lubricant addition followed the order: MgSt > SSF > SA; which could be linked to particle size, specific surface area and particle shape of the lubricants. Although differences in tensile strength were observed between the lubricant types, comparable ejection forces were obtained. The impact of PS on tensile strength was higher compared to lubricant blending time for both tableting machines. A good correlation of tensile strength and lubricant sensitivity between the compaction simulator and rotary tablet press was observed based on the calculation of paddle passes (N PP )., (Copyright © 2022. Published by Elsevier B.V.)

Polypod-like structured nucleic acids (polypodnas), which are nanostructured DNAs, are useful for delivering cytosine-phosphate guanine oligodeoxynucleotides (CpG ODNs) to antigen-presenting cells (APCs) expressing Toll-like receptor 9 (TLR9) for immune stimulation. Lipid modification is another approach to deliver ODNs to lymph nodes, where TLR9-positive APCs are abundant, by binding to serum albumin. The combination of these two methods can be useful for delivering CpG ODNs to lymph nodes in vivo. In the present study, CpG1668, a phosphodiester-type CpG ODN, was modified with stearic acid (SA) to obtain SA-CpG1668. Tripodna, a polypodna with three pods, was selected as the nanostructured DNA. Tripodnas loaded with CpG1668 or SA-CpG1668 were obtained in high yields. SA-CpG1668/tripodna bound more efficiently to plasma proteins than CpG1668/tripodna and was more efficiently taken up by macrophage-like RAW264.7 cells than CpG1668/tripodna, whereas the levels of tumor necrosis factor-α released from the cells were comparable between the two. After subcutaneous injection into mice, SA-CpG1668/tripodna induced significantly higher interleukin (IL)-12 p40 production in the draining lymph nodes than SA-CpG1668 or CpG1668/tripodna, with reduced IL-6 levels in plasma. These results indicate that the combination of SA modification and nanostructurization is a useful approach for the targeted delivery of CpG ODNs to lymph nodes.

Here, Cotton fabric was functionalized via hybrid coating including 2D MgAl LDH (layered double hydroxide) and SA (stearic acid). The urea hydrolysis was employed for construction of vertically aligned LDH on surface of cellulose fibers under hydrothermal condition. The in situ formation mechanism of LDH on cotton surface was nucleation, growth, and interaction with activated cellulose chains. The partial cellulose ionization in the alkaline solution led to nucleophilic behavior towards electron deficient atom. The effect of different ageing, synthesis temperature, and amount of SA were investigated and optimized at 100 °C for 24 h with 0.05 M. The superhydrophobic surface architecture of treated cotton with hierarchical micro/nanostructure was inspired from the Taro leaf structure with continuous contact line presented WCA of 154 ° and CAH of 9 °. The Cotton@LDH@SA exhibited efficient oil/water separation after several washes (>90%) with good stain resistant. Also, the physico-mechanical properties were studied., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin's bioavailability and therapeutic effects.

The main focus of the current work was to design, evaluate and clinically compare the efficiency of novel metronidazole (MTD) loaded solid lipid nanoparticles (SLNs) vaginal emulgel with the marketed vaginal gel (Metron ® ) against Bacterial vaginosis (BV). Eight formulations were fabricated using 2 3 full factorial design and prepared by stearic acid and tween 80 as solid lipid and surfactant, respectively. Lipid and surfactant concentrations in addition to sonication amplitude were chosen as the independent variables (X 1 -X 3 ). Then, the prepared MTD loaded SLNs were evaluated based on the dependent variables which were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative % drug release for 24 h (Y 1 -Y 5 ). The in vitro release study exhibited a sustained release of MTD from the SLNs up to 24 h. The optimal MTD loaded SLNs showed nanosized particles (256 nm) with EE% (52%), and an acceptable ZP value (-29.5 mV). Also, the optimized MTD-SLNs formulation was incorporated into Carbopol emulgel and investigated clinically for its effect against BV. Clinical studies recorded significant enhancement in therapeutic response of MTD from optimized SLNs vaginal emulgel formulation regarding the clinical treatment ( p  < .05) and low recurrence rate ( p  < .001) against the marketed product. In conclusion, our findings recommend that the fabricated MTD loaded SLNs vaginal emulgel have significant therapeutic effect in terms of BV management over commercially obtainable marketed vaginal gel (Metron ® ).

Therapeutic peptides have an important effect on physiological function and human health, so it is momentous to quantify and detect low levels of these biomolecules in biological samples for treatment and diagnostic purposes. In the present study, an efficient magnetic solid-phase extraction (MSPE) method was developed based on stearic acid-functionalized magnetic hydroxyapatite nanocomposite (MHAP/SA) as a novel and cost-effective adsorbent for extraction of five hypothalamic-related peptides (goserelin, octreotide, triptorelin, somatostatin, and cetrorelix) from biological samples. To characterize the morphology and physicochemical properties of MHAP/SA, Fourier transform infrared spectroscopy (FT-IR), energy-dispersive X-ray spectroscopy (EDS), field emission scanning microscopy (FE-SEM), CHNS elemental analysis, Brunauer-Emmett-Teller (BET), and vibrating sample magnetometry (VSM) were applied. Under optimum conditions, the proposed method (MSPE-HPLC-UV) represented favorable linearity with R 2  ≥ 0.9987, suitable intra- and inter-day precisions (RSD ≤ 6.9% and RSD ≤ 8.1%, respectively, n = 3), and limits of detection and quantification in the range of 0.75-1.12 ng mL -1 and 2.50-3.75 ng mL -1 , respectively. Eventually, the proposed method was used for the extraction and quantification of target therapeutic peptides in plasma and urine samples, and satisfactory relative recoveries were achieved in the range of 90.6-110.3%., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Small molecule-chemotherapeutic drug conjugate nanoparticles (SMCDC NPs) has a great advantage in improving drug loading. However, the factors which influence these conjugates forming stable nanoparticles (NPs) are currently unclear. In our previous studies, we synthesized a series of fatty acid-paclitaxel conjugates and suggested that the changes in the hydrophobic parameters (XlogP), solubility parameters and crystallinity of these fatty acid-paclitaxel conjugates were the key factors for affecting these small molecule-chemotherapeutic drug conjugates (SMCDCs) forming stable NPs in water. Here, we selected clinically widely used chemotherapeutic drug (docetaxel (DTX), doxorubicin (DOX) and irinotecan (Ir)) as model drug, and chose three straight-chain fatty acids (acetic acid (Ac), hexanoic acid (HA) and stearic acid (SA)) and one branched small molecule (N-(tert-butoxycarbonyl) glycine (B-G)) to synthesize 12 SMCDCs. Our results indicated that our prediction criterions obtained from paclitaxel conjugates were also appropriated for these synthesized SMCDCs. We suggested that the present studies expanded the scope of application of the above-mentioned influencing factors, provided research ideas for the rational design of SMCDC forming NPs and a basis for screening NPs with good anticancer activity.

Berberine, an isoquinoline alkaloid, is reported for the treatment of Alzheimer's disease. Despite having substantial therapeutic potential, it exhibits poor absorption, low oral bioavailability and limited penetration in the brain. In this study, berberine-loaded nanostructured lipid carriers (Berb-NLCs) were developed by melt-emulsification and ultrasonication using Geleol, Miglyol 812 N, Solutol HS 15 as a solid lipid, liquid lipid and surfactant, respectively. The Berb-NLC formulation was statistically optimized by a 3 2 factorial design in which the effect of surfactant and berberine concentration was assessed on particle size and entrapment efficiency of Berb-NLCs. Optimized Berb-NLCs (Trial-5) exhibited particle size of 186 nm, polydispersity index of 0.108, the zeta potential of -36.86 mV and 88% entrapment efficiency. The in vitro release of berberine from Batch-B5 was 82% in phosphate buffer at the end of 24 h. The comparative results of pharmacodynamic studies involving behavioral assessment by locomotor activity, passive avoidance test, elevated plus maze test and spatial memory assessment by Morris water maze demonstrated improved behavioral parameters in vivo by Berb-NLCs compared to pure berberine in Albino Wistar rats. Thus, berberine-loaded nanostructured lipid carriers have the potential of brain targeting and were effective in an animal model of Alzheimer's disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

With an aim to prepare the functional chocolate, corn oil was used as the base oil and β-sitosterol was combined with oryzanol/stearic acid/lecithin to prepare respective oleogels (GO, SO, and LO). Oleogels (12%) were prepared by adding compound oleogelators at different ratios [GO-2:3, SO-1:4, and LO-4:1 (w/w)] in corn oil. The microstructure, interaction, thermodynamic, crystalline, and rheological behavior of formulated oleogels were studied by microscopic observation, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and rotational rheometer, respectively. The results showed that GO had the strongest gel forming ability and the densest gel crystallization network. Moreover, chocolate prepared with GO (cocoa butter and oleogels-1:1) had the similar texture, crystal structure, rheological, and sensory properties to that of dark chocolate. This study provides the possibility for the wider application of oleogel prepared with lower saturated and trans-fatty acids in the chocolate industry., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Arabinoxylan (AX) and cellulose were extracted from wheat straw, whereas starch was extracted from potato peel. Thereafter, cellulose and starch were esterified with lauric, myristic, palmitic and stearic acids to prepare corresponding cellulose (CFAs) and starch fatty acid esters (SFAs) with DS 2.1-2.8. XRD study revealed remarkable loss of crystallinity in cellulose and starch due to fatty acid esterification. The addition of palmitate and stearate esters of cellulose and starch to AX formed laminar film microstructures which limited water vapor permeability whereas films prepared by blending AX with laurate and myristate esters of starch and cellulose were less effective as water vapor barrier due to their non-layer microstructures. The laminar structures also resulted significant reduction in mechanical strength of the composite films. Furthermore, all AX-CFAs and AX-SFAs films were thermally more stable than native composite films. These films might be used to produce industrially useful coating material for food products., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

During forced degradation, the intrinsic stability of active pharmaceutical ingredients (APIs) could be determined and possible impurities that would occur during the shelf life of the drug substance or the drug product could be estimated. Vildagliptin belongs to relatively new oral antidiabetic drugs named gliptins, inhibiting dipeptidyl peptidase 4 (DPP-4) and prolonging the activities of the endogenous incretin hormones. At the same time, some gliptins were shown as prone to degradation under specific pH and temperature conditions, as well as in the presence of some reactive excipients. Thus, forced degradation of vildagliptin was performed at high temperature in extreme pH and oxidative conditions. Then, selective LC-UV was used for quantitative determination of non-degraded vildagliptin in the presence of its degradation products and for degradation kinetics. Finally, identification of degradation products of vildagliptin was performed using an UHPLC-DAD-MS with positive ESI. Stability of vildagliptin was also examined in the presence of pharmaceutical excipients, using mid-IR and NIR with principal component analysis (PCA). At 70 °C almost complete disintegration of vildagliptin occurred in acidic, basic, and oxidative media. What is more, high degradation of vildagliptin following the pseudo first-order kinetics was observed at room temperature with calculated k values 4.76 × 10 -4 s -1 , 3.11 × 10 -4 s -1 , and 1.73 × 10 -4 s -1 for oxidative, basic and acidic conditions, respectively. Next, new degradation products of vildagliptin were detected using UHPLC-DAD-MS and their molecular structures were proposed. Three degradants were formed under basic and acidic conditions, and were identified as [(3-hydroxytricyclo- [3.3.1.13,7]decan-1-yl)amino]acetic acid, 1-{[(3-hydroxytricyclo[3.3.1.13,7]decan-1-yl)amino]acetyl}-pyrrolidine-2-carboxylic acid and its O -methyl ester. The fourth degradant was formed in basic, acidic, and oxidative conditions, and was identified as 1-{[(3-hydroxytricyclo[3.3.1.13,7]-decan-1-yl)amino]acetyl}pyrrolidine-2-carboxamide. When stability of vildagliptin was examined in the presence of four excipients under high temperature and humidity, a visible impact of lactose, mannitol, magnesium stearate, and polyvinylpirrolidone was observed, affecting-NH- and CO groups of the drug. The obtained results (kinetic parameters, interactions with excipients) may serve pharmaceutical industry to prevent chemical changes in final pharmaceutical products containing vildagliptin. Other results (e.g., identification of new degradation products) may serve as a starting point for qualifying new degradants of vildagliptin as it is related to substances in pharmacopoeias.

Beeswax is intended for use in the beekeeping sector but also in the agro-food, pharmaceutical or cosmetics sectors. The adulteration of beeswax is an emerging issue that was reported lately at several occasions in the scientific literature. This issue tends to become more frequent and global, but its exact extent is not accurately defined. The present study aims to assess the current situation in Belgium through a nationwide survey. Randomized beeswax samples originating from Belgian beekeepers (N = 98) and commercial suppliers (N = 9) were analysed with a Fourier transform infrared spectroscopy (FTIR) coupled with Attenuated Total Reflectance (ATR) accessory (FTIR-ATR spectroscopy) for adulteration. The survey revealed a frequency of 9.2% and 33.3% of adulteration in beekeepers beeswax samples (9 samples out of 98: 2 with paraffin and 7 with stearin/stearic acid) and commercial beeswax samples (3 samples out of 9: all adulterated with stearin/stearic acid), respectively. The analysed samples were adulterated with various percentages of paraffin (12 to 78.8%) and stearin/stearic acid (1.2 to 20.8%). This survey indicates that in the beekeepers samples, beeswax adulteration was more frequent in comb foundation and crude beeswax than in comb wax. With the example of this nationwide survey conducted in Belgium, this study shows the emergence of the issue and the urgent need for action to safeguard the health of both honey bees health and humans, in particular with the setting of a proper regulation legal framework and a specific routine analytical testing of commercial beeswax to ensure beeswax quality., Competing Interests: The authors have declared that no competing interests exist.

As natural potential antioxidants suffer from low cellular uptake, the development of drug-loaded nanoplatforms may provide useful information about the treatment of spinal cord injury (SCI). In the present study, sesamol (SM)-loaded stearic acid (SA) -chitosan (CS) nanomicelles were fabricated and well-characterized. Afterwards, the neuroprotective effects of SM@SA-CS nanomicelles against lipopolysaccharide (LPS)-induced oxidative stress in NSC-34 cells was assessed by different cellular and molecular pathways. It was deduced that the size of synthesized SM@SA-CS was in the range of 10-20 nm and the hydrodynamic radii of SA-CA and SM@SA-CA nanomicelles were 53.12 ± 6.21 nm and 59.12 ± 7.31 nm, respectively. Furthermore, SM@SA-CS nanomicelles displayed a sustained drug release at physiological pH, potential dissolution rate and stability even up to 15 days. Cellular assay showed that SM@SA-CS nanomicelles co-incubation with LPS for 24 h in comparison with free drug remarkably regulated cell survival, membrane leakage, generation of ROS, activity of non-enzymatic and enzymatic antioxidant systems, and apoptotic and inflammatory signaling pathway through NF-ĸB signaling pathway. These data indicated that SM@SA-CS nanomicelles can be developed as a promising platform for the mitigation of oxidative stress-mediated apoptosis in neural cells., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This work investigated the modification of low-methoxy pectin with stearic anhydride through microwave action with 4-dimethylaminopyridine as catalyst. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analyses indicated that stearic acid was grafted on the pectin through esterification reaction, with the maximum stearic acid grafting ratio (SGR) of 10.7% for the modified pectin. The introduction of stearic acid was shown to significantly improve the emulsifying activity and stability of pectin. Composite films were prepared by blending the modified pectins and chitosan, and compared with the contact angle of 65.3° for the film with native low-methoxy pectin (PC0), the films with modified pectins showed a significant angle increase, with the highest contact angle reaching 101.9°, indicating a hydrophobic surface. Moreover, an appropriate amount of aliphatic chains could improve the tensile strength and elongation at break of the composite films due to the "anchoring effect"., (Copyright © 2021. Published by Elsevier B.V.)

Background: Melt crystallization is typically recognized as a highly efficient and green method for oil fractionation. This work concentrated on novel layer melt crystallization for preparing desirable olein and stearin products from palm oil and the evaluation of fraction quality. Layer melt crystallization was performed at various temperatures and the effects on fractions were evaluated using iodine value (IV), solid fat content (SFC) and melting point. The lipid composition, thermal and crystallization properties, and phase behaviors of the final optimized fractions were determined using gas chromatography, high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry and differential scanning calorimetry., Results: Increasing crystallization tube temperatures under the same jacket temperature increased the melting point and SFC, while decreasing the IV of the olein product. Opposite results were observed for the stearin product. Major fatty acids in fractions were determined as palmitic acid and oleic acid. 1,2-Dioleoyl-3-palmitoylglycerol and 1,3-dipalmitoyl-2-oleoylglycerol were identified as the main triacylglycerols in olein and stearin fractions, respectively. A critical effect of crystallization temperature on co-crystallization of oleins and stearins was revealed. A transition from plate-like crystal growth to spherulitic growth with spontaneous nucleation was indicated in palm oil and stearin fractions with increasing crystallization temperature. As for olein fractions, a temperature increase resulted in heterogeneous nucleation from instantaneous nucleation., Conclusions: Novel layer melt crystallization was successfully applied and optimized for fractionating palm oil. The composition and property changes of obtained fractions were analyzed and explained at both macroscopic and microscopic levels. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

We developed an alternative whipping cream fat using shea butter but with low saturation. Enriched stearic-oleic-stearic (SOS) solid fat was obtained from shea butter via solvent fractionation. Acyl migration reactant, which mainly contains asymmetric SSO triacylglycerol (TAG), was prepared through enzymatic acyl migration to obtain the creaming quality derived from the β'-crystal form. Through enzymatic acyl migration, we obtained a 3.4-fold higher content of saturated-saturated-unsaturated (SSU) TAG than saturated-unsaturated-saturated (SUS) TAG. The acyl migration reactant was refined to obtain refined acyl migration reactant (RAMR). An alternative fat product was prepared by blending RAMR and hydrogenated palm kernel oil (HPKO) at a ratio of 4:6 ( w / w ). The melting points, solid fat index (SFI), and melting curves of the alternative products were similar to those of commercial whipping cream fat. The alternative fat had a content of total unsaturated fatty acids 20% higher than that of HPKO. The atherogenic index (AI) of alternative fat was 3.61, much lower than those of whipping cream fat (14.59) and HPKO (1220.3), because of its low atherogenic fatty acid content and high total unsaturated fatty acids. The polymorphic crystal form determined by X-ray diffraction spectroscopy showed that the β'-crystal form was predominant. Therefore, the alternative fat is comparable with whipping cream that requires creaming quality, and has a reduced saturated fat content.

Nigella sativa (NS) is a well-known plant for its various benefits and multiuse in traditional medicine. This study is aimed at investigating the chemical composition of the different NS fractions by using GC-MS for the esterified fatty acids or HPLC-UV for organic fraction and at evaluating the inhibitory effect on pancreatic α -amylase ( in vitro , in vivo ) and intestinal glucose absorption. Among all the investigated fractions, it was shown that they are rich with different molecules of great interest. The n-hexane fraction was characterized by the presence of linoleic acid (44.65%), palmitic acid (16.32%), stearic acid (14.60%), and thymoquinone (8.7%), while among the identified peaks in EtOH fraction we found catechin (89.03 mg/100 g DW), rutin (6.46 mg/100 g DW), and kaempferol (0.032 mg/100 g DW). The MeOH fraction was distinguished with the presence of gallic acid (19.91 mg/100 g DW), catechin (13.79 mg/100 g DW), and rutin (21.07 mg/100 g DW). Finally, the aqueous fraction was marked by the existence of different molecules; among them, we mention salicylic acid (32.26 mg/100 g DW), rutin (21.46 mg/100 g DW), and vanillic acid (3.81 mg/100 g DW). Concerning the inhibitory effect on pancreatic α -amylase, it was found that in the in vitro study, the best IC 50 registered were those of EtOH (0.25 mg/ml), MeOH (0.10 mg/ml), aqueous (0.031 mg/ml), and n-hexane fraction (0.76 mg/ml), while in the in vivo study an important inhibition of α -amylase in normal and diabetic rats was observed. Finally, the percentage of intestinal glucose absorption was evaluated for all tested extracts and it was ranging from 24.82 to 60.12%. The results of the present study showed that the NS seed fractions exert an interesting inhibitory effect of α -amylase and intestinal glucose absorption activity which could be associated with the existent bioactive compounds. Indeed, these compounds can be used as antidiabetic agents because of their nontoxic effect and high efficacy., Competing Interests: The authors of this work declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Mohammed Dalli et al.)

Interesterification is widely employed as an effective technique to modify oils and fats. This study utilizes palm-based oil (palm olein: palm kernel oil: palm stearin, 5:3:2, w/w/w) as the raw material for the interesterification process performed in a pilot-scale packed bed reactor. Enzymatic interesterification (EIE) was catalyzed by Lipozyme TL IM (813.0 g) at 60℃ with reaction flow rate of 100 mL/min. Chemical interesterification (CIE) was catalyzed using sodium methoxide (0.3 wt%) as catalyst at 105 °C for 30 min. The results showed that the EIE fats had lower solid fat content tendency compared to that of CIE fats. The crystallization onset temperature was higher in EIE fats (23.09℃) compared to that of CIE (19.08℃). The results were consistent with the crystallization kinetics whereby the Avrami K constants of EIE fats were higher than that of CIE fats at various temperatures, indicating rapid crystallization and instant nucleation. Linear growth mechanism was dominant and the crystals formed were smaller in size as observed using polarized light microscope. The interesterified fats exhibited the presence of β and β'-crystals. While most of the tocopherol content was retained after EIE (386.18 ug/g), the molecular distillation process reduced the tocopherol concentration (110.01 ug/g) which consequently affected the oxidative stability. The findings in this work contribute to the fundamental understanding on the differences between CIE and EIE fats and provides data to support the preparation of modified fats via EIE that shows great potential as a controllable technique for industrialization., (Copyright © 2021 Elsevier Ltd. All rights reserved.)