Surface Active Agents

We report the observation of bilayer fragments, some of which close to form vesicles, over a large range of pH at room temperature from mixtures of single-chain biocompatible commercially available nontoxic alkyl carboxylic surfactants after neutralization with HCl. The pH at which the morphological transitions occur is varied only by changing the ratio between two surfactants: the alkyloligoethyleneoxide carboxylate and sodium laurate. The effect of aging of the mixed surfactant systems in the pH region desired for dermatologic application (4.5 < pH < 7) is also studied. Finally, we show results of cytotoxicity studies on the surfactant mixtures.

Halotolerants microorganisms able to live in saline environments, offer a multitude of actual or potential applications in various fields of biotechnology. This is why some strains of Halobacteria from an Algerian culture collection were screened for biosurfactant production in a standard medium using the qualitative drop-collapse test and emulsification activity assay. Five of the Halobacteria strains reduced the growth medium surface tension below 40mNm-1 and two of them exhibited high emulsion-stabilising capacity. Diesel oil-in-water emulsions were stabilized over a broad range of conditions, from pH 2 to 11, with up to 35% sodium chloride or up to 25% ethanol in the aqueous phase. Emulsions were stable to three cycles of freezing and thawing. The components of the biosurfactant were determined; it contains sugar, protein and lipid. The two Halobacteria strains with enhanced biosurfactants producers designed strain A21 and strain D21 were selected to identify by phenotypic, biochemical characteristics and by partial 16S rRNA gene sequencing. The strains have Mg2+and salt growth requirements are always above 15% (w/v) salts with an optimal concentration of 15% to 20%. Analyses of partial 16S rRNA gene sequences of the two strains suggested that they were halophiles belonging to genera of the family Halobacteriaceae, Halovivax (strain A21) and Haloarcula (strain D21). To our knowledge, this a first report of biosurfactant production at such a high salt concentration.

Dedicated to my mother, my wife, our daughter Dedicated to my mother, my wife, our daughter Dedicated to my mother, my wife, our daughter Dedicated to my mother, my wife, our daughter and and and and to the spirit of my father who dreamed first… to the spirit of my father who dreamed first… to the spirit of my father who dreamed first… to the spirit of my father who dreamed first…

Many modern drugs have poor water solubility, which limits their absorption in the gastrointestinal tract and reduces their effectiveness. Self Nano
Emulsifying Drug Delivery Systems (SNEDDS) have emerged as an innovative solution to improve the oral delivery of such drugs by enhancing their
solubility and bioavailability.SNEDDS are formulated using a combination of oils, surfactants, and co-surfactants. The oil phase dissolves lipophilic drugs,
while surfactants reduce surface tension to allow spontaneous formation of nanoemulsions in the presence of gastrointestinal fluids. Co-surfactants further
stabilize the system. Upon oral administration, natural movements in the GI tract help the formulation disperse into fine droplets, typically below 100 nm in
size.The formation of nano-sized droplets increases the surface area of the drug, leading to faster dissolution and improved absorption through the intestinal
lining. SNEDDS also protect drugs from degradation caused by gastric acid and enzymes. Additionally, they reduce variability in drug absorption due to food
intake and can be developed in both liquid and solid dosage forms.The use of SNEDDS significantly enhances the solubility, stability, and bioavailability
of poorly water-soluble drugs, resulting in more consistent and effective therapeutic outcomes.SNEDDS represent a promising and versatile drug delivery
system, especially for drugs with low solubility and permeability. Their ability to improve drug performance makes them an important advancement in
pharmaceutical technology.

The orally administered self nano emulsifying drug delivery system (SNEDDS), an uniform blend with nano scaled globules, is composed of oil, surfactant and co-surfactant. The aim of the investigation was to develop and optimize Nicardipine loaded liquid SNEDDS via Box Behnken design and characterised based on physicochemical features, DSC and stability profile. Further to achieve sustain drug release, the optimized SNEDDS was compressed as self nano emulsifying tablet (SNET). Furthermore, the in vivo and pharmacokinetic study of the drug loaded SNET (NT) were performed. The NOF indicated droplet size (75.62 nm ± 2.01), self emulsification time (37 s ± 1.01), and 87.6% ± 0.08drug release (at 1 h). The bias was found to be within the range of-0.72 to + 1.19 for stable, almost spherical, amorphous formulation. The sustained release (following Higuchi kinetics) of drug from NT was observed. The mean systolic blood pressure of NT treated rats were found to be significantly reduced (*p < 0.01) to normal range up to 48 h and the plasma NIC concentrations were found to be maintained up to 36 h with enhanced bioavailability in comparison to pure drug suspension. The enhanced NIC exposure of NT (AUC 0-α : 156.1 ± 13.7) compared to pure NIC suspension (AUC 0-α : 89.7 ± 8.1) demonstrated the potentiality of NIC SNET for hypertension treatment.

Amphiphiles are molecules such as surfactants or lipids that have a polar head group (hydrophilic) attached to nonpolar hydrophobic alkyl chains. Because of this characteristic they self-assemble in water and give rise to a wide range of phases with different structures and properties. Aqueous dispersions of amphiphiles are present in every aspect of day-to-day life-e.g., forming biological cell membranes, stabilizing emulsified food, or being used as soap. Time-resolved x-ray diffraction has been used to study the hexadecylhexa(oxyethylene glycol) ether (C 16 EO 6 )͞water system, which shows an intermediate phase whose structure depends on the thermal path between lamellar and hexagonal structures. Heating the hexagonal phase from room temperature leads to a lamellar phase via an Ia3d cubic structure. Cooling from the lamellar phase initially leads epitaxially to an intermediate R3 m before the hexagonal phase is reached. Both cubic and R3 m phases are formed by very similar rod units, but the overall structures differ because of their spatial distribution and they both bridge morphologically the hexagonal and lamellar phases. The Ia3d does so on heating, whereas the R3 m does on cooling. The structural path during the phase transitions is determined by topological similarities between the forming phase and the one from which it originates. Although the estimated curvature energies for these two phases are similar, on cooling, kinetics and topology are initial factors determining the path for the phase transitions, whereas on heating energy is the dominant factor.

Amphiphiles are molecules such as surfactants or lipids that have a polar head group (hydrophilic) attached to nonpolar hydrophobic alkyl chains. Because of this characteristic they self-assemble in water and give rise to a wide range of phases with different structures and properties. Aqueous dispersions of amphiphiles are present in every aspect of day-to-day life—e.g., forming biological cell membranes, stabilizing emulsified food, or being used as soap. Time-resolved x-ray diffraction has been used to study the hexadecylhexa(oxyethylene glycol) ether (C 16 EO 6 )/water system, which shows an intermediate phase whose structure depends on the thermal path between lamellar and hexagonal structures. Heating the hexagonal phase from room temperature leads to a lamellar phase via an Ia3d cubic structure. Cooling from the lamellar phase initially leads epitaxially to an intermediate R3̄m before the hexagonal phase is reached. Both cubic and R3̄m phases are formed by very similar rod un...

The tri-headed anionic dendritic amphiphile, 4-(2-carboxyethyl)-4-[(icosyloxycarbonyl)amino]heptanedioic acid (3CCb20), forms solid-like gel-state mixed micelles with dipalmitoylphosphatidylcholine (DPPC) in excess water at 3CCb20 : DPPC = 0.91 : 1 molar ratio. On heating, these micelles transform into fluid bilayers stacked in the liquid crystalline lamellar L α phase at about 40 °C. This phase transition and the microstructure of 3CCb20 + DPPC aggregates were studied using smalland wide-angle synchrotron X-ray diffraction. The ability of 3CCb20 to solubilize solid-like lipid bilayers could be important in microbiocidal activities of 3CCb20, including in its anti-HIV activity.

The modular synthesis of 7 libraries containing 51 self-assembling amphiphilic Janus dendrimers with the monosaccharides D-mannose and D-galactose and the disaccharide D-lactose in their hydrophilic part is reported. These unprecedented sugar-containing dendrimers are named amphiphilic Janus glycodendrimers. Their self-assembly by simple injection of THF or ethanol solution into water or buffer and by hydration was analyzed by a combination of methods including dynamic light scattering, confocal microscopy, cryogenic transmission electron microscopy, Fourier transform analysis, and micropipet-aspiration experiments to assess mechanical properties. These libraries revealed a diversity of hard and sof t assemblies, including unilamellar spherical, polygonal, and tubular vesicles denoted glycodendrimersomes, aggregates of Janus glycodendrimers and rodlike micelles named glycodendrimer aggregates and glycodendrimermicelles, cubosomes denoted glycodendrimercubosomes, and solid lamellae. These assemblies are stable over time in water and in buffer, exhibit narrow molecular-weight distribution, and display dimensions that are programmable by the concentration of the solution from which they are injected. This study elaborated the molecular principles leading to single-type soft glycodendrimersomes assembled from amphiphilic Janus glycodendrimers. The multivalency of glycodendrimersomes with different sizes and their ligand bioactivity were demonstrated by selective agglutination with a diversity of sugar-binding protein receptors such as the plant lectins concanavalin A and the highly toxic mistletoe Viscum album L. agglutinin, the bacterial lectin PA-IL from Pseudomonas aeruginosa, and, of special biomedical relevance, human adhesion/growth-regulatory galectin-3 and galectin-4. These results demonstrated the candidacy of glycodendrimersomes as new mimics of biological membranes with programmable glycan ligand presentations, as supramolecular lectin blockers, vaccines, and targeted delivery devices.

Surfactant accumulates in alveolar macrophages of granulocyte-macrophage colony-stimulating factor (GM-CSF) knockout (KO) mice and pulmonary alveolar proteinosis (PAP) patients with a functional loss of GM-CSF resulting from neutralizing anti-GM-CSF antibody. Alveolar macrophages from PAP patients and GM-CSF KO mice are de-ficient in peroxisome proliferator-activated receptor-gamma (PPARgamma) and ATP-binding cassette (ABC) lipid transporter ABCG1. Previous studies have demonstrated that GM-CSF induces PPARgamma. We therefore hypothesized that PPARgamma promotes surfactant catabolism through regulation of ABCG1. To address this hypothesis, macrophage-specific PPARgamma (MacPPARgamma) knockout mice were utilized. MacPPARgamma KO mice develop foamy, lipid-engorged Oil Red O positive alveolar macrophages. Lipid analyses revealed significant increases in the cholesterol and phospholipid contents of MacPPARgamma KO alveolar macrophages and extracellular bronchoalveolar lavage (BAL)-deriv...

Surfactant accumulates in alveolar macrophages of granulocyte-macrophage colony-stimulating factor (GM-CSF) knockout (KO) mice and pulmonary alveolar proteinosis (PAP) patients with a functional loss of GM-CSF resulting from neutralizing anti-GM-CSF antibody. Alveolar macrophages from PAP patients and GM-CSF KO mice are defi cient in peroxisome proliferator-activated receptor-␥ (PPAR ␥ ) and ATP-binding cassette (ABC) lipid transporter ABCG1. Previous studies have demonstrated that GM-CSF induces PPAR ␥ . We therefore hypothesized that PPAR ␥ promotes surfactant catabolism through regulation of ABCG1. To address this hypothesis, macrophage-specifi c PPAR ␥ (MacPPAR ␥ ) knockout mice were utilized. MacPPAR ␥ KO mice develop foamy, lipid-engorged Oil Red O positive alveolar macrophages. Lipid analyses revealed signifi cant increases in the cholesterol and phospholipid contents of MacPPAR ␥ KO alveolar macrophages and extracellular bronchoalveolar lavage (BAL)-derived fl uids. MacPPAR ␥ KO alveolar macrophages showed decreased expression of ABCG1 and a defi ciency in ABCG1-mediated cholesterol effl ux to HDL. Lipid metabolism may also be regulated by liver X receptor (LXR)-ABCA1 pathways. Interestingly, ABCA1 and LXR ␤ expression were elevated, indicating that this pathway is not suffi cient to prevent surfactant accumulation in alveolar macrophages. These results suggest that PPAR ␥ mediates a critical role in surfactant homeostasis through the regulation of ABCG1. -Baker,

Purpose Currently, the FDA allows biowaivers for Class I (high solubility and high permeability) and Class III (high solubility and low permeability) compounds of the Biopharmaceutics Classification System (BCS). Scientific evidence should be provided to support biowaivers for BCS Class I and Class III (high solubility and low permeability) compounds. Methods Data on the effects of excipients on drug permeability are needed to demonstrate that commonly used excipients do not affect the permeability of BCS Class III compounds, which would support the application of biowaivers to Class III compounds. This study was designed to generate such data by assessing the permeability of four BCS Class III compounds and one Class I compound in the presence and absence of five commonly used excipients. The permeability of each of the compounds was assessed, at three to five concentrations, with each excipient in two different models: Caco-2 cell monolayers, and in situ rat intestinal perfusion. No substantial increases in the permeability of any of the compounds were observed in the presence of any of the tested excipients in either of the models, with the exception of disruption of Caco-2 cell monolayer integrity by sodium lauryl sulfate at 0.1 mg/ml and higher. The results suggest that the absorption of these four BCS Class III compounds would not be greatly affected by the tested excipients. This may have implications in supporting biowaivers for BCS Class III compounds in general.

Zinc meso-tetra (4-pyridyl) porphyrin (ZnTPyP) was purchased from Frontier Scientific, Inc., Myristyltrimethylammonium bromide (MTAB) was purchased from Aldrich Chemical Co. and used without further purification. Hydrochloric acid (HCl 1M) and Sodium hydroxide (NaOH 1M) solution were purchased from Aldrich Chemical Co. All the solutions were prepared in ultrapure water from a Barnstead Nanopure water system, and filtered through a 0.2-μm syringe filters to remove particles. Sample preparation methods. The porous nanodiscs of ZnTPyP were synthesized through a simple solution procedure. In a typical preparation, 0.5 ml fresh stock ZnTPyP solution (0.01 M ZnTPyP dissolved in 0.2 M HCl solution) was quickly added into 9.5 mL of continuously stirred aqueous solution of MTAB (0.01 M) and NaOH (0.008 M) at room temperature (25 o C). After the mixture was stirred for 30 min, the solution became green. The green solution was centrifuged at 7000 rpm and washed twice with Millipore water to remove the surfactant.

Lipopolysaccharide-defective mutants ofPseudomonas aeruginosa strain PAO have been isolated on the basis of their resistance to lipopolysaccharide-specific bacteriophages. These mutants have been differentiated by their agglutination in NaCl and acriflavine, phage sensitivity, and chemical analysis of the lipopolysac- charides. The susceptibility of the wild-type strain and four mutants to a series of twenty-six agents, including dyes, detergents, antibiotics, and lysozyme, was examined. The roughest mutant (AK-43) exhibited increased susceptibility to sodium deoxycholate, hexadecylpyridinium chloride, benzalkonium chloride, am- picillin, penicillin G, erythromycin, colymycin, and polymyxin B. The role of cell envelope fractions in antibiotic resistance in P. aeruginosa is discussed.

Objective: Azelnidipine (AZL), a biopharmaceutical classification system (BCS) class II calcium channel blocker, exhibits poor water solubility and limited oral bioavailability (22%) due to extensive first-pass metabolism. This study aimed to enhance its absorption by formulating it into a selfmicroemulsifying drug delivery system (SMEDDS) and further converting it into a solid dosage form. Methods: SMEDDS was developed using capmul MCMC8 (oil), transcutol HP (surfactant), and tween 80 (co-surfactant), depending on the results of solubility study. A ternary phase diagram identified the microemulsification region, while a D-optimal mixture design was used to optimize the formulation. Liquid SMEDDS was then converted into a solid powder using aeroperl 300 as adsorbing agent and ultimately converted into a tablet form. Results: The optimized liquid SMEDDS exhibited a droplet size of 96.71 nm, solubility of 26.2 mg/ml, and emulsification time of 41 seconds. It was subsequently adsorbed onto a porous carrier to produce solid SMEDDS. Scanning electron microscopy (SEM) confirmed that the solid particles were discrete and non-agglomerated. In vitro drug release studies showed enhanced release profiles for both liquid and solid SMEDDS (~100%) compared to the marketed tablet available (72%) at 60 min. Thus, SMEDDS showed a 1.3-fold increase in drug release. The formulation also remained stable for 6 mo under accelerated storage conditions (45 ± and 75%±5% RH). Conclusion: SMEDDS effectively improved the solubility, dissolution rate, and stability of azelnidipine. The application of D-optimal design enabled precise optimization of the formulation, supporting its potential as a promising strategy for enhancing the oral bioavailability of poorly watersoluble drugs.

Objective: Azelnidipine (AZL), a biopharmaceutical classification system (BCS) class II calcium channel blocker, exhibits poor water solubility and limited oral bioavailability (22%) due to extensive first-pass metabolism. This study aimed to enhance its absorption by formulating it into a selfmicroemulsifying drug delivery system (SMEDDS) and further converting it into a solid dosage form. Methods: SMEDDS was developed using capmul MCMC8 (oil), transcutol HP (surfactant), and tween 80 (co-surfactant), depending on the results of solubility study. A ternary phase diagram identified the microemulsification region, while a D-optimal mixture design was used to optimize the formulation. Liquid SMEDDS was then converted into a solid powder using aeroperl 300 as adsorbing agent and ultimately converted into a tablet form. Results: The optimized liquid SMEDDS exhibited a droplet size of 96.71 nm, solubility of 26.2 mg/ml, and emulsification time of 41 seconds. It was subsequently adsorbed onto a porous carrier to produce solid SMEDDS. Scanning electron microscopy (SEM) confirmed that the solid particles were discrete and non-agglomerated. In vitro drug release studies showed enhanced release profiles for both liquid and solid SMEDDS (~100%) compared to the marketed tablet available (72%) at 60 min. Thus, SMEDDS showed a 1.3-fold increase in drug release. The formulation also remained stable for 6 mo under accelerated storage conditions (45 ℃±2 ℃ and 75%±5% RH). Conclusion: SMEDDS effectively improved the solubility, dissolution rate, and stability of azelnidipine. The application of D-optimal design enabled precise optimization of the formulation, supporting its potential as a promising strategy for enhancing the oral bioavailability of poorly watersoluble drugs.

Problemes química: Fórmules, gases. 1. La progesterona és un component habitual dols compostos farmacèutics indicats pel control de la natalitat. La seva fórmula molecular és C 21H30O2. ¿Quina serà la seva composició centesimal? R: 80,25% C; 9,55 H; 10,20 % O. 2. Una mostra d'un mineral impur de sulfurs conté un 42,34% de Zn. Trobar el percentatge de ZnS pur a la mescla. R: 63,1% En 100 g de mineral tenim (42.34+20.78)=63.12 g Zn S 3. El cianat de mercuri s'utilitza on la munició de calibre curt. En una anàlisi d 'un compost d 'aquest tipus es va trobar : 70,48 % Hg; 8 ,44,% C,9.84 % N i 11.2 % O. Determinar la fórmula empírica del cianat de mercuri. R: HgC 2N2O2. Fórmula: HgC 2 N 2 O 2 .

The removal of the non-ionic surfactant Triton X-100, dosed at 30 and 300 mg/L in a pilot-scale subsurface horizontal flow reed bed, and the aerobic heterotrophic cultivable community associated with the roots and with the substrate gravel in both absence and presence of Triton X-100 were investigated. t-Octylphenol (OP) and its mono-, di-and tri-ethoxyl derivatives, among others, were found in the outlet. A mass balance allowed us to calculate that approximately 40% of the Triton X-100 metabolites OP and octylphenol polyethoxylate derivatives flowed out of the reed bed during the dosage and postdosage experiments. More aerobic heterotrophic microorganisms adhered to the roots than to the gravel. The appearance of new strains (Aeromonas, Flavobacterium, and Aquaspirillum) and the increased presence of others (Pseudomonas) during the dosage of Triton may be linked to the capacity of these bacteria to adapt to the presence of the surfactant or to use it as a nourishment. Water Environ. Res., 78, 000 (2006).

Resistensi obat terhadap berbagai jenis mikroba menjadi salah satu permasalahan yang cukup mengkhawatirkan di dunia kesehatan. Kondisi ini disebabkan oleh penyalahgunaan antibiotik dalam spektrum yang cukup luas . Salah satu upaya dalam mengatasi resistensi antibiotik ini adalah dengan pencarian metabolit sekunder yang memiliki aktivitas antibakteri. Salah satu sumber yang berpotensi menghasilkan senyawa antibakteri tersebut adalah jamur endofitik .

Poly(sodium undecenoyl-L-leucinate) (poly-L-SUL) was fractionated by the use of different molecular weight cutoff (MWCO) filters to narrow the polydispersity of the macromolecular sizes of the polymeric surfactant. The resulting polymeric surfactant fractions were characterized by the use of three techniques: (1) pulsed field gradient nuclear magnetic resonance (PFG-NMR) was used to determine the hydrodynamic radii, (2) analytical ultracentrifugation (AUC) was used to determine the molecular weights, and (3) steadystate fluorescence was used to determine the polarity of the nonfractionated and fractionated polymeric surfactants. From the data acquired from PFG-NMR, AUC, and fluorescence, it was noted that the hydrodynamic radii and molecular weight of the fractionated poly-L-SUL increased, while the polarity decreased with the increase in the size of the MWCO filter. However, a similarity in physical properties was observed between the nonfractionated and 10-30K fractionated poly-L-SUL except for the hydrodynamic radius and diffusion coefficients. The influence of different macromolecular sizes of poly-L-SUL on the chiral separation of phenylthiohydantion (PTH)-amino acids and coumarinic derivatives, as test analytes, was elucidated by the use of micellar electrokinetic chromatography (MEKC). The size of polymeric surfactants as a prerequisite for chiral separation was demonstrated by comparing the separation properties of fractionated versus nonfractionated polymeric surfactants. Fractionated poly-L-SUL resulted in enhanced resolution and separation efficiency of the test analytes as compared to the case of the nonfractionated poly-L-SUL. This observation indicates that minimizing polydispersity of polymeric surfactants may be important for some chiral separation applications.

Several in vitro studies have shown nonoxynol-9 (N-9) to be toxic to lactobacilli, especially to strains that produce H 2 O 2 . Data from a randomized, double-blind, placebo-controlled crossover trial that investigated the safety and toxicity of 2 weeks of daily vaginal application of an N-9 gel were analyzed, to examine the effect of N-9 use on vaginal lactobacilli and bacterial vaginosis. In vivo, N-9 promoted sustained colonization by H 2 O 2 -producing lactobacilli among women already colonized (relative risk [RR], 1.8; 95% confidence interval [CI], 1.2 -2.7). In addition, use of N-9 for 2 weeks reduced the likelihood of bacterial vaginosis (RR, 0.5; 95% CI, 0.3 -1.0). In contrast, N-9 use by women initially colonized only by non -H 2 O 2 -producing lactobacilli resulted in loss of vaginal lactobacilli (RR, 2.5; 95% CI, 1.2 -5.3). These data suggest that daily use of N-9 does not adversely affect vaginal colonization by H 2 O 2 -producing lactobacilli but that such use may promote loss of non -H 2 O 2 -producing strains.

This chapter was reviewed by following the Advanced Open Peer Review policy. This chapter was thoroughly checked to prevent plagiarism. As per editorial policy, a minimum of two peer-reviewers reviewed the manuscript. After review and revision of the manuscript, the Book Editor approved the manuscript for final publication. Peer review comments, comments of the editor(s), etc. are

The purpose of this work was to analyze the efÞcacy of Bacillus thuringiensis Berliner on the control of Phyllocnistis citrella Stainton (Lepidoptera: Phyllocnistidae) in laboratory and Þeld trials. In the laboratory, four B. thuringiensis were used: Dipel (commercial formulation) tested at the concentrations of 25 ϫ 10 6 and 25 ϫ 10 8 spores/ml and the isolates K, 6, and 15 (collections of the University of Azores) at the concentration of 25 ϫ 10 6 spores/ml. A surfactant solution of nonoxinol also was tested with or without the different suspensions of B. thuringiensis. Leaves of Citrus sinensis (L.) Osbeck with second or third instars of leafminer larvae were used in all tests. Bacterial suspensions were applied topically on the surface of intact leaf mines or by injection inside the mine, near the head of the leafminer. When injecting both concentrations of Dipel into the mines, mortality of the leafminers increased compared with the topical application, although no signiÞcant differences were observed. The addition of the nonoxinol to the Dipel suspension, applied topically, increased the effect of B. thuringiensis, but differences were not signiÞcant. The mortality of the leafminers treated only with the nonoxinol solution increased signiÞcantly 48 h after treatment, compared with the control group, suggesting an insecticidal effect of this surfactant when used at a concentration of 0.01%. All the tested B. thuringiensis were equally active against the leafminer, either when applied topically or by mine injection. Field trials showed a signiÞcant difference between larval mortality of the control group and the results observed at the trees treated with B. thuringiensis 48 h after treatments.

Topical formulations undergo radical structural changes after application and the action on the skin is not directly related to the original structure of the formulation. This fact has been well established in the scientific literature. However, and more essential, is the fact that these changes in the formulation structure are not equilibrium ones. Especially so, with the hydroxy acids, which are widely used in cosmetic and dermatological treatment of skin. The article reports the first investigation into the non-equilibrium conditions in a hydroxy acid system. Different phases in the title system, which were not in mutual equilibrium, were brought in contact while avoiding convection. The transfer of substance between them was estimated from the changes in volume of each phase. The results showed, unexpectedly, that the systems were far from equilibrium even after prolonged times in contact. The kinetics of the changes varied to significant degree, from extremely slow, when solid phases were involved to fast for liquid phases. In one case was observed a separated layer, which was not found in the phase diagram under equilibrium conditions.

Introductions: While "pea-sized" toothpaste recommendations are widely promoted to minimize fluoride ingestion in young children, caregiver interpretation of this guideline remains inconsistent. Variability in toothpaste form and child age may influence dispensing behaviour. Aims: To evaluate parental perceptions and practices regarding toothpaste dosing, specifically concerning the "pea-sized" recommendation, across different age groups and toothpaste consistencies. Settings and Design: The study was conducted among 300 mothers with children aged 6 months to 5 years at the Baby Oral Health Promotion Clinic, Department of Pediatrics, Tertiary Care Hospital, using a cross-sectional study design Materials and Methods: Participants were categorized into four subgroups based on child age (<3 or >3 years) and toothpaste type (gel or paste). All the participants (mothers) were asked to dispense toothpaste in two scenarios: one as they would regularly dispense it for their child and the second, their interpretation of a "pea-sized" quantity. The toothpaste was dispensed onto a pre-weighed toothbrush, and the amount was calculated by weight difference Statistical analysis used: Descriptive statistics, including mean, median, standard deviation, and interquartile ranges, were used for analysis. Results: Most caregivers dispensed more than the recommended 0.25g in both scenarios. Gel formulations were associated with slightly higher quantities than paste. Caregivers of older children consistently dispensed larger amounts, indicating possible misconceptions about age-related needs or control. Conclusions: Caregiver dosing often exceeds recommended levels, particularly for gel-based products and older children. These findings highlight the need for improved parental education, clearer visual guidelines, and consideration of pre-measured dispensing solutions.