Globule Size Distribution Research Articles

Synthesis of TiO2 and TiO2—SiO2 xerogels by hydrolysis of tetrabutoxytitanium and tetraethoxysilane in acetic acid atmosphere

The TiO2 and TiO2—SiO2 xerogels were prepared by hydrolyzing tetrabutoxytitanium or its mixture with tetraethoxysilane. The synthesis was conducted in an acetic acid—water atmosphere under stationary conditions followed by calcinations. The final TiO2 and TiO2—SiO2 xerogels represented 3D globular pore structure with a narrow globule size distribution. At hydrolysis of terabutoxytitanium, acetic acid vapors favored formation of TiO2 xerogel with a higher surface area compared to the material produced without acidic catalyst.

STUDY OF ENHANCED ANTI-INFLAMMATORY POTENTIAL OF NIGELLA SATIVA IN TOPICAL NANOFORMULATION

Objective: Formulate a nanocarrier for enhancing the anti-inflammatory activity of thymoquinone (Tq), a major active constituent of Nigella sativa.Methods: Nanoformulation of Tq was developed by low energy emulsification techniques. NanoTqs were pre-screened by different thermodynamic stability tests, followed by in vitro release, zeta potential, viscosity, the transmittance (%), globule size distribution and ex vivo studies. The morphology of the optimized NanoTq was determined by transmission electron microscopy (TEM) which revealed fairly spherical shape and good correlation with particle size distribution study. The formulation used for assessment of the anti-inflammatory potential and permeability enhancement contained mixture of essential oil of Nigella sativa: Capryol 90 (3:7, 10%, v/v), Tween 80 (21.75%, v/v), PEG 400 (7.25%, v/v) and double distilled water (61%, v/v).Results: The in vitro permeation of Tq from optimized formulations was found extremely significant (p<0.001) in comparison to apiTq. The steady state flux (Jss), the permeability coefficient (Kp) and enhancement ratio (Er) of NanoTq gel was determined and compared with apiTq. The comparative anti-inflammatory effects of the optimized formulations NanoTq, apiTq and DicloGel was assessed on the edema in the carrageenan-induced paw model in Wistar rats. Therapeutic potential of NanoTq was found statistically extremely significant (P<0.0001) compared to apiTq and insignificant comparable with standard DicloGel. Storage stability of NanoTq showed insignificant changes in the zeta potential, droplet size and was free from any physical instability.Conclusion: The optimized nano formulation with a lower dose of Tq showed better anti-inflammatory effects, indicating greater absorption capability through the stratum corneum.

Effects of processing conditions on the texture and rheological properties of model acid gels and cream cheese

Manufacture of cream cheese involves the formation of an initial acid-induced gel made from high-fat milk, followed by a series of processing steps including shearing, heating, and dewatering that complete the conversion of the acid gel into a complex cheese product. We investigated 2 critical parameters for their effect on the initial gel: homogenization pressure (HP) of the high-fat cheese milk, and fermentation temperature (FT). The impact of a low (10 MPa) and high (25 MPa) HP, and low (20°C) and high (26°C) FT were investigated for their effects on rheological and textural properties of acid-induced gels. Intact acid gels were sheared and heated to 80°C, and then their rheological properties were analyzed to help understand the effect of shearing/heating processes on the gel characteristics. The effect of HP on fat globule size distribution and the amount of protein not involved in emulsion droplets (i.e., in the bulk phase) were also studied. For cream cheese trials, a central composite experimental design was used to explore the effect of these 2 parameters (HP and FT) on the texture, rheology, and sensory properties of experimentally manufactured cream cheese. Storage modulus (G') and hardness values of cream cheeses were obtained from small amplitude oscillatory rheology tests and texture profile analysis, respectively. Quantitative spectrum descriptive sensory analysis was also performed. Consistency of acid gels (measured using a penetration test) increased with an increase in FT and with an increase in HP. Although stiffer acid-induced gels were formed at high FT, after the heating and shearing processes the apparent viscosity of the samples formed at high FT was lower than those formed at low FT. For the cream cheeses, significant prediction models were obtained for several rheological and textural attributes. The G' values at 8°C, instrumental hardness, and sensory firmness attributes were significantly correlated (r > 0.84); all these attributes significantly decreased with an increase in FT, and HP was not a significant parameter in the prediction models developed for these attributes. Significant interactions were observed between the HP and FT terms for these prediction models. Higher HP increased the amount of protein adsorbed at interface of fat globules but decreased bulk phase protein content (which may be important for crosslinking this gelled emulsion system). At higher FT temperature, coarser gel networks were likely formed. The combined effect of a coarser acid gel network at high FT, and less bulk phase casein available for crosslinking the acidified emulsion gel with an increase in HP, could have contributed to the lower stiffness/firmness observed in cream cheese made under conditions of both high FT and high HP. Stickiness of cream cheese greatly increased under conditions of high FT and high HP, whereas the sensory attributes cohesiveness of mass and difficulty to dissolve decreased. This study helped to better understand the complex relationships between the initial acid-induced gel phase and properties of the (final) cream cheese.

Effect of temperature on the microstructure of fat globules and the immunoglobulin-mediated interactions between fat and bacteria in natural raw milk creaming

Natural creaming of raw milk is the first step in production of Grana Padano and Parmigiano Reggiano Protected Denomination of Origin cheeses. This process decreases the fat content and plays an important role in the removal of clostridia species that may cause late-blowing defects in ripened cheeses. Partial coalescence of fat globules-that may influence fat behavior in cheese making and affect the microstructure of fat in the final cheese product-was observed at creaming temperatures higher than 22°C by confocal laser scanning microscopy. The widespread practice of heating of milk at 37°C before creaming at 8°C resulted in important changes in the size distribution of fat globules in raw milk, potentially altering the ability of fat to entrap clostridia spores. We investigated the role of immunoglobulin classes in both the clustering of fat globules and the agglutination of Clostridium tyrobutyricum to fat globules during creaming. Immunogold labeling and transmission electron microscopy showed that IgA and IgM but not IgG were involved in both clustering and agglutination. Both vegetative cells and spores were clearly shown to agglutinate to fat droplets, a process that was suppressed by thermal denaturation of the immunoglobulins. The debacterization of raw milk through natural creaming was improved by the addition of purified immunoglobulins. Overall, these findings provide not only a better understanding of the phenomena occurring during the natural creaming but also practical insights into how the process of creaming may be optimized in cheese production plants.

Asymmetric flow field flow fractionation for the characterization of globule size distribution in complex formulations: A cyclosporine ophthalmic emulsion case

Commonly used characterization techniques such as cryogenic-transmission electron microscopy (cryo-TEM) and batch-mode dynamic light scattering (DLS) are either time consuming or unable to offer high resolution to discern the poly-dispersity of complex drug products like cyclosporine ophthalmic emulsions. Here, a size-based separation and characterization method for globule size distribution using an asymmetric flow field flow fractionation (AF4) is reported for comparative assessment of cyclosporine ophthalmic emulsion drug products (model formulation) with a wide size span and poly-dispersity. Cyclosporine emulsion formulations that are qualitatively (Q1) and quantitatively (Q2) the same as Restasis® were prepared in house with varying manufacturing processes and analyzed using the optimized AF4 method. Based on our results, the commercially available cyclosporine ophthalmic emulsion has a globule size span from 30 nm to a few hundred nanometers with majority smaller than 100 nm. The results with in-house formulations demonstrated the sensitivity of AF4 in determining the differences in the globule size distribution caused by the changes to the manufacturing process. It is concluded that the optimized AF4 is a potential analytical technique for comprehensive understanding of the microstructure and assessment of complex emulsion drug products with high poly-dispersity.

Preparation and Physical Stability Evaluation of Palm Oil-Based Nanoemulsion as a Drug Delivery System for Propofol

The objective of this study was to develop a formulation for propofol injection at various concentrations (1 and 2%) using palm oil-based nanoemulsion as the carrier. The nanoemulsions were characterized by globule size distribution (Dv 90 value), zeta potential, pH and viscosity determination. The physicochemical stability and accelerated stability of the formulations were also evaluated. Stability studies were performed for 6 month at 4, 16, 25 and 40 o C. The propofol content was analysed by HPLC study. The characterization result of propofol nanoemulsion (1 and 2%) showed a good in globule size distribution in Dv 90 values of 284±1.15 nm and 304±1.20 nm, and also stable zeta potential values ( -43.37±0.96 mV and -40.97±1.36 mV), respectively. A ccelerated test exhibited that the formulations have excellent stability with no physical changes observed after centrifugation, autoclaving at 121 o C for 15 min, shaking for 12 hours and thermal cycling test. The stability studies indicated that propofol emulsion show good stability for 6 months when stored at 4±1 o C and 16±1 o C based on Dv 90 values, zeta potential, and pH readings. No changes in propofol concentrations were observed after 6 months storage. Overall, propofol in palm oil-based nanoemulsions as carrier were stable and can be used as an alternative anaesthetic injection. DOI : http://dx.doi.org./10.17576/JSKM-2018-1602-02

The presence of inorganic calcium in pediatric parenteral admixtures.

Newborn infants and small children require large amounts of calcium and phosphate in a low volume of solution which can increase the risk of precipitation of calcium phosphate. Calcium gluconate is the predominant calcium salt form employed in parenteral nutrition (PN) compounding due to its solubility profile with phosphate. Unfortunately, calcium gluconate contains higher levels of aluminum contamination than calcium chloride, resulting in an increased potential for aluminum toxicity in patients receiving traditional PN. The physicochemical stability of 30 total parenteral admixtures containing inorganic calcium salts was evaluated. Parenteral admixtures were prepared in one-chamber ethylene vinyl acetate bags: amino acids, glucose, electrolytes including only inorganic calcium salt and 20% (w/w) lipid emulsions (SMOFlipid®, Omegaven® or Lipofundin MCT/LCT®) were placed together in a one chamber bag. Admixtures were stored at +4 °C for up to eight days after preparation. Visual observations, globule size distribution (using optical microscopy, laser diffraction and photon correlation spectroscopy methods), pH analysis and zeta potential measurements were performed. The physicochemical stability of 29 of parenteral admixtures in the presence of inorganic calcium salt was confirmed. One admixture was deemed unsuitable for use in clinical practice due to the coalescence of oil droplets. Despite the presence of inorganic calcium salts, pediatric parenteral admixtures were stable up to eight days of storage. Due to presence of multiple components and a high risk of incompatibilities, physicochemical studies should be performed for each admixture before use in clinical practice.

Stability assessment of neonatal parenteral nutrition solutions with various amino acid concentrations

Objective To explore the influence of various concentrations of amino acid on the stability of neonatal parenteral nutrition solutions. Methods Five formulations were designed with 5 different amino acid concentrations containing the same components. The final amino acid concentrations of admixtures were 0%, 1%, 2%, 3%, and 3.5%, respectively. The appearance, pH, and osmolality were observed or measured after preparation (0 hour) and at 12, 24, 48 and 72 hours after preparation. The average size and the size distribution of the lipid globules were also evaluated by laser nanometer particle size analyzer. Results There was no observable alteration in color, phase separation, precipitate, and flocculation in any admixture at any of the observation time points. The mean pH values for all groups were between (5.49±0.01) to (6.19±0.01) within 72 hours. The mean osmolalities for all groups were between (774±3) to (1 106±13)mOsm/kg. The mean diameters of lipid globules for all groups were between (280.6±0.7)mm to (332.2±2.0)nm. The mean polydispersity for all groups were between (0.200±0.011) to (0.245±0.012). The enrichment of amino acid concentration was linked to lower pH (P=0.000), higher osmolality (P=0.000) and larger average lipid globules size (P=0.000). However, there was no distinct linear dependence between amino acid concentration and polydispersity value (P=0.628). Conclusion After 72 hours of storage at room temperature, the appearance, pH, osmolality, and the average lipid globules diameter of the parenteral nutrition solutions are within the safe range when the amino acid is not contained or the concentrations are no more than 3.5%. Key words: Amino acid; Fat emulsions, intravenous; Stability; Neonatal parenteral nutrition

Optimization of Green Multiple Emulsions Processing to Improve Their Physical Stability

AbstractThe effect of processing protocol on physical stability and the microstructure of water‐in‐oil‐in‐water multiple emulsions containing a mixture of two amphiphilic copolymers with opposed hydrophilic‐lipophilic balance as emulsifiers and a green solvent, 2‐ethylhexyl lactate, as the dispersed phase, has been assessed. Emulsions were obtained in at least two steps: a homogenization step by using a rotor‐stator device, followed by one or two homogenization steps carried out in a high‐pressure device that used microfluidizer technology. To study the microstructure and physical stability of these emulsions, a combination of different techniques, such as transmitted‐light optical microscopy, globule size distribution, viscous flow tests, and multiple light scattering measurements, were performed.

Milk fat globule size affects Cheddar cheese properties

Cheddar cheese was prepared using milk separated into large (d4,3 = 5.07 ± 0.06 μm) and small (d4,3 = 2.76 ± 0.07 μm) milk fat globule (MFG) size distributions using microfiltration. MFG size did not influence the moisture-adjusted yield or the amount of protein and lactose. However differences in the texture, microstructure, lipolysis and other compositional factors were found between cheeses. Notably, the small MFG milk (SMM) cheese retained more salt and contained more moisture and polar lipids, observed through a novel confocal staining regime, compared with the large MFG milk (LMM) cheese. Fewer intact MFG and more pockets of coalesced milk fat were observed in the LMM cheese. However both SMM and LMM cheese were softer, and less resistant to melting than the Control. These findings show that MFG separation can influence cheese mechanical behaviour and allow for the development of differentiated cheese products.

Production and characterization of ice cream with high content in oleic and linoleic fatty acids

Ice creams produced with unsaturated fats rich in oleic (OO, 70.7% of oleic) and linoleic (LO, 49.0% of linoleic) fatty acids, were compared to ice cream based on saturated coconut oil (CO, 50% of lauric acid). The globule size distribution of OO mix during aging (72 h at 4°C) followed a similar trend to CO mix, being stable after 48 h; whereas LO mix destabilized after 24 h. CO mix showed higher destabilization during ice cream production, but no significant differences among fats were observed in the particle size of the ice cream produced. The overrun was also lower for OO and LO ice creams (34.19 and 27.12%, respectively) compared to CO based ice cream (45.06%). However, an improved melting behavior, which gradually decreased from 88.69% for CO to 66.09% for LO ice cream, was observed.Practical applications: This work evaluates the use of high unsaturated fats in the production of ice cream as alternative to highly saturated coconut oil. Common unsaturated fats normally lead to ice cream with low quality in terms of overrun and melting points. Nevertheless, the results obtained in this study indicated that the two fats assayed, rich in oleic and linoleic acids, are adequate for the production of ice cream. Therefore, these highly unsaturated fats are a promising alternative for the development of healthier ice creams.Unsaturated fats are introduced in ice cream and compared to saturated coconut oil. Similar fat globule size and viscosity are found, while melting behavior is improved.

Solidification pathways of ternary Cu62.5Fe27.5Sn10 alloy modulated through liquid undercooling and containerless processing

The active control of microstructure evolution is still a challenging factor for the development of advanced immiscible alloys. Here, we make an attempt to modulate the solidification pathways of undercooled Cu62.5Fe27.5Sn10 alloy by glass fluxing and drop tube techniques. Through regulating the liquid undercooling, three types of microstructures, dendrite, dispersive structure and macrosegregation pattern, were formed under the normal gravity condition. Below the first critical undercooling of 15 K, the alloy melt displayed the normal peritectic solidification. At moderate undercoolings above 15 K, the metastable liquid phase separation took place and the solidified microstructure appeared as homogeneously dispersed structure. If undercooling further overtook the second threshold of 107 K, macrosegregation occurred and the bulk alloy separated into an Fe-rich zone and a Cu-rich zone. Under the free fall condition, the alloy droplets with the droplet diameter beyond 805 μm showed the equilibrium peritectic solidification. If the droplet diameter decreased below 805 μm, the metastable liquid phase separation was induced and the microstructural morphology of Cu62.5Fe27.5Sn10 alloy droplet evolved from dendrite into dispersive structure. Furthermore, experimental and simulated results revealed that the temperature gradient had great influence on the size distribution of Fe-rich globules.

Olive oil based edible W/O/W emulsions stability as affected by addition of some acylglycerides

Olive oil based W/O/W double emulsions (DEs) were prepared with polyglycerol polyricinoleate (PGPR, 3 or 6%) and sodium caseinate as emulsifiers both singly in a control sample, and with the addition of two fat-crystallizers (Verols V10 or V50) at two concentrations (3 or 6%). Globule size distribution was essentially monomodal with area-volume mean diameter (d32) values ∼2 μm. Creaming along an 8 d refrigerated storage was always minor. The predominant elastic behavior in control samples evolved to viscous in samples with Verols. DSC revealed that V10 and V50 crystalized as α- and β′-polymorphs respectively, that can absorb at a W/O interface, potentially producing interfacial crystallization (V10 < V50). Instead, (V10 > V50) concerning DEs stabilization because V50 plus 3 or 6% PGPR produced essentially glassy matrices, thus impeding Pickering effects. V10 plus 3 or 6% PGPR formed crystalline DEs with presence of lyotropic mesophases, which yielded W/O Pickering stabilization effects.

0040 Ultrasonic separation of milk to select for fat globule size distribution

0040 Ultrasonic separation of milk to select for fat globule size distribution

Physicochemical compatibility and emulsion stability of propofol with commonly used analgesics and sedatives in an intensive care unit

ObjectivesThe purpose of this study was the determination of the physicochemical compatibility and emulsion stability of propofol with other sedatives and analgesics (clonidine hydrochloride, dexmedetomidine, 4-hydroxybutyric acid, (S)-ketamine, lormetazepam, midazolam...

Effect of Pasteurization, Freeze-drying and Spray Drying on the Fat Globule and Lipid Profile of Human Milk

Human milk is the ideal food to nourish newborn babies; it contains important nutrients: proteins, carbohydrates, fat, vitamins and minerals, which are needed to provide agood health to the infants. Milk fat provides about 50% of energy to infants and its fatty acids are essential for brain and retina development. Therefore, analysis of the lipid fraction of human milk is an important task, especially when this milk is processed. The objective of this research was to study the effect of pasteurization, freeze-drying and spray drying on some characteristics of human milk fat. The fatty acid profile was analyzed by HPLC and gas chromatography. Fat content, globule size and distribution were measured. The HPLC method for the analysis of fatty acids showed accuracy, precision and linearity in the concentration range studied. Non-significant differences in fat content between the different processes were found; however, there was a decrease of 23% in the fat content of spray dried milk. The fat mean globule size decreased considerably in all treatments, varying from 2138 to 529 nm. The size distribution of fat globules increased during pasteurization and drying from 0.24 in raw milk to 0.78 in pasteurized milk. With respect to the fatty acid profile, we found that human milk samples had an elevated content of palmitic (27%), and oleic (30%) acids and significant variations were observed in the pasteurized samples for oleic and linoleic acid. Preservation processes applied to human milk caused a decrease on the fat globule diameter; the change in size increased the surface area and could improve the bioavailability of the fat components. This is the first report of human milk drying as a preservation method.

Influence of casein as a percentage of true protein and protein level on color and texture of milks containing 1 and 2% fat

Combinations of fresh liquid microfiltration retentate of skim milk, ultrafiltered retentate and permeate produced from microfiltration permeate, cream, and dried lactose monohydrate were used to produce a matrix of 20 milks. The milks contained 5 levels of casein as a percentage of true protein of about 5, 25, 50, 75, and 80% and 4 levels of true protein of 3.0, 3.76, 4.34, and 5.0% with constant lactose percentage of 5%. The experiment was replicated twice and repeated for both 1 and 2% fat content. Hunter color measurements, relative viscosity, and fat globule size distribution were measured, and a trained panel documented appearance and texture attributes on all milks. Overall, casein as a percentage of true protein had stronger effects than level of true protein on Hunter L, a, b values, relative viscosity, and fat globule size when using fresh liquid micellar casein concentrates and milk serum protein concentrates produced by a combination of microfiltration and ultrafiltration. As casein as a percentage of true protein increased, the milks became more white (higher L value), less green (lower negative a value), and less yellow (lower b value). Relative viscosity increased and d(0.9) generally decreased with increasing casein as a percentage of true protein. Panelists perceived milks with increasing casein as a percentage of true protein as more white, more opaque, and less yellow. Panelists were able to detect increased throat cling and mouthcoating with increased casein as a percentage of true protein in 2% milks, even when differences in appearance among milks were masked.

Mixed surfactant based (SNEDDS) self-nanoemulsifying drug delivery system presenting efavirenz for enhancement of oral bioavailability

This study aims to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on non-ionic surfactant mixtures to improve the oral bioavailability of efavirenz (EFZ) categorized as a class II according to the BCS, for HIV- therapy. The result of solubility studies of EFZ in various excipients utilized for construction of the pseudo ternary phase diagram containing surfactant mixtures. Surfactants in 1:1 combination are used with different co-surfactants in different ratio to delineate the area of monophasic region of the pseudo ternary phase diagram. Different accelerated physical stability studies and self-emulsification assessment were performed on the formulations. The formulations clearing the above studies are considered for percentage transmittance and turbidity analysis. The globule size distributions of post diluted SNEDDS having percentage transmittance above 90 were estimated. The TEM analysis of two optimized post diluted SNEDDS formulations further confirm the size in nanometric range (below 50nm). FT-IR studies showed the retention of the characteristic peaks of EFZ in the preconcentrate. The in vitro dissolution profile of SNEDDS established advantages of SNEDDS over plain drug as more than 80% drug was released within 30min in case of optimized SNEDDS while it was approximately 18.3% in the case of plain drug powder. Pharmacokinetic parameters were calculated after performing the in vivo studies of best optimized formulation in rats. The Pharmacokinetic data reveal a 2.63 fold increase in AUC(0-∞) in comparison to plain EFZ suspension. The designed delivery system showed the faith in generating an effective formulation of EFZ for HIV treatment.

Influence of Processing on the Physical Stability of Multiple Emulsions Containing a Green Solvent

AbstractThe influence of the emulsification process on the microstructure and physical stability of model water‐in‐oil‐in‐water (W/O/W) emulsions formulated with a green solvent and a mixture of amphiphilic copolymers as emulsifiers was investigated. Emulsions were prepared by applying a homogenization step with a rotor‐stator device followed by high‐pressure homogenization. Viscous flow tests, transmitted light optical microscopy, globule size distribution (GSD), and multiple light scattering (MLS) measurements were carried out. The GSDs obtained were the result of a recoalescence due to overprocessing and the coalescence of inner droplets with the outer water phase. MLS detected a main destabilization mechanism by creaming. The passing of the emulsion through a high‐pressure homogenizer (HPH) significantly delayed the creaming process.

Improving thermal stability of hydrolysed whey protein-based infant formula emulsions by protein–carbohydrate conjugation

Whey protein hydrolysate (WPH) ingredients are commonly used in the manufacture of partially-hydrolysed infant formulae. The heat stability of these emulsion-based formulae is often poor, compared with those made using intact whey protein. The objective of this study was to improve the heat stability of WPH-based emulsions by conjugation of WPH with maltodextrin (MD) through wet heating. Emulsions stabilised by different protein ingredients, whey protein isolate (WPIE), whey protein hydrolysate (WPHE), heated WPH (WPH-HE), and WPH conjugated with MD (WPH-CE) were prepared and heat treated at 75°C, 95°C or 100°C for 15min. Changes in viscosity, fat globule size distribution (FGSD) and microstructure, evaluated using confocal laser scanning microscopy (CLSM), were used to monitor the effects of hydrolysis, pre-heating and conjugation on the heat stability of the emulsions. Heat stability increased in the order WPHE<WPIE<<WPH-HE<<<WPH-CE; emulsions WPHE, WPIE and WPH-HE destabilised on heating at 75°C, 95°C or 100°C, respectively. Flocculation and coalescence of oil droplets were mediated by protein aggregation (as evidenced by CLSM) on heat treatment of WPH-HE emulsion at 100°C, while no changes in FGSD or microstructure were observed in WPH-CE emulsion on heat treatment at 100°C, demonstrating the excellent thermal stability of emulsions prepared with the conjugated WPH ingredient, due principally to increased steric stabilisation as a result of conjugation.