Influence of Two Salicylate Components on the Particle Size of an Oil-in-Water Emulsion with Nonionic Surfactants

Abstract

This paper reports a study undertaken using techniques of static and dynamic light scattering to investigate the influence of sodium salicylate and methyl salicylate on droplet size of oil-in-water emulsions. The rates of changes were measured by determining the size and distribution of the oil droplet in the material. All emulsions showed a bimodal size distribution; the mean diameters and polydispersity were calculated from intensity. These data were analyzed with nonlinear regressions and bootstrap methodology. An amount of methyl salicylate component induced a decrease of mean diameter and standard deviation. On the contrary, sodium salicylate entailed the growth of all droplet populations and coalescence for the highest concentration.     

Evaluation of the emulsifying properties of some cationic starches

Different cationic potato, maize, and waxy maize starches were evaluated for their emulsifying properties. Emulsions were prepared using 20% (w/w) arachidic oil and 80% (w/w) water. Emulsions with the cationic starches as emulsifier in a concentration ranging from 1% to 5% (w/w) were prepared and characterized by droplet size and viscosity measurements, and the stability was evaluated visually and by electrical conductance measurements. None of the cationic potato, waxy maize starches, and maize starches with a low degree of substitution (DS) showed adequate emulsifying properties. Emulsions prepared using non-pregelatinized (C ☆ bond 05914, 2% and 5% w/w; C ☆ bond 05907, 5% w/w) and pregelatinized (C ☆ bond 12504, 5% w/w) cationic maize starches with high-DS were visually stable. The initial mean droplet volume diameter of the emulsions prepared with these cationic starches in a 5% (w/w) concentration was similar and ranged from 2.40 to 2.84 μm however, there was an important difference in droplet size distribution. The droplet size distribution of the emulsions prepared using the non-pregelatinized high-DS cationic starches was markedly narrower than in the case of the emulsions prepared using the pregelatinized high-DS cationic starches. The droplet size of the emulsions remained almost constant during 120 days of storage. Visual inspection and electrical conductance measurements showed that these emulsions were stable for at least 120 days.     

Ultrasensitive methyl salicylate gas sensing determined by Pd-doped SnO2

Efficient chemical warfare agents (CWAs) detection is required to protect people from the CWAs in war and terrorism. In this work, a Pd-doped SnO₂ nanoparticles-based gas sensor was developed to detect a nerve agent simulant named methyl salicylate. The sensing measurements of methyl salicylate under different Pd doping amounts found that the 0.5 at.% Pd-doped SnO₂ exhibited a significant improvement in the detection of methyl salicylate at the ppb (1 ppb = 10⁻⁹) level, and the response value to 160 ppb methyl salicylate is 0.72 at 250 °C. Compared with the pure SnO₂, the response value is increased by 4.5 times, which could be attributed to the influence of the noble metal Pd on the oxygen state and its catalytic effect. In addition, the 0.5 at.% Pd-doped SnO₂ sensor still has an obvious response to 16 ppb methyl salicylate with a response value of 0.13, indicating the lower detection limit of the sensor.     

Development of novel bepotastine salicylate salt bioequivalent to the commercial bepotastine besilate in beagle dogs

To develop a novel salt form of bepotastine with bioequivalent to the commericial bepostastine besilate, bepostastine salicylate was prepared and its physicochemical properties were investigated. Furthermore, the bepotastine salicylate-loaded tablet was prepared by the wet granulation method, and the dissolution and bioavailability in beagle dogs were evaluated compared to the bepotastine besilate-loaded commercial product. Bepotastine salicylate improved the solubility of bepotastine, and the extent of solubility improvement by salicylate form was similar to that by besilate form. However, this novel salt exhibited negligible hygroscopicity similar to besilate form, and showed slightly higher melting point than besilate form. It was stable in various pH solutions. Furthermore, the bepotastine salicylate-loaded tablet composed of bepotastine salicylate, microcrystalline cellulose, D-mannitol, povidone, sodium starch glycolate and sodium stearyl fumarate at the weight ratio of 9.63/60.97/38/3.6/6/1.8 showed similar dissolution to the bepotastine besilate-loaded commercial product in water, pH 1.2, pH 4.0 and pH 6.8 and was bioequivalent to the commercial product in beagle dogs. Thus, this bepotastine salicylate-loaded tablet would be a promising candidate with bioequivalence to the bepotastine besilate-loaded commercial product.     

Design and evaluation of an emulsion vehicle for paclitaxel. II. Suppression of the crystallization of paclitaxel by freeze-drying technique

Although paclitaxel is soluble in vitamin E up to 40 mg per g, crystallization was detected at loadings higher than 15 mg per g. Water appeared to be an important factor causing the observed crystallization, and therefore, a freeze-drying technique was investigated to produce reconstitutible vitamin E emulsions, to increase drug loading without crystal formation after reconstitution. The emulsion was freeze-dried using a laboratory freeze-drier and the droplet size was measured using dynamic light scattering. The freeze-dried emulsions using sucrose as a cryoprotectant could be easily reconstituted. The loading of paclitaxel in the freeze-dried emulsions could be increased to 25 mg per g of vitamin E without crystal formation, and the mean emulsion droplet size remained smaller than 0.2 μm over 430 days (4 ± 2°C). The previously observed surfactant-enhanced crystallization could also be suppressed using the freeze-drying technique.     

Design and Evaluation of an Emulsion Vehicle for Paclitaxel. II. Suppression of the Crystallization of Paclitaxel by Freeze-Drying Technique

Although paclitaxel is soluble in vitamin E up to 40 mg per g, crystallization was detected at loadings higher than 15 mg per g. Water appeared to be an important factor causing the observed crystallization, and therefore, a freeze-drying technique was investigated to produce reconstitutible vitamin E emulsions, to increase drug loading without crystal formation after reconstitution. The emulsion was freeze-dried using a laboratory freeze-drier and the droplet size was measured using dynamic light scattering. The freeze-dried emulsions using sucrose as a cryoprotectant could be easily reconstituted. The loading of paclitaxel in the freeze-dried emulsions could be increased to 25 mg per g of vitamin E without crystal formation, and the mean emulsion droplet size remained smaller than 0.2 μm over 430 days (4 ± 2°C). The previously observed surfactant-enhanced crystallization could also be suppressed using the freeze-drying technique.     

乳状液制备新工艺——膜乳化过程实验研究

用膜乳化系统制备了Ｏ／Ｗ型乳状液,考察了乳化时间、平均膜孔径、壁面剪应力、膜两侧压差和乳化剂等因素对乳化效果的影响．实验显示,分散相液滴平均直径不随乳化时间而变化;在此条件下,该直径约是膜平均孔径的５～１２倍．随着连续相一侧壁面剪应力的增大液滴平均直径减小,但当壁面剪应力大到一定值后,减小的幅度变得很小．增大膜平均孔径和膜两侧压差都将增加分散相透过膜的通量．此外,乳化剂分子的吸附速度越快,分散相液滴平均直径越小．     

Effect of non-ionic surfactant concentration and type on the formation and stability of W/O/W multiple emulsions: Microscopic and conductometric evaluations

W/O/W multiple emulsions with sodium salicylate as a model drug were prepared and evaluated for the effect of surfactant concentration and type on stability using microscopic and conductometric methods. Primary (W/O) emulsions were prepared with lipophilic surfactants (2-31% W/W relative to the oily phase). W/O/W emulsions were formed by mixing the primary emulsions with solutions containing 0.5 to 2% W/V hydrophilic surfactants. Optimum concentration of the lipophilic surfactant was 26% W/W. The optimum hydrophilic surfactant concentration was 1% W/V. Best stability was achieved with HLB 3.7 lipophilic and HLB 15.6 hydrophilic surfactants.     

Effect of non-ionic surfactant concentration and type on the formation and stability of W/O/W multiple emulsions: Microscopic and conductometric evaluations

Abstract

W/O/W multiple emulsions with sodium salicylate as a model drug were prepared and evaluated for the effect of surfactant concentration and type on stability using microscopic and conductometric methods. Primary (W/O) emulsions were prepared with lipophilic surfactants (2-31% W/W relative to the oily phase). W/O/W emulsions were formed by mixing the primary emulsions with solutions containing 0.5 to 2% W/V hydrophilic surfactants. Optimum concentration of the lipophilic surfactant was 26% W/W. The optimum hydrophilic surfactant concentration was 1% W/V. Best stability was achieved with HLB 3.7 lipophilic and HLB 15.6 hydrophilic surfactants.     

Formation of drug-loaded nanoemulsions in stirred media mills

The feasibility of stirred media mills for the production of nanoemulsions loaded with active pharmaceutical ingredients (API) using plant oils as disperse phase and different types of the non-ionic emulsifier polysorbate is demonstrated. The influence of the emulsion formulation, namely oil type, surfactant and surfactant-to-oil-weight-ratio (SOR) on the product droplet size at constant stressing conditions is studied in detail. At similar stressing conditions and SOR, the type of the used plant oil and surfactant did not influence the product droplet size and the smallest achievable median droplet size was 20 nm. The API saturated oil phases and the pure oil phases exhibit similar viscosities, emulsification kinetics and final product droplet sizes, i.e. no influence of the API on the emulsification process could be identified. However, a strong dependency of the emulsion droplet size on the SOR has been observed. Moreover, very good long-term stabilities could be achieved for the obtained emulsions. A release test with fenofibrate-loaded peanut oil-polysorbate 80-water nanoemulsions showed remarkably fast drug distribution as compared to a formulation containing the same amount of the non-dissolved micronized drug.     

Effect of bioadhesive polymers,sodium salicylate,polyoxyethylene-9-lauryl ether,and method of preparation on the relative hypoglycemia produced by insulin enteric-coated capsules in diabetic beagle dogs

The hypoglycemic effect of oral insulin capsules coated with pH-dependent Eudragit® S100 and containing various absorption promoters was studied in hyperglycemic beagle dogs. The absorption enhancers used were bioadhesive polymers, sodium salicylate, and non-ionic surfactants. A comparative study of the bioadhesive polymers, polycarbophil (PC), hydroxypropyl methylcellulose (HPMC), and carbopol 934 in insulin-coated capsules revealed no significant difference between the insulin capsules containing these polymers, giving relative hypoglycemia (RH) values ranging from 4.3±2.3% to 6.5±5.1%. It was also found that the method of preparation of the mixture of the bioadhesive polymer with insulin either by physical mixing or freeze-drying did not affect the RH values obtained. Sodium salicylate, when used in insulin enteric-coated capsules (50 mg) mixed with insulin as a physical mixture, or prepared by wet granulation using 10% polyvinyl pyrollidone (PVP), or by freeze-drying, produced RH values ranging from 7.3±2.9% to 9.4±3.7%. When sodium salicylate (100 mg) was used with insulin in freeze-dried granules an RH value of 10±2.6% was produced. As the dose of insulin increased from 6 to 9 U/kg, the area under curve (AUC) of the enteric-coated capsules containing 50 mg sodium salicylate increased from 73.2±27.8% to 121.4±102.7% reduction, but the RH did not change significantly. Insulin capsules containing polyoxyethylene-9-lauryl ether (POELE) used in its optimum concentration (2%), found in these experiments, produced RH of 9.5±6.8% when prepared as granules by wetting with a few drops of absolute alcohol in the presence of PC (50 mg). Insulin capsules containing lower (1%) or higher (3%) concentrations of POELE and prepared with PC, 50 mg by wet granulation produced lower RH of about 6%. The enteric-coated oral insulin capsules containing insulin (6 or 9 U/kg) and sodium salicylate (50 mg) as an absorption promoter, together with the bioadhesive polymer polycarbophil (50 mg), and prepared either by wet granulation using ethanol or by freeze-drying, are the best formulations to be used. They achieved a reduction in plasma glucose levels of about 25-30% and RH of about 10%. Also insulin (9 U/kg) capsules containing 2% POELE produced a 28% reduction in plasma glucose levels and RH of 9.6±6.8%.     

Synthesis of nano-sized ceria powders by two-emulsion method using sodium hydroxide

In the present study, nano-sized ceria powders were prepared by the two-emulsion method in the presence of aqueous sodium hydroxide. The effect of the ceria precursor concentration and the addition of an aqueous sodium hydroxide on the crystallite size, the size distribution and the morphology of the synthesized powders were investigated. The precipitates were obtained by mixing two water-in-oil emulsions with kerosene containing cerium nitrate aqueous solution and sodium hydroxide aqueous solution. The synthesized ceria powders were characterized by XRD and TEM. The synthesized ceria powders had nearly spherical shape and a uniform crystallite size in a range of 10 to 20 nm depending on the concentration of precursor solution and an addition amount of mineralizer.     

相互缠结的PMMA/SPS复合水基微乳液的研究Ⅱ.体系反应前后的粒度分布及形态表征

将聚苯乙烯磺化制成聚苯乙烯离聚体（SPS），利用相反转技术，将磺化聚苯乙烯离聚体制成具有纳米级稳定的水基微乳液，利用SPS微粒核为反应场所，引发另一单体MMA聚合，制备具有相互缠结结构的PMMA／SPS复合水基微乳液。通过粒度分布仪、透射电镜等分析仪器对体系反应前后粒径形态、大小变化进行了探讨；用DSC仪器分析了复合材料的玻璃化转变，发现体系具有良好的相容性。     

Lipid emulsions as a potential delivery system for ocular use of azithromycin

Objective: To obtain stable positively charged Azithromycin (AZI) emulsions with a mean droplet size of 120 nm for the treatment of eye diseases. Methods: The emulsions were obtained by using a suitable homogenization process. The physical stability was monitored by measuring the particle size, zeta potential, and visible appearance. The drug entrapment efficiency was measured by both ultracentrifugation and ultrafiltration methods. Compared with a phosphate solution of AZI, the stability profiles of AZI in lipid emulsions at various pH values were monitored by high-performance liquid chromatography. A pharmacokinetic study was performed to determine the drug levels in rabbit tear fluid using Ultra-performance liquid Chromatography–mass spectrometry. Results: Almost all the AZI in the lipid emulsion was distributed in the oil phase and small unilamellar liposomes without contact with water, thereby avoiding hydrolysis. The elimination of the AZI lipid emulsions in tear fluid was consistent with the basic linear pharmacokinetic characteristics. The AUC_0-t of the AZI lipid emulsion (1%, w/v) and aqueous solution drops (1%, w/v) was 1873.58 ± 156.87 and 1082.46 ± 179.06 μgh/ml respectively. Conclusions: This study clearly describes a new formulation of AZI lipid emulsion for ocular administration, and lipid emulsions are promising vehicles for ophthalmic drug delivery.     

A Grain-Size Series of Ammoniacal Emulsions and their Chemical Sensitization

. A grain size series of ammoniacal emulsions in the range 0-05 - lOµm₂ mean grain projective area were prepared and then sensitized with sodium thiosulphate and sodium lelrachloroaurale. The grains were all of roughly spherical shape and exhibited a covering power that was inversely proportional to the mean linear grain dimension.

The relation between the concentration of sulphur sensitizer, C, and the time of digestion, t_s, for optimum speed is shown to take the form C^0-8t_s = constant for a single emulsion which when applied to ihe series as a whole implied that the concentration was inversely proportional to mean grain projective area. In the case of sulphur and gold sensitization these relations were much more complex.

The level of sulphur sensitizer inherent to the gelatin was comparable to the levels added in the case of the emulsions of large grain size. When the total sulphur content was taken into consideration the ratio of sulphur to gold for optimum speed to light was approximately 9, regardless of grain size.     

Stability of orange oil/water nanoemulsions prepared by the PIT method

This article reports the preparation and characterization of orange oil/water nanoemulsions stabilized by commercial nonionic surfactants based on ethoxylated lauryl ether (Ultrol line), by the phase inversion temperature (PIT) method. The orange oil/surfactant/water dispersions were prepared at different HLB values, by varying the concentrations of the surfactants as well as the concentration of the oil phase. The stability of the o/w nanoemulsions and the size distribution of the dispersed particles in these systems in general depended on the concentration of the oil phase used: the emulsions prepared with an oil phase of 14 wt% had smaller droplet size in the dispersed phase than the emulsions prepared in the presence of oil phases of 20 and 30 wt%. The nanoemulsions prepared with pure surfactants were more stable in the presence of Ultrol L60, but the surfactants' cloud point had a strong influence on the stability of the emulsions formed when this was very near room temperature. Because of this, we prepared systems containing mixtures of surfactants. Among these systems, the most stable nanoemulsions were those prepared with a Ultrol L100/Ultrol L20 mixture with HLB of 12.40. This behavior can be attributed to the complete solubilization in mixed micelles of the more hydrophobic surfactant.     

高固含量丙烯酸酯共聚物乳液的单体组成与流变行为

合成了一系列固体含量为70%的丙烯酸丁酯/甲基丙烯酸甲酯/α-甲基丙烯酸(BA/MMA/MAA)共聚物乳液,研究了软(BA)、硬(MMA)段单体用量比对乳液体系流变行为的影响,并对其乳胶粒的粒径分布和微观形态进行了表征。结果表明,所合成乳液乳胶粒的粒径在50nm~650nm范围内,呈宽分散分布状态。当BA/MMA<60/40时,乳液可保持低黏度;而当BA/MMA>60/40时,乳液的黏度急剧增加。随着乳液中软、硬段单体比的不同,乳液的乳胶粒分布状态和凝聚形态均有显著变化。     

Viscosity and Stability Studies of Liquid Pafzaffin Emulsions Prepared by Hydroxypropyl Methylcellulose

Liquid paraffin-water emulsions were prepared by three viscosity grades of hydroxypropyl methylcellulose (HPMC) polymer which showed pseudoplastic behavior. The viscosity of emulsions increased, but the mean droplet diameter of globules decreased on increasing the concentration of the polymer. On storage at 25°C. the viscosity of emulsions stabilized by low viscosity grade polymers increased. For higher viscosity polymer, the emulsion viscosity initially increased and then decreased slightly on aging. Lower viscosity grade HPMC polymers have higher emulsifying efficiency. whereas higher viscosity grade polymer emulsion is much more stable towards centrifugation.     

Development of industrially feasible concentrated 30% and 40% nanoemulsions for intravenous drug delivery

Emulsions for parenteral nutrition loaded with drugs are used for optimized drug delivery, but in case of poorly oil soluble drugs, the injection volume can be too large when using commercial 10–20% oil emulsions. To reduce the injection volume, the feasibility of producing injectable, physically stable concentrated emulsions up to 40% oil content was investigated. Emulsions were made from fish oil, stabilized with egg lecithin, using high-pressure homogenization. Emulsions with oil contents of 10%–40% were investigated to assess basic correlations between increasing oil content, applied production pressures, homogenization cycles and resulting bulk droplet size, content of larger particles, zeta potential, viscosity and short-term stability. The observed correlations showed that in high-pressure homogenization, the contribution of the dispersive effect dominated the coalescence effect at low and Optimum production conditions for 30% and 40% nanoemulsions, i.e. 800 bar and 2 -3 homogenization cycles, were established on lab scale. These production conditions are industrially feasible. The obtained droplet sizes (about 200?nm) and the content of larger droplets were comparable to 10% commercial emulsions of parenteral nutrition, being important for in vivo tolerability and organ distribution. Despite the high oil concentration, the viscosity of the nanoemulsions was sufficiently low for injection. The short-term storage study showed physical stability for 1 month. A concentrated nanoemulsion base formulation from regulatory accepted excipients is now available, ready for loading with drugs.     

Stability Study of W/O/W Viscosified Multiple Emulsions

Stable multiple emulsions with a small proportion of primary emulsion containing different viscosifying agents in the outer aqueous phase were formulated. The multiple systems were assessed by evaluating several parameters, such as the macroscopic aspect, droplet size, release rate, and accelerated stability under elevated temperatures. The effect of different viscosifying agents at different concentrations on the stability and the multiplicity of the multiple emulsions was examined. The viscosity increased by increasing the concentration of the viscosifying agents. It also appeared that the viscosifying agents increased the temperature stability of the multiple emulsions. As a result, the formulation viscosified with Klucel was more stable, while the one prepared with carbomer viscosified the outer phase at much lower concentrations with much better skin feel.