油水相界面张力对乳化炸药性能的影响

采用白金环法测定了乳化炸药复合油相与硝酸铵水溶液的界面张力,并研究了乳化剂质量分数、温度、分子结构和热值对油水相界面张力的影响以及界面张力对乳胶基质微观结构和储存稳定性的影响。结果表明,随着乳化剂质量分数的升高,界面张力先下降后保持恒定;随着温度升高,界面张力呈线性下降趋势;复合蜡组分的异构化烷烃含量越高,环状化合物越少,热值越低,油水相界面张力越低。随着界面张力和临界质量分数的降低,乳胶基质的粒径减小。乳胶基质的储存稳定性随着油相材料界面张力的降低而增强。     

乳化炸药组分对体系界面张力的影响

采用吊片法分析乳化剂对碳质燃料油的表面张力以及乳化炸药组成材料对乳化炸药体系界面张力的影响。实验结果表明,油相材料的表面张力随乳化剂质量分数的增加而减小;在乳化炸药体系的水相中加入硝酸钠,可以降低体系的界面张力;油相材料的黏度增加,乳化炸药体系的界面张力也相应的增加;乳化剂质量分数大于1.0%时,乳化炸药体系的界面张力值趋向恒定。     

乳化炸药组分对体系界面张力的影响

采用吊片法分析乳化剂对碳质燃料油的表面张力以及乳化炸药组成材料对乳化炸药体系界面张力的影响。实验结果表明,油相材料的表面张力随乳化剂质量分数的增加而减小;在乳化炸药体系的水相中加入硝酸钠,可以降低体系的界面张力;油相材料的黏度增加,乳化炸药体系的界面张力也相应的增加;乳化剂质量分数大于1.0%时,乳化炸药体系的界面张力值趋向恒定。     

Development of a Novel Parenteral Formulation for Tetrazepam Using a Lipid Emulsion

A novel parenteral formulation for tetrazepam (10 mg/ml) was developed using lipid emulsions. This formulation utilized a new lipid emulsion formulation, which was developed by changing the polarity of the oil phase. It was found that increasing the polarity of the oil phase resulted in enhanced solubility of tetrazepam. Tetrazepam showed higher solubility in a mixture of castor oil and middle-chain triglycerides (MCTs) (1:1) than in any other oil investigated. This mixture resulted in low interfacial tension and moderate viscosity, which seemed to be the optimum oil phase. In addition, to increase the concentration of tetrazepam, an emulsion formulation containing 30% oil phase was produced and optimized. The drug-free emulsion formulation showed fine particle sizes with an imperceptible change in physicochemical properties after more than 2 years on the shelf. As a result, it was possible to produce a parenteral emulsion formulation containing 10 mg/ml tetrazepam. No change in the physicochemical properties of the emulsion was observed after the addition of tetrazepam. The tetrazepam emulsion showed stable behavior during the autoclaving process and good shelf stability for at least 10 months as well. Tetrazepam itself also displayed good stability during the autoclaving process and also showed good shelf stability in this emulsion formulation.     

Interaction of Gelatin and Sodium Dodecyl Benzene Sulphonate at Oil and Water Interfaces

Abstract

Interaction between sodium dodecyl benzene sulphonate (SDBS) and gelatin ivas studied in relation to emulsification behaviour and emulsion stability. We chose two different oils to study influences of oil phase characteristics, namely, tricresyl phosphate (TCP) as an oil with polar and slightly hydrophilic nature, and n-dodecane (n-C₁₂) as its apolar contrast. Our interfacial tension measurements showed that both TCP and n-C₁₂ give critical values (i.e., cac and cmc) very close to I hose of surface tension measurement. This result indicates that the complexation behaviour in bulk solution is independent of the presence or the nature of the oil phase. Absolute tension values above the cmc and slope value at the cmc in gelatin free systems, however, imply SDBS’s weaker adsorption to TCP than to n-C₁₂ Our emulsification results for the TCP system revealed the existence of an optimal point for emulsion stability in the SDBS concentration region between the cac and the cmc. Above this point, emulsion stability deteriorates remarkably. The behaviour is in line with our findings from the dynamic sorption experiments (ellipsomelry, TIRF, and SPR) reported elsewhere, which showed a rapid desorption of gelatin from the hydrophobic surfaces above the cac. The results suggest that the adsorption of gelatin/surfactant complexes at the interface is a key factor for stability of the polar oil emulsion system. Contrary to that, the n-C₁₂ system did not show any deterioration, even above the cmc, which is presumably due to a strong double layer effect from the firmly adsorbed layer of SDBS at the interface.     

丁二酰亚胺乳化机理的探讨

文中讨论了用于制备乳化炸药的丁二酰亚胺的乳化机理，根据丁二酰亚胺的分子结构，认为油溶性丁二酰亚胺作为油相和水相的媒介，与水之间除存生物在物理吸附之外，还存在以氢键为主的化学吸附，从而能显著地降低油水两相界面张力，构成稳定的乳胶颗粒。     

Interfacial Tension Measurement With an Optofluidic Sensor

This paper reports a novel optofluidic sensor for measuring dynamic interfacial tensions. The field of optofluidics utilizes both microfluidics and micro-optics. Thus, our sensor consists of a microfluidic network and an optical detection system. The sensor is able to measure both surface tension and liquid/liquid interfacial tension. In the case of surface tension measurement, the liquid sample is introduced into a main channel, while air is injected through a T-junction. In the case of liquid/liquid interfacial tension measurement, a second immiscible liquid such as oil is introduced into a main channel, while the sample liquid is injected through the T-junction. The formation frequency of the microbubbles or microdroplets is a function of the interfacial tension between the two phases. This frequency can be measured easily by optical detection. Measurements were carried out for aqueous solutions with different concentrations of the ionic surfactant cetyl trimethyl ammonium bromide (CTAB). The actual interfacial tensions of these solutions were calibrated with a commercial tensiometer (FTA200, First Ten Angstrom). The measurement results show a clear relation between the interfacial tension and the formation frequency. Furthermore, our sensor can be used to identify the critical micelle concentration (CMC) of a surfactant. The sensor potentially allows the use of a minute amount of sample compared to the relatively large amount required for existing commercial systems     

Phase diagram studies of microcapsule formation using hydroxypropyl methylcellulose phthalate

Abstract

Microcapsules of hydroxypropyl methylcellulose phthalate were prepared using a non-aqueous emulsion method. The study was designed to determine the region of microcapsule formation in the ternary system of mineral oil, acetone and polymer and to present the data by means of phase diagrams. Increasing amounts of sorbitan monooleate were added to mineral oil to determine the effect of surfactant concentration on the phase diagram. The effect of sorbitan monooleate, sorbitan trioleate and sorbitan monolaurate on the microcapsule region of the phase diagram was also investigated. Particle size analysis was carried out to determine if the concentration and type of surfactant used had a significant effect on the size of the microcapsules obtained. Tartrazine was encapsulated as a model drug and its dissolution was studied in acidic and neutral mediums. The results indicate that the addition of sorbitan monooleate increased the microcapsule region of the phase diagram and sorbitan trioleate had a similar effect. However, the microcapsule region in the phase diagram decreased when sorbitan monolaurate was used. The particle size increased with increasing concentration of polymer, irrespective of the type and concentration of surfactant used.     

Separation of aniline from aqueous solutions using emulsion liquid membranes

An emulsion liquid membrane process is developed to separate aniline from dilute aqueous solution. Aniline (amino-benzene) is a carcinogenic chemical common in industry and industrial wastewater. Due to aniline's high boiling point (183°C) and low concentration in wastewater, more traditional methods of separation such as distillation are very energy intensive. This emulsion process is offered as a low energy alternative. All separations occur in a Rushton stirred tank. The membrane phase consists of kerosene and the surfactant sorbitan monooleate (span 80). Hydrogen chloride solution is the internal phase. This study also examines the effects of HCl concentration, aniline concentration, and the amount of emulsion on separation. Up to 99.5% of the aniline is removed from solutions containing 5000 ppm in as little as 4 min depending on process conditions. Leakage is minimal and swelling is only about 3% after 5 min of processing. Approximately 98% of the membrane phase (both kerosene and span 80) is successfully recovered and recycled by using heat and/or adding 2-propanol for demulsification.     

Assessment of drug release from oil depot formulations using an in vitro model -- potential applicability in accelerated release testing

In vitro drug release and transport rates from oil depot formulations under nonsink conditions have been investigated in the rotating dialysis cell model. Eight model drug compounds and eight oil vehicle compositions were used for the releaseexperiments. The experimentally obtained apparent first-order rate constants related to the drug appearance in the acceptor phase after initial instillation of a drug-containing oil solution were found to be in excellent agreement with the rate constants obtained from a theoretically derived expression. It was observed that the drug oil-water distribution coefficient was the key parameter influencing the release characteristics. As compared with ketoprofen, flurbiprofen exhibited a higher affinity for the oil, resulting in a significantly lower and more slowly decreasing drug concentrations in the aqueous donor compartment. Release profiles for prilocaine and the more lipophilic agent bupivacaine after incorporation of both drugs in fractionated coconut oil were characterized by a fast release of prilocaine, whereas bupivacaine was liberated much slower to the acceptor phase. The high oil-buffer interfacial area generated in vitro by rotation of the donor cell tends to overestimate release rates in comparison to those expected in vivo, for example, after intra-articular administration of oil solutions. The present in vitro method may constitute a valuable tool in accelerated in vitro release testing of parenteral oil depot formulations in areas comprising formulation design and product quality control.     

In vitro-in vivo characterization of release modifying agents for parenteral sustained-release ketorolac formulation

One of the prerequisites for a parenteral preparation is that the excipients incorporated are biocompatible and biodegradable. In the present study hydrophilic and hydrophobic excipients were investigated for developing an intramuscular sustained-release formulation of ketorolac. Kollidon® 17 PF, Peceol (glyceryl monooleate), and castor oil were chosen as the potential release-retarding agents, each with a distinct mechanism of action. They were evaluated by in vitro drug-release profiles and in vivo pharmacodynamic and pharmacokinetic study in mice. Cumulative drug release was determined for standard and test formulations in modified Franz diffusion cell. Pharmacodynamic parameter, T = 70% response of peak analgesic response, was used to compare the performance of test formulations. Based on pharmacodynamic/pharmacokinetic correlation in the animal studies, Css_max and Css_min of 51.39 and 30.0 µg/mL, respectively, were determined and considered as performance markers for pharmacokinetic evaluation of test formulations. The study suggested that the sustained-release capability of glyceryl monooleate was maximum followed by that of castor oil and Kollidon 17 PF, when compared to conventional ketorolac tromethamine formulation. It was inferred that water soluble excipient, though, showed release retarding property in vitro but could not maintain it in the in vivo environment. Glyceryl monooloeate-based formulation produced the most favorable drug blood concentration vs. time profile.     

表面活性剂浓度对乳胶基质平均粒径的影响和机理分析

乳胶基质内相液滴的平均粒径大小直接反映了可燃剂和氧化剂的混合均匀程度,是影响乳化炸药爆炸性能和稳定性能的重要因素。主要研究了油相中表面活性剂浓度对乳胶基质内相液滴平均粒径的影响。使用5种含有不同表面活性剂浓度的外相材料制备乳胶基质,并且使用激光粒度仪测试了所有样品的平均粒径。实验结果表明:油相材料中表面活性剂的浓度越大,则制备出的乳胶基质平均粒径越小。然后通过表面张力的理论分析和外相动力粘度的实验测试,进而分析出增加表面活性剂降低乳胶基质的平均粒径的机理:表面活性剂的增加导致了外相材料的动力粘度的增大,进而使乳胶基质平均粒径变小,和表面张力无关。     

In Vitro–In Vivo Characterization of Release Modifying Agents for Parenteral Sustained‐Release Ketorolac Formulation

One of the prerequisites for a parenteral preparation is that the excipients incorporated are biocompatible and biodegradable. In the present study hydrophilic and hydrophobic excipients were investigated for developing an intramuscular sustained‐release formulation of ketorolac. Kollidon® 17 PF, Peceol (glyceryl monooleate), and castor oil were chosen as the potential release‐retarding agents, each with a distinct mechanism of action. They were evaluated by in vitro drug‐release profiles and in vivo pharmacodynamic and pharmacokinetic study in mice. Cumulative drug release was determined for standard and test formulations in modified Franz diffusion cell. Pharmacodynamic parameter, T?=?70% response of peak analgesic response, was used to compare the performance of test formulations. Based on pharmacodynamic/pharmacokinetic correlation in the animal studies, Css_max and Css_min of 51.39 and 30.0 µg/mL, respectively, were determined and considered as performance markers for pharmacokinetic evaluation of test formulations. The study suggested that the sustained‐release capability of glyceryl monooleate was maximum followed by that of castor oil and Kollidon 17 PF, when compared to conventional ketorolac tromethamine formulation. It was inferred that water soluble excipient, though, showed release retarding property in vitro but could not maintain it in the in vivo environment. Glyceryl monooloeate‐based formulation produced the most favorable drug blood concentration vs. time profile.     

Generation of High‐Order All‐Aqueous Emulsion Drops by Osmosis‐Driven Phase Separation

Droplets containing ternary mixtures can spontaneously phase‐separate into high‐order structures upon a change in composition, which provides an alternative strategy to form multiphase droplets. However, existing strategies always involve nonaqueous solvents that limit the potential applications of the resulting multiple droplets, such as encapsulation of biomolecules. Here, a robust approach to achieve high‐order emulsion drops with an all‐aqueous nature from two aqueous phases by osmosis‐induced phase separation on a microfluidic platform is presented. This technique is enabled by the existence of an interface of the two aqueous phases and phase separation caused by an osmolality difference between the two phases. The complexity of emulsion drops induced by phase separation could be controlled by varying the initial concentration of solutes and is systematically illustrated in a state diagram. In particular, this technique is utilized to successfully achieve high‐order all‐aqueous droplets in a different aqueous two‐phase system. The proposed method is simple since it only requires two initial aqueous solutions for generating multilayered, organic‐solvent‐free all‐aqueous emulsion drops, and thus these multiphase emulsion drops can be further tailored to serve as highly biocompatible material templates.     

Preparation and characterization of a submicron lipid emulsion of docetaxel: submicron lipid emulsion of docetaxel

Docetaxel, a widely used anticancer agent, has sparingly low aqueous solubility, thus Tween 80 and ethanol need to be added into its formulation, probably resulting in the toxic effects. In this study, we aimed to utilize submicron lipid emulsions as a carrier of docetaxel to avoid these potential toxic vehicles. Preformulation study was performed for rational emulsions formulation design, including drug solubility, distribution between oil and water, and degradation kinetics. Supersaturated submicron lipid emulsion of docetaxel was prepared by temperature elevation method. Soya oil and Miglyol 812 can incorporate docetaxel up to 1.0% (drug to lipid ratio) and were used as the oil phase of emulsions. The optimal formulation of docetaxel is composed of 10% oil phase, 1.2% soybean lecithin, 0.3% Pluoronic F68, and 0.4 or 0.8 mg/mL docetaxel, with particle size in the nanometer range, entrapment efficiency more than 90%, and is physicochemically stable at 4 and 25 degrees C for 6 months. Animal studies showed that docetaxel emulsion has significantly higher area under the curve (AUC) and C(max) in rats compared to its micellar solution. The results suggested that the submicron lipid emulsion is a promising intravenous carrier for docetaxel in place of its present commercially available docetaxel micellar solution with potential toxic effects.     

High drug loading self-microemulsifying/micelle formulation: design by high-throughput formulation screening system and in vivo evaluation

Purpose: To design a high drug loading formulation of self-microemulsifying/micelle system.

Methods: A poorly-soluble model drug (CH5137291), 8 hydrophilic surfactants (HS), 10 lipophilic surfactants (LS), 5 oils, and PEG400 were used. A high loading formulation was designed by a following stepwise approach using a high-throughput formulation screening (HTFS) system: (1) an oil/solvent was selected by solubility of the drug; (2) a suitable HS for highly loading was selected by the screenings of emulsion/micelle size and phase stability in binary systems (HS, oil/solvent) with increasing loading levels; (3) a LS that formed a broad SMEDDS/micelle area on a phase diagram containing the HS and oil/solvent was selected by the same screenings; (4) an optimized formulation was selected by evaluating the loading capacity of the crystalline drug. Aqueous solubility behavior and oral absorption (Beagle dog) of the optimized formulation were compared with conventional formulations (jet-milled, PEG400).

Results: As an optimized formulation, d-α-tocopheryl polyoxyethylene 1000 succinic ester: PEG400?=?8:2 was selected, and achieved the target loading level (200?mg/mL). The formulation formed fine emulsion/micelle (49.1?nm), and generated and maintained a supersaturated state at a higher level compared with the conventional formulations. In the oral absorption test, the area under the plasma concentration-time curve of the optimized formulation was 16.5-fold higher than that of the jet-milled formulation.

Conclusions: The high loading formulation designed by the stepwise approach using the HTFS system improved the oral absorption of the poorly-soluble model drug.     

Influence of Surfactants in Aqueous-Based Polymeric Dispersions on the Thermomechanical and Adhesive Properties of Acrylic Films

Good adhesion between a polymeric film and the surface of a solid substrate is critical to the performance of coated pharmaceutical products. Previous research has shown that tablet wettability by an organic-based cellulosic solution could predict the extent of film-tablet adhesion. Using an aqueous-based acrylic polymeric dispersion, the current study investigated the relationship between film adhesion and tablet wettability. Up to 10% (w/w based on dry polymer weight) polysorbate 80 or sorbitan monooleate was incorporated into the film-coating formulations. While the contact angle between the polymeric dispersion and the tablet surface was dependent on the type and concentration of surfactants added to the coating formulation, no correlation between tablet wettability and polymer adhesion could be established. The addition of surfactants to formulations containing the hydrophobic plasticizer tributyl citrate (TBC) caused lowering of the glass transition temperature of the polymer. Increased force of adhesion, elongation at adhesive failure, and adhesive toughness, however, were noted only in the TBC-plasticized films containing polysorbate 80. These findings demonstrate that our understanding of the mechanisms involved in film-tablet adhesion is still quite limited.     

Stability studies on colloidal suspensions of polyurethane nanocapsules

Generally nanocapsules suspensions are a colloidal system in a metastable state, there is aggregation due to attraction and repulsion forces between particles. The objective of this work was to bring the role of the polymeric membrane in the protection of the active drug against damaging caused by external agents and to select the monomer which leads to obtain stable formulation with the highest possible payload of the active drug. The stability testing involving visual aspect, particle size measurement, transmission electron microscopy (TEM) examination, and drug loss was conduced after 6 months of storage at different temperatures (4, 25, and 45 degrees C). The colloidal suspensions of nanocapsules were obtained using the combined interfacial polycondensation and spontaneous emulsification, the technique was used to encapsulate alpha-tocopherol using polyurethanes polymers. It is a one step procedure: An organic phase composed of a water miscible solvent (acetone), lipophilic monomer (Isophorone diisocyanate IPDI), oil, and a lipophilic surfactant, is injected in an aqueous phase containing hydrophilic monomer (diol with various molecular weight: 1,2-ethanediol (ED), 1,4-butanediol (BD), and 1,6-hexanediol (HD)) and hydrophilic emulsifying agent. The water miscible solvent diffuses to the aqueous phase, the oil precipitates as nano-droplets, and the two monomers react at the interface, forming a membrane around the nanoemulsion leading to nanocapsules. A good physical stability of suspensions corresponds to absence of symptoms such as sedimentation or agglomeration, significant size change and alpha-tocopherol degradation due to external agents such as oxygen, temperature, and ultraviolet (UV) irradiation. The size of nanocapsules before storage was about 232 +/- 3, 258 +/- 29, and 312 +/- 4 nm for ED, BD, and HD, respectively. After 6 months of storage, polyurethanes nanocapsules possess good stability against aggregation at 4 and 25 degrees C. Comparing results obtained using different monomers, it reveals that the polyurethane based on HD offers good protection of alpha-tocopherol against damaging caused by the temperature and UV irradiation.     

Study of electron transfer across the liquid/ice-like matrix interface by scanning electrochemical microscopy

In this work, we report the findings of a study on scanning electrochemical microscopy (SECM) to investigate the interfacial electron-transfer (ET) reaction between the 7,7,8,8-tetracyanoquinodimethane radical anion (TCNQ*-) in 1,2-dichloroethane and ferricyanide in an ice-like matrix (a mixture of insulting ice and conductive liquid) under low temperatures. Experimental results indicate that the formed liquid/ice-like matrix interface is superficially similar in electrochemical characteristics to a liquid/liquid interface at temperatures above -20 degrees C. Furthermore, imaging data show that the surface of the ice-like matrix is microscopically flat and physically stable and can be applied as either a conductive or an insulting substrate for SECM studies. Perchlorate ion was selected as the common ion in both phases, the concentrations of which controlled the interfacial potential difference. The effect of perchlorate concentration in the DCE phase on interfacial reactions has been studied in detail. The apparent heterogeneous rate constants for TCNQ*- oxidation by Fe(CN)6(3-) in another phase under different temperatures have been calculated by a best-fit analysis, where the experimental approach curves are compared with the theoretically derived relationships. Reaction rate data obey Butler-Volmer formulation before and after the freezing point, which is similar to most other known cases of ET reactions at liquid/liquid interfaces. However, there is a sharp change observed for heterogeneous rate constants around the freezing point of the aqueous phase, which reflects the phase transition. At temperatures below -20 degrees C, surface-confined voltammograms for the reduction of ferricyanide were obtained, and the ice-like matrix became an insulating one, which indicates that the aqueous phase is really a frozen phase.     

Some Properties of an Ethoxylated Castor Oil and Ethoxylated Oleyl Alcohol

Abstract

Ethoxylated derivates have been used as surfactants for some years. In this work, ethoxylated castor oil and ethoxylated oleyl alcohol alone and/or their I:I mixtures were used as surfactants in oil/water type of emulsion systems.

The physicochemical properties of ethoxylated castor oil (Simulsol OL 50) and ethoxylated oleyl alcohol (Simulsol 98) have been investigated.

Both of these materials have properties associated with non-ionic surfactants, although considerably soluble in water, the compounds have slight solubility in nonpolar solvents.

Surface tensions of aqueous solutions were measured over a temperature range of 20°C to 40°C. CMC were determined by surface tension measurements. pH, refractive index, conductivity and density of the two surfactants were also determined.