Manufacture of large uniform droplets using rotating membrane emulsification

A new rotating membrane emulsification system using a stainless steel membrane with 100 microm laser drilled pores was used to produce oil/water emulsions consisting of 2 wt% Tween 20 as emulsifier, paraffin wax as dispersed oil phase and 0.01-0.25 wt% Carbomer (Carbopol ETD 2050) as stabilizer. The membrane tube, 1 cm in diameter, was rotated inside a stationary glass cylinder, diameter of 3 cm, at a constant speed in the range 50-1500 rpm. The oil phase was introduced inside the membrane tube and permeated through the porous wall moving radially into the continuous phase in the form of individual droplets. Increasing the membrane rotational speed increased the wall shear stress which resulted in a smaller average droplet diameter being produced. For a constant rotational speed, the average droplet diameter increased as the stabilizer content in the continuous phase was lowered. The optimal conditions for producing uniform emulsion droplets were a Carbomer content of 0.1-0.25 wt% and a membrane rotational speed of 350 rpm, under which the average droplet diameter was 105-107 microm and very narrow coefficients of variation of 4.8-4.9%. A model describing the operation is presented and it is concluded that the methodology holds potential as a manufacturing protocol for both coarse and fine droplets and capsules.     

Master curves for elastic and plastic properties of highly concentrated emulsions

Critical comparison of dependences of elastic and plastic properties of highly concentrated emulsions (so-called “compressed” emulsions) on the concentration and droplet sizes is performed. The studied emulsions of water-in-oil type are so-called “liquid explosives.” They are characterized by different mean sizes and different droplet size distributions of the dispersed phase. Different average values (D _av, D ₃₂, and D ₄₃) are used as characteristics of droplet sizes. Experiments are carried out with emulsions of two concentrations. Aqueous phase (dispersed droplets) is presented by supercooled solutions of inorganic salt in water in a metastable state. The concentration limit of the existence of highly concentrated emulsions is determined by the condition of the closest packing of liquid droplets, which lies in the φ* = 0.77–0.80 range. In addition, there is a limiting value of the maximal size of droplets. This limiting value depends on the concentration and meets the requirement that droplets should be small enough for the solution to exist in a supercooled state. The elastic modulus and the yield stress of emulsions studied are proportional to the square of the reciprocal linear size of droplets, which contradicts some theoretical models, according to which these parameter should be proportional to the reciprocal size of droplets. Using the obtained experimental data, we constructed generalized dependences of the elastic modulus and the yield stress on the concentration and size of droplets. These characteristics are in good agreement with the experimental data.     

Preparation of monodisperse crosslinked polymelamine microcapsules by phase separation method

Monodisperse polymelamine microcapsules were prepared by phase separation method. Control of microcapsule diameter was investigated using the uniform-sized oil-in-water emulsion droplets as the capsule core. The monodisperse emulsion droplets were prepared using the Shirasu porous glass (SPG) membrane emulsification technique. The effects of the diameter of the oil droplet and concentration of sodium dodecyl sulfate (SDS), which is a typical emulsifier in SPG membrane emulsification, on microencapsulation were investigated. The microcapsules were aggregated when oil droplets with small size were microencapsulated at high SDS concentration. To reduce the SDS concentration, the creamed emulsion was used. The monodisperse polymelamine microcapsules were successfully prepared by using the creamed emulsion. The microcapsule diameter was almost similar to the diameter of the encapsulated oil droplet. The coefficient of variation values was about 10% for all microcapsules prepared in this study. Control of microcapsule diameter was achieved in the range of 5–60 μm.     

Preparation of Uniform Microspheres and Microcapsules by Modified Emulsification Process

Summary: Uniform microspheres and microcapsules have been prepared by developing a direct membrane emulsification technique from O/W, W/O and W/O/W emulsions in previous studies, and have been applied in bio-separation and drug delivery systems. The diameter can be controlled from several microns to above 100 microns. However, smaller microsphere with submicron size, especially from W/O/W emulsion was difficult to be prepared. In this article, a modified emulsification technique was developed to overcome the problem. That is, a pre-emulsion (W/O or W/O/W) with broad size distribution of droplets was prepared firstly by homogenization, sonification or mechanical stirring method, then the pre-emulsion was pressed through the uniform pores of a Shirasu Porous Glass (SPG) membrane to obtain relatively uniform smaller droplets, finally the droplets were solidified to form uniform microsphere or microcapsule. Uniform chitosan microsphere and poly(lactic-glycolic acid) (PLGA) microcapsule with submicron size were prepared from W/O and W/O/W emulsions, respectively. Further more, uniform polymer-magnetite microcapsule was prepared by combining this technique and a new post-precipitation process of magnetite.     

PLA/MSM缓释微球的制备及生物活性

采用膜乳化-液中干燥法制备出担载二甲基砜(MSM)的聚乳酸(PLA)微球(PLA/MSM), 并研究了膜孔径、 搅拌转速和MSM浓度对载药微球形貌、 尺寸、 载药量、 体外释放及细胞活性的影响; 采用场发射环境扫描电子显微镜(ESEM)观察微球形貌、 尺寸及分布, 用等离子体发射光谱(ICP-AES)法检测PLA/MSM微球载药量、 包封率及体外释放, 采用ESEM观察微球内部结构, 并通过体外细胞培养和噻唑蓝(MTT)法检测MC-3T3-E1细胞的增殖能力. 研究结果表明, 膜乳化法制备的载药微球规整, 呈典型的圆球状, 表面光滑, 内部有多孔结构. 当膜孔径为5.1 μm且搅拌转速为500 r/min时, PLA/MSM微球大小更为均一; 当体系中MSM质量分数为8.6%时, 载药量可达到77.43%. 随着膜孔径减小及药物浓度的增加, 体外释放速率加快, 但初期均无明显的突释现象, 约10 d后累积释放量达到89.2%. 细胞实验结果显示, 在膜孔径为5.1 μm且MSM质量分数为8.6%的条件下, 制备的载药微球在细胞培养7 d时表现出明显的促增殖作用.     

Formulation and Optimization of Alkaline Extracted Ispaghula Husk Microscopic Reservoirs of Isoniazid by Box-Behnken Statistical Design

The main objective of the present work was to formulate and optimize a microparticulate sustained release drug delivery system of isoniazid by using a novel, alkaline extracted ispaghula husk as a polymer. Isoniazid microspheres of alkaline extracted ispaghula husk were prepared by emulsification internal ionic gelation method. Results of preliminary trials indicated that the polymer concentration, cross-linking agent and stirring speed had a noticeable effect on size and surface morphology. A four-factor three-level Box-Behnken design was employed to study the effect of independent variables on dependent variables. The particle size and entrapment efficiency varied from 30.75 to 61.78 µm and 62.27% to 85.80% respectively, depending on the polymer concentration, concentration of cross-linker and stirring speed. Optimized microspheres batch based on point prediction tool of design software exhibited 83.43% drug entrapment and 51.53 µm particle size with 97.80% and 96.37% validity, respectively at the following conditions: sodium alginate (3.55% w/v), alkaline extracted ispaghula husk (3.60% w/v), cross-linker concentration (7.82% w/v), and stirring speed (1200 rpm). The optimized formulation showed controlled drug release for more than 12 hours. The drug release followed Higuchi kinetics via a non-Fickian diffusion.     

Shear-induced deformations of polyamide microcapsules

The application of microcapsules for technical, cosmetic and pharmaceutical purposes has attracted increased interest in recent years. The design of new capsule types requires a profound knowledge of their mechanical properties. Rheological studies provide interesting information on intrinsic membrane properties and this information can be used to avoid premature release of encapsulated compounds due to the action of external mechanical forces (stirring, swallowing, spreading). In this publication we report a systematic study of polyamide microcapsules. These particles were synthesized by reacting 4-aminomethyl-1,8-diaminooctane and sebacoyl dichloride at the interface between silicone oil and water. Two different experiments were performed to get information on the mechanical properties of the capsule walls. First of all, we used an optical rheometer (rheoscope) to observe the capsule deformation and orientation in shear flow. The polymerization kinetics, relaxation properties, the regime of linear-viscoelastic behavior and the shear modulus of the flat membranes were independently measured in an interfacial rheometer. Both experiments gave complementary results. It turned out that the two-dimensional elongational modulus was about 3–4 times larger than the shear modulus. This result is in fairly good agreement with a theoretical model recently proposed by Barthès-Biesel. Due to the simple synthesis and well-defined structure, polyamide microcapsules can also serve as simple model systems to understand the complicated flow properties of red blood cells. Received: 5 July 1999/Accepted in revised form: 30 August 1999     

Preparation of raspberry-like nanocapsules by the combination of Pickering emulsification and solvent displacement technique

Well-defined raspberry-like nanocapsules were prepared by the combination of Pickering emulsification and solvent displacement technique by using silica particles as stabilizer and hexadecane (HD) as soft template. The formation of the capsule morphology is caused by the phase separation of poly(styrene-co-4-vinyl pyridine) (poly(St-co-4-VP)) in the droplets due to the diffusion of good solvent for the (co)polymer to the aqueous continuous phase. The size of capsules was successfully reduced from tens of micrometers in the dispersion by simply stirring to the nanorange by the employment of sonication and Ostwald ripening. The formation of silica-particles-armored nanocapsules was confirmed by transmission electron microscopy (TEM), high-resolution scanning electron microscopy (HRSEM), dynamic light scattering (DLS), and zeta potential measurement. The colloidal stability and particle properties, including size and morphology, depend on the amount of HD, and copolymers, the sonication time, the dispersion pH value, the type of solvent, and the copolymer composition.     

Mechanical properties of liquid-filled shellac composite capsules

This paper describes the mechanical properties of thin-walled, liquid-filled composite capsules consisting of calcium pectinate and shellac. In a series of experiments we measured the deformation of these particles in a spinning drop apparatus. For different pH-values we studied the elastic properties of these particles and compared the obtained results with the mechanical response measured by squeezing capsule experiments. In analogy to these experiments, we also investigated liquid-filled unloaded calcium pectinate capsules without the addition of shellac. The deformation properties of these experiments and the surface Young moduli were in good agreement. Furthermore we investigated the liquid-filled calcium pectinate and the composite capsules by NMR microscopy. These experiments allowed investigations of the membrane thickness and the kinetics of membrane growing. Additional characterizations by stress controlled small amplitude surface shear experiments of similar composed gel layers provided coherent results for the surface Young modulus.     

Preparation of insulin-loaded PLA/PLGA microcapsules by a novel membrane emulsification method and its release in vitro

Uniform-sized biodegradable PLA/PLGA microcapsules loading recombinant human insulin (rhI) were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and a double emulsion-evaporation method. An aqueous phase containing rhI was used as the inner water phase (w1), and PLA/PLGA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene, which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores of a SPG membrane into an outer water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. The solid polymer microcapsules were obtained by simply evaporating solvent from droplets. Various factors of the preparation process influencing the drug encapsulation efficiency and the drug cumulative release were investigated systemically. The results indicated that the drug encapsulation efficiency and the cumulative release were affected by the PLA/PLGA ratio, NaCl concentration in outer water phase, the inner water phase volume, rhI-loading amount, pH-value in outer water phase and the size of microcapsules. By optimizing the preparation process, the drug encapsulation efficiency was high up to 91.82%. The unique advantage of preparing drug-loaded microcapsules by membrane emulsification technique is that the size of microcapsules can be controlled accurately, and thus the drug cumulative release profile can be adjusted just by changing the size of microcapsules. Moreover, much higher encapsulation efficiency can be obtained when compared with the conventional mechanical stirring method.     

A review of: “Nineteenth Century Attitudes: Men of Science (Chemists and Chemistry Series,Vol. 13)”. Sydney Ross. Kluwer Academic Publishers; Dordrecht, 1991. pp. xi+235. $69.00.

Abstract

The potential of polytetrafluoroethylene (PTFE) membranes as water‐in‐oil (W/O) emulsification devices was investigated to obtain uniformly sized droplets and to convert them into microcapsules and polymer particles via subsequent treatments. Uniform W/O emulsion droplets have not been achieved using glass membranes unless the membrane was rendered hydrophobic by treatment with silanes. If a PTFE membrane is capable of providing uniform droplets for a W/O emulsion, a coordinated membrane emulsification system can be established since glass membranes have been so successful for O/W (oil‐in‐water) emulsification. In order to examine the feasibility of PTFE membrane emulsification, O/W and W/O emulsion characteristics prepared using PTFE membranes were compared with those prepared by the conventional SPG (Shirasu porous glass) membrane emulsification method. A 3 wt.% sodium chloride solution was dispersed in kerosene using a low HLB surfactant. Effects of the membrane pore size, permeation pressure, and the type of emulsifiers and concentration on the droplet size and on the size distribution (CV, coefficient of variation) were investigated. The CV of the droplets was fairly low, and the average droplet size was correlated with the critical permeation pressure of the dispersed phase, revealing that the PTFE membrane could be used as a one‐pass membrane emulsification device. Low CV values were maintained with a Span 85 (HLB = 1.8) concentration, 0.2–5.0 wt.% and a range of HLB from 1.8–5.0. For a brief demonstration of practical applications, nylon‐6,10 microcapsules prepared by interfacial polycondensation and poly(acrylamide) hydrogels from inverse suspension polymerization are illustrated.     

Novel polymer capsules from amphiphilic graft copolymers and cross-metathesis

We report the synthesis of polymer capsules from amphiphilic graft copolymers composed of reactive, hydrophobic polyolefin backbones and hydrophilic poly(ethylene glycol) (PEG) grafts. The capsules are produced by self-assembly of the polymers at the oil-water interface, followed by cross-linking with bis-cyclooctene PEG derivatives. The fluorescence of these capsules results from integration of rhodamine B functionalized cyclooctene 1 into the polymer structure. The use of the graft copolymer architecture in capsule synthesis provides significant opportunities to tune both the surface properties, in terms of recognition, and the membrane properties, in terms of mechanical strength, encapsulation, and release.     

Soy glycinin microcapsules by simple coacervation method

Encapsulation of a dispersed oil phase (hexadecane) was realized by simple coacervation method using soy glycinin as the wall forming material. Suitable emulsification and coacervation conditions, that favor the formation of microcapsules wall, were identified and investigated. Mild acid (pH 2.0) and heat (55 degrees C) treatments of the reaction medium during the emulsification step enhanced significantly the deposition of coacervated glycinin around oil droplets. A pronounced correlation between glycinin concentration in the continuous phase, specific surface of the dispersed phase and the microencapsulation efficiency was also observed. Coacervation step study concerned the morphology and the stability of microcapsules. Controlled initiation of the coacervation, by slow readjustment of the pH, allowed a homogeneous precipitation of glycinin around oil droplets as well as the absence of aggregation phenomena. Since the morphology of microcapsules was considerably affected by a prolonged stirring of the reaction medium, the coacervation and reticulation time were optimized in order to preserve the homogeneity of the microcapsules size distribution and the microencapsulation efficiency.     

Miniemulsion cross-linking: A convenient route to hollow polymeric nanocapsule with a liquid core

Miniemulsion stabilized by poly(2-(dimethylamino) ethyl methacrylate)-block-poly(butyl methylacrylate) (PDMAEMA-b-PBMA) diblock copolymers has been used as liquid templates for the synthesis of polymer nanocapsules via quaternization cross-linking of PDMAEMA segments of the copolymer by 1,2-bis(2-iodoethoxy)ethane (BIEE) crosslinkers. PDMAEMA-b-PBMAs here as a stabilizer in miniemulsion with different molecular weights led to a size variation in diameters of nanocapsules, demonstrating the capsules have potential design capability of this technique. The solution behavior of the capsules has been also investigated in this paper.     

Microcapsule synthesis via RAFT photopolymerization in vegetable Oil as a green solvent

Polymeric capsules with an aqueous core have great potential for a wide range of applications, for example food/biomedical applications. However, synthesis of such capsules often involves the use of toxic organic solvents. Herein, an organic solvent‐free approach is developed for the synthesis of polymeric microcapsules with an aqueous core. The method is based on RAFT polymerization of divinyl monomer around the periphery of inverse emulsion water droplets acting as templates, with an amphiphilic macroRAFT species fulfilling the dual roles of RAFT agent and colloidal stabilizer. Vegetable oils, which are non‐toxic and renewable, are used as the continuous phase of these inverse emulsions, which are prepared using membrane emulsification to control the emulsion droplet size and size distribution. Relatively monodisperse emulsions with tunable droplet size in the range of approximately 10–30 µm are prepared, followed by the RAFT polymerization step to generate polymeric microcapsules having similar size as the initial droplets. This approach will be beneficial for various applications where toxic solvents need be minimized or removed completely to avoid adverse effects. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 831–839     

The Role of Internal Droplet Size on Emulsion Stability and the Extraction Performance of Kraft Lignin Removal from Pulping Wastewater in Emulsion Liquid Membrane Process

It has been discovered that the size of internal droplets in primary emulsion determines emulsion dispersion and stability in emulsion liquid membrane (ELM) process for removal of lignin from pulping wastewater. Generally, primary emulsion contains kerosene, Aliquat 336, sodium bicarbonate, as well as Span 80 as diluent, carrier, internal phase, and surfactant, respectively. Hence, this study had looked into the parameters, including concentration of surfactant, carrier, and stripping agent; emulsification speed and time; as well as agitation speed and time. As a result, the diameter of the smallest droplets (1.4 µm) was formed with maximum lignin extraction (95%), minimum swelling (5%) at 3% (w/v) surfactant concentration, 12,000 rpm of emulsification within 5 minutes, 0.01 M of Aliquat 336, 0.1 M of NaHCO_3, and 250 rpm of extraction within 10 minutes.     

Structural evolution of polymer-stabilized double emulsions

Polymer-stabilized double emulsions are produced by a two-step process, high shear emulsification in the primary and membrane emulsification in the secondary. By repeated fractionation after each emulsification, we obtain monodisperse double emulsions with the size of the complex droplets ranging from submicrometer to a few micrometers. With osmotic pressure balance between the inner and outer phases, the polymer-stabilized double emulsions remain stable for a year at room temperature without structure deterioration. We generalize laser light scattering to probe the structure and internal dynamics of the complex system by including the effects of the amplitude fluctuations of the scattered fields. Both static light scattering (SLS) and dynamics light scattering (DLS) can resolve the inclusions inside the complex droplets. Water-soluble nonionic surfactants are used to induce destabilization of double emulsions. We find that a double emulsion turns into a simple emulsion within a minute at a surfactant concentration of less than 10(-)(3) mol/L. We demonstrate that DLS is a powerful technique to study the kinetics of destabilization of double emulsions. Coalescence between the internal droplets and the external continuous phase is identified as a major release pathway.     

Porous microcapsule formation with microsieve emulsification

A simple route is presented to prepare core-shell Eudragit microcapsules through a solvent extraction method with the use of microsieve emulsification. Droplets from a solution of Eudragit FS 30D (a commercial copolymer of poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) 7:3:1) and hexadecane in dichloromethane are dispersed into water, using a micro-engineered membrane with well-defined pores, in a cross-flow setting. The dichloromethane is extracted from the droplets, which induces demixing in the droplets, leading to a hexadecane-rich core, and an Eudragit-rich shell. The obtained microcapsules have a narrow size distribution due to the microsieve emulsification process. The capsules have a porous shell as shown by SEM and AFM measurements. Their porosity and pore size is dependent on the ratios of Eudragit and hexadecane in the dispersed phase. At pH 7.1 and above Eudragit (FS 30D) dissolves in water; this pH change is used to release the contents of the microcapsule.     

Microfluidic production of biopolymer microcapsules with controlled morphology

We report a microfluidic approach to generating capsules of biopolymer hydrogels. Droplets of an aqueous solution of a biopolymer were emulsified in an organic phase comprising a cross-linking agent. Polymer gelation was achieved in situ (on a microfluidic chip) by diffusion-controlled ionic cross-linking of the biopolymer, following the transfer of the cross-linking agent from the continuous phase to the droplets. Gelation was quenched by collecting particles in a large pool of cross-linking agent-free liquid. The structure of microgels (from capsules to gradient microgels to particles with a uniform structure) was controlled by varying the time of residence of droplets on the microfluidic chip and the concentration of the cross-linking agent in the continuous phase. We demonstrated the encapsulation of a controlled number of polystyrene beads in the microgel capsules. The described approach was applied to the preparation of capsules of several polysaccharides such as alginate, kappa-carrageenan, and carboxymethylcellulose.     

Osmotically Driven Formation of Double Emulsions Stabilized by Amphiphilic Block Copolymers

Double emulsions are valuable for the formation of multi‐compartmental structures. A variety of pathways to prepare double emulsions have been developed, but high‐throughput routes to droplets of controlled size and architecture remain scarce. A new single‐step process is introduced for preparation of water‐in‐oil‐in‐water double emulsions by a previously unexplained process of self‐emulsification. We show that the origin of this process is the osmotic stress resulting from the presence of salt impurities within the amphiphilic block copolymers used for emulsion stabilization. Further, we utilize osmotically driven emulsification to tailor the structures of multiple emulsions, which upon solvent evaporation can yield multi‐compartmental capsules or hierarchically structured porous films.