Capsules phase separation

Several parenteral microencapsulated products have been commercialized the cote materials ate polypeptides with hormonal activity. Poly(lactide— glycohde) copolymers ate the sheU materials used. The capsules ate produced by solvent evaporation, polymer-polymer phase separation, or spray-dry encapsulation processes. They release their cote material over a 30 day period in vivo, although not at a constant rate. 

There are a variety of routes currently utilized to fabricate a wide range of hollow capsules of various compositions. Among the more traditional methods are nozzle reactor processes, emnlsion/phase-separation procednres (often combined with sol-gel processing), and sacrificial core techniques [78], Self-assembly is an elegant and attractive approach for the preparation of hollow capsules. Vesicles [79,80], dendrimers [81,82], and block hollow copolymer spheres [83,84] are all examples of self-assembled hollow containers that are promising for the encapsnlation of various materials. 

Hollow and porous polymer capsules of micrometer size have been fabricated by using emulsion polymerization or through interfacial polymerization strategies [79,83-84, 88-90], Micron-size, hollow cross-linked polymer capsules were prepared by suspension polymerization of emulsion droplets with polystyrene dissolved in an aqueous solution of poly(vinyl alcohol) [88], while latex capsules with a multihollow structure were processed by seeded emulsion polymerization [89], Ceramic hollow capsules have also been prepared by emulsion/phase-separation procedures [14,91-96] For example, hollow silica capsules with diameters of 1-100 micrometers were obtained by interfacial reactions conducted in oil/water emulsions [91],... 

The term aqueous phase separation is often more simply described as oil-in-water microencapsulation. The two encapsulation processes described above are examples of this oil-in-water encapsulation. In this process the core material is the oil and it should be immisible in the continuous phase, namely water. A commercial example of aqueous phase separation would be the microencapsulation of an oily flavor such as sour cream with a gelatin wall. These microcapsules would then be dispersed in a dry cake mix. The mechanism of release would be during the moist baking cycle of the cake, moist-heat causing the capsule walls to first swell and then rupture. 

It was found that the nanocapsules are formed in a miniemulsion process by a variety of monomers in the presence of larger amounts of a hydrophobic oil. Hydrophobic oil and monomer form a common miniemulsion before polymerization, whereas the polymer is immiscible with the oil and phase-separates throughout polymerization to form particles with a morphology consisting of a hollow polymer structure surrounding the oil. The differences in the hydro-philicity of the oil and the polymer turned out to be the driving force for the formation of nano capsules. 

Fig. 16 Capsule formation by phase separation, (a) Scheme a solution of monomer and hydrophobic oil (ie/t) is dispersed in an aqueous surfactant solution middle). Phase separation between the growing polymer and the oil occurs, leading to core shell morphology with encapsulated liquid, (b) Nanocapsules with hexadecane by phase separation [35]. (c) Encapsulation of Lucirin TPO [173] and (d) the fragrance 1,2-dimethyl-1-phenyl-butyramide [174]...

Microencapsulation is common in pharmaceutical industry, particularly when sustained release of a medication is required. Ethyl cellulose is a common coating material. Most capsules are formed by solvent evaporation, polymer-polymer phase separation, or fluidized-bed coating process. Common examples of encapsulated drugs include aspirin, acetaminophen, ampidlhn, and potassium chloride. Orally administered capsules serve to conceal an unpleasant taste and reduce gastrointestinal irritation that can be caused by oral unencapsulated drug. 

Phase separation process takes advantage of the phenomenon called polymer- lymer incompatibility. The process utilizes two polymers that are soluble in a common solvent yet do not mix with one another in the solution. The polymers form two separate phases one polymer intended to form the capsnle walls, the other incompatible polymer meant to induce the separation of the two phases, but not meant to be part of the capsule wall material. This process is somewhat related to the complex coacervation process. The phase separation process is considered as the oldest true encapsulation technology first developed by the National Cash Register Company for carbonless copy-paper. Microencapsnlation by coacervation involves the phase separation of one or more hydrocolloids from the initial solntion, and the subseqnent deposition of the newly formed coacervate phase around the active ingredient suspended or mnulsified in the same reaction media. The size of the miCTocapsules formed may be in the range of 10-250 pm. 

Based on phase-separation mechanisms, coacervation systems can be classified into two general types simple coacervation and complex coacervation. When only one polymer is involved, the process is referred to as simple coacervation, and when two or more polymers with opposite charges are involved, it is referred to as complex coacervation. In both cases, the coacervation takes place just before precipitation from solution. This separated phase in the form of amorphous, liquid droplets constituted the coacervate which is the polymer-rich solution. Deposition of this coacervate around the individual insoluble oil droplets or solid particles dispersed in the equilibrium liquid forms the embryonic capsules, and subsequent gelling of the deposited coacervate results in microcapsules. 

Miniemulsion is a special class of emulsion that is stabilized against coalescence by a surfactant and Ostwald ripening by an osmotic pressure agent, or costabilizer. Compared with conventional emulsion polymerization process, the miniemulsion polymerization process allows all types of monomers to be used in the formation of nanoparticles or nanocapsules, including those not miscible with the continuous phase. Each miniemulsion droplet can indeed be treated as a nanoreactor, and the colloidal stability of the miniemulsion ensures a perfect copy from the droplets to the final product. The versatility of polymerization process makes it possible to prepare nanocapsules with various types of core materials, such as hydrophilic or hydrophobic, liquid or solid, organic or inorganic materials. Different techniques can be used to initiate the capsule wall formation, such as radical, ionic polymerization, polyaddition, polycondensation, or phase separation from preformed polymers. 

Irrespective of the technique applied for capsule formation, the resulting morphology delicately depends on thermodynamic and kinetic factors. The polymer used for the shell formation has to be sufficiently insoluble in the core liquid if the solubility is too high, no phase separation can occur and homogenous structures are formed (i.e., particles or gels). If the phase separation cannot proceed smoothly ... 

Coacervation n. The separation of a polymer solution into two or more liquid phases, one of which is a polymer-rich liquid. The term was introduced to distinguish this phenomenon from the precipitation of a polymer solute in solid form. The process is used in microencapsulation by emulsifying or dispersing the material to be encapsulated with a solution of the polymer. By changing the temperature or concentration of the mixture, or by adding another polymer or solvent, a phase separation may be induced and the polymeric portion forms a thin coating on the external surfaces of the particles. After further treatment to solidify the polymeric wall, the capsules can be isolated in powder form by filtration. It is an intermediate stage between sol and gel formation. 

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