Figure Emulsion Multiple

Cosmetic technology is constantly developing raw materials and formulation with active ingredients. The new surfactant molecules, the search for original active substances and efficient combinations, and the design of novel vehicles or carriers has led to the implementation of new cosmetic systems in contrast to the classic forms such as creams or gels.

The achievements of recent extensive research has resulted in the development of controlled delivery systems. Some of these systems have been extensively investigated for their therapeutic potential while simultaneously being examined for their possible cosmetic uses. One objective in the design of novel drug delivery systems is controlled delivery of the active to its site of action at an appropriate rate. Novel polymers and surfactants in different forms, sizes, and shapes can aid in this goal. Encapsulation techniques are used in pharmaceuticals, cosmetics, veterinary application, food, copying systems, laundry products, agricultural uses, pigments, and other less well-known uses to control the delivery of encapsulated agents as well as to protect those agents from environmental degradation.

DESIGN ASPECTS OF A VECTOR J

Microparticles ^

Microencapsulation is a process by which very thin coatings of inert natural or synthetic ^

polymeric materials are deposited around microsized particles of solids or droplets of liquids. Products thus formed are known as microparticles, covering two types of forms: microcapsules, micrometric reservoir systems, and microspheres, micrometric matrix systems (Fig. 1).

Sponge Like Structures Microparticles

Microcapsules Microspheres

Figure 1 Schematic representation of microparticles.

Microcapsules Microspheres

Figure 1 Schematic representation of microparticles.

These systems consist of two major parts. The inner part is the core material containing one or more active ingredients. These active ingredients may be solids, liquids, or gases. The outer part is the coating material that is usually of a high-molecular weight polymer or a combination of such polymers. The coating material can be chosen from a variety of natural and synthetic polymers. The coating material must be nonreactive to the core material, preferably biodegradable, and nontoxic. Other components, such as plasticizers and surfactants, may also be added.

Initially, microparticles were produced mainly in sizes ranging from 5 |m to as much as 2 mm, but around 1980 a second generation of products of much smaller dimensions was developed. This includes nanoparticles from 10 to 1000 nm in diameter [1], as well as 1 to 10 | m microspheres, overlapping in size with nonsolid microstructures such as liposomes. Commercial microparticles typically have a diameter between 1 and 1000 |m and contain 10 to 90 wt% core. Most capsule shell materials are organic polymers, but fat and waxes are also used. Various types of physical structures of the product of microencapsulation such as mononuclear spheres, multinuclear spheres, multi-nuclear irregular particles, and so on can be obtained depending on the manufacturing process.

Recently, a polymeric system consisting of porous microspheres named Micro-sponge has been developed (Microsponge System [2]; Advanced Polymer System Inc., Redwood City, CA). These systems are made by suspension polymerization and typically consist of cross-linked polystyrene or polymethacrylates.

No encapsulation process developed to date is able to produce the full range of capsules desired by potential capsule users. The methods, which are significantly relevant to the production of microparticles used in pharmaceutical products and cosmetics, are shown in Table 1. Many techniques have been proposed for the production of micropar-ticles, and it was suggested [9] that more than 200 methods could be identified in the literature. A thorough description of the formation of microparticles are given by several reviews [4,6,10,11].

Nanoparticles

Nanoparticles can generally be defined as submicron (<1|m) colloidal systems, but are not necessarily made of polymers (biodegradable or not). According to the process used for the preparation of nanoparticles, nanocapsules or nanospheres can be obtained. Nano-capsules are vesicular systems in which the drug is confined to a cavity surrounded by a

Encapsulation to Deliver Topical Actives Table 1 Microencapsulation Methods

Type Reference

Coacervation-phase separation procedures using 3

aqueous vehicles

Coacervation-phase separation procedures using 4

nonaqueous vehicles

Interfacial polymerization 5

In situ polymerization 6

Polymer-polymer incompatibility 3

Spray drying, spray congealing, spray embedding, 4

and spray polymerization

Droplet extrusion 7

unique polymeric membrane; nanospheres are matrix systems in which the drug is dispersed throughout the particles.

Several methods have been developed for preparing nanoparticles. They can be classified in two main categories according to whether the formation of nanoparticles requires a polymerization reaction (Table 2) or whether it is achieved from a macromolecule or a preformed polymer (Table 3). De Vringer and Ronde [25] proposed a water-in-oil (w/o) cream containing nanoparticles of solid paraffin to obtain a topical dermatological product with a high degree of occlusivity combined with attractive cosmetic properties. Kim et al. [26] reported the encapsulation of fat vitamin series in nanospheres prepared with soybean lecithin coated with a nonionic surfactant. Miiller [27,28] believes that the solid lipid nanoparticles (SLN) appear as an attractive carrier system for cosmetic ingredients— unloaded and loaded. In the case of unloaded particles, the SLN themselves represent the active ingredient, e.g., when made from skin-carrying lipids. Alternatively, the SLN can be blended with special lipids, e.g., ceramides. Finally, good reviews with methods of preparation for nanoparticles can be found in the literature, such those by Kreuter [12] and Couvreur et al. [29].

Multiple Emulsions

Multiple emulsions are emulsions in which the dispersion phase contains another dispersion phase. Thus, a water-in-oil-in-water (w/o/w) emulsion is a system in which the globules of water are dispersed in globules of oil, and the oil globules are themselves dispersed

Table 2 Nanoparticles Obtained by Polymerization of a Monomer

Type

Reference

Nanospheres

Poly(methylmethacrylate) and Polyalkyl-

cyanoacrilate nanoparticles Polyalkylcyanoacrylate nanospheres Nanocapsules

Polyalkylcyanoacrylate nanocapsules

Table 3 Nanoparticles Obtained by Dispersion of Preformed Macromolecules

Type

Reference

Nanospheres prepared by emulsification

Solution emulsification

16

Phase inversion

17

Self-emulsification

18

Nanospheres of synthetic polymers

19, 20, 21

Nanospheres of natural polymers

21

Nanospheres prepared by desalvation

Nanospheres of synthetic polymers

22

Nanospheres of natural polymers

23, 24

Nanocapsules

14, 22

in an aqueous environment. A parallel arrangement exists in oil-in-water-in-oil (o/w/o) type of multiple emulsions in which an internal oily phase is dispersed in aqueous globules, which are themselves dispersed within an external oily phase (Fig. 2).

Multiple emulsions, first described by Seifriz in 1925, have recently been studied in detail. The operational technique plays an even more important role in the production of multiple emulsions than in the production of simple emulsions [30-35]. Multiple emulsions have been prepared in two main modes: one-step and two-step emulsification.

One-step emulsification is prepared by forming w/o emulsion with a large excess of relatively hydrophobic emulsifier and a small amount of hydrophilic emulsifier followed by heat treating the emulsion until, at least in part, it will invert. At a proper temperature, and with the right hydrophilic lipophilic balance (HLB) of the emulsifiers, w/o/w emulsion can be found in the system. In most recent studies, multiple emulsions are prepared in a two-step emulsification process by two sets of emulsifiers: a hydrophobic emulsifier I (for the w/o emulsion) and a hydrophilic emulsifier II (for the oil-in-water (o/w) emulsion). The primary emulsion is prepared under high shear conditions (ultrasonification, homoge-nization), whereas the secondary emulsification step is carried out without any severe mixing (an excess of mixing can rupture the drops, resulting in a simple emulsion).

The composition of the multiple emulsions is of significant importance, because the different surfactants along with the nature and concentration of the oil phase will affect the stability of the double emulsion. Parameters such as HLB, oil phase volume, and the

Types Multiple Emulsions

Figure 2 Schematic representation of multiple emulsions.

Figure 2 Schematic representation of multiple emulsions.

nature of the entrapped materials have been discussed and optimized. Several reviews and studies include Florence and Whitehill [36-38], Matsumoto et al. [39,40] and Frenkel [41-43].

Microemulsions

Miocroemulsions are stable dispersions in the form of spherical droplets whose diameter is in the range of 10 to 100 nm. They are composed of oil, water, and usually surfactant and cosurfactant. These systems show structural similarity to micelles and inverse micelles, resulting in o/w or w/o microemulsions, respectively. They are highly dynamic systems showing fluctuating surfaces caused by forming and deforming processes.

The main characteristics of microemulsions are the low viscosity associated with a Newtonian-type flow, a transparent or translucid appearance, and isotropic and thermody-namic stability within a specific temperature setting. Certain microemulsions may thus be obtained without heating, simply by mixing the components as long as they are in a liquid state. One of the conditions for microemulsion formation is a very small, rather than a transient negative, interfacial tension (44). This is rarely achieved by the use of a single surfactant, usually necessitating the addition of a cosurfactant. The presence of a short chain alcohol, e.g., can reduce the interfacial tension from about 10 mN/m to a value less than 10~2mN/m. Exceptions to this rule are provided by nonionic surfactants which, at their phase inversion temperature, also exhibit very low interfacial tensions.

A microemulsion is usually created by the establishment of pseudoternary diagram for which a ratio of surfactant/cosurfactant is fixed, representing a sole constituent. The establishment of a ternary diagram is generally accomplished for locating the microemulsion or the microemulsion zones by titration. Using a specific ratio of surfactant/cosurfac-tant, various combinations of oil and surfactant/cosurfactant are produced. The water is added drop by drop. After the addition of each drop, the mixture is stirred and examined through a crossed polarized filter. The appearance (transparence, opalescence, isotropy) is recorded, along with a number of phases. In this way, an approximate delineation of the boundaries can be obtained in which it is possible to refine through the production of compositions point by point beginning with the four basic components.

Nanoemulsions (Submicron Emulsions)

Emulsions are heterogeneous systems in which one immiscible liquid is dispersed as droplets in another liquid. Such a system is thermodynamically unstable and is kinetically stabilized by the addition of one further component or mixture of components that exhibits emulsifying properties. Depending on the nature of the diverse components of the emulsifying agents, various types of emulsions can result from the mixture of immiscible liquids. The main characteristic of nanoemulsions or submicron emulsions is the droplet size,

which must be inferior to 1| m.

Emulsions prepared by use of conventional apparatus, e.g., electric mixers and mechanical stirrers, show large droplet sizes and wide particle distribution. The techniques usually used to prepare submicron emulsions involve the use of ultrasound, evaporation of solvent (45), two-stage homogenizer [46,47], and the microfluidizer [48,49]. The nano- jjj emulsion preparation process involves the following steps:

1. Three approaches can be used to incorporate the drug and/or the emulsifiers in the aqueous or oil phase. The most common is to dissolve the water-soluble ingredients in the aqueous phase and the oil-soluble ingredients in the oil phase. The second approach, which is used in fat emulsion preparations [46], involves the dissolution of an aqueous-insoluble emulsifier in alcohol, the dispersion of the alcohol solution in water, and the evaporation and total removal of the alcohol until a fine dispersion of the alcohol solution of the emulsifer in the aqueous phase is reached. The third, which is mainly used for amphotericin B incorporation into an emulsion, involves the preparation of a liposome-like dispersion. The drugs and phospholipids are first dissolved in methanol, dichloromethane, chloroform, or a combination of these organic solvents, and then filtered into a round-bottom flask. The drug-phospholipid complex is deposited into a thin film by evaporation of the organic solvent under reduced pressure. After sonica-tion with the aqueous phase, a liposome-like dispersion is formed in the aqueous phase. The filtered oil phase and the aqueous phase are heated separately to 70°C and then combined by magnetic stirring.

2. The oil and aqueous phases are emulsified with a high-shear mixer at 70 to 80°C.

3. The resulting coarse emulsion (1 -5|m) is then rapidly cooled and homogenized into a fine monodispersed emulsion.

Vesicles

Bangham [50] clearly shows that the dispersion of natural phospholipids in aqueous solutions leads to the formation of ''closed vesicles structures,'' which morphologically resemble cells. Since 1975 [51], vesicles have been prepared from surfactants. In 1986, the first commercial product incorporating liposomes identical to those described by Bangham appeared on the market (Capture). At the same time, a synthetic one made by nonionic surfactants [52] was also launched (Niosomes). Several different compositions, for scientific, economic and business reasons, prevailed in cosmetic vesicles. None of them really resembles the liposomes we have seen in medical applications. These main groups include: (1) liposomes made from soya phospholipids; (2) sphingosomes, i.e., liposomes made from sphingolipids, and (3) nonionic surfactant vesicles (niosomes) which are a proprietary product ofL'Oreal and other synthetic amphiphiles. In the 1990s, transfersomes, i.e., lipid vesicles containing large fractions of fatty acids, were introduced. Transfersomes [5355] consist of a mixture of a lipidic agent with a surfactant. Consequently, their bilayers are much more elastic than those of most liposomes.

This chapter focuses on nonionic surfactant vesicles and transfersomes. Nonionic surfactant vesicles (NSVs or niosomes) consist of one or more nonionic surfactant bilayers enclosing an aqueous space. NSVs consisting of one bilayer are designed as small unila-

Table 4 Vesicles Preparation Methods

Method

Reference

Sonication Ether injection Handshaking

Reversed phase evaporation Method as described by Handjani-Vila

mellar vesicles (SUVs) or large unilamellar vesicles (LUVs). Vesicles with more bilayers are called multilamellar vesicles.

Niosomes can be prepared from various classes of nonionic surfactants, e.g., poly-glycerol alkyl ethers [52,56], glucosyl dialkyl ethers [57], crown ethers, and polyoxyeth-ylene alkyl ethers and esters [58]. The preparation methods used should be chosen according to the use of niosomes, because the preparation methods influence the number of bilayers, size, size distribution, entrapment efficiency of the aqueous phase, and membrane permeability of the vesicles [56,59]. NSVs can be formed using the same methods that are used for the preparation of liposomes (Table 4).

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Responses

  • alfreda
    Which polymer used in the preparation of microsponge using amphotericin b?
    7 years ago

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