Formulation multiple emulsions

Drug-disposition studies were performed with formulated multiple emulsions to assess stealth behavior. The results suggest that PEG-PC-coated multiple emulsions are superior as prolonged-release and extended blood circulating carriers compared to multiple emulsions bearing either SM or GM. 

The number of the constituent phases of a disperse system can be higher than two. Many commercial multiphase pharmaceutical products cannot be categorized easily and should be classified as complex disperse systems. Examples include various types of multiple emulsions and suspensions in which solid particles are dispersed within an emulsion base. These complexities influence the physicochemical properties of the system, which, in turn, determine the overall characteristics of the dosage forms with which the formulators are concerned. 

In addition to the necessary protection of the contents of the emulsion droplets, effective encapsulation technology requires that the release of the active matter be controlled at a specified rate. Benichou et aL (2004) have demonstrated that a mixture of whey protein isolate (WPI) and xanthan gum can be successfully used for the controlled release of vitamin Bi entrapped within the inner aqueous phase of a multiple emulsion. The release profile, as a function of the pH of the external aqueous phase, is plotted in Figure 7.25. We can observe that the external interface appears more effectively sealed against release of the entrapped vitamin at pH = 2 than at pH = 4 or 7. It was reported that an increase in the protein-to-potysaccharide ratio reduced the release rate at pH = 3.5 (Benichou et aL, 2004). More broadly, the authors suggest that compatible blends of biopolymers (hydrocolloids and proteins) should be considered excellent amphiphilic candidates to serve as release controllers and stability7 enhancers in future formulations of double emulsions. So perhaps mixed compatible biopolymers wall at last allow researchers to... 

There are also personal cleansing products formulated so as to provide certain ingredients that will be left behind on the skin once the cleansing product is washed off. Such (water soluble) ingredients may be formulated into multiple emulsions or liposomes. 

Besides W/O and O/W emulsions there are so-called multiple emulsions of the W/O/W type. These emulsions can be produced in a one-stage modified PIT process [32] or by emulsification of a primary W/O emulsion in an outer water phase. These systems are an approach to protect sensitive active substances such as vitamins or enzymes in a formulation. 

Multiple emulsions can also be formed by mixing an oil-in-water emulsion with a thermodynamically incompatible biopolymer mixture. Depending on the formulation and conditions of preparation, oil-in-water-in-water or mixed oil in water/water-in-water multiple emulsions may be formed. These have potential for the controlled delivery of a range of bioactives (Kim et al. 2006). 

Lipid-based formulations of poorly water soluble drugs offer large versatility for oral administration as they can be formulated as solutions, gels, suspensions, emulsions, self-emulsifying systems, multiple emulsions, microemulsions, liposomes, and solid dispersions. " Administration of a drug in a lipidic vehicle/formu-lation can enhance the absorption and oral bioavailability via a combination of various mechanisms " " that are briefly summarized as follows ... 

In addition to traditional dermal and transdermal delivery formulations, such as creams, ointments, gels, and patches, several other systems have been evaluated. In the pharmaceutical semisolid and liquid formulation area,these include sprays, foams, multiple emulsions, microemulsions, liposomal formulations, transfersomes, niosomes, ethosomes, cyclodextrins, glycospheres, dermal membrane structures, and microsponges. Many of these novel systems use vesicles to modulate drug delivery. Novel transdermal... 

Polyoxyethylene alkyl ethers are nonionic surfactants widely used in topical pharmaceutical formulations and cosmetics, primarily as emulsifying agents for water-in-oil and oil-in-water emulsions and the stabilization of microemulsions and multiple emulsions. 

Sesame oil may be used as a solvent in the preparation of subcutaneous injections, oral capsules, rectal suppositories, and ophthalmic preparations it may also be used in the formulation of suspensions and emulsions. Multiple-emulsion formulations, in which sesame oil was one of the oil phases incorporated, have been investigated as a prolonged-release system for rifampicin microemulsions containing sesame oil have been prepared for the transdermal delivery of ketoprofen. Sesame oil has also been used in the preparation of liniments, pastes, ointments, and soaps. A sesame paste... 

Emulsions - liquid dispersions usually of an oil phase and an aqueous phase - are a traditional pharmaceutical dosage form. Oil-inwater systems have enjoyed a renaissance as vehicles for the delivery of lipid-soluble dmgs (e.g. propofol). Their use as a dosage form necessitates an understanding of the factors governing the formulation and stability of oil-in-water (o/w) and water-in-oil (w/o) emulsions, multiple emulsions (w/o/w or o/w/o) and microemulsions, which occupy a position between swollen micelles and emulsions with very small globule sizes. Photomicrographs of o/w, w/o systems and multiple emulsions are shown in Fig. 7.10. It is also possible to formulate nonaqueous or anhydrous emulsions, that is oil-in-oil systems and even multiple oil-in-oil-in-oil systems. 

Most emulsions, unless very dilute, display hoth plastic and pseudoplastic flow behaviour rather than simple Newtonian flow. The flow properties of fluid emulsions should have little influence on their biological behaviour, although the rheological characteristics of semisolid emulsions may affect their performance. The pourability, spreadability and syringeability of an emulsion will, however, be directly determined by its rheological properties. The high viscosity of w/o emulsions leads to problems with intramuscular administration of injectable formulations. Conversion to a multiple emulsion (w/o/w), in which the external oil phase is replaced by an aqueous phase, leads to a dramatic decrease in viscosity and consequent improved ease of injection. 

The formulation and stability of multiple emulsion systems has recently been reviewed by the present authors (17). 

The presence of liquid crystal structures at both the w-o and o-w interfaces in multiple emulsions has been investigated by Kavaliunas and Frank (31). Microscopic examination of w/o/w emulsions between crossed polarizers revealed the presence of liquid crystal phases at both inner (w-o) and outer (o-w) interfaces in a w/o/w system composed of water, p-xylene and nonylphenol diethylene glycol ether. Liquid crystalline phases were also detected in o/w/o emulsions at both interfaces. The presence of these liquid crystal structures was found to improve the stability of the emulsions markedly. Matsumoto (32, 33) have concluded that the oil layers in w/o/w systems are likely to be composed of or contain,at least in proximity to the aqueous phase,multilamellar layers of the lipophilic surfactant used in the formulation this is postulated in part to explain the rate of volume flux of water through the oily layer. 

Knowledge of surfactant equilibration and interactions will probably lead to improved formulations of multiple emulsions. Failing this the use of polymerisable surfactants can lead to obvious strengthening of interfacial barriers and allow control of stability and drug release. Nonetheless further detailed work on both w/o/w and o/w/o systems is justified. 

This led to the inclusion of two types of particles into the emulsions and the formation of multiple emulsions. For example, hydrophobically modified particles were dispersed in toluene, while hydrophilically modified particles were dispersed in water. Emulsification of this system produced water-in-toluene-in-water or toluene-in-water-in-toluene multiple emulsions. Formulations of one type over the other were achieved... 

Silva Chunha, A. Grossiord, J.L. Seiller, M. The formulations and industrial applications of multiple emulsions an area of fast development. In New Products and Applications in Surfactant Technology, Karsa, D.R., Ed. CRC Press LLC Boca Raton, FL, 1998 Vol. 1, 205-226. 

Several classes of formulations of disperse systems are encountered in the chemical industry, including suspensions, emulsions, suspoemulsions (mixtures of suspensions and emulsions), nanoemulsions, multiple emulsions, microemulsions, latexes, pigment formulations, and ceramics. For the rational preparation of these multiphase systems it is necessary to understand the interaction forces that occur between the particles or droplets. Control of the long-term physical stability of these formulations requires the application of various surfactants and dispersants. It is also necessary to assess and predict the stability of these systems, and this requires the application of various physical techniques. 

Several industrial systems involve emulsions, of which the following are worthy of mention. Food emulsions include mayonnaise, salad creams, deserts, and beverages, while personal care and cosmetics emulsions include hand creams, lotions, hair sprays, and sunscreens. Agrochemical emulsions include self-emulsifiable oils that produce emulsions on dilution with water, emulsion concentrates with water as the continuous phase, and crop oil sprays. Pharmaceutical emulsions include anaesthetics (O/W emulsions), hpid emulsions, and double and multiple emulsions, while paints may involve emulsions of alkyd resins and latex. Some dry-cleaning formulations may contain water droplets emulsified in the dry cleaning oil that is necessary to remove soils and clays, while bitumen emulsions are prepared stable in their containers but coalesce to form a uniform fihn of bitumen when apphed with road chippings. In the oil industry, many crude oils (e.g.. North sea oil) contain water droplets that must be removed by coalescence followed by separation. In oil slick dispersion, the oil spilled from tankers must be emulsified and then separated, while the emulsification of waste oils is an important process for pollution control. 

All of the above processes are influenced by the nature of the two emulsifiers used to prepare the multiple emulsion. Most reports on multiple emulsions are based on conventional nonionic surfactants, but unfortunately most of these surfactant systems produce multiple emulsions with Hmited shelf-Uves, particularly if the system is subjected to large temperature variations. During the past few years, multiple emulsions have been formulated using polymeric surfactants for both the primary and multiple emulsion preparation. These polymeric surfactants proved to be superior over conventional nonionic surfactants in maintaining the physical stability of the multiple emulsion, such that today they may be applied successfully to the formulation of agrochemical multiple emulsions. The results obtained using these polymeric surfactants offer several potential applications in formulations. The key in the latter cases is to use polymeric surfactants that are approved by the FDA for pharmacy and food, by the CTA for cosmetics, and by the EPA for agrochemicals. 

In this chapter, the formulation of multiple emulsions with particular reference... 

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