Pharmaceutical emulsions preparation

Oils used in the preparation of pharmaceutical emulsions are of various chemical types, including simple esters, fixed and volatile oils, hydrocarbons, and turpe-noid derivatives. The oil itself may be the medicament, it may function as a carrier for a drug, or even form part of a mixed emulsifier system as in the case of some fixed oils that contain sufficient free fatty acids. 

The range of surfactant emulsifiers used in pharmaceutical preparations is illustrated in Table 2. Surfactants are manufactured from a variety of natural and synthetic sources and consequently they show considerable batch-to-batch variations in their homologue compositions and in trace impurities from the starting material. For example, batch variations in the number of neutral phospholipids occur in lecithin surfactants and non-ionic polyethylene surfactants show variations in the number of moles of ethylene oxide. The mechanisms by which such batch variations lead to differences in emulsifying properties are now better understood. Although synthetic and semisynthetic surfactants form by far the largest group of emulsifiers studied in the scientific literature and many of them are available commercially, their use in pharmaceutical emulsions is limited by the fact that the majority are toxic (i.e., haemolytic) and irritant to the skin and mucous... 

Emulsions and suspensions are disperse systems that is, a liquid or solid phase is dispersed in an external liquid phase. While emulsions are sometimes formulated from oily drugs or nutrient oils their main function is to provide vehicles for drug delivery in which the drug is dissolved in the oil or water phase. Suspensions, on the other hand, are usually prepared from water-insoluble drugs for delivery orally or by injection, usually intramuscular injection. An increasing number of modern delivery systems are suspensions - of liposomes or of polymer or protein microspheres, nanospheres or dendrimers, hence the need to understand the formulation and stabilization of these systems. Pharmaceutical emulsions and suspensions are in the colloidal state, that is where the particles range from the nanometre size to visible (or coarse) dispersions of several micrometres. 

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. 

The most common emulsions used in dermatological therapy are creams. These are two-phase preparations in which one phase (the dispersed or internal phase) is finely dispersed in the other (the continuous or external phase). The dispersed phase can be either hydrophobic based (oil-in-water creams, O/W) or aqueous based (water-in-oil creams, W/O). Whether a cream is O/W or W/O is dependent on the properties of the system used to stabilize the interface between the phases. Given the fact that there are two incompatible phases in close conjunction, the physical stability of creams is always tenuous, but may be maximised by the judicious selection of an appropriate emulsion stabilizing system. In most pharmaceutical emulsions, stabilizing systems are comprised of either surfactants (ionic and/or non-ionic), polymers (non-ionic polymers, polyelectrolytes or biopolymers) or mixtures of these. The most commonly used surfactant systems are sodium alkyl sulphates (anionic), alkylammonium halides... 

A relatively stable emulsion formulation may be prepared from a simple four component mixture oil, water, surfactant and fatty amphiphile. In practice, however, things are never this straightforward. In addition to the four principle components, a pharmaceutical emulsion... 

Class 10,000 areas are suitable to prepare solutions that shall be sterile but cannot be sterilized in their final containers (referring to that sterile filtration is needed before filling) to prepare solutions of large volume parenterals that can be sterilized in their final containers to prepare, filter, fill and seal solutions of small volume parenterals fc50ml) and eye drops to prepare, filter, fill and seal oral solutions that can not be sterilized by steam sterilization to prepare, fill and seal ointments, creams, suspensions, emulsions that can not be sterilized in their final containers and to purify, dry, and package bulk pharmaceuticals for preparing injections. 

Figure 1 Steps or the dr)- adsoitied emulsion preparation. (Reproduced with permi.

Many pharmaceutical emulsions are semi-solid oil-in-water systems, prepared with mixed emulsifiers [92]. Often combinations of anionic, cationic or non-ionic surfactants with a fatty alcohol are used as the emulsifying system. Emulsifying... 

The O/W stabilizing ability of Tweens and Spans, widely used in the food and pharmaceutical industries, have been studied by a Japanese group [116, 117]. O/W emulsions prepared with Tween 20-Span 80 mixtures were unstable over the whole HLB range possible with these surfactants (4.3 to 16.9) the authors... 

Indeed emulsions are everywhere and find extensive applications in the food, pharmaceutical, and cosmetics industries. Emulsions arc highly complex multicomponent systems containing emulsifiers, foam stabilizers, surfactants, solubilizers, viscosity conditioners and numerous other compounds. About 80% of emulsion preparations in the market are of... 

Larch arabinogalactan is approved in 21 CFR 172.610 as a food additive for use as an emulsifier, stabilizer, binder or bodying agent for essential oils and noimutritive sweeteners, flavor bases, nonstandardized dressings, and pudding mixes. It has also been used in the preparation of cosmetic and pharmaceutical dispersions and as an emulsifier in oil—water emulsions (69). Industrially, the main use has been in Hthography as a gum arabic substitute. 

The development of monoalkyl phosphate as a low skin irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste and liquid-type skin cleansers, and also phosphorylation reactions from the viewpoint of industrial production [26]. Amine salts of acrylate ester polymers, which are physiologically acceptable and useful as surfactants, are prepared by transesterification of alkyl acrylate polymers with 4-morpholinethanol or the alkanolamines and fatty alcohols or alkoxylated alkylphenols, and neutralizing with carboxylic or phosphoric acid. The polymer salt was used as an emulsifying agent for oils and waxes [70]. Preparation of pharmaceutical liposomes with surfactants derived from phosphoric acid is described in [279]. Lipid bilayer vesicles comprise an anionic or zwitterionic surfactant which when dispersed in H20 at a temperature above the phase transition temperature is in a micellar phase and a second lipid which is a single-chain fatty acid, fatty acid ester, or fatty alcohol which is in an emulsion phase, and cholesterol or a derivative. 

This chapter describes the basic principles involved in the development of disperse systems. Emphasis is laid on systems that are of particular pharmaceutical interest, namely, suspensions, emulsions, and colloids. Theoretical concepts, preparation techniques, and methods used to characterize and stabilize disperse systems are presented. The term particle is used in its broadest sense, including gases, liquids, solids, molecules, and aggregates. The reader may find it useful to read this chapter in conjuction with Chapters 8, 12, and 14, since they include some of the most important applications of disperse systems as pharmaceutical dosage forms [1]. 

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