Multiple-phase oil-in-water emulsions

j. Soc. Cosmet. Chem., 41, 1-22 (January/February 1990)

Multiple-phase oil-in-water emulsions

GILLIAN M. ECCLESTON, Department of Pharmacy, University of Strathclyde, Glasgow GI IXW, Scotland, U.K.

Received November 8, 1989. Presented at the Annual Meeting of the Society of Cosmetic Chemists, New York, December 1989.

Synopsis

Cosmetic oil-in-water emulsions such as lotions and creams are complex multiple-phase systems. In their preparation, combinations of fatty amphiphiles (glyceryl monoesters or fatty alcohols) and ionic or nonionic surfactants are widely used. The mixed emulsifier combinations interact in the aqueous continuous phases to form lameliar or crystalline structures. These both stabilise and sometimes control the consistencies of emulsions between wide limits. There is, however, confusion as to the type of lameliar phase that forms in a specific emulsion. The majority of the literature fails to distinguish between the lamellar liquid crystalline state and the equally important lamellar gel state. Although liquid crystalline phases form in many emulsions at the high temperatures of manufacture, these often convert to gel phases when the emulsion cools so that the properties of this phase dominate the emulsion.

In this article the structures and swelling properties of the different lameliar phases that occur in emulsions are discussed, as well as the formation of other crystalline phases. Attention is given to the conditions over which each type of phase forms and, in particular, the relevance of the gel-liquid crystalline transition temperature to emulsions. It will be shown how the behaviour of many complex emulsions during manufacture, storage, and use can be related to the component phases.

INTRODUCTION

Most of the literature published about emulsions is based on attempts to apply classical theories of colloid stability to well characterised "model" systems. These are invariably dilute, monodispersed, two-phase oil-and-water emulsions stabilised by a single surfactant emulsifier. The surfactant forms a monomolecular film at the oil-water interface

where it introduces additional repulsive (e.g., electrostatic, steric, or hydrational) forces that provide an energy barrier to droplet coalescence.

Cosmetic and pharmaceutical emulsions such as lotions and creams are rarely such simple two-phase preparations. They are more likely to be complex polydispersed systems containing several surfactant and amphiphilic emulsifiers and to be composed of additional phases to oil-and-water. The additional phases generally form in aqueous systems when the emulsifier, in excess of that required to form a monomolecular film, interacts with continuous-phase water. Thus investigation into the phase behaviour of emulsifiers and their mixtures in water provides valuable information about the microstructures of emulsions prepared with them.

2 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

There is now substantial evidence that the formation of specific lamellar phases that are capable of incorporating large quantities of water is an essential requirement for the stability of many commercial emulsions. Such phases can also impart the required rheological properties (for example, ranging from mobile lotions to thick semisolid creams) to some products (1-3). However, there is much confusion as to the type of lameliar phase that forms in a specific emulsion. Most of the literature concentrates on the formation of liquid crystalline phases and fails to identify the equally important gel phases, even though each phase imparts totally different properties to emulsions containing them. It is not always appreciated that the lameliar liquid crystalline state is rarely dominant in cosmetic emulsions containing long-chain alcohols, acids, or monoglycerides as co-emulsifiers. The commercial literature contains many articles that incorrectly discuss the presence of bilayer liquid crystalline phases in emulsions that are actually composed mainly of gel phases.

In this paper, the microstructures and properties of multiple-phase oil-in-water emulsions of cosmetic use (in particular dermatological) will be described. Particular attention will be given to the various lameliar liquid crystalline and gel phases as well as to other crystalline phases that occur in such emulsions. It will be shown how the behaviour of many real emulsions during manufacture, storage, and use (i.e., after application to the skin) can be related to their component phases.

STRUCTURE OF LAMELLAR LIQUID CRYSTALLINE AND GEL PHASES

Lamellar phases in which surfactant molecules are arranged in bilayers separated by layers of water are formed in water by a range of surface-active materials under specific conditions. The hydrocarbon chains of the bilayers can exist in a number of physical states (4,5), the most relevant to emulsions being the so-called ordered, or gel, and disordered, or liquid crystalline, states (Figure 1). In the gel state the hydrocarbon chains are packed in a hexagonal subcell with rotational motion about the long axes, whereas in the liquid crystalline state they are disordered and liquid-like. The order- disorder transition, Tc, is essentially the melting of the hydrocarbon chains without any loss of long-range stacked bilayer structure. The transition occurs at a characteristic temperature, influenced primarily by the characteristics of the hydrophobic portion of the surfactant. Transition temperatures increase with increasing acyl chain length and decrease when unsaturated or branched chains are present.

Such bilayer states are of interest in several scientific areas, and consequently a con- fusing number of different nomenclatures are used to describe them. The lameliar liquid crystalline phases that occur above the phase transition temperature have been called neat, G, or L= phase. Bilayer gel phases that occur below the transition temperature are also referred to as c•-crystalline gel or L• phase (4), and the transition temperature as the chain melting temperature, CMT, or the penetration temperature, Tpen (1). The designation L, i.e., lameliar, with the subscript c•- for the disordered liquid crystalline phase and the subscript [3- for the more rigid gel phase, is not entirely satisfac- tory. Confusion can arise because identical Greek letters c•- and [3- are used to describe crystalline polymorphs of some amphiphilic emulsifiers, including the fatty alcohols. In this paper the ordered and disordered states will be described simply as gel and liquid crystalline phases. Several other types of gel phase have been reported in the general

OIL-IN-WATER EMULSIONS 3

//

WAT E R

Below Above --

T½ • Tc WATER

GEL LIQUID CRYSTAL

Figure l. The order-disorder transition, T o and the lameliar gel and liquid crystalline phases that form spontaneously when a natural surfactant (polar lipid) is dispersed in water.

literature about surfactants (for example, the tilted L•' gel phases or inderdigited monolayer phases (4-6)), but these have not been reported in emulsions.

Both the gel and liquid crystalline states formed by bi-alkyl lipids (Figure 1) are well known to biological scientists, as they represent the fundamental structure of most animal cell membranes and are also an important structural element in the barrier function of the stratum corneum (7). Many polar lipids such as the lecithins are natural surfactants with a hydrophobic portion composed of two hydrocarbon chains of different lengths and degrees of unsaturation. In cell membranes these are finely balanced to give the required levels of order and disorder, and the transition temperature is close to physiological temperature. Small changes of temperature, pressure, or other biological stimuli can locally fluidise or crystallise the membrane to make it more or less perme- able. In the skin the long hydrocarbon chains and high transition temperatures of the stratum corneum lipids imply that the normal organisation of this barrier is the gel state.

There is less information about these states in the emulsion literature, although both natural and synthetic emulsifiers often form liquid crystalline and gel phases in water


over the range of temperatures relevant to the manufacture and storage of emulsions. The rest of this paper will describe the importance of these phases in emulsion tech- nology.

EMULSIFIERS USED IN MULTIPHASE EMULSIONS

Most commercial emulsions contain mixtures of emulsifiers formed from combinations

of fatty amphiphiles and surfactants. Mixtures of sparingly soluble long-chain alcohols or glyceryl esters, such as glyceryl stearate (G.M.S.) with more soluble ionic or nonionic surfactants, are well known in cosmetic science. The emulsifier components are either added separately during the manufacture of the emulsion by dispersing the surfactant in water and the amphiphile in the oil with the aid of gentle heat, or, alternatively, they are added combined as a previously blended emulsifying wax. A selection of commonly used surfactants, amphiphiles, and emulsifying waxes is included in Table I. The surfactants, which alone are capable of stabilising simple oil-in-water emulsions, are generally referred to as the primary emulsifier, and the fatty amphiphiles, which are too lipophilic to promote oil-in-water emulsions, as the secondary, auxiliary, or co- emulsifier. It will be shown that this terminology is misleading, for the fatty amphiphile is usually the dominant or primary emulsifier in such mixtures.

INTERACTION OF EMULSIFIERS IN WATER

EMULSIFIER COMPONENTS

Surfactants. Polar lipids such as the soybean lecithins are sometimes used in preference to synthetic surfactants in dermatological emulsions, as they are considered less harmful to the skin. Lecithins from this source are usually composed of homologue admixtures of unsaturated C•6-C18 acids and may have gel-liquid crystalline transition temperatures as low as -22 ø (8). This means that although theoretically they can form gel phases, liquid crystals are present in most of the aqueous solutions studied.

Table I

Selection of Commonly Used Amphiphiles, Surfactants, and Emulsifying Waxes

Amphiphiles Surfactants

Cetearyl alcohol Triethanolamine stearate Cetyl alcohol Sodium lauryl sulphate Stearyl alcohol Cetrimonium bromide Glycerol stearate Ceteth 20 Stearic acid Lecithin

Cholesterol PEG-20 stearate

Emulsifying Waxes Components

Emulsifying wax U.S.N.F. Cationic emulsifying wax B.P.C. Glyceryl stearate, S.E. Cetomacrogol emulsifying wax B.P.C.

Cetearyl alcohol, polysorbate Cetearyl alcohol, cetrimonium bromide Glyceryl stearate, soap Cetearyl alcohol, ceteth 20


In contrast, synthetic surfactant emulsifiers do not form bilayer gel phases, although liquid crystalline phases are common. The chemical structures of synthetic surfactants in general are much simpler than those of the natural lipids, as most have only one hydrocarbon chain, containing 12-18 carbon atoms. In water, as the surfactant concentration is increased, a variety of structures, including the bilayer neat phase, can form (Figure 2a). In the neat phase, the hydrocarbon chains are in the disordered or liquid crystalline state, similar to that described above for lipids above the phase transition temperature. The thickness of the water layers is limited because excess water induces a phase transition to a miceliar solution. On cooling the neat phase to below the transition temperature, the surfactant crystallises out (Figure 2a).

Fatty amphiphiles. Fatty amphiphiles such as long-chain alcohols, acids, and monoglycerides and pure saturated synthesised lecithins are too lipophilic to form bilayer phases in water, although they do exhibit marked crystalline polymorphism. For example, pure long-chain alcohols show at leat three solid modifications. The high-temperature o•-form separates first from the melt and is stable over a narrow temperature range. In this form the' hexagonally packed hydrocarbon chains are fully extended in the trans- conformation and there is rotational motion about the long axis of the molecule (cf. L• phase described above). At lower temperatures the [3 and 'y forms, where the hydrocarbon chains are non-rotating ([3-form) or tilted ('y-form), can co-exist, although the [3-form is usually in excess. The o•-[3 (or 'y-) transition temperature is lowered in the homologue admixtures such as cetearyl alcohol and in the presence of water, where the crystals often show limited swelling (9-11). These hydrated crystals (Figure 2b) are not usually referred to as gel phase, for their swelling is limited by the considerable strength of the van der Waals attractive forces between the lipid layers that balance osmotic repulsions. They are sometimes called "coagel"phase when dispersed as microcrystals in water.

MIXTURES OF SURFACTANTS AND AMPHIPHILES

It is emphasised above that gel phases do not form when either surfactants or fatty amphiphiles alone are dispersed in water. However, under certain conditions (for example, in the presence of charged groups), the limited swelling of the fatty amphiphiles described above can be increased markedly to give gel phases. When heated to above the hydrocarbon chain melting temperature, the gel phase transforms to swollen lameliar liquid crystalline phase (Figure 2c).

The charge may arise from ionisable polar groups in the amphiphile itself. This is the case with neutralised monoglyceride emulsifiers, where neutralisation of free fatty acids normally present in the crude source material introduces small quantities of ionic surfactant (12-14). Alternatively, the charge can arise from the addition of an ionic surfactant, as in some fatty alcohol emulsifying waxes and the glyceryl monoester self- emulsifying waxes. Gel phases also form with fatty alcohols in the presence of small quantities of nonionic surfactant.

Both the gel and liquid crystalline phases formed from these mixtures can swell to incorporate significant quantities of water in the interlamellar space. This distinguishes them from the "neat" liquid crystalline phases described above, where excess water will induce a phase transition. The swelling that occurs in the presence of charged groups is electrostatic and in some systems is so extensive at high water concentrations that it is


(a)

liquid crystal

i Above T c Tc

Below T c

Soap crystal

(b)

molten state

Above T c

I,c Below Tc

hydrated crystal

(c)

Water

swollen liquid crystal

'IT• bøve Tc Below T c

Water

swollen gel phase

Figure 2. Summary of the aqueous phases that form below and above the hydrocarbon chain-melting temperature for mixed emulsifiers and their components. (a) hydrophilic surfactant: soap crystals below and liquid crystals above the transition temperature. (b) fatty amphiphile: hydrated crystals below and the melt above the transition temperature. (c) fatty amphiphile combined with small quantities of surfactant: swollen gel phases below and swollen liquid crystalline phases above the transition temperature.

described as "infinite." Gel phases that form in the presence of nonionic surfactants are a result of hydration mechanisms. The significance of lamellar phase swelling to emulsion stability will be discussed in more detail with specific examples below.


EMULSIONS STABILISED BY LIQUID CRYSTALLINE PHASES

Liquid crystals form in the continuous phases of emulsions containing single-surfactant emulsifiers and various nonionic surfactant mixtures. They also form in emulsions prepared with commercial lecithins, and with mixtures composed of surfactants combined with medium-chain (less than C•2) alcohols where the liquid crystalline-gel transition temperatures are below the storage and testing temperatures of the emulsions. Such medium-chain alcohols are not used as bodying agents because of their low transition temperatures.

The reasons for the increased emulsion stability in the presence of liquid crystalline phases are not fully understood. Friberg and his school (15-16) relate this phenomenon to the equilibrium conditions in ternary phase diagrams. They showed that stable emulsions are produced in the regions of the phase diagram where the oil, water, and lameliar liquid crystal (Lb) phase are in equilibrium. They suggest that multilayers of liquid crystals form around the oil droplets (Figure 3) that protect the disperse phase from coalescence by two major mechanisms: first, the reduction of the van der Waals forces of attraction between oil droplets to a very low value, and second, the retardation of the film-thinning process during coalescence due to the increased "viscosity" of the liquid crystalline phase.

Rydhag and co-workers (17-18) demonstrated that emulsion stability is further enhanced when the liquid crystalline multilayers are extensively swollen with water. With phospholipid emulsifiers, the swelling is controlled by the number of dissociated ionic groups and can be enhanced further by the addition of ionic surfactant. Batch variations in the amounts of negatively charged lipids contained in commercial lecithins can lead to differing emulsifying powers because of the variations in swelling properties of the resultant liquid crystalline multilayers.

Liquid crystalline phases also form in emulsions containing long-chain fatty alcohols during the high temperatures of manufacture. These are of a transient nature, for they convert to gel phases as the emulsions cool, and will be discussed in the next section.

EMULSIONS STABILISED BY GEL PHASES

The gel-liquid crystalline transition temperatures of many amphiphile/surfactant combinations are above ambient, so that liquid crystalline phases occur only during the high temperatures of preparation. On cooling, gel phases form, which are responsible for the structure and stabilities of many "bodied" oil-in-water emulsions.

THE GEL NETWORK THEORY OF EMULSION STABILITY

The gel network theory of emulsion stability gives a coherent explanation for the manner in which fatty amphiphiles and surfactants combined as mixed emulsifiers not only stabilise multiphase oil-in-water lotions and creams but also control their consistencies. Although most of the early work was performed using long-chain (i.e., C16-C18) fatty alcohols, the theory is general, and the same broad principles apply whichever amphiphile or surfactant (ionic or nonionic) is used. The theory relates the stabilities and physicochemical properties of multiphase oil-in-water emulsions to the presence or absence of viscoelastic gel networks in their continuous phases. The network


Figure 3. Schematic diagram of an emulsion droplet stabilised by multilayers of lamellar liquid crystals.

phases form when the fatty amphiphile and surfactant, in excess of that required to form a mixed monomolecular film at the oil-water interface, interact with water. Thus the properties and phase behaviour of mixed emulsifiers and their component surfactants in water both above and below T o as well as the corresponding emulsions, are often investigated in parallel. Equilibrated emulsifier/water ternary systems containing concentrations of mixed emulsifier similar to those used to stabilise emulsions have proved useful as structural "models" for the continuous phases of the emulsions (Table II). Data used to develop the gel network theory, including evaluation of the viscoelastic properties of ternary systems and emulsions, are summarised in reviews (1,2).

MICROSTRUCTURE OF THE GEL NETWORK PHASE

The fine structure of the ternary viscoelastic continuous phase is complex. Recent high- and low-angle x-ray diffraction studies (sometimes using a powerful synchrotron radiation source), together with light and electron microscopy, have confirmed unequivo-


Table II

Composition of Emulsions and Corresponding Ternary Systems

Emulsion Ternary system

Liquid paraffin 100 -- g Water 300 300 g Fatty amphiphile

(cetearyl alcohol) Varied 7-57 Varied 7-57 g Surfactant

(ionic or nonionic) Varied 0.8-6.4 Varied 0.8-6.4 g

cably that complex crystalline gel phases are a major component of emulsions stabilised by combinations of fatty alcohols and ionic or nonionic surfactants (19-21).

Figure 4 shows a schematic diagram of a typical o/w emulsion stabilised in this manner. At least four phases can be identified:

1. Dispersed oil phase 2. Crystalline gel phase composed of bilayers of surfactant and amphiphile separated by

"thick" layers of water 3. Crystalline hydrates of amphiphile 4. Pockets of bulk "free water"

The oil droplets are surrounded by multilayers of gel phase that become more randomly oriented as they progress further into the continuous phase. The gel phase can exist in equilibrium with crystalline regions and pockets of bulk water. The oil droplets are

Surface of

Oil Droplet Interlamellar Water

GEL PHASE

Figure 4. Schematic diagram of a typical multiple-phase oil-in-water cream to illustrate the composition of the viscoelastic continuous phase (redrawn from ref. 19).


essentially immobilised in the structured continuous phase, and both flocculation and coalescence on storage are inhibited. These emulsions are more stable than those containing liquid crystals described above because of the large amounts of incorporated water and the substantial mechanical strength of the crystalline chains. It is interesting to note that in these multiple-phase emulsions the forces of repulsion (electrostatic or hydrational) between the bilayers, rather than similar forces on the surface of the oil droplets, are responsible for preventing the close approach of droplets.

These crystalline and swollen gel phases can be identified microscopically. In model mixed emulsifier/water ternary systems, crystalline masses of alcohol appear to form a focus for various bilayer structures (vesicles) of heterogeneous composition, size and complexity. In emulsions, the gel phase bilayers are focused as a rigid matrix around oil droplets (Figure 5).

More detailed analysis of the viscoelastic phases has been obtained from x-ray investi- gations of both emulsions and emulsifier/water systems using a synchrotron radiation source (20). The progressive swelling properties in water (0-94%) of a series of emulsifying waxes composed of cetearyl alcohol combined with either ionic (cetrimonium bromide) or nonionic (ceteth 20) surfactants are shown in Figures 6 and 7a. They dem- onstrate that different swelling mechanisms are involved in gel phase formation with each type of surfactant.

Cetrimide emulsifying wax exhibits the phenomenal swelling observed with some charged lipids (14); the lameliar spacing that incorporoates the interlamellar water increases from 75• at 28% water to approximately 500A at 93% water (model continuous phase). The hydrocarbon bilayer distance (-50•) does not change markedly as the water content increases (Figure 6). In contrast, there is comparatively limited incorporation of water between the bilayers of the alcohol in the presence of nonionic surfactant. The water thicknesses of gel phase vary from approximately 75• at 10% w/w water to approximately ! 10• for 84% water (Figure 7). Both types of system show phase separation at high water concentrations.

The x-ray data confirmed that swollen gel phase of similar bilayer thicknesses was present in significant amounts in emulsions containing these mixtures. The infinite swelling with ionic surfactants is essentially electrostatic in nature. Charged groups at the surface of the bilayers significantly increase the forces of repulsion between the bilayers. In the presence of nonionic surfactant, the swelling is due to hydration of the polyoxyethylene chains of the interpositioned surfactant that are orientated and extended into the interlamellar water layer (Figure 7b). Stabilisation of the nonionic gel phase is essentially by steric repulsions (22).

FORMATION OF THE GEL NETWORK PHASE

Emulsions are manufactured by mixing the molten components and then cooling to the storage temperature. At the high temperatures of manufacture, the emulsion formed by homogenisation is stabilised by an adsorbed monomolecular film at the oil droplet/ water interface. During the cooling process, fatty amphiphile becomes progressively less soluble in the oil and diffuses from this phase into the aqueous miceliar environment to form either spherical mixed micelies or lameliar liquid crystals that will further stabilise the emulsion. A small portion of the oil is also solubilised. When the temperature falls below the transition temperature, which is between 40 ø and 50øC for most fatty


Figure 5. Photomicrographs of (a) a cetearyl alcohol/cetrimonium bromide/water ternary system (93% water) and (b) a diluted semisolid liquid paraffin-in-water emulsion stabilised by cetearyl alcohol and cetrimonium bromide.


6OO

30O

0 I I I I I 20 40 60 80 100

OloWater (w/w) Figure 6. Low angle x-ray diffraction (synchrorron radiation source) of the swelling of an ionic cetearyl alcohol/cetrimonium bromide emulsifying wax in water (20).

alcohol/surfactant systems, the liquid crystals convert to the gel phase and any unreacted alcohol precipitates to give the complex viscoelastic gel networks. If the gel phase is thermodynamically stable, then further interaction between unreacted crystalline alcohol and surfactant solution may occur on storage, with the formation of additional gel phase.

SETTING TEMPERATURE

The transition temperature is sometimes referred to as the "setting temperature," as many commercial emulsions, especially those containing ionic emulsifying waxes, change from milky fluids to thick semisolids at this temperature during the manufacturing process.

INFLUENCE OF PROCESSING VARIABLES, STORAGE, AND USE

Differences in manufacturing techniques such as the rate of the heating or cooling cycle and the extent and order of mixing can cause variations in the consistencies and rheol- ogy of the final product, as can batch variations of either emulsifier component. Many of these phenomena can be directly related to the formation and microstructures of the phases described above. Of particular relevance to the properties of real emulsions are the mechanisms of formation and the stability of the gel phase, the thickness of the


z

200

160

120

40

I i i I

20 40 60 8O 100

• WATER (W/W)

Figure 7a. Low angle x-ray diffraction (synchrotron radiation source) of the swelling of a nonionic cetearyl alcohol/ceteth 20 emulsifying wax in water (20).

•i(-7' "-Z-Z-7 '-Z-Z-Z-Z-Z%Z-Z-Z-' .... -Z-Z-Z-'

50A Interlamellar distance Bilayer L

I I

120-170 A

Figure 7b. Schematic diagram of the gel phase formed from cetearyl alcohol and nonionic polyoxyethylene surfactant (ceteth 20).


interlamellar water layers, and the relative amounts of the crystalline, gel, and water phases.

CONSISTENCY CHANGES ON STORAGE

Emulsions prepared with fatty alcohols and ionic surfactants reach their final consistencies within hours of manufacture. This is because interaction to form both liquid crystals above the transition temperature and gel phase below the transition temperature is rapid. Phase equilibrium is reached soon after preparation so that there are relatively minor microstructural changes on extended storage. In contrast, systems prepared with fatty alcohols and nonionic surfactants often gel up considerably on extended storage (Figure 8a), and this may result in a cosmetically unacceptable product.

Structural build-up occurs in nonionic emulsions because significant amounts of gel phase form below the transition temperature on storage after manufacture (23). A very complex phase situation is envisaged during the preparation of such emulsions because hydration of the polyoxyethylene (POE) chains is limited at high temperature but increases progressively as the emulsion cools. Above the transition temperature, large masses of molten surfactant and alcohol are present in addition to liquid crystals. In these, the hydrocarbon chains of the surfactant are dispersed among those of the alcohol, and clusters of POE groups are present both at the surfaces and within the masses. As systems cool, the POE groups become more soluble and, if hydration forces are strong enough, lamellar liquid crystals separate. When the transition temperature is reached, the liquid crystals transform to gel phase and the unreacted emulsifier precipitates as crystalline masses. The partially interacted masses of alcohol and surfactant are often visible microscopically in freshly prepared formulations (Figure 8b). On storage, aqueous surfactant continues to penetrate the crystalline mases, which disappear as additional gel phase forms. As this involves the incorporation of significant quantities of water, there are marked consistency increases. The structure builds up relatively slowly because the crystalline nature of the hydrocarbon chains limits both the rate of penetration by water and the subsequent rearrangement into swollen bilayers.

PROCESSING VARIABLES

It is well known that processing variables affect the structure and properties of emulsions. However, these effects are not dramatic with fatty alcohols combined with ionic surfactants. Differences in consistencies of oil-in-water creams prepared with cetearyl alcohol and an ionic surfactant (cetrimonium bromide) were shown to be due to variations in size of the crystalline hydrates rather than to variations in the gel phase structure (24).

In contrast, preparation techniques, in particular cooling rates and mixing procedures, have a marked effect on initial and final consistencies of emulsions prepared with fatty alcohols and nonionic surfactants. For example, "shock" cooling and limited mixing produces initially very mobile systems, whereas slow cooling with adequate mixing produces semisolid emulsions (25). These variations in rheological properties are also related to the mechanisms by which nonionic gel phases form. Little gel phase is present initially in the system after shock cooling. Mixing time, when the emulsifiers are in the molten state, influences the distribution of surfactant within the molten masses and bilayers and the relative lamellar order within the system.


1671 Initial l'5hr 8hr

-1 24hr

•/•"• 32•80

I

1640

I

328O

Shear Stress (dyne cm -2)

Figure 8. Emulsion prepared with cetearyl alcohol and ceteth 20: (a) flow curves for the emulsions aged for the stated times; (b) photomicrograph of the freshly prepared emulsion.


The situation is more complex when fatty acids are used as the amphiphile. Gel phases formed with stearic acid are metastable and convert to coagel phases (microcrystals and water) when mixed at high shear rates. Thus a semisolid product results if mixing is discontinued at the transition (i.e., setting) temperature and the emulsion is allowed to cool undisturbed. A more mobile emulsion is formed if it is mixed below the transition

temperature, as considerable mobile coagel phase develops.

BATCH VARIATIONS OF EMULSIFIERS

Batch variations in the emulsifier components as well as in the mixed emulsifier composition can influence the microstructure and properties of emulsions.

Fatty alcohols. Homologue composition of fatty alcohols markedly influences the quality and properties of lotions and creams prepared with them and may be the cause of unexpected instabilities in established formulations (26-28). For example, emulsions prepared with pure alcohols and ionic surfactants, although semisolid initially and of a relatively high consistency, break down on storage to form mobile liquids. These changes occur because the gel phase formed by pure amphiphiles after the heating and cooling cycle of manufacture is metastable at low temperatures. On storage the interlamellar water gradually reduces to more stable [3- and %forms, accompanied by poly- morphic phase transitions, possibly from the u-crystalline configuration. As the networks entrapping the oil droplets disintegrate, emulsions thin, and the lamellar structures visible microscopically in emulsions disappear and are replaced by crystals (cf. Figures 9b and 5b). Concurrently, in DSC a low-temperature endotherm representing network crystallization develops and increases in intensity (Figure 9).

These differences between the abilities of pure and mixed homologue amphiphiles to form stable gel phases have caused much confusion in the past. In early work the gel network phase was called "frozen liquid crystalline" phase because it was thought to be a metastable state that formed on cooling lamellar liquid crystalline phases to below their chain-melting temperatures. More recent information indicated that this terminology was misleading, as it is now known that metastable gel phases form only with pure homologue amphiphiles. With mixed homologues such as cetearyl alcohol, thermodynamically stable gel phases can form spontaneously at low temperature without a prior heating and cooling cycle. In fact, emulsions can be prepared at room temperature using solid micronised cetearyl alcohol, although the extensive mixing required and the resultant aeration of the product do not make this a commercially viable method of preparation. (2).

Surfactants. The homologue composition of the ionic surfactant does not markedly influence consistency, probably because it is present in small amounts and its function is essentially to provide charged groups. With nonionic surfactants, batch variations in the lengths of the POE chains can influence consistency. If longer POE chains are used, more water is trapped interlamellarly, and hence consistencies are higher (23).

Ratio ofsurfactant to fatty alcohol. Traditionally, commercial emulsifying waxes and those of the various pharmacopoeas contain a large excess of alcohol. For example, the official waxes of the British Pharmacopoea contain ! part by weight of surfactant to 9 (ionic) or 4 (nonionic) parts of cetearyl alcohol, representing approximate molar ratios of 1:9 and 1:20, respectively. Although these ratios are not critical, for gel phase can form with as


Cetyl Alcohol Emulsion

Exo

Endo

I mv/cm

I day

7 days

-- 10 days

I ,,I, I 1 20 4'0 60 80 100

ø C

Figure 9. Emulsion prepared with cetrimonium bromide and pure cetyl alcohol: (a) differential scanning calorimetry as emulsion ages; (b) emulsion after six months aging showing platy crystals.


Exo

1:10

1:20

1:30

1:60

1:120 __

,,,

Endo

I I I t 50 6•0 70

TEMPERATURE (øC) Figure 10. Differential scanning calorimetry scans of aged ternary ceteth 20/cetearyl alcohol/water systems. The numbers are the molar ratios of surfactant to alcohol (29).

little as 1 mole % surfactant, there does appear to be a definite range of surfactant concentrations over which the ternary viscoelastic gel network phases form. Within the range, the relative proportions of the gel, crystalline, and bulk water phases change as surfactant concentration alters.


The effect of surfactant concentration in a ceteth 20/cetearyl alcohol/water ternary system was investigated recently (29). At surfactant concentrations greater than t0 mole % (l:t0), there is little crystalline phase and the system is translucent. As the surfactant concentration reduces, the crystalline phases become more prominent and the gel phases reduces, until at a molar ratio of 1:120 little gel phase is present. The changes in the relative proportions of the phases were followed by DSC where the low-temperature crystalline endotherm develops and the high-temperature gel endotherm diminishes as surfactant concentration increases (Figure t0). With high surfactant concentrations (greater than approximately 30 mole %), the gel networks convert to an isotropic phase and systems are mobile.

4'0-

3.0

o

>

.> 2.0

1'0

' 2'5 3'5 I •' 5 •5 6'0 ' Temperature (øC)

Figure 11. Variation of apparent relative viscosity with temperature for a cetearyl alcohol/cetrimonium bromide emulsi•ing wax in 94% water and a liquid paraffin-in-water emulsion prepared with the same wax (1).


I

I: I i i • o ao •o

Time {min)

i I

70 90 s(iA)

Figure 12. Correlation between (a) the weight of water evaporated from a ternary cetearyl alcohol/cetrimonium bromide/water system and (b) the changes in the low angle x-ray diffraction pattern of this system during evaporation. Each frame represents a two-minute collection period (31).

ACCELERATED STABILITY

A common method of assessing the physical stability of emulsions is to subject them to adverse storage conditions, including extreme variations in temperature (30). Attempts are then made to correlate stability at an elevated temperature with that at room temperature over a much longer time scale. Such data can, however, be misleading in emulsions stabilised by gel phases if the testing temperature is above the phase transition temperature (unless, of course, such temperatures are relevant to normal storage and use). Figure 11 shows the effect on rheological properties of heating an ionic ternary system and emulsion to above the transition temperature. Consistency increases with increase in temperature up to the transition temperature, possibly because of increased incorporation of water between the bilayers, and then rapidly decreases above T c as the systems become mobile. The information gained at temperatures above the transition temperature is thus of limited usefulness in the evaluation of instabilities that might occur on extended storage at lower temperatures.

MICROSTRUCTURAL CHANGES DURING USE

So far the bulk microstructural properties of complex multiphase emulsions have been considered. However, when an aqueous emulsion such as a "bodied" lotion or cream is applied to the skin as a thin film, its composition will change as a result of the shearing forces of application, the penetration of skin secretions into, or the evaporation of water and volatile solvents out of the film. In recent work, the microstructural changes that occur when thin layers of o/w emulsions and their corresponding ternary systems evaporate were followed by simultaneous evaporation and x-ray diffraction measure- ments (Figure 12). The evaporation process proceeded in three distinct stages: an initial rapid stage where approximately 25 % of the bulk water was lost and there was little change in interlamellar distance; a second stage where a further 15 % of the water was released and the first order diffraction patterns moved to shorter interlamellar distances, implying some loss of interlamellar water; and the final very slow stage where only interlamellar water is lost and diffraction peaks move to shorter distances. Evaporation


under controlled conditions was not complete after 90 minutes, and the microstructural changes were kinetically driven.

REFERENCES

(1) G. M. Eccleston, "Properties of Materials Used in Semi-Solid Formulations," in Materials Used in Pharmaceutical Formulation, Critical Reports on Applied Chemistry, A. T. Florence, Ed. (Blackwell Scien- tific Publications, London, 1984), Vol. 6, pp. 124-156.

(2) G. M. Eccleston, The microstructure of semisolid creams, Pharmacy International, 7, 63-70 (1986). (3) G. M. Eccleston, Application of emulsion stability theories to mobile and semisolid o/w emulsions,

Cosmet. Toiletr. 101, 73-92 (1986). (4) G. J. T. Tiddy, Surfactant-water liquid crystal phases, Physics Reports, 57, 1-46 (1980). (5) P. J. Quin and D. Chapman, Membrane lipids, Crit. Reviews Blochem., 8, 1-101 (1980). (6) C. D. Adam, J. A. Durrant, M. R. Lowry, and G. J. T. Tiddy, Gel and liquid crystal phase struc-

tures of the trioxyethylene glycol monohexadecyl ether/water system, J. Chem. Soc., Faraday Trans., 80, 789-801 (1984).

(7) W. Curatolo, The lipoidal permeability barriers of the skin and alimentary tract, Pharmaceut. Res., 4, 271-277 (1987).

(8) R. Rydhag, The importance of the phase behaviour ofphospholipids for emulsion stability, Fette Seifen Anstrich., 4, 168-173 (1979).

(9) K. Tanaka, T. Seto, and T. Hayashida, Phase transformations of n-higher alcohols, Bull. Inst. Chem. Res., Kyoto Univ., 35, 123-139 (1958).

(10) F. H. C. Stewart, Phase relationships and spreading behaviour of cetyl alcohol mixtures, Austn. J. Appl. Sci., 11, 157-168 (1960).

(11) S. Fukushima, M. Yamaguchi, and F. J. Harusawa, Effect of cetostearyl alcohol on stabilization of oil-in-water emulsions, J. Colloid Int. Sci., 59, 159-165 (1977).

(12) K. Larsson and N. Krog, Structural properties of the lipid-water gel phase, Chem. Phys. Lipids, 10, 177-180 (1973).

(13) N. Krog and A. P. Borup, Swelling behaviour of lameIlar phases of saturated monoglycerides in aqueous systems,J. Sci. Fd. Agric., 24, 691-701 (1973).

(14) H. Hauser, Some aspects of the phase behaviour of charged lipids, Biochim. Biophys. Acta, 772, 37-50 (1984).

(15) S. Friberg and K. Larsson, "Liquid Crystals and Emulsions," in Advances in Liquid Crystals, G. M. Brown, Ed. (Academic Press, London, 1976), Vol. 2, pp. 173-195.

(16) K. Mandani and S. Friberg, Van der Waals' interactions in three phase emulsions, Progr. Colloid Polymer Sci., 65, 164-178 (1978).

(17) L. Rydhag and I. Wilton, The function ofphospholipids of soybean lecithin in emulsions, J. Am. Oil. Chem. Soc., 58, 830-837 (1981).

(18) L. Rydhag and T. Gabran, Phase equilibria in the system dimyristoyl phosphatidyl choline/hexadecyl trimethylammonium bromide/water at 30øC. Swelling behaviour of the lameliar phase with different electrolyte solutions, Chem. Phys. Lipids, 30, 309-324 (1982).

(19) H. E. Junginger, Colloidal structures of o/w creams, Pharmaceut. Weekblad, 6, 141-149 (1984). (20) G. M. Eccleston, M. K. Behan, G. R. Jones, and E. Towns-Andrews, Swelling properties of emul-

sifying wax/water gel phases, J. Pharm. Pharmac., 39P (1988). (21) H. K. Patel, R. C. Rowe, J. McMahon, and R. F. Stewart, A systematic microscopical examination

of gels and emulsions containing cetrimide and cetostearyl alcohol. Int. J. Pharmaceut., 25, 13-25 (1985).

(22) T. de Vringer, J. G. H. Jooster, and H. J. Junginger, Characterisation of the gel structure in a nonionic ointment by small angle x-ray diffraction, Colloid and Polymer Sci., 262, 56-60 (1984).

(23) G. M. Eccleston and L. Beattie, Microstructural changes during the storage of systems containing cetostearyl alcohol/polyoxyethylene alkyl ether surfactants, Drug Develop. and Indust. Pharm., 14, (15-17), 2499-2518 (1988).

(24) H. K. Patel, R. C. Rowe, J. McMahon, and R. F. Stewart, Properties of cetrimide/cetostearyl alcohol ternary gels; preparation effects. Int. J. Pharmaceut., 25, 237-242 (1985).

(25) G. M. Eccleston and L. Beattie, to be published. (26) G. M. Eccleston, The influence of fatty alcohols on the structure and stability of creams prepared with

polyethylene glycol 1000 monostearate/fatty alcohols, Int. J. Cosmet. Sci., 4, 133-142 (1982).


(27) G. M. Eccleston, Phase transitions in ternary systems and oil-in-water emulsions containing cetrimide and fatty alcohols, Int. J. Pharmaceut. 27, 311-323 (1985).

(28) H. K. Patel, R. C. Rowe, J. McMahon, and R. F. Stewart, A comparison of the structure and properties of ternary gels containing cetrimide and cetostearyl alcohol obtained from both normal and synthetic sources. Acta. Pharmaceut. Technol., 31, 243-247 (1985).

(29) G. M. Eccleston and L. Beattie, The influence of emulsifier composition in the microstructure of nonionic semisolids,J. Pharm. Pharmac., 12, 77P (1989).

(30) H. K. Patel, R. L. Rowe, J. McMahon, and R. F. Stewart, An investigation of the structural changes occurring in a cetostearyl alcohol/cetrimide/water gel after prolonged low temperature (4øC) storage, J. Pharm. Pharmacol., 37, 899-902 (1985).

(31) G. M. Eccleston, M. K. Behan, G. R. Jones, and E. Towns-Andrews, Microstructural changes during evaporation of dermatological semisolids, J. Pharm. ?harmc., 12, 9P (1989).

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Multiple-phase oil-in-water emulsions

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