J. soc. cos. CHEM.

15, 473-483 (1964)

SOME

USES

AND

APPLICATIONS IN COSMETIC

OF AND

POLYGLYCEROL

ESTERS

PHARMACEUTICAL

PREPARATIONS

By V. K. B^B^AN, B.S., T. G. KAufMaN, B.S., H. L.Mx, B.S. and R. J. TaczuK, M.S.*

Presented November 6, 1963, New York Chapter

ABSTR&GT

Polyllycerol esters as a class of emulsifiers having a wide range of hydrophilic-lipophilic characteristics have been prepared and characterized. Their properties and characteristics are discussed and compared with those of other groups and classes of emulsifiers. Applications and uses of the polyllycerol esters are discussed, with particular emphasis on their use as emulsifiers. It is shown that some esters are especially suitable for use and give the most stable W/O emulsions with certain oils. In addition, the results of microbiological tests are given, indicating that hydrophilic polyllycerol esters do not
interfere with the bacteriostatic action of G-11.

INTRODUCTION

The large numberof emulsifiers that is currentlyavailableto the cosmeticand pharmaceutical industriesis generallydivided into four classes: anionic,nonionic, cationicand amphoteric. Typical examples of anionicemulsifiers are materialssuchas soaps, sodiumlauryl isethionate, sulfatedoils,etc. Anionicsurfactants have the advantages of beinguseful in small concentrations; however,they are sensitive to the presence of other ions,acidsand cationicemulsifiers (1). In addition,their internal
use is limited.

Typical examples of nonionic emulsifiers are materials suchas polyethylene glycol esters, sorbitan and polyoxyethylene sorbitan esters, ethoxylated fatty alcohols, alkanolamides, etc. Nonionicemulsifiers de* Drew Chemical Corp., Boonton, N.J.
473

474

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

pend chieflyupon ether linkagesand hydroxylgroupsto create their hydrophilicaction. Sincethey do not ionize, they are claimedto be the least irritating of emulsifiers(1). However, nonionicsand especially thosethat are ethoxylatedhave beenreportedby many authorsto inactivate preservatives (2-7). The most frequently encounteredcationic emulsifiersare quaternary ammonium compoundssuch as stearyl dimethyl benzyl ammonium chloride. Cationic emulsifiersare generallystable only at neutral and acid pH's, are considered to be the most irritating class of surfactants,and are not allowedfor internal use (8). In addition, there are relatively few
cationicedible and W/O emulsifiers available. Thus, there is a definiteneedfor a new class of emulsifiers which is edible, coversa wide rangeof hydrophilic-lipophilic propertiesand is nonethoxy-

late& This hasbecome particularlyimportantwith the establishment of stringent controls on food,drugandcosmetic ingredients andadditives.
THE POLYGLYCEROL ESTERS

Although polyglycerolestershave been known for over thirty years, very little hasbeen writtenandevenless usehasbeen madeof their unique physicaland chemicalproperties. The major reasonfor this neglectis, perhaps,the difficultiesof preparing materials with reproducibleresults (9). In recentyears,suitablemethods have beendeveloped, and patents for the preparationand analysisof the polyglycerols and polyglycerol esters arenowpending(10). The statusof thepolyglycerol esters canbesummed up asfollows:

1. Polyglycerol esters areprepared fromglycerine, fats andoilsandfatty

acids.

2. Functionalitycan be built into the structureas desired, rangingfrom complete oil solubilityto completewater solubility. 3. Tailor-made emulsifiers from polyglycerols can be made to suit or fit the needsof the cosmeticand pharmaceutical industries. 4. A process hasbeendeveloped in our laboratories whichyieldsproducts of goodcolor,odor and flavor. 5. They are readilyavailable,and the costis within reason. 6. The humanbodyis ableto utilizethe polyglycerol derivatives just like
the common fats and oils (12).

7. No accumulation or toxic effect couldbe found in the usageof poly-

glycerol esters evenwhenusedasthe sole source of fat. As products that couldachieve low or high molecular weight,solidor liquidconsistency, wateroroilsolubility in thecomplete absence oftoxicity, thesepolyglycerol estersbecamea welcome addition to the line of acceptable emulsifiers oncethe F.D.A. gavethe necessary clearance to their
use.

POLYGLCEROL

ESTERS

IN

PHARMACEUTICAL

PREPARATIONS

475

TABLE I--SOME

PHYSICAt, AND CHEMICAL CHAR.ACTEKISTICSOF POLYGLYCEKOLS

Compound
Glycerol Di-glycerol

Molecular Weight
92 166

Number of OH Groups
3 4

Calculated OH Value
1830 1352

Found OH Value
1828 1320

Specific Gravity
1.24

Tri-glycerol
Tetra-glycerol Penta-glycerol Hepta-glycerol Octa-glycerol Nona-glycerol

240
314 388 536 610 684

l 169
1071 1012 941 920 903

1166
972 951 903

l'.
...

Hexa-glycerol 462
Deca-glycerol 758

6 7

970

1010
888

1082 1028

1"2'4
... ...

9 10 11

12

880

l'

Polyglycerols are prepared by the polymerizationof glycerineunder alkaline conditions. The processhas been recently developed, and a patent is pendingwith the U.S. Patent OfFice. The controlledpolymerization of glycerolto yield a specific molecularweight polymer produces water white to pale yellow productswith pleasantodor and flavor. The polyglycerols thus preparedare then esterifiedwith specific fatty acidsor subjectedto alcoholysis or ester exchange to preparea mixed fatty acid ester. Thus, a hexaglycerol monostearate may best be made by reacting hexaglycerol with stearicacid, while a hexaglycerol coconutoil ester may best be prepared by the alcoholysis of coconut oil with hexaglycerol. Investigationsthus far indicate that the polymerizationof glycerol is progressing in a straightline mannerwithout cyclization or ring formation. Although Markley (11) indicatescyclic structure formation, we have not been able to identify the presence of any ring structuresin our product. Work is continuingto shedlight on the mechanism of this reaction, but it appears,at present,that the polymerizationgives rise to the type of chaingrowthwhichis shownbelow:
OH HC H OH H H OH H C--C-4)--C--C--C---O--C--C H OH OH C--H

The polymerizationcan continuein this manner, with the terminal hydroxylgroups formingetherlinkages by eliminationof water.
CHEMICAL AND PHYSICAL PROPERTIES

The polyglycerolshave the characteristics normally associatedwith polyols. They are water-soluble in all proportionsand have excellent emollientand humectantproperties. They differ from glycerolmainly in that the viscosityincreases as the chain lengthdoes. Table I shows some

476

JOURNAL OF THE SOCIETY OF COSMETIC

CHEMISTS

of thechemical properties of polyglycerols, starting with thesingle glycerol molecule and goingup to the decaglycerol molecule which contains10 moles of glycerol. It should be notedthat therewill always be two more hydroxyl groups thantherearemoles of glycerol. These figures show the numerical increase in thehydroxyl groups in each polyglycerol asthepolymer is increased in sizeandmolecular weight. Also,the calculated hydroxylvaluesand the actualhydroxyl valuesobtained by analysis are given to demonstrate the correlation between hydroxylvalueandmolecular weight.

It has beenpossible to preparepolymers from diglycerol(2 molesof glycerol) to tricontaglycerol (30 moles of glycerol) in the initial stages of polymerization.The polyglycerols are high-molecular weight, watersoluble fluidswhichmay be usedasthickening agents, humectants, chemicalintermediates andfor otherpurposes.

Oneor moreof the hydroxyl groups present in a polyglycerol molecule may be esterified;thus,since decaglycerol contains 12 hydroxyl groups, any esterfrom monoto dodeca may be prepared. Sinceany number of fatty acids may be used in the esterification, the number of possible polyglycerolestersbecomes virtually unlimited. These polyglycerol esters may be liquidto waxy; saturated or unsaturated; low to highmolecular weight; and hydrophilic or lipophilic, depending on the numberof hydroxylgroups that arereacted with the fatty acids and/oroilsin question. Polyglycerol esters ranging fromcomplete oil solubilityto complete water solubilitymay be prepared,with the possibilityof many intermediate properties between these two extremes. Therefore, it becomes possible to synthesize an entireclass of emulsifiers, tailor-made to perform anyspecific function. TableII illustrates some of the chemical andphysical properties of a selected list of the polyglycerol esters, and Table III shows their
solubilities in various solvents.

Regardless of the molecular weightof the polyglycerol and regardless of the typeof fatty acidor amount of such fatty acidpresent in thepolyglycerol ester, feeding studies (12) have indicated that such esters are

completely nontoxic and are degraded fully by the bodyto yieldglycerol and the fatty acid. Why a three-carbon ether linkageshould be utilized by the bodywhilea two-carbon etherlinkage of thepolyoxyethylene productsshould not be utilizedis not clearlyunderstood.The repeated resultsof testing,however,leave no questionthat this is true. Basedon thesefeedingstudies,which were conductedwith saturated and unsatu-

ratedesters of polyglycerol ranging from twoto thirty moles of glycerine, the F.D.A. not only gaveapproval on the useof these polyglycerol esters in foodbut alsoplacedno limits on the amounts that couldbe used(13). This F.D.A. approval currentlycovers esters up to and including the decaglycerol esters of the fatty acids derivedfrom corn,cottonseed, lard,

POLYGLYCEROI. ESTERS IN PHARMACEUTICAL

PREPARATIONS

477

478

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

POLYGLYCEROL

ESTERS

IN

PHARMACEUTICAL

PREPARATIONS

479

palm fruit, peanut, safflower, sesame and soybeanoils, and tallow. Further approvals areexpected in the nearfuture.
APPLICATIONS

1. Since a number of theseestersare lipophilic in nature, they should constitutea family of W/O emulsifiers with a particularly wide range of properties. The literature containsmany references to work on the selectionof suitable O/W emulsifiersfor various oils (14-15), but apparently little suchwork has beendoneon W/O emulsions;in fact, difFiculties had been encounteredin preparing stable W/O emulsionswith vegetableoils as the externalphase (16). It seemed important, therefore, to test a series of the polyglycerol esters asW/O emulsifiers for various oils to determine the mostsuitable polyglycerol esterfor emulsification of
each oil.

The following oils were used: two grades of mineral oil; isopropyl

myristate; peanut oil; Neobee MSS*; NeobeeO*; corn oil; Robanent;

and lanolin oils.

The tabulatedmaterialswereemployed asemulsifiers:

1. A 50/50 mixture of decaglycerol dodecaoleate and decaglycerol decaoleate.

2. A 50/50 mixture of decaglycerol decastearate and decaglycerol decaoleate.

3. 4. 5. 6. 7.

Decaglycerol decaoleate. Decaglycerol hexaoleate. Decaglycerol octaoleate. Decaglyceroltetraoleate. Sorbitansesquioleate (as control).

All emulsions were preparedin 500 g. quantities,using 65% oil, 25% water and 10% emulsifier. The oil (containing the emulsifier) and the water were heatedseparatelyto 78 C, and the water was slowly addedto the oil phaseusingrapid agitation,mixingbeingcontinued for 30 minutes. The emulsions were observed initially, after one and three days, after one
and two weeks and after one month.

Figure1 shows theseries using lightmineraloil astheexternal phase after intervalsof one day and one and two weeksrespectively. Figure 2 shows the equivalentseries for heavy mineral oil. It is noted that the greatest stability was obtained with decaglycerol tetraoleate (10-4-0). Similar resultswere obtainedwith isopropyl myristateand with Robane. Figure 3 showsa similar seriesusing Neobee O as the external phase. In this case, the beststabilitywasobtained with a blendof decaglycerol decaoleate
* Neobeeis Drew ChemicalCorporation's trademarkfor synthetictriglycerides. t Robaneis RobecoChemicals' Inc. trademarkfor hydrogenated squalene.

480

JOURNAl. OF THE SOCIETY OF COSMETIC

CHEMISTS

and decaglycerol decastearate (10-10-0/10-10-s); the secondbest stability was obtained with decaglycerol decaoleate(10-10-0) alone. Similar results wereobtainedwith NeobeeMS, peanutoil and cornoil. Basedon theseresults severalW/O emulsions which could be readily adaptedfor cosmetic or pharmaceutical usewereprepared. Theseformulations are shown in Table IV.

It has been possibleto prepare many excellent cosmeticcreams and lotionsby the useof theseesters. Decaglycerol monoesters, such as the

7-/' AV

IN.A.O/

LIGHTMINEAL OIL.i.
. .

-.'" ,,:; . :m; ...s. ......

Figure 1.--Stabilityof emulsions prepared Figure2.--Stability of emulsions prepared withlightmineral oil. with heavy mineral oil.

palmitate,stearate andoleate, havebeenfoundto be veryeffective hydrophilic emulsifiers, while decaglycerol tri- and tetra-esters,such as decaglycerol tristearate or decaglycerol tetraoleate, are excellent auxiliary emulsifiers. Two formulationsusing theseestersare includedin Table
IV.

2. Althougha great variety of nonionic O/W emulsifiers is currently available, thereare still some problems that occur in the useof nonionics,

POLYGLYCEROL

ESTERS IN PHARMACEUTICAL

PREPARATIONS

481

......

.''."c":' "" '..>":.:.'.:.." .'.:::.:...:V.%.:...: .....................

.'::.

0o-0 --o

............... .:::...... ....

' NEOBE.E 0
. .

: ' :. : .. ....
.... =.:

.'-

.: .......

..- .o:--..2%'.:...::=: '.: ...... ..-

...........

'..... ' :':::": ...

" ', ".4.: . ..... . ....... . ....

Figure &--Stability of emulsions preparedwith NeobeeO.

primarily those containingpolyoxyethylene. One of these problemsis the interferencethat has been frequently reported between ethoxylated emulsifiers and bacteriostats of the bisphenoltype, such as Hexachlorophene,* or of the alkyl parahydroxybenzoates (2-7). It was, therefore, decidedto use zone of inhibition teststo compareseveral of the polyglycerol esterswith other nonionic surfactants. To date, these tests have been run using a 0.5% alcoholicsolution of Hexachlorophene with eight different emulsifiersat concentrations up to 2%. Test organismsinclude two gram negative bacteria(Escherichia coli and Pseudomonas aeruginosa) and a mold (/Ispergillusniger). Tests usinggram positiveorganisms will bepublished at a later date. The resultsin Table V suggest that the polyglycerolestersshow promiseof being lesslikely to interferewith Hexachlorophene than other nonionic emulsifiers. Further experimentsto substantiate theseresultsare now beingundertaken. 3. Many other applications of the polyglycerolestersare possibleas a result of their unique chemicaland physical properties. Thus, the stearates can be used as gellingagentsfor mineral oils, vegetable oils and glycols. For instance,decaglycerol monostearatewill gel mineral oil, and the resulting gel can be readily rinsed with water. Materials such as decaglycerol tristearateand polyglycerol oleatescan be usedto formulate
* G-11--Sindar Corporation, Delawanna,N.J. (7).

482

JOURNAL OF THE SOCIETY OF COSMETIC

TABLE VI--CoMPOSlTION

CHEMISTS

OF EMULSIONS PREPARED WITH POLYGLYCEROLESTEKS

Formula #1 (Vegetable Oil Emulsion) Neobee 54* .................... 6%

Decaglycerol decaoleate ......... Decaglycerol decastearate ........

Neobee t .................... Water ........................

5%
45% 39%

Formula #2 (Peanut Oil Emulsion) Beeswax:..................... Neobee 54* .................... 3% Magnesium stearate............ 1% Decaglycerol decaoleate ...... 10% Peanut oil .................... 45% Borax....................... 0. Water ..................... 37.8%
Formula//t (Mineral Oil Emulsion) Mineral oil ................... 25% Petrolatum ........... 25% Decaglycerol decaoleate ......... Decaglycerol decalinoleate ....... 3% Beeswax ....................... 7% Glycerol ...................... 3% Borax ....................... 0.5% Water ...................... 32. Formula//6 (Cosmetic Emulsion) Neobee M5 :................... 3% Cetyl alcohol ................. Decaglyceroldecalinoleate ....... Decaglyce ol monopalmitate ..... 4% Drewmulse 1128{} ............... 8%

Formula//3 (Mineral Oil Emulsion) Mineral oil (50--60risc.) ........ 38% Petrolatum ................... Decaglycerol decastearate ........ 3% Decaglycerol tetraoleate ......... 5% Lanolin ........................ Beeswax ....................... 3% Magnesiumstearate ............. Water ...................... 32.6% Borax...................... 0.4%

Formula//5 (Cosmetic Emulsion)

Isopropyl myristate .............

.4/0 Cetyl alcohol .................. Decaglycerol tetraoleate......... l Decaglycerol mono61eate ......... Stearic acid .................. 18% Spermaceti ..................... Glycerol ....................... 4% Hexachlorophene ............. 0.5% Water ...................... 66.5%

Cabosil[[ .....................
Glycerol....................... Water.......................

1%
3% 73%

* Glyceryl tripalmitate (Drew Chem. Corp.). t Modifiedcoconut triglyceride (Drew Chem.Corp.). :[: Modifiedcoconuttriglyceride (Drew Chem.Corp.). {} Self-emulsifying glycerylmonostearate (Drew Chem Corp.). [[ A gradeof silicamanufactured by G. L. CabotCo.
'I-ABLE V---ZONES OF INHIBITIOq

E. coli
, Emulsifier
POE Sorbitan

Ps. aeroginosa
Concentration of Emulsifier Used

d. niger

0 o. 5% 1.0% 2.0% 0 o. 5% 1.0% 2.0% 0 0.5% 1.0% 2.0%

7
..

mono61eate
POE Sorbitan monolaurate

5
..

8
.. -'

POE (39) stearate .. POE (23) laurylalcohol .. Decaglycerol

mono61eate* ..

10

12

10

.. ..
..

.. ..
..

Decaglycerol
monolaurate* .. 15 15 10 .. 5 3 2 .. 6 8 7

Decaglycerol monopalmitate* Hexaglycerol

monoiJleate*

..
..

12
20

8
10

10 ..
5 ..

5
5

2
1

1
-

..
..

6
9

6
7

7
3

All testswere run using0.5% G-11 in alcoholic soluiion,with and without emulsifiers.
- indicates no inhibition. Numbers indicate the zone of inhibition in ram.

* Please note that no precipitate occurred in alcohol at these concentrations of emulsifier.

POLYGLYCEROL

ESTERS

IN

PHARMACEUTICAL

PREPARATIONS

483

self-emulsifying waxes. Thus, the addition of hexaglycerol mono61eate to mineraloil produces a clearoil whichis readilyrinsedoff the handswith
water. Other esters,such as decaglyceroltetraoleate, can be used in a similarfashion with vegetable oil.

The fact that the polyglycerol estersare edibleopens up many possible applications in the pharmaceutical field. Thus, their useas emulsifiers in edibleemulsions containing vegetable oils and as solubilizers for vitamins iscurrentlyunderinvestigation.
SUMMARY

The chemical andphysical characteristics of a series of polyglycerol esters are presented. The utility of this versatilegroupof compounds is illustrated. The stability of O/W and W/O emulsions preparedwith the aid of these estersis examined. Formulationsof practical cosmetics containingpolyglycerol esters are given. Preliminarytestssuggest that these emulsifiers do not interferewith the activity of Hexachlorophene.
(ReceivedJanuary 15, 1964)
REFERENCES

(1) W. C. Griffinin E. Sagatin,Cosmetics: Science and Technology, Interscience Publishers, Inc., New York, 1004-05 (1955). (2) W. F. Rehm,Milchwissenschaft, 16, 310 (1961). (3) A. Bille and A. Mirimanoff, y. Pharm. Pharmacol., 2, 685 (1950). (4) M. G. deNavarreandH. E),Bailey,y.Soc.Cosmetic Chemists, 7, 427 (1956). (5) M. G. deNavarre,Ibid., 8, 68 (1957). (6) L. F. Tice and M. Bart, Ibid., 9, 171 (1958). (7) D. L. Wedderburn, Ibid., 9, 210 (1958). (8) R.G. Harry, ModernCosmeticology, LeonardHill (Books)Ltd., London,1962,p. 566. (9) N.H. Nash and V. K. Babayan,Baker'sDigest,37, 72 (1963). (10) Patent PendingSerialNo. 14477. (11) K. S. Markley, Fatty .4cids, Part 2, Interscience Publishers, Inc., New York, 1961,pp.
826-27.

(12) H. Kaunits,C. A. SlanetzandV. K. Babayan,y..4m. 01l Chemists' Soc.,41, 434 (1964). (13) Federal Register, July 2, 1963,p. 6783; March 19, 1963,pp. 2675-76.

(15) W. C. Griffinin E. Sagatin, Cosmetics: Science and Technology, Interscience Publishers, Inc., New York, 1955,.pp.1018-20. (16) [dem., Ibid., p. 1029.

(14) W. C. Griffin, y. Soc. Cosmetic Chemists, 1, 311(1949).