Poly Glycerol

8/22/2019 Poly Glycerol

1/11

J. soc. cos. CHEM. 15, 473-483 (1964)

SOME USES AND APPLICATIONS OFPOLYGLYCEROL ESTERS IN COSMETIC AND

PHARMACEUTICAL PREPARATIONS

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

Presented ovember , 1963, New York Chapter

ABSTR&GTPolyllycerol esters as a class of emulsifiers having a wide range ofhydrophilic-lipophilic characteristics have been prepared and charac-terized. Their properties and characteristics are discussed and com-pared with those of other groups and classes of emulsifiers.Applications and uses of the polyllycerol esters are discussed, withparticular emphasis on their use as emulsifiers. It is shown that someesters are especially suitable for use and give the most stable W/O emul-sions with certain oils. In addition, the results of microbiologicaltests are given, indicating that hydrophilic polyllycerol esters do not

interfere with the bacteriostatic action of G-11.

INTRODUCTION

The large numberof emulsifiershat is currently available o thecosmeticand pharmaceuticalndustries s generallydivided into fourclasses: nionic,nonionic, ationicand amphoteric. Typical examples fanionicemulsifiers re materialssuchas soaps, odium auryl isethionate,sulfatedoils,etc. Anionicsurfactants ave the advantages f beinguse-ful in small concentrations; owever, hey are sensitive o the presence fother ions,acidsand cationicemulsifiers1). In addition, heir internaluse is limited.Typical examples f nonionic mulsifiersre materials uchas poly-ethylene glycol esters, sorbitan and polyoxyethylene orbitan esters,ethoxylatedatty alcohols, lkanolamides,tc. Nonionicemulsifiers e-* Drew ChemicalCorp., Boonton,N.J.

473


2/11

474 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

pend chieflyupon ether linkagesand hydroxyl groups o create their hy-drophilicaction. Since they do not ionize, they are claimed to be theleast irritating of emulsifiers 1). However, nonionicsand especiallythose hat are ethoxylatedhave been reportedby many authors o inac-tivate preservatives 2-7).The most frequently encounteredcationic emulsifiersare quaternaryammonium compoundssuch as stearyl dimethyl benzyl ammoniumchloride. Cationic emulsifiersare generally stable only at neutral andacid pH's, are consideredo be the most rritating classof surfactants,andare not allowed for internal use (8). In addition, there are relatively fewcationicedible and W/O emulsifiers vailable.Thus, there is a definiteneed or a new classof emulsifierswhich is edible,coversa wide range of hydrophilic-lipophilic ropertiesand is nonethoxy-late& This has become articularly mportantwith the establishment fstringent ontrols n food,drugandcosmeticngredients nd additives.

THE POLYGLYCEROL ESTERS

Although polyglycerolestershave been known for over thirty years,very little hasbeenwritten andeven essusehasbeenmadeof their uniquephysicaland chemicalproperties. The major reason or this neglect s,perhaps,the difficultiesof preparing materials with reproducible esults(9). In recentyears,suitablemethodshave beendeveloped, nd patentsfor the preparationand analysisof the polyglycerols nd polyglycerolestersare nowpending 10).The statusof the polyglycerol sters anbesummed p as ollows:1. Polyglycerolsters repreparedromglycerine,ats andoilsand attyacids.2. Functionalitycan be built into the structureas desired, anging romcompleteoil solubility to completewater solubility.3. Tailor-made emulsifiersrom polyglycerols an be made to suit or fit

the needsof the cosmeticand pharmaceutical ndustries.4. A process asbeendevelopedn our aboratories hichyieldsproductsof goodcolor,odor and flavor.5. They are readilyavailable,and the cost s within reason.6. The humanbody s able o utilizethe polyglycerolerivativesust likethe common fats and oils (12).7. No accumulation r toxic effect could be found in the usageof poly-glycerol sters venwhenusedas the solesource f fat.As products hat couldachieveow or high molecularweight,solidorliquidconsistency,ateror oil solubilityn thecompletebsencef toxicity,

thesepolyglycerol stersbecamea welcomeaddition to the line of ac-ceptable mulsifiersnce he F.D.A. gave he necessarylearanceo theiruse.


3/11

POLYGLCEROL ESTERS IN PHARMACEUTICAL PREPARATIONS 475

TABLE I--SOME PHYSICAt, AND CHEMICAL CHAR.ACTEKISTICSOF POLYGLYCEKOLSMolecular Number of Calculated Found SpecificCompound Weight OH Groups OH Value OH Value Gravity

Glycerol 92 3 1830 1828 1.24Di-glycerol 166 4 1352 1320Tri-glycerol 240 5 l 169 1166 l'.Tetra-glycerol 314 6 1071 1082 ...Penta-glycerol 388 7 1012 1028Hexa-glycerol 462 8 970 1010 1"2'4Hepta-glycerol 536 9 941 972 ...Octa-glycerol 610 10 920 951 ...Nona-glycerol 684 11 903 903Deca-glycerol 758 12 880 888 l'

Polyglycerols re prepared by the polymerizationof glycerine underalkaline conditions. The processhas been recently developed, and apatent is pendingwith the U.S. Patent OfFice. The controlledpolym-erization of glycerol o yield a specificmolecularweight polymer produceswater white to pale yellow productswith pleasantodor and flavor. Thepolyglycerols hus preparedare then esterifiedwith specific atty acidsorsubjected o alcoholysis r ester exchange o prepare a mixed fatty acidester. Thus, a hexaglycerolmonostearatemay best be made by reactinghexaglycerolwith stearicacid, while a hexaglycerol oconutoil ester maybest be prepared by the alcoholysis f coconut oil with hexaglycerol.Investigations hus far indicate that the polymerizationof glycerol isprogressingn a straight ine mannerwithout cyclizationor ring formation.Although Markley (11) indicatescyclic structure formation, we have notbeen able to identify the presenceof any ring structures n our product.Work is continuingto shed ight on the mechanismof this reaction, butit appears,at present, hat the polymerizationgives rise to the type ofchaingrowth which s shownbelow:

OH OH H H OH H H OH OHHC C--C-4)--C--C--C---O--C--C C--HH H H H H H H H HThe polymerizationcan continue n this manner, with the terminal hy-droxylgroups ormingether inkagesby eliminationof water.

CHEMICAL AND PHYSICAL PROPERTIES

The polyglycerolshave the characteristicsnormally associatedwithpolyols. They are water-solublen all proportionsand have excellentemollientand humectantproperties. They differ from glycerolmainly inthat the viscosity ncreases s the chain engthdoes. Table I shows ome


4/11


of the chemicalropertiesf polyglycerols,tartingwith thesingle lycerolmolecule nd going up to the decaglycerol oleculewhich contains10molesof glycerol. It should e noted hat therewill alwaysbe two morehydroxyl roupshan therearemoles f glycerol. These igures how henumericalncreasen thehydroxyl roupsn each olyglycerols hepoly-mer is increasedn sizeand molecular eight. Also, he calculated y-droxylvaluesand the actualhydroxylvaluesobtainedby analysis regiven to demonstratehe correlation etween ydroxylvalueand molec-ular weight.It has beenpossible o preparepolymers rom diglycerol 2 molesofglycerol)o tricontaglycerol30 moles f glycerol)n the initial stages fpolymerization.The polyglycerols re high-molecular eight, water-solubleluidswhichmay be usedas thickening gents, umectants,hemi-cal ntermediates ndfor otherpurposes.Oneor moreof the hydroxylgroups resentn a polyglycerol oleculemay be esterified; hus,sincedecaglycerolontains 2 hydroxylgroups,any ester rom mono o dodecamay be prepared. Sinceany numberoffatty acidsmay be used n the esterification,he numberof possibleoly-glycerolestersbecomes irtually unlimited. These polyglycerol stersmay be liquid to waxy; saturated r unsaturated; ow to highmolecularweight; and hydrophilic r lipophilic,depending n the numberof hy-droxylgroupshat arereactedwith the fatty acids nd/oroils n question.Polyglycerolsters anging rom complete il solubility o complete atersolubilitymay be prepared,with the possibilityof many intermediateproperties etweenhese wo extremes. Therefore,t becomesossibleosynthesizen entireclass f emulsifiers,ailor-madeo perform nyspecificfunction. Table I illustrates omeof the chemical ndphysical roper-ties of a selectedist of the polyglycerol sters,and Table III shows heirsolubilities in various solvents.Regardlessf the molecularweightof the polyglycerol nd regardlessof the typeof fatty acidor amountof such atty acidpresentn the poly-glycerol ester, feeding studies (12) have indicated that such esters arecompletely ontoxic nd are degradedully by the body o yieldglyceroland the fatty acid. Why a three-carbonther inkageshouldbe utilizedby the bodywhilea two-carbonther inkage f thepolyoxyethylenerod-uctsshould ot be utilized s not clearlyunderstood.The repeated e-sults of testing, however, eave no question hat this is true. Basedonthese eedingstudies,which were conductedwith saturated and unsatu-rated esters f polyglycerolanging rom two to thirty moles f glycerine,the F.D.A. not only gaveapproval n the useof thesepolyglycerolstersin foodbut alsoplacedno limits on the amounts hat couldbe used 13).This F.D.A. approvalcurrentlycovers stersup to and includinghedecaglycerolsters f the fatty acidsderived rom corn,cottonseed,ard,


5/11

POLYGLYCEROI. ESTERS IN PHARMACEUTICAL PREPARATIONS 477


6/11



7/11

POLYGLYCEROL ESTERS IN PHARMACEUTICAL PREPARATIONS 479

palm fruit, peanut, safflower,sesame nd soybeanoils, and tallow. Fur-ther approvals re expectedn the nearfuture.APPLICATIONS

1. Since a number of theseestersare lipophilic in nature, they shouldconstitutea family of W/O emulsifierswith a particularly wide range ofproperties. The literature contains many references o work on theselectionof suitable O/W emulsifiers or various oils (14-15), but ap-parently little suchwork has beendoneon W/O emulsions; n fact, difFi-culties had been encountered n preparing stable W/O emulsionswithvegetableoils as the externalphase (16). It seemed mportant, there-fore, to test a series f the polyglycerol stersasW/O emulsifiersor variousoils to determine he most suitablepolyglycerol ster or emulsification feach oil.

The following oils were used: two grades of mineral oil; isopropylmyristate; eanut il; Neobee SS*; NeobeeO*;corn il; Robanent;and lanolin oils.The tabulatedmaterialswereemployed semulsifiers:1. A 50/50 mixture of decaglycerol odecaoleate nd decaglycerol eca-oleate.2. A 50/50 mixture of decaglycerol ecastearate nd decaglycerol eca-oleate.3. Decaglycerol ecaoleate.4. Decaglycerolhexaoleate.5. Decaglyceroloctaoleate.6. Decaglycerol etraoleate.7. Sorbitansesquioleateas control).All emulsionswere prepared n 500 g. quantities,using 65% oil, 25%water and 10% emulsifier. The oil (containing the emulsifier) and thewater were heatedseparately o 78 C, and the water was slowly added tothe oil phaseusing apid agitation,mixing beingcontinued or 30 minutes.The emulsionswere observednitially, after one and three days, after oneand two weeks and after one month.Figure1 showshe series sing ight mineraloil asthe externalphaseafterintervalsof one day and one and two weeks espectively. Figure 2 showsthe equivalentseries or heavy mineral oil. It is noted that the greateststability was obtained with decaglycerol etraoleate (10-4-0). Similarresultswere obtainedwith isopropylmyristateand with Robane. Figure3 showsa similar seriesusing Neobee O as the external phase. In thiscase, he beststability wasobtainedwith a blendof decaglycerol ecaoleate* Neobee s Drew ChemicalCorporation'srademark or synthetic riglycerides.t Robane s RobecoChemicals' nc. trademark or hydrogenated qualene.


8/11

480 JOURNAl. OF THE SOCIETY OF COSMETIC CHEMISTS

and decaglycerol ecastearate 10-10-0/10-10-s); the secondbest stabil-ity was obtained with decaglyceroldecaoleate 10-10-0) alone. Similarresultswereobtainedwith NeobeeMS, peanutoil and cornoil.Based on theseresults severalW/O emulsionswhich could be readilyadapted or cosmetic r pharmaceutical sewereprepared. These ormula-tions are shown in Table IV.It has been possible o prepare many excellent cosmetic creams andlotionsby the useof theseesters. Decaglycerolmonoesters, uch as the

7-/' AV IN.A.O/

LIGHTMINEALIL i.. .

-- ,

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

Figure 1.--Stabilityof emulsionsrepared Figure2.--Stability of emulsionsreparedwith ight mineral il. with heavymineral il.palmitate,stearate ndoleate,havebeen ound o be very effective ydro-philic emulsifiers,while decaglycerolri- and tetra-esters,such asdecaglycerolristearate r decaglyceroletraoleate, re excellent uxiliaryemulsifiers. Two formulationsusing theseestersare included n TableIV.

2. Althougha great variety of nonionicO/W emulsifierss currentlyavailable, hereare still some roblemshat occur n the useof nonionics,


9/11


...... . .

.' ."c":'""..>":.:.'.:.."'.:::.:...:V.%.:...:.................... 0o-0 --o.'::................ .:::.........

' NEOBE.E 0. . : ' :. : .:...... .. ... . -

.... =.: ..- .o:--..2%'.:...::=: '.: ...... ..-- ' .... ' :':::": " ', ".4.:........... ... . ..... . ...... . ....Figure &--Stability of emulsions reparedwith NeobeeO.

primarily those containingpolyoxyethylene. One of these problems sthe interference hat has been frequently reported between ethoxylatedemulsifiersand bacteriostatsof the bisphenol ype, such as Hexachloro-phene,* or of the alkyl parahydroxybenzoates2-7). It was, therefore,decided o use zone of inhibition tests to compareseveralof the polyglyc-erol esters with other nonionic surfactants. To date, these tests havebeen run using a 0.5% alcoholicsolution of Hexachlorophenewith eightdifferent emulsifiersat concentrations p to 2%. Test organisms ncludetwo gram negative bacteria(Escherichia oli and Pseudomonaseruginosa)and a mold (/Ispergillusniger). Tests using gram positiveorganismswillbe published t a later date. The results n Table V suggesthat the poly-glycerolestersshow promiseof being less ikely to interferewith Hexa-chlorophene han other nonionic emulsifiers. Further experiments tosubstantiate hese esultsare now beingundertaken.3. Many other applicationsof the polyglycerolestersare possibleas aresult of their unique chemicaland physical properties. Thus, the stea-rates can be used as gelling agents or mineral oils, vegetableoils and gly-cols. For instance, decaglycerolmonostearatewill gel mineral oil, andthe resulting gel can be readily rinsed with water. Materials such asdecaglycerolristearateand polyglycerol leatescan be used o formulate

* G-11--Sindar Corporation, Delawanna,N.J. (7).


10/11

482 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTSTABLE VI--CoMPOSlTION OF EMULSIONS PREPARED WITH POLYGLYCEROLESTEKS

Formula #1 (Vegetable il Emulsion)Neobee 54* .................... 6%Decaglycerol ecaoleate........ 5%Decaglycerol ecastearate.......Neobee t .................... 45%Water ........................ 39%

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

Formula//5 (Cosmetic mulsion)Isopropylmyristate............Cetyl alcohol ................. .4/0Decaglycerol etraoleate ........ lDecaglycerolmono61eate........Stearic acid ................. 18%Spermaceti....................Glycerol ...................... 4%Hexachlorophene............ 0.5%Water ...................... 66.5%

Formula #2 (Peanut Oil Emulsion)Beeswax: ....................Neobee 54* .................... 3%Magnesium stearate ........... 1%Decaglycerol ecaoleate..... 10%Peanut oil .................... 45%Borax ...................... 0.Water ..................... 37.8%

Formula//t (Mineral Oil Emulsion)Mineral oil ................... 25%Petrolatum ........... 25%Decaglycerol ecaoleate........Decaglycerol ecalinoleate...... 3%Beeswax ...................... 7%Glycerol ...................... 3%Borax ...................... 0.5%Water ...................... 32.

Formula//6 (Cosmetic mulsion)Neobee M5 : .................. 3%Cetyl alcohol ................Decaglyceroldecalinoleate......Decaglyce l monopalmitate.... 4%Drewmulse 1128{}.............. 8%Cabosil[[.................... 1%Glycerol ...................... 3%Water ...................... 73%* Glyceryl tripalmitate (Drew Chem. Corp.).t Modifiedcoconut riglyceride Drew Chem.Corp.).:[:Modifiedcoconut riglyceride Drew Chem. Corp.).{} Self-emulsifying lycerylmonostearateDrew Chem Corp.).[[ A gradeof silicamanufactured y G. L. CabotCo.

'I-ABLE V---ZONES OF INHIBITIOq

EmulsifierE. coli Ps. aeroginosa d. niger, Concentration of Emulsifier Used0 o. 5% 1.0% 2.0% 0 o. 5% 1.0% 2.0% 0 0.5% 1.0% 2.0%

POE Sorbitanmono61eate 7 - - - 5 - - - 8POE Sorbitanmonolaurate .. 5 - - .. - - - .. -'POE (39) stearate .. - - - .. - - - .. - -POE (23) laurylalcohol .. - - - .. - - - .. - - -Decaglycerolmono61eate* .. 10 12 10 .. 3 2 - .. 6 6 6Decaglycerolmonolaurate* .. 15 15 10 .. 5 3 2 .. 6 8 7Decaglycerolmonopalmitate* .. 12 8 10 .. 5 2 1 .. 6 6 7HexaglycerolmonoiJleate* .. 20 10 5 .. 5 1 - .. 9 7 3All testswere run using0.5% G-11 in alcoholic oluiion,with and without emulsifiers.- indicates no inhibition.Numbers indicate the zone of inhibition in ram.* Please ote that no precipitate ccurredn alcohol t theseconcentrationsf emulsifier.


11/11


self-emulsifying axes. Thus, the addition of hexaglycerolmono61eateto mineraloil produces clearoil which s readily rinsedoff the handswithwater. Other esters, such as decaglycerol etraoleate, can be used in asimilar ashionwith vegetable il.The fact that the polyglycerol stersare edibleopensup many possibleapplicationsn the pharmaceuticalield. Thus, their use as emulsifiersnedibleemulsions ontaining egetable ils and as solubilizersor vitaminsis currentlyunder nvestigation.SUMMARY

The chemical ndphysical haracteristicsf a series f polyglycerol stersare presented. The utility of this versatilegroup of compoundss illus-trated. The stability of O/W and W/O emulsions reparedwith the aidof these esters s examined. Formulationsof practical cosmeticscon-tainingpolyglycerol stersare given. Preliminary testssuggesthat theseemulsifiers o not interferewith the activity of Hexachlorophene.

(ReceivedJanuary 15, 1964)REFERENCES

(1) W. C. Griffin n E. Sagatin,Cosmetics: ciencend Technology,nterscience ublishers,Inc., New York, 1004-05 (1955).(2) W. F. Rehm,Milchwissenschaft,6, 310 (1961).(3) A. Bille and A. Mirimanoff, y. Pharm. Pharmacol., , 685 (1950).(4) M. G. deNavarreand H. E),Bailey, y.Soc.Cosmetic hemists,, 427 (1956).(5) M. G. deNavarre, bid., 8, 68 (1957).(6) L. F. Tice and M. Bart, Ibid., 9, 171 (1958).(7) D. L. Wedderburn,bid., 9, 210 (1958).(8) R.G. Harry, ModernCosmeticology,eonardHill (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 ublishers,nc., New York, 1961,pp.826-27.(12) H. Kaunits,C. A. Slanetzand V. K. Babayan,y..4m. 01l Chemists' oc.,41, 434 (1964).(13) FederalRegister,uly 2, 1963,p. 6783; March 19, 1963,pp. 2675-76.

(14) W. C. Griffin, . Soc.Cosmetichemists,, 311 1949).(15) W. C. Griffin n E. Sagatin,Cosmetics: ciencend Technology,nterscienceublishers, Inc., New York, 1955,.pp.1018-20.(16) [dem., Ibid., p. 1029.

Poly Glycerol

Documents

Transcript of Poly Glycerol