j. Soc.Cosmet.

Chem.,40, 215-229 (July/August1989)

Effectsof variationsin physicochemical

propertiesof
glycerylmonostearate
on the stabilityof an oil-inwater cream
R. O'LAUGHLIN,

C. SACHS, H. BRITTAIN,

E. COHEN,

P. TIMMINS, and S. VARIA,* TheSquibbInstitute

for Medical
Research,
New Brunswick,
NJ 08903-0191 (R.O., C.S., H.B., E.C.,
S.V. ), andInternational
Development
Labs,E. R. Squibb& Sons,Reeds
Lane,Moreton,Merseyside,
U.K. (P.T.). * To whomcorrespondence
should be addressed.

Received
March 22, 1989.
Synopsis

During the development

of an oil-in-watercreamformulation,syneresis
of theaqueous
phasewasobserved.
A quantitativesyneresis
test wasdevisedto studythe separation
of the aqueousphase.Variationsin the
physical
andchemicalcharacteristics
of glycerylmonostearate
obtainedfromvarioussources
wereidentified
as the principalfactorsinfluencingsyneresis
of the formulation.A groupof diagnostic
tests,including
variabletemperature
x-raydiffraction
analysis
developed
forscreening
variouslotsofglycerylmonostearate,
wasusedto successfully
predictthe possibilityof the occurrence
of syneresis
in a creambatch.The acid
valueof the variouslots of glycerylmonostearates
correlatedwell with the propensityof the creamto
producesyneresis.
Increasing
the acidvalueof the glycerylmonostearate
by the additionof smallamounts
of fattyacidseliminatedthe observed
syneresis.
Further,the storage
temperature
hada profoundeffecton
the syneresis
and consistency.
INTRODUCTION

Pharmaceuticalcream basesare essentiallysemisolidemulsionsystemsthat appear

"creamywhite" due to reflectionof light by the internaldispersed
phase.The most
commoncreamsare oil-in-water emulsionsystems,whosestructureor semisolidcharacteris dependentuponemulsifiedliquid dropletsor particlesthat comprisethe internalphase.Creamsare usuallypreparedat high temperature(fusionmethod)using
internal-phase
materialssuchasmineralor vegetableoils, liquid emollientesters,solid
long-chainfatty acids, alcohols,and esters.Upon cooling, theseingredientsexist as
dispersed
or emulsifiedmicroscopic
droplets,liquid crystals,solidparticles,or spheres,
creatinga three-dimensional
gel structureor matrix that entrapsthe aqueousexternal
phase(1,2). In many formulationsthe gel structuremay be metastable.Creamsare
dynamiccompositions
that are influencedby temperaturestorageand shearforces.The
gel structuremaystiffen,contract,andshrinkat coldtemperatures,
or soften,expand,
and fluidize at warm temperatures.Gel structuremay be brokendown due to shear
thinning by mechanicalmixing, pumping, or rubbing. Many creamspossess
thixotropicproperties
that allowrecovery
of gel structureuponstorageafterexposure
to shear
thinning.
215

216

JOURNAL OF THE SOCIETYOF COSMETICCHEMISTS

Someof the generalindicationsof emulsioninstabilityare:

1. Inversionof emulsiontype(e.g., oil-in-wateremulsionchanges

to water-in-oiltype
emulsion or vice versa)

2. Coalescence
of dispersed
internal-phase
droplets,globules,spheres,or particles
3. Phaseseparation
characterized
by liquid "bleed"or syneresis
4. Decrease
in viscosityor lossof consistency
resultingin softness
or fluidity
Externalfactorssuchas packaging,storagetime, temperatureconditions,and shear
forcesmay induceemulsioninstability.Internalfactorsof creamcomposition
relatedto
variabilityof the excipientsor raw materialsand their sourcemay alsoaffectemulsion
stabilityand creamconsistency.

Mostcommercially
availablecosmetic
rawmaterialsusedin oil-in-wateremulsion-type
creamsare not pure excipients,but mixturesof two or more components.
Someare
complexmixturesthat may vary dependingon the vendorsource.Glycerylmonostearate is an excellentexampleof a commonlyusedcreamexcipientthat exhibitsa wide
rangeof variabilityin its constituent
composition,
andalsoin its effecton the consistencyand quality of the finishedcreamformulation(3). Glycerylmonostearate
is a
mixture of the monoglycerides
of stearicand palmitic acids,togetherwith variable
quantitiesof di- and triglycerides.It usuallycontainsnot lessthan 90% of total fatty
acidglycerides,
of whichat least35% aremonoglycerides
(4). Smallquantitiesof free
stearic,palmiticandoleicacids,glycerol,water,andoleate,esters
mayalsobepresent.
Sinceglycerylmonostearate
is usedmainlyasan emollientlipophilicthickeningagent
and stabilizerfor oil-in-waterandwater-in-oilemulsion-type
creamsandlotions,variability of this raw materialcanresultin manufacturing
problems.This reportdiscusses
someof the causesresultingin soft consistency
and syneresis
encountered
during the
scale-upphaseof development
for an oil-in-wateremulsioncreamproduct,whenraw
materialsfrom multiple vendorsources
wereused.
The main objectivesof the presentwork were:

1. Investigatethe creamformulationand its methodof manufacture

to determinethe
causeof the softconsistency
and syneresis
2. Identify test methodsto evaluatecreamconsistency
and syneresis
potential
3. Identify methodsto test the raw materialsto predicttheir propensityto causesoft
creamconsistency
and syneresis
4. Recommend
optionsto the manufacturing
plantsto overcome
variablecreamconsistencyandsyneresis
problems

EXPERIMENTAL
MATERIALS

Glycerylmonostearate
NF XII, cetylalcoholNF, Syncrowax
ERL-C(ethylene
glycol
esterof C18-36 wax fatty acids),AmercholL-101 (mineraloil and lanolinalcohol),
GlucamE-20 (methylgluceth-20),Tween60 (polysorbate
60 NF), propylene
glycol
U.S.P., sodiumcitrateU.S.P., edetatedisodiumU.S.P., sodiummetabisulfite
NF,
aluminumhydroxide
wet gel, dimethicone,
andpurifiedwaterU.S.P. wereusedas
received.Thesematerialswereobtainedfrom a varietyof sources.

OIL-IN-WATER

CREAM

CREAM

STABILITY

217

PREPARATION

Glycerylmonostearate,
cetyl alcohol,Syncrowax
ERL-C, and AmercholL-101 were

heatedto 80-85Cin a suitablecontainer

with mixingto producethe oil phase.
In a separate10-gallonGroenkettleequippedwith an Arde-Barinco
homogenizer
setat
3000 rpm, edetatedisodium,sodiumcitrate,andsodiummetabisulfiteweredissolved
in a mixtureof purifiedwater,GlucamE-20, Tween60, andpropyleneglycolheatedto

80-85C.A dispersion
of aluminumhydroxide
in purifiedwater(previously
homogenized)wasaddedto the aqueoussolutionand the combinedaqueousphaseheatedto
90-95C.

The oil phaseheatedto 90-95Cwasaddedto the aqueous

phaseat 90-95C.The
combined
mixturewashomogenized
for 30 minutesat 90-95C.The batchwascooled
to 70-75Cby passingcoolingwaterthroughthe jacketof the kettle. Dimethicone
wasaddedandthebatchwasfurthercooledto 54-56Cwith continuous
homogenization. Batchweightwasadjustedwith purifiedwaterat this temperature,followedby
furthercoolingto 50- 52Cwith homogenization.
At theonsetof congealing,
homogenizationwas discontinued.Slow-speed
Groen mixing wasusedto cool the creamto

44C, whereuponmixing was discontinued.The creamwas allowedto cool to

25-30Cby standing
overnight.In orderto allowtheadditionof the activedrugto
the batch,a portionof the propyleneglycolwasretained.In the placebobatchesmade
aspart of thisstudy,a portionof thepropyleneglycolwasalsoretainedsoasto simulate
the manufacture
of an activebatch.This portionof the propyleneglycolwasaddedto
the creambaseat 25-30Candmixedat slowspeedfor 30 minutes.
In orderto determinethe reproducibilityof the physicalpropertiesof a creambatch
type, preparations
wereperformedat leastin duplicate.Full physicalcharacterization
was performedon eachpreparation,and the data reportedreflect averagesof these
determinations.

WIRE-MESH

BLEED

TEST

A 30-g sampleof creamwasspreadevenlywith a spatulaontoa rectangular

stainless
1',

steel30-mesh
wirescreen
(13 X 13")supported
bya 1-ozclear-glass
jar(height15/8
",
base
diameter
15/8
", neckdiameter
13")contained
withina 4-ozclear-glass
jar(height
2_v,
basediameter--4'
7_v,neckdiameter
2"). Duringthetransfer
of thecreamsample
onto
2'
thescreen,verylittle sheer,if any,wasappliedandnomixingwasperformed.The 4-oz
jar wascovered
with a tight-fittinglinercapandstoredat 20-25Cfor observations
of
separated
liquid until nofurtherbleedwasobserved.
Any separated
liquid wascollected
at the bottomof the jars.This liquid wasthenremovedandquantitatedby weight.The
reportedpercentbleedwasobtainedby dividingthe massof collectedliquid by the
total massof the creamsampleusedfor the test. Eachreporteddatapoint represents
an
averageof four individualdeterminations.
UNIVERSAL

CONE

PENETROMETER

FOR MEASUREMENT

OF CREAM

CONSISTENCY

A universalgreaseconemadeof brasswith a steelstemand needletip (wt. 102.5 g),

affixedto the baseof a metalrod, wasinitially held in a stationarypositionwith needle
tip justin contactwith the surface
of the creamsample,containedin an aluminumcup

218

JOURNAL OF THE SOCIETYOF COSMETICCHEMISTS

(83 ml volume). The creamsamplewasplacedwith a spatulainto the aluminum cup

without applying any significantshearto the product. When the releasemechanism
wasactivated,the needletip conewasallowedto penetratethe samplefor 5 seconds.
Depth of penetrationwas then measuredin scaleunits up to 380 on scaledial. Consistencymeasurement
wasreportedas scaleunits for convenience
but couldalsobe convertedto mm (eachscaleunit is equalto 0.1 mm). Eachreporteddatapoint represents
an averageof threeindividualdeterminations.
DSC MEASUREMENTS

DSC measurements
wereobtainedon the DuPontmodel9900 thermalanalysis
system.
1-mg sampleswere accuratelyweighedinto the DSC pan, and the panswere hermeticallysealed.ConventionalDSC curveswereobtainedby heatingthe samplesat a rateof
10C/minute,
up to a final temperature
of 100C.The DSCprofilesof thermallyprocessed
glycerylmonostearate
materialswereobtainedby heatingthe sealedsampleonly
to 95C,maintainingthistemperature
for 10 minutes,allowingthesystemto coolback
to room temperature,and then obtaininga conventionalDSC thermogramof this
melted and congealedmaterial. The melting pointsof the variousmaterialswereobtainedas the temperaturemaximaassociated
with the DSC melting endotherms.
X-RAY

DIFFRACTION

MEASUREMENTS

Powderx-ray diffraction(XRD) measurements

wereobtainedon a PhilipsmodelAPD
3720 powderdiffractionsystem,equippedwith a verticalgoniometerin the theta/2theta geometry.The x-ray generator(PhilipsmodelXRG 31000) wasoperatedat 45
kV and40 ma, usingthe K-alphaline of copperat 1.544056A asthe radiationsource.
The samplewasscanned
between2and32 2-theta,at a scanrateof 0.04 2-theta/sec,
andin stepssizesof 0.04 2-theta.The XRD powderpatternsof meltedandcongealed
glycerylmonostearate
materialswere obtainedusingthe Anton-ParrXRD hot stage,
with the x-ray data being collectedas just described.The powderpattern of initial
materialwasobtained,andthenthe stagewasheatedto 95C.The glycerylmonostearatewasheld at this temperaturefor 10 minutesandthenallowedto coolbackto room
temperature,whereuponthe full XRD powderpatternwasremeasured.
CHEMICAL

TESTS

The determinationof acidvalue, saponification

value, estervalue, and iodinevalueof
eachlot of glycerylmonostearate
wasperformedasdescribed
in USP XXI.

RESULTS
CREAM

AND

FORMULATED

DISCUSSION
WITH

U.S.-SOURCED

RAW

MATERIALS

A thixotropiccosmeticoil-in-watertypevanishingcreambasevehiclefor a topicaldrug
productwasformulatedusingcommercially
availableU.S.-sourcedraw materials.Penetrometerconsistency
resultsfor the creaminitially after manufacturewere within the

rangeof 260-295. After storage

at 24 ___3Cfor several
weeks,the creamdeveloped
firmer consistency
due to formationof the gel structure(1) andexhibitedpenetrometer

OIL-IN-WATER

CREAM

STABILITY

219

valueswithin the range of 230-280. No liquid bleed separationwas observedin

samples
of creamafter 24-monthstoragebetween-20C and 40C.Additionally,
samplesof creampackagedin tubesdid not exhibit any liquid separation.Scale-up
batchsizesof 50 kg to 200 kg werepreparedsuccessfully
usingplanetary(Glen) type
mixersequippedwith variable-speed
homogenizer
agitatorsfor emulsification.
CREAM

FORMULATED

WITH

U.K.-SOURCED

RAW

MATERIALS

In consideration
of worldwidemanufacture
of the creamproductandaspart of scale-up
developmentevaluationsto supportthe useof raw materialsourcedfrom other countries, hatchingstudieswere initiated usingselectedraw materialsobtainedfrom the
United Kingdom(U.K.). A 20-kg placebocreambatchwaspreparedin a 10-gallon
Groenmixer. The creamcontainedU.K.-sourcedglycerylmonostearate,
cetyl alcohol,
Syncrowax
ERL-C, AmercholL-10! (oil phasecomponents
essentialfor gel structure
and consistency),
Tween 60 (emulsifier)and Glucam E-20 (humectant),which was
solublein the aqueous
phase.All otheringredientsin the creamwereU.S.-sourced.

The finishedbulk creamimmediatelyaftermanufacture

hada softfluid consistency
and
exhibitedexcessive
liquid bleedwhenstoredin tubesandwhensubjectedto the wiremeshbleed test. This was also obviouswhen pocketsor creviceswere made in the
surfaceof the cream.A portionof the bleedwasanalyzedandfoundto containmainly
waterandpropyleneglycol, which indicatedthat the externalaqueous
phasewasnot
entirelyentrappealwithin the gel matrix of the cream.Also, the soft fluid gel consistencyof the creamindicatedthe absence
of a rigid gel structure,whichmayhavebeen
due to shearthinning or delayedgel formation.A comparison
of the key differences
betweencreamspreparedusingU.S.- and U.K.-sourcedingredientsis summarizedin
Table I.

EFFECTS OF STORAGE

TIME

AND

CREAM

U.K.

INGREDIENTS

CONTAINING

TEMPERATURE

ON CONSISTENCY

AND

BLEED POTENTIAL

OF

The creambatchcontainingU.K.-sourcedexcipientswassubdividedon the secondday

after manufacture.Portionsof the creamwere placedin tightly sealedstainlesssteel

containers
and storedat 5C, 24 + 3C,and 33C.Consistency
and the extentof
bleedweredeterminedafter3, 6, and 17 daysof storage.The resultsshownin Figures
1 and2 indicatethatwarmtemperature
storage
(33C)for 3 dayscaused
accelerated
gel

Table

Observed
Differences
ImmediatelyUpon Manufacture
of CreamBasesPreparedUsingU.S. and U.K.
Raw Materials

CreampreparedusingU.S. ingredients

CreampreparedusingU.K. ingredients

Appearance
Consistency

Firm
282-288

Soft, flowable

Bleed (% w/w)

8-12

Microscopic

Finelydispersed
spheres
of internaloilwax phase

Uniformlydistributedspheres
of clear
aqueousphaseinterdispersed
with
internal oil-wax phase

315-320

220

JOURNALOF THE SOCIETYOF COSMETIC

CHEMISTS
20

;11o

290

280

270

260

240

I
0

I
2

'" I

i
B

i
10

12

I
14

16

nu,= (day,)

Figure1. Timedependence
of the consistency
asa function
of storage
temperature
for creamprepared
usingU.K.-sourced
ingredients.
Dataareshown
for 5C(+), 24C([) and33C() storage
temperatares.

10

10

12

14

nuE (dy)

Figure2. Timedependence
of theextentof bleedasa function
ofstorage
temperature
forcreamprepared
usingU.K.-sourced
ingredients.
Dataareshownfor 5C(q-), 24C([2])and33C() storage
temperatares.

OIL-IN-WATER

CREAM

STABILITY

221

formation,promotedfirmer consistency,
and eliminatedthe bleed potential of the
cream.Storageat 5Cfor 3 to 6 daysinhibitedor delayedgel formation,promoteda
softerconsistency,
andincreased
the bleedpotentialof the cream.Storageat 24Cfor 3
to 6 daysgraduallyincreased
the consistency
firmnessanddecreased
the bleedpotential
of the cream.

Microscopic
observations
weremadein studyingthe effectsof storagetemperatureon
the consistency
and bleedpotentialof the bulk cream.Initially after manufacture,the
creamhad the appearance
of discretemicroscopicspheresof internal phase,closely
packed,but floating freelyin the aqueousexternalphase.The sphereswere not fused
togetheranda rigid three-dimensional
gel structurewasnot observed,whichaccounted
for the softcreamconsistency
and bleedpropensity.The presence
of uniformlydistributed dropletsof clearaqueous
phaselooselyentrappedthroughoutthe internaloil-wax
phasealsosignifiedan increased
bleedpotential.

Microscopic
examination
of the creamsamplestoredat 33Cshowedthat the internal
phasesphereswere fusedtogetherand that the aqueousexternalphasewas securely
entrappedin the matrix. Through the useof polarizingopticalmicroscopyit wasconcluded that the gel structurewas liquid crystallinein nature. Thesepropertiesyield
firm creamconsistency
without the potentialfor the creamto bleed.

The 5C-stored
sampleof the creamwassimilarmicroscopically
to thesamplestoredat
24C.The oil-waxspheres
werepackedmorecloselydueto shrinkage
of the waxstructure at 5C,but afterthe sampleequilibratedat 24 __ 3C,it wasobserved
that the
spheres
werenot fusedanda rigid gel structurewasnot present.The physicalshrinkage
of thewaxstructureat 5Capparently
expelledor "squeezed
out"a largerportionof the
aqueousexternalphasefrom the looselybound matrix, which resultedin a greater

amountof bleedafter6 daysstorage

at 5C.
EFFECT OF INDIVIDUAL

U.K.

EXCIPIENTS

ON CREAM

CONSISTENCY

AND

BLEED

POTENTIAL

A seriesof 20-kg creambatcheswas preparedusing a 10-gallonGroen mixer. The

batchesconsisted
of the U.S.-sourcedexcipientsanda systematic
substitutionby U.K.sourcedexcipients.
Penetrometerand bleedtestingindicatedthat the creambasecontainingU.K.-sourced
glycerylmonostearate
(with all otherexcipientsU.S.-sourced)demonstrated
softerconsistencyand extensivebleed. U.K.-sourcedcetyl alcohol,Syncrowax
ERL-C, Tween
60, andAmercholL-101 did not promotebleedin the creambasespreparedusingthe
Groen mixer (Table II). The resultsof this study led to a focuson the differences
betweenU.S.- and U.K.-sourcedglycerylmonostearate.
ANALYTICAL
GLYCERYL

AND

THERMAL

ANALYSIS

TESTING

OF U.S.-

AND

U.K.-SOURCED

MONOSTEARATE

Thermal analysis,including DSC and powder x-ray diffractionmeasurements,were

determinedfor eachcreamexcipient.No significantdifferences
wereobservedbetween
U.S. and U.K. excipientsexceptfor glycerylmonostearate.

Differentialscanningcalorimetrywasusedasthe first characterization

tool for glyceryl
monostearate
sinceslight variationsin chemicalcompositioncouldyield variationsin

222

JOURNAL OF THE SOCIETY OF COSMETICCHEMISTS

Table

II

Initial Consistency
and BleedPotentialin CreamBasesContainingIndividuallySubstituted
U.K.SourcedExcipients
Substituted

U.K. excipient

Penetrometer

Bleed

consistency

(% w/w)

Glyceryl monostearate
Cetyl alcohol

299
281

9-10
0

Syncrowax
ERL-C

284

Amerchol L- 101

282

Tween 60

270

the glycerylmonostearate
meltingpoints.Furthermore,sincethe processing
usedin the

manufacture
of the creaminvolvedmeltingandcongealing
of glycerylmonostearate,
the DSC thermogramof meltedandcongealed
glycerylmonostearate
wasalsoobtained.
The DSC profileof U.S.-sourcedglycerylmonostearate,
asit wasreceived,is shownin
Figure3, asis the DSC thermogramobtainedon glycerylmonostearate
whichhadbeen
meltedand allowedto solidify.It is evidentfrom the data that glycerylmonostearate
doesnot solidifyback into its originalphysicalstate. Most sampleswere found to

exhibit an initial melt around60C, and after the melting/congealing

process
they

(+)

(-)

Temperature

(oC)

Figure 3. Differentialscanningcalorimetrythermograms
obtainedfor U.S.-sourcedglycerylmonostearate
asreceived(solidtrace)and afterbeingmeltedand congealed
(dashedtrace).

OIL-IN-WATER

CREAM STABILITY

223

(+)

(-)

Temperature (oC)
Figure 4. Differentialscanning
calorimetry
thermograms
obtainedfor U.K.-sourcedglycerylmonostearateasreceived
(solidtrace)andafterbeingmeltedandcongealed
(dashed
trace).

yieldeda meltingpointaround55C.Thisbehavior
of glycerylmonostearate
is consistent with previousfindings(5,6).
The DSC profileof U.K.-sourcedglycerylmonostearate
(seeFigure4) wasfoundto
exhibita slightlydifferenttrend.The DSC meltingpoint of materialasreceived
averagedaround65C,andafterbeingallowedto melt andsolidifythe DSCmeltingpoint
decreased
to 59C. This material also appearsto undergoa structuralchangeupon
meltingandcongealing,
but the differenttemperature
valuesnotedbetweenU.S.- and
U.K.-sourcedglycerylmonostearate
suggests
that thestructuralchanges
arenot equivalent.

The acidvaluesof the two sourced

glycerylmonostearates
werefoundto differ signifi-

cantly(seeTableIII). The acidvalueof the U.S.-sourced

materialwasfoundto be 5.1
eq. KOH/gm, whilethe acidvalueof the U.K.-sourcedmaterialwasmeasured
as 1.1
eq. KOH/gm. Thesedifferences
in acidvalueare significantanddefinitelyindicate
differences
in chemicalcomposition
betweenthe two lots. In fact, whenU.K.-sourced

glycerylmonostearate
wasspikedwith approximately
2% w/w stearicacid(raisingthe
acid value of this materialto about 5), its DSC melting point wasfound to decrease
downto 60C. The estervalue, whichis the differencebetweenthe saponification
value
lessthe acid value, was 166.9 for the U.K. materialand 158.9 for the U.S. material,
whichindicatedthat the U.K. glycerylmonostearate
wasslightlymorelipophilic.Fur-

224

JOURNALOFTHE SOCIETYOFCOSMETIC
CHEMISTS
Table

III

ComparativePropertiesof GlycerylMonostearate
SourcedFrom U.S. and U.K.
U.S.

Appearance
Total % monoglyceride

U.K.

Flakes
41.0

Powder
36.3

Iodine value

1.6

0.6

Acid value

5.1

1.1

Saponification
value

164.0

168.0

Ester value

158.9

166.9

MeltingpointBy DSC

60C

65C

ther, the total monoglyceride

and diglyceridecontentswere lowerand the triglyceride
contentwashigherfor the U.K. source,whichindicatedfewerfreehydroxylgroupsand
thereforea more lipophiliccharacter.

Since the DSC experimentsimplicated the existenceof a structural changeupon

melting and congealing,variabletemperatureXRD experimentswere carriedout to
identify the nature of this structuralalteration.Although the material is of relatively
low crystallinity, sufficientstructureexiststo yield somex-ray scatteringat 2-theta

anglesbetween18 and25. As shownin Figure5, the XRD patternof U.S.-sourced

glycerylmonostearate
consistsof at leastfour features.A new XRD patternwasob-

18.8

15.6

Degrees 2-Theta
Figure 5. X-ray powderdiffractionpatternsobtainedfor U.S.-sourced
glycerylmonostearate
asreceived
(solidtrace)and afterbeingmeltedand congealed
(dashedtrace).

OIL-IN-WATER

CREAM STABILITY

225

tainedafter melting this sampleon the XRD hot stageand allowingthe materialto
congeal.Thisnewpatternis farsimplerthanoriginallyobserved
andconsists
of at least
two features.The width and locationof the XRD peakssuggestthat they do not
represent
individuald-spacings,
but insteadreflectthe orderingof the materialas a
whole.

Quite differentbehaviorwasobserved
for U.K.-sourcedglycerylmonostearate.
As evident in Figure 6, the materialconsisted
of the samefour-peaksystem,althoughthe
relativeintensitiesof thesewerenot equivalentto the U.S.-sourcedmaterial. Melting

andcongealing
the U.K.-sourced
materialcaused
the totalcollapse
of all peaksinto a
singlegaussian
peak,centered
at 222-theta.Thisobservation
is interpretated
to imply
that the U.K.-sourcedglycerylmonostearate
congeals
into a single-phased
material.

The implications
of the XRD studiesarethat a chemicaldifference
betweenthe U.S.and U.K.-sourcedglycerylmonostearate
yields structuraldifferences
after theseare
meltedand congealed.A materialcapableof solidifyinginto a singlephasewould
contractsignificantlyuponcooling,while a materialthat wouldsolidifyinto a multiphasicmixturewould not be able to contractuponsolidification.This behaviorhas
indeedbeenobservedfor bulk glycerylmonostearate:
if the slide holding the U.K.sourced
materialis invertedafterthe melt congeals,
the materialwill actuallyfall out of
the XRD slide holderof its own accord.The U.S.-sourcedmaterial is extremelydiffi-

cult to removefromthe slideholderandrequiresmechanical

scrapingfor its removal.It

10.0

15.0

0.0

5.

30.8

Degrees 2-Theta
Figure6. X-raypowder
diffraction
patterns
obtained
forU.K.-sourced
glyceryl
monostearate
asreceived
(solidtrace)andafterbeingmeltedandcongealed
(dashed
trace).

226

JOURNALOF THE SOCIETYOF COSMETICCHEMISTS

Degrees 2-Theta
Figure 7. X-ray powderdiffractionpatternsobtainedfor U.K.-sourcedglycerylmonostearate
to which
sufficientstearicacidhadbeenaddedsoasto raisetheacidvalueto approximately
5. Dataareshownfor the
unheatedmaterial(solidtrace)andfor the sampleafterit had beenmeltedand congealed
(dashedtrace).

wouldappearthat the chemicalcomposition

of the U.K.-sourcedglycerylmonostearate
is such that all non-idealities cancel and the overall material behaves as if it were a

chemicallypure material.

To test this hypothesis,U.K.-sourced glycerylmonostearate

spikedwith stearicacid
was subjectedto the variabletemperatureXRD study. As evidentin Figure 7, the
complicatedinitial XRD pattern simplifiedafter the materialwas melted and con-

gealed,but the resultingXRD patternnowcontained

several
scattering
peaks.In addition, the congealedmaterialremainedfirmly attachedto the XRD slideholderafter
solidification
and wasremovableonly with difficulty.Theseobservations
indicatethat
additionof the stearicacidalteredthe composition
of the glycerylmonostearate
sufficiently that it couldnot congealinto a singlephasecapableof contraction.

The effecton creampropertiesresultingafter chemicalmodificationof the glyceryl

monostearate
compositionwasthen investigated.U.K.-sourcedglycerylmonostearate
(acidvalue 1.1) wasmodifiedby the additionof stearicaciduntil the final acidvalue
wasadjustedto approximately
5. Upon manufacture
of a 20-kg creambatch,no initial
bleedwasobserved.
Relativeto a creammadewith U.K.-sourcedglycerylmonostearate, the consistency
of the modifiedformulation(with stearicacid)wasfirmerinitially,
and the gel structuredevelopedmore rapidly (seeFigures8 and 9).

OIL-IN-WATER

CREAM

STABILITY

227

320

310

29O

280

270

I -]'"

I --

lO

l:Z

--r' ' ' I

14

nu,

Figure$. Timedependence
of theconsistency
asa functionof creamprepared
withU.K.-sourced
glyceryl
monostearate
with ([2])andwithout (+) addedstearicacid.

1o -'
g-

o-

7-

6-

4 -

10

12

14

111dE
(dM)

Figure9. Time dependence

of the extentof bleedasa functionof creamprepared
with U.K.-sourced
glycerylmonostearate
with ([2])and without (+) addedstearicacid.

228

JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS

EVALUATIONS

OF GLYCERYL

MANUFACTURING

MONOSTEARATE

SOURCED

FROM

NON-U.S.

PLANTS

Glycerylmonostearate
samplessourced
from inventorysuppliesof manufacturing
plants
locatedin Canada,Germany,Greece,SouthAfrica, and Spainwereobtained.Analytical and thermalanalysisresultswerecomparedto thosepreviouslyobtainedfor U.S.
and U.K. samples.Five creambatches(20 kg each)wereprepared.Eachof the cream
basescontainedglycerylmonostearate
suppliedfromoneof the above-mentioned
plant
sources.

As shownin Table IV, thereappearedto be a rankcorrelationbetweenthe bleedpotential of the creamand the acid value of the glycerylmonostearate
raw material. The
creamscontainingglycerylmonostearate
with very low acid valuesof about 1 or less
exhibitedthe mostinitial bleed.Thosewith acidvaluesof 2-3.5 showedslightinitial
bleed, and thosewith acid valuesof about 5 and greaterdid not exhibit bleed. Initial
higherpenetrometerresults,which are indicativeof softercreamconsistency,
wereobtainedfor creamscontainingglycerylmonostearate,
havinglower acidvalues.Thermal
analysisand variabletemperaturex-ray diffractionmeasurements
accuratelyclassified
andpredictedthe probableeffectsthat eachglycerylmonostearate
sourcewouldhaveon
the consistency
and bleedpropensityof the finishedcream.All of the multi-sourced
glycerylmonostearate
creambasesdevelopedfirmer consistency
and diminishedbleed
potentialafter7 daysof bulk storageat 24 ___3C.

CONCLUSIONS

Glycerylmonostearate
wasidentifiedasthe key excipientinfluencingthe gel structure,
consistency,
and bleedpropertiesof the oil-in-wateremulsion-type
creambase.
Acid value,which is a measureof the freefatty acidsin the glycerylmonostearate,
was
found to be an importantindicatorof raw materialquality. Creamspreparedusing
glycerylmonostearate
with low acidvalue(1-3.5) had softconsistency
and exhibited
liquid bleedseparationinitially aftermanufacture.Creamscontainingglycerylmonostearatewith higheracidvalue(5- 15) had satisfactory
firm consistency
without bleed.
Table

IV

Influenceof GlycerylMonostearates
Sourced
FromVariousCountrieson the Consistency
andthe
Propensityfor the Occurrence
of Bleedin CreamBase
Observation

on wire-mesh

test for bleed

Sourced

Acid

X-ray

from

value

type

0.85
1. !
2.0
3.5

2
2
2
2

Germany
U.K.
Greece
Spain
U.S.

After 7 days
storageat

Initial

penetrometer

Initial

24 + 3C

298
317
297
293

Bleed
Bleed
Slight bleed
Slight bleed

Slightbleed
Slight bleed
No bleed
No bleed

5. !

285

No bleed

No bleed

Canada

10.0

266

No bleed

No bleed

South Africa

14.9

284

No bleed

No bleed

OIL-IN-WATER

CREAM

STABILITY

229

DSC and VTXRD thermal analysismethodswere used to characterizeand classify

multi-sourcedgradesof glycerylmonostearate.
Theseaccuratelypredictedthe effects
that eachlot of glycerylmonostearate
wouldhaveon the consistency
andbleedpropensity of the finishedcream.

Conepenetrometer
andwire-meshscreentestingwereutilizedfor assessing
consistency
and bleedpotentialof the bulk creamimmediatelyaftermanufacture
and during bulk
creamstorageprior to approvalfor packaging.

Basedon this study,in orderto overcome

variableconsistency
andbleedproblems,the
followingrecommendations
canbe made:
1. If possible,useonly glycerylmonostearate
with higheracidvalue(5-15) and optimal thermal analysisVTXRD pattern.

2. Creambatchespreparedusingglycerylmonostearate
with low acidvalue(below5)
shouldbe storedat 20-33Cuntil a firm consistency
develops
and no bleedis
evidentwhentestedby the wire-meshscreenmethod.

REFERENCES

(1) G. L. Flynn, "Unique Physicochemical

SystemsUsed Topically," in ModernPharmaceutics,
G. S.
Bankerand C. T. Rhodes,Eds. (MarcelDekker, New York and Basel, 1979), Vol. 7, pp. 298-309.
(2) H. Schott, "Rheology:Self-BodyingAction of Mixed Emulsifiers,"in Remington's
Pharmaceutical
Sciences,
17th ed., A. J. Gennaro,Ed. (Mack PublishingCompany,Easton,Pennsylvania,1985), pp.
341-342.

(3) R. G. Harry, "PolyhydricAlcoholEstersof Fatty Acids," in The Principles

And Practiceof Modern
Cosmetics,
W. W. Myddleton, Ed. (ChemicalPublishingCompany,New York, 1963), pp.
357-367.

(4) "GlycerylMonostearate,"
in Handbook
ofPharmaceutical
Excipients
(AmericanPharmaceutical
Association, 1986), pp. 125-126.
(5) R. M. Cornish,Studiesofglycerylmonostearate,
J. Soc.Cosmet.
Chem.,19, 109-117 (1968).
(6) N.H. Kuhrt, R. A. Broxholm,andW. P. Blum, Conjoinedcrystals.1. Composition
andphysical

properties,J.Am. Oil Chemists

Soc.,4, 725-733 (1963).