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Synthesisandcharacterizationsof naproxenintercalated MgAllayered


doublehydroxides
BaoZhongDu1,2*,RuMinWang
1.DepartmentofAppliedChemistry,NorthwesternPolytechnicalUniversity,Xian710072,China
2.DepartmentofAppliedChemistry,XianUniversityofTechnology,Xian710054,China

Abstract:Naproxen(Nap),anonsteroidalantiinflammatorydrug(NSAIDs),wasintercalatedintothegalleryofMgAllayered
double hydroxides (LDHs) by ion exchange and coprecipitation with different location of magnesium ion and aluminum ion
solutions,respectively.TheproductwascharacterizedwithpowderXraydiffraction(XRD),FourierTransformInfraredspectral
(FTIR)andThermogravimetry(TG).TheresultsshowedanexpandedLDHstructure,indicatingthatthedrugwassuccessfully
intercalatedintoLDHwiththemonolayerperpendicularto(alongtheshortaxisorientationinproperangle)Napanion.Ascompared

n
tothepureformofNap,thethermalstabilityoftheintercalatedNapwassignificantlyenhancedduetothehostguestinteraction

. c
involvinghydrogenbondandelectrostaticattraction.WefurtherinvestigatedthedrugreleasecharacteristicsofthepillaredLDH

.ac
materialsbyadissolutiontestinsimulationgastrointestinalandintestinalfluidsunderdifferentpHvalues.Theresultsindicated
thatthereleasepercentagesdecreaseuponincreasingpHfrom4.60to7.43,likelyduetothedependenceofreleasemechanism

s
onpH.Wehavecarriedoutakineticsimulationtothereleasedataandfoundthatthedissolutionmechanismwasmainlyresponsible

p
forthereleasebehaviorofNapLDHsatpH4.60,whiletheionexchangemechanismwasresponsibleforthatatpH7.43.

c
Inaddition,theinitialreleaseratesandequilibriumpercentreleasesofthenanohybridsdependedsignificantlyonthesynthesis

. j
methods, from which wehave proposeda schematic model. Thecurrent study clearly showedthatthis druginorganiclayered
materialhasprospectiveapplicationsindrugdeliverysystem.

w
Keywords: LDHNaproxenIntercalationDrugdeliverysystem

w
CLCnumber:R943 Documentcode:A ArticleID:10031057(2010)537108

w
1.Introduction

Increasing attention has been focused on hybrid


materials represented by the general formula
M2+1xM3+x(OH)2(An)x/nmH2O,whereM2+ andM3+
area divalent and trivalent metal, respectively, and
systems such as inorganicinorganic and organic
An istheinterlayeranion[3].Asthehostcompounds,
inorganichybridsbecauseoftheirsynergisticeffects
LDHs are layered solids having positively charged
unattainablefromindependentsystemalone[1].Hybrid
layersandnegativelychargedanionintheinterlayer
systems for drug delivery require biocompatible
spaces. Among the properties of LDHs, anion
inorganicmatricesthatpermitsaferetentionaswell
exchange provides a simple method to replace the
ascontrolleddeliveryofdrugs.Amongavarietyof
interlayeranionandthusleadtoavarietyofdifferent
inorganicmaterials,layereddoublehydroxides(LDHs)
layered materials. These materials have been used
are endowed with great potential as an inorganic
asanionexchangersandcatalysts[3].Recently,more
matrixforthispurpose.Becausethereleaseofdrugs
attention has been paid to the organicinorganic
in drugintercalated layered materials is potentially
controllable,these new materials have great potential LDHs hybrid that contains drug molecules, and

asadeliveryhostinthepharmaceuticalfield[2]. many of its unique properties have been explored

LDHs, commonly known as hydrotalcites or such as enhanced dissolution property[4], increased


anionic clays, are a family of natural and synthetic thermalstability[5] andcontrolledreleaserate[6].
Naproxen (Nap), (+)6methoxymethyl2
Receiveddate:20091115.
Foundation item: Science and Technique Foundation of Xian City
naphthalene acetic acid, is a nonsteroidal anti
(GrantNo.YF07058). inflammatorydrug(NSAIDs)frequentlyusedasrelief
*
Correspondingauthor.Tel.:862982066325
email:bzhdu@xaut.edu.cn ofsymptomsofrheumatoidarthritisandosteoarthritis
Copyright 2010 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University http://www.jcps.ac.cn
372 B.Z.Du etal./JournalofChinesePharmaceuticalSciences19(2010)371378

based on its analgesic property. However, one of absorption spectrum was recorded on a UVVis
theseriousproblemsintheapplicationsofNapis spectrophotometer (Shanghai Younike Instruments
its poor solubility in water and readily absorbing Ltd.). DZ2BCtype vacuum drying oven (Tianjin
characteristics. The use of Nap is often limited by Taisite Instruments Ltd.) was used to dry samples.
thefrequentsideeffects,whichaffectbothgastroin Differentialthermalanalyses(DTA)andthermogra
testinal irritation and central nervous system. To vimetricanalyses(TG)wereobtainedonDTA7and
make the drug therapy most effective, the desired TGA7instruments(PerkinElmer),respectively.The
pharmacological response must be obtained at the analysis wascarried out under nitrogenatmosphere
[7]
target without harmful interactions at other sites , ataheatingrateof10C/min.SimultaneousTGMS
whichrequirescertainamountofdrugtobeabsorbed analysiswasperformedinaPyrisDiamondTGDTA
into the body and transported to the target at con coupledwithThermoStarQM220 massspectrometer

n
trolled drug input rate. In the previous researches, withaquartzcapillarytransferline.

. c
aimingtoimprove or enhance itsstability, solubility, Alltheexperimentalreagentssuchas Mg(NO3)26H2O,

.ac
dissolutionrateandbioavailability,naproxenhasbeen Al(NO3)39H2O, NaOH, NaH2PO3, and NaCl were

s
intercalatedintovariousLDHsbythe meansofion analytical grade. Naproxen was purchased from

p
[811]
exchange, coprecipitation and reconstruction . Aldrich,andtheothersfromBeijingChemicalPlant

. jc
However, the majority of these methods have the Inc.

w
disadvantagesoflongtimecostingduringtheprocess
2.2.SynthesisofnitrateLDHs

w
of NapLDHs synthesis, along with nonuniform

w
particlesize. We prepared the Al(NO3)3 solution by dissolving
Inthispaperwehavereportedthepreparationof 18.75gofAl(NO3)39H2Oin75mLdeionizedwater
NapLDH following two wellknown procedures and transferred to a fourneck flask with vigorous
(coprecipitation and ion exchange) by gradually stirringat60Cundernitrogengasflow.Thenwe
increasing Mg2+ concentration in the solution of addedasolution(75mL)ofMg(NO3)26H2O(51.2g,
Al3+ at different experimental conditions (e.g. pH, 0.2mol)andasolution(100mL)ofNaOH(24.0g,
temperature and reaction time). We emphasize our 0.6 mol) by two constant pump. The feeding time
efforts to enhance the Nap solubility in water and wasfixedat2h.ThepHvalue ofreactionsolution
optimize the synthetic routes of NapLDH. The was kept constant (10.50.5) during the reaction
resultant samples were characterized by different processbyadjustingtheflowrateofthesetwosolu
physicochemical techniques. Finally, we systemati tions. After the reaction process, the resultant slurry
callystudiedthereleasebehaviorofNapLDH. wasagedat65Cfor24h.Theprecipitatewascen
trifugedand washedwithdeionizedwater until the
2.Experimental pH value reached 7. Then the clean precipitated
wasdriedinvacuumat85Cfor16h.
2.1.Instrumentandchemicalreagents
2.3.SynthesisofNapNO3LDHsbycoprecipitation
The pH value was detected by a PHS3C pH
meter (Shanghai Kangyi Instrument Ltd.). Infrared Nap (5.94 g) was dissolved in 100 mL of decar
spectra was collected in a FTIR8900 infrared bonated waterand neutralized withNaOHsolution.
spectrometer (Shimadzu Corporation, Japan). The Al(NO3)39H2O(1.13g)wasdissolvedin50mLof
XRDpatternsweremeasuredonaXRD7000Xray decarbonatedwaterandtransferredintoafourneck
diffractioninstrument(ShimadzuCorporation,Japan) flask, which was kept in water bath at 60C under
usingCuKradiationat40kVand40mA.TheUV nitrogengasflow.Withvigorousstirringfor5min,
Copyright 2010 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University http://www.jcps.ac.cn
B.Z.Du etal./JournalofChinesePharmaceuticalSciences19(2010)371378 373

theabovementionedNapsolution wasslowlyadded 2.6.Drugreleaseproperties


to Al(NO3)3 solution. The pH value of the reaction
Asimulatedsolutionofgastrointestinalandintes
solutionwaskeptconstant(9.5)andthenasolution
tinal fluid at pH 4.60 (phosphate buffer) and 7.43
(50 mL) of Mg (NO3)26H2O (1.54 g, 0.006 mol)
(phosphatebuffer),physiologicalsalineanddistilled
wasaddeddropwiselytothereactionsolutionover
waterwereemployedasreleasemedium,respectively.
3 h. The precipitate was filtered and the solid was
WehaveperformedtheNapreleasefromNapLDHs
washedseveraltimeswith decarbonatedwateruntil
intothemediabyaddingca.0.25gNapLDHsinto
the pHreached7.Finally,thecleanprecipitatewas
100mLreleasemediumat(370.5)C.Thepaddle
driedinvacuumat70Cfor24h.
rotation speed was 100 r/min. A sample of 5 mL
2.4.SynthesisofNapLDHsbyanionexchange product was withdrawn at predetermined intervals
and centrifuged. The accumulated amount of Nap

n
The naproxen intercalated nitrate LDHs was pre

c
releasedintothesolutionwas measuredmomentarily

.ac .
paredbytheionexchangemethod.Weaddedasolu using UVVis spectrophotometer at the wavelength
tion containing 5.94 g Nap in 50 mL decarbonated of331nm.

s
water into 100 mL aqueous suspension containing

jc p
4.00 g precursor Mg/AlNO3LDHs, and the pH of

.
3.Resultsanddiscussion
the solution was kept at 10.0 by adding 2 mol/L

w
NaOHsolutionduringthereactionprocess.Themix

w
3.1.XRDcharacterization
turewas vigorously stirred at 60 C for 5 min, 0.5,

w
1.5 and 4 h in nitrogen atmosphere, respectively. Figure1illustratestheXRDpatternsofNapinter
Thentheresultantwasfiltrated,washedwithdecar calated MgAlLDHs materials prepared by different
bonated water until the pH reached 7.0 and finally methods. The XRD pattern of Mg/AlNO3LDHs

driedinvacuumat70Cfor24h.Theproductswere was also shown for comparison. The characteristic

denoted as NLIEb, NLIEc, NLIEd and NLIEe, peaks for LDHs (2 = 11.35, 23.23, 34.54 and

respectively. 60.65),correspondingtoMillerindices(003),(006),
(009)and(110)wereobserved(Fig.1a).Thesesharp
2.5.MeasurementsofloadingamountsofNapin and symmetric peaks demonstrate the formation of
NapNO3LDHs wellcrystallized Mg/AlNO3LDHs with the inter
layer distance d003 value of 0.77 nm. In Figures 1b
The loading amounts (A) of Nap in NapLDHs
prepared by the abovementioned methods were
measured by the UVVis spectroscopy using the
following method.NapLDHssamples(0.05g)and
0.5mLof1mol/LHNO3 solutionweremixedintoa
50mLvolumetricflask.Thebalancewasfilledwith a
phosphate buffer at pH 7.43. The concentration of
Napin theresultingsolutionwas determinedbased b

on the absorbance at 331 nm, from which we have


c
calculatedtheamounts ofNapbyregressionanaly
sisofthestandardcurve. The measurement ofNap 1020304050607080
2 ()
loadingamountswasperformedintriplicateandthe
Figure 1. XRD patterns of LDH(a),NapLDH sample preparedby
averageresultswererecorded. coprecipitation(b)andionexchange(c)methods.

Copyright 2010 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University http://www.jcps.ac.cn
374 B.Z.Du etal./JournalofChinesePharmaceuticalSciences19(2010)371378

and 1c, the characteristic reflections of LDHs com Thesecondsharpevent(290410C)wasduetothe


pounds,andthebasalreflection(003)shiftedtolower naproxen decomposition (weight loss of 25.1%). It
2angles(for(003)reflection:2=8.04)compared should be noted that this temperature region was
withthoseofNO3LDHs(2 =11.35).Theinterlayer obviously higher than that of the pure free Nap[8],
spacing of d003 increases 0.32 nm compared with suggestingthatthethermalstability oforganicNap
NO3LDHs, indicating the successful intercalation speciesinNapLDHswere clearly enhanced dueto
[810]
of Nap anions into the interlayer region . The the hostguestinteractioninvolving hydrogenbond.
absence of diffraction lines of crystalline naproxen It is also supported by the following IR analysis.
excludes the possibility of a heterogeneous phase Thethirdlossevent(410530C)couldbeattributed
and confirms that the entire drug was intercalated to the further decomposition of drug with CO2 and
between the brucitelike layers. In the case of watervaporevolution(weightlossof19.2%)[9].The

n
intercalation by ionexchange technique (Fig. 1c), laststage(530800C)wasmainlyattributedtothe

. c
the XRD pattern shows two types of (003) peak: dehydroxylation of the host layer accompanying

.ac
theoneoflowintensityatlowerangle(2=8.19) with the formation of layered double oxide at the

s
corresponds to the intercalated Nap while the other weight loss of 2.5%. Compared with the thermal

c p
one (2 = 11.76) is for the original NO3LDHs. stability datareportedbyPengetal.[11], four distin

. j
Thisindicatesthatthelayergallerycontainedboth guishableweightlossstepsindicatedthatthethermal

w
the drug with low content and nitrate with high stabilityofNapLDHspreparedfromdifferentloca

w
content, which is contrary to that observed in the tion of magnesium ion and aluminum ion solutions

w
coprecipitation technique. The XRD data are in wasgreatlyimprovedwithwellcrystallizedstructure.
agreement with the drug loading ratios obtained
by the UV quantitative method (12.8% for the 100 0

sampleobtainedbycoprecipitation,while5.6%for
ionexchangetechnique).
WeightLoss(%)

80 10
DTA T(C)
3.2.Analysisofthermalstability
60 20
TGDTA curves for Mg/AlNO3LDHs precursor TG

and NapLDHs are shown in Figures 2 and 3,


0 30
respectively.InFigure2,threemainthermalevents 50200350500650800
T(C)
were clearly observed. The first endothermic peak
Figure2. TGandDTAcurvesforLDH.
locatingat(50230)Ccorrespondedtotheremoval
of external and interlayer absorbed water (Weight
100 40
loss:15.9%).Thefollowedstage(270465C)was TG
30
the result of decomposition of NO3 (Weight loss:
80
WeightLoss(%)

26.9%). The last stage (465800 C) demonstrated 20


T(C)

that the interlayer structure had been destroyed at 10


60
theweightlossof7.3%. 0
DTA
ThethermaldecompositionofNapLDHscomplex 10

wascharacterizedbyfourstepsasshowninFigure3. 30 20
50200350500650800
The first (50260 C) was due to the loss of both T(C)

adsorbedandinterlayerwaterat15.1%weightloss. Figure3. TGandDTAcurvesforNapLDH.

Copyright 2010 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University http://www.jcps.ac.cn
B.Z.Du etal./JournalofChinesePharmaceuticalSciences19(2010)371378 375

3.3.Infraredspectra

(f)
Figure 4 shows the FTIR spectra of LDH, Nap
LDHspreparedbyionexchangefor5min,0.5,1.5, (e)
(d)
4handtheNapLDHspreparedviacoprecipitation
process. In Figure 4a, a broad strong adsorption
(c)
band at 3454 cm1 could be attributed to the (b)

stretching vibration of hydroxyl groups of water


molecules in the interlayer and physicaladsorbed (a)

water. The adsorption band at 1631 cm1 was 3800 3400300026002200180014001000600200


Wavenumber(cm1)
assigned to the weak bend vibration of water. The
Figure4.FTIRspectraofLDH(a),NapLDHssynthesizedbyion
bandsat1396and610cm1 wereduetotheNO3 exchange after exchange for5min(b),0.5h(c),1.5h(d),4h(e)

n
andNapLDHsprepared via coprecipitationmethod(f),respectively.
stretching vibration. Thebandat450cm1 wasdue

. c
toOMOvibrationrelatedtoLDHlayers.Theband

.ac
at2362cm1wasassignedtoCO2fromatmosphere. 3.4.AssemblymechanismofNapLDHs

s
InFigure4e,twoweakbandsat2956and2875cm1

p
InthegeneralformulaM2+1xM3+x(OH)2(An)x/nmH2O

c
were attributed to the asymmetric and symmetric

j
of LDHs, An was an exchangeable inorganic or

.
vibration of CH3, respectively. The asymmetric

w
andsymmetricstretchingvibrationofcarboxylate organicanion, which couldbeeasilysubstitutedby

w
COO were observed at 1561 and 1387 cm1, re otheranion(Xn)withhighanionexchangecapacity

w
spectively.ComparedwithFigure4a,theabsorption and released from the layer of LDHs with simple
peakofC=O movedtolowfrequency,indicatingthe ionexchangemethod[8].AccordingtotheXRDand
interaction of Nap in the interlayer space involving IR spectra, the amount of Nap in the NapLDHs
hydrogen bonding, and the obvious electrostatic prepared with ionexchange process could be
attraction between guest Nap and host layer[8]. The affected by several parameters such as pH value,
peaksat1653,1609and1507cm1 wereassignedto reaction temperature and time. Small amount of
theskeletonstretchingvibrationmodeofaromatic Nap was found at the end of intercalation as the
ring. The bands at (13001000) cm1 were attributed exchange balance setting up. However, the Nap
tothebend vibration mode ofaromaticring.The LDHs prepared by coprecipitation with high drug
bandsat1036and847cm1 wereascribedtoabsorp loading ratios could easily be obtained when the
tion of COC groups in Nap. The characteristic
magnesiumionandaluminumionwereaddedsepa
absorption peaks of Nap could be clearly observed
rately.Itmightbeexplainedasfollows:(1)aninter
in Figure 4f, indicating the drug has been success
mediatesolgelstate,formedintheprocessofinter
fully intercalated into the gallery of LDHs. How
layer construction, wasbeneficial to the intercalation
ever,itwasclearlyobservedthatthebandsat1396
oftheguestintothegalleryofLDHsastheaddition
and610cm1 duetotheNO3 disappearedgradually,
ratioofMg2+controlled(2)astheintermediatestate
while the bands belonging to Nap increased upon
increasing exchange time. The transition from formed,thepossibilityofionexchangewassignifi
Figures 4b4e demonstrated that NapLDH could cantly improved between the Nap guest and the
not be obtained in short time via ionexchange nitrate intheLDHsprecursor.Asaresult,theloading
method. On the contrary, the Nap could be easily ratioofdrugwasincreased,aswellasthesustained
intercalated into the interlayer within 2 h by co releaseeffectwasenhancedobviously(delayed50min
precipitationwiththedifferentlocationofMg2+ and compared with the physical mixture of drugs and
Al3+. LDHs).
Copyright 2010 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University http://www.jcps.ac.cn
376 B.Z.Du etal./JournalofChinesePharmaceuticalSciences19(2010)371378

3.5.LoadingamountsofNaponLDHs 3.6.Drugreleaseproperties

The linear regression analysis of the standard Wehaveinvestigatedtheinvitroreleaseproperties


curvewasshowninFigure5.Theloadingamounts ofthedrugbyaddingtheintercalationcompoundin
(A,inmgNap/gLDHs)ofNaponLDHswerelisted distilled water(a), physiologicalsaline(b),simulated
in Table 1. The A value of NapLDHs obtained by intestinal buffer (c, pH 7.43), and gastrointestinal
fluid(sodiumdihydrogenphosphatebuffer,pH4.60)
the former method was much higher than (the
(d),respectively.TheresultswereshowninFigure6,
percent of Nap in NapLDHs about 12.8%) that of
whichindicatedthatthereleaseprofilesreachedan
the NapLDHs obtained by the later. The A values
almostconstantlevelafter50min(Fig.6aand6b).
might be dominated by some factors including
However,thereleaseratesreachedequilibriumstate
surfacechargedensity,unoccupiedinterlayerspace,
after150minand80minatbothpH7.43and4.60,

n
thepolarityofguestspecies,etc[12].

c
respectively. This observation may be explained as

.ac .
follows.First,theNapintercalatedinLDHmaterials
0.7 was ionexchanged by CO32, which was formed by

s
Nap
the dissolution of CO2 and delayed the release of

p
0.6

c
y =0.013x +0.0041

j
r2=0.9983 naproxen in distilled water. Second, the release

.
0.5
behaviour of NapLDHs in physiological saline

w
0.4
exhibitedahighinitialdrugreleaserateintheinitial
A

w
0.3
10minandreachedanalmostconstantlevelafter

w
0.2
50min.ComparedwithNap,Cl waseasilyinterca
0.1 latedintoLDHlayers,whichacceleratedtherelease
0 of Nap. However, in thesimulated intestinal buffer
0 1234 56
c (g/mL) (pH7.43,Fig.6c),thereleaseofNapLDHsshowed
Figure5.StandardabsorptioncurveofNap. a slow and persistent process originating from the
ionexchange process between the intercalated
Table1. LoadingamountsofNapinNapLDHs
anions and phosphate anions in the buffer[13]. In
Synthesismethod Loadingamounts(mgNap/gLDHs) addition,thereleasebehaviouratpH4.60wasvery
Coprecipitation 16.4
fastduringthefirst5min,whichcouldbeattributed
Anionexchange 7.4
to the partial dissolution of LDHs layer at weak
acidic solutions[13]. After 80 min, a slower release
0.8
(d) stepcharacterizedasreachedanequilibriumstate,as
(c)
showninFigure6d.
0.6
Thereleasecurvesforphysicalmixture(Napwith
(b)
LDHs, Fig. 7a)and Nap from NapLDHs (Fig. 7b)
A

0.4
in solution at pH 7.43 were shown in Figure 7. It
was obvious that the physical mixture of drug and
0.2
LDHs indicated inconspicuous sustainedrelease
(a)
effect in the solution at pH 7.43. For this mixture,
0
050100150200260 the total Nap content was immediately released at
t(min)

Figure 6. Release profiles of Nap from NapLDHs in different pH


the initial 20 min. However, the Nap intercalated
values. (a) Distilled water (b) Physiological saline (c) Simulated LDHspresentedagradualreleaseofNapanionsasa
intestinal buffer (pH 7.43) and (d) Gastrointestinal fluid (sodium
dihydrogenphosphatebuffer,pH4.60). function of time until the equilibrium state formed
Copyright 2010 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University http://www.jcps.ac.cn
B.Z.Du etal./JournalofChinesePharmaceuticalSciences19(2010)371378 377

after 170 min. These data indicated that the Nap monolayer vertical (along the short axis orientation
LDHspreparedviacoprecipitationsystemwas more in proper angle) between layer, where the carboxyl
effectivethanthatpreparedviaionexchangemethod groupsofadjacentanionsattachedalternatelytothe
sincethedrugreleaserateofNapLDHswasslower upperandlowerhydroxidelayersthroughhydrogen
and the amount of drug gradually increases over a bondingandelectrostaticattraction,respectively.
longerperiod. ForthelayeredstructureofLDHs,interlayeranions
could be exchanged by other functional anions that
3.7. Intercalation structure models and release
make LDHs useful for various applications. Ion
mechanism
exchange process could be carried out slowly be
Using Gaussian 03 software, we have calculated tweentheanionsinNapLDHandinorganicanions
the long axis, short axis and molecular thickness sothatsustainedreleasecanberealized(Fig.6).

n
of Nap from the PM3 semiempirical molecular

. c
orbitalmethod,andtheirvaluesare0.581,0.407and

.ac
4.Conclusions
0.385 nm, respectively. Since the thickness of the

s
LDH layer was a constant value (0.48 nm), the WehavesuccessfullyassembledNapintercalated

p
gallery height of NapLDHs was 0.68 nm, which

c
Mg/AlNO3LDHswithMg/Alratioof2.0asdrug

j
was well consisted with the value of short axis

.
inorganiccompositebycoprecipitationwithdifferent
0.407 nm for Nap. Based on previous research

w
location of magnesium ion and aluminum ion re
resultsandtheabovementionedanalysis[9],wehave

w
sources,whichis2hslowerthanionexchangetech
proposedaformationmodelofNapLDHs,asshown

w
niques.Wehavedeterminedtheinterlayerspacingof
inFigure8.TheorientationofguestinLDHsinter
0.61nm,whichislargerthan the molecularsizeof
layer might be accommodated as alternately and
Nap(0.581 nm0.407 nm0.385 nm). FTIRspectra
analysis indicated that the guest only adopted a
0.8
monolayer arrangement with the naphthalene ring
(b)
perpendicular (along the short axis orientation in
0.6
properangle)tothelayerplane,andthecarboxylof
Absorbance

adjacent anions attaching alternately to the upper


0.4
andlowerhydroxidelayers(theloadingamountwas
(a)
12.8%).Inaddition,thesharpandsymmetricpeaks
0.2
inXRDspectrademonstratedthatNapLDHsiswell
crystallized with small size and high dispersion, as
0
050100150200260 the addition rate of Mg2+ was controlled. The host
t (min)
layersandtheguestswerebridgedthroughhydrogen
Figure 7. Release profilesof physical mixture of drug ofLDHs(a)
andNapLDHs(b)atpH7.45. bondingandelectrostaticattraction.

Inorganicanion

H2O
1.09nm

Naproxen

Figure8.SketchesofthepossiblelocationofNapintheinterlayerspaceofLDHsandreleasemechanism.

Copyright 2010 Journal of Chinese Pharmaceutical Sciences, School of Pharmaceutical Sciences, Peking University http://www.jcps.ac.cn
378 B.Z.Du etal./JournalofChinesePharmaceuticalSciences19(2010)371378

From TGDTA analysis, the thermal stability of References


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p
organicanionsandphosphateanionspresentinbuffer.

c
[8] Wei, M. Shi, S.X. Wang, J. Li, Y. Duan, X. J. Solid

j
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[9]Arco,M.D.Gutierrez,S.Martin,C.Rivers,V.Rocha, J.
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w
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viacoprecipitationprocesswasmoreeffectivethan

w
[10] Berber, M.R. Minagawa, K. Katoh, M. Mori, T.
those prepared via ionexchange method, because
Tanaka,M. Eur.J.Pharm.Sci. 2008, 35,354360.
the drug release rate of NapLDHs was slower and
[11] Peng,X.H. Huang, K.L.Jiao, F.P. Zhao, X.H. Yu,
theamountof drug graduallyincreased overalong
J.Funct.Mater. 2006, 37,415417.
period.
The present study might offer broad perspectives [12] Quan, Z.L Yang, H. Zheng, B. Hou, W.G. Colloids

in utilizing Mg/AlNO3LDHs as a biocompatible Surf.A. 2009, 348,164169.

inorganicmatrixfor drugreservoiror drug delivery [13]Zhang,H.Zou,K.Guo,S.H.Duan,X.J.SolidState


carrier. Chem.2006, 179,17921801.


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