research article the effect of polymer content on the non...

Hindawi Publishing CorporationJournal of Drug DeliveryVolume 2013 Article ID 907471 5 pageshttpdxdoiorg1011552013907471

Research ArticleThe Effect of Polymer Content on the Non-NewtonianBehavior of Acetaminophen Suspension

Eskandar Moghimipour12 Maryam Kouchak23 Anayatollah Salimi23

Saeed Bahrampour3 and Somayeh Handali2

1 Cellular and Molecular Research Center Ahvaz Jundishapur University of Medical Sciences Ahvaz 61357-33184 Iran2Nanotechnology Research Center Ahvaz Jundishapur University of Medical Sciences Ahvaz 61357-33184 Iran3Department of Pharmaceutics Faculty of Pharmacy Ahvaz Jundishapur University of Medical Sciences Ahvaz 61357-33184 Iran

Correspondence should be addressed to Somayeh Handali handali s81yahoocom

Received 9 May 2013 Revised 20 July 2013 Accepted 1 August 2013

Academic Editor Morteza Rafiee-Tehrani

Copyright copy 2013 Eskandar Moghimipour et alThis is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in anymedium provided the originalwork is properly cited

Acetaminophen is used as an analgesic and antipyretic agentThe aim of the study was evaluation of the effect of different polymerson rheological behavior of acetaminophen suspension In order to achieve controlled flocculation sodiumchloridewas addedThenstructural vehicles such as carboxymethyl cellulose (CMC) polyvinyl pyrrolidone (PVP) tragacanth and magnesium aluminumsilicate (Veegum) were evaluated individually and in combination Physical stability parameters such as sedimentation volume (119865)redispersibility (119899) and growth of crystals of the suspensions were determined Also the rheological properties of formulationswere studied The results of this study showed that the combination of suspending agents had the most physical stability andpseudoplastic behavior with some degree of thixotropy Viscosity of suspensions was increased by adding NaCl 002 Presence ofPVP is necessary for improving rheological behavior of suspensions by NaCl This may be related to the cross-linking between thecarbonyl group in the PVP segment and Na+ ions

1 Introduction

A suspension is a dispersed system in which the internalphase consists of solid particles and the external phase is aliquid vehicle Suspensions are the best conventional liquiddosage forms of drugs with high bioavailability in compar-ison to other dosage forms except solutions and they havepatient compliance [1 2] Rheological study of suspensionsprovides valuable information for efficient utilization trans-port and handling of materials in industrial applications[3] The thixotropy and hysteresis loop are rheological phe-nomena In non-Newtonian systems if the rate of shear wasreduced once the desired maximum rate had been reachedthe down curve can be displaced relative to the up curveWithpseudoplastic systems the down curve is frequently displacedto the left of the up curve This phenomenon known asthixotropy can be defined as an isothermal and compara-tively slow recovery on standing of a material which has lostits consistency through shearing [4 5] The area surrounded

between ascending and descending curves that is calledhysteresis loop can give information about the structurebreakdown and rebuilding [4 6 7] Controlled flocculationand rheologic modification are important factors in prepa-ration of suspensions Flocculated suspensions are settledrapidly to form large loose and easily dispersible sediments[8] Non-Newtonian polymers are utilized in the industriessuch as food textile pharmaceutical and cosmeticsThey areemployed in suspensions as structural vehicles and exhibitnon-Newtonian (plastic or pseudoplastics) flow with somedegree of thixotropy Various types of polymers are usedas rheology control agents such as CMC methylcelluloseNaCMC PVP xanthan gum [6 9ndash11] poloxamer [12] traga-canth [13] chitosan [6] and Veegum [14]

Acetaminophen is an analgesic and antipyretic agentwhose oral delivery especially to children is combined withtrouble due to bitter and unpleasant taste One of themethodsto achieve themaximum tastemasking characteristic is to for-mulate the drug in suspension form which creates a physical

2 Journal of Drug Delivery

Table 1 Composition of different formulations of acetaminophen suspensions

Formulation Tragacanth () Veegum () CMC () PVP () NaCl ()1198651

0 0 0 0 01198652

075 0 0 0 01198653

0 0 05 0 01198654

0 2 0 0 01198655

0 0 0 1 01198656

075 2 0 1 01198657

075 2 0 1 0021198658

075 2 0 1 0041198659

075 2 05 1 011986510

075 2 05 1 00211986511

075 2 05 1 00411986512

075 2 05 0 011986513

075 2 05 0 002

fence around the drug [15 16] The objective of this work wasto formulate acetaminophen as a relatively stable liquid formand study the influence of different polymers such as CMCVeegum tragacanth andPVPon its rheologic characteristics

2 Experimental

Polysorbates 80 sodium chloride carboxymethyl cellulose(CMC) polyvinyl pyrrolidone (PVP) tragacanth and mag-nesium aluminum silicate (Veegum) were purchased fromMerck Germany Acetaminophen was kindly donated byChemidarou Pharmaceutical Co Iran

21 Preparation of Suspensions Finely powdered (120 mesh)acetaminophen (32)was used to prepare suspensions usingVeegum (2) CMC (05) PVP (1) or tragacanth (075)alone and their different combinations as structural vehicles(Table 1) Polysorbate 80 (035) and sodium chloride (002and 004) were added as wetting and flocculating agentsrespectively Then physical stability and rheological proper-ties of the formulations were evaluated

22 Physical Stability After preparation sedimentation vol-ume (119865) of the suspensions was measured daily and heightsof sediments were measured when there was no change in 3consecutive readings In order to evaluate the ease of redis-persion suspension samples were rotated periodically at 180degreeThe number of revolutions (119899) was recordedwhen thesuspension restored to homogeneity [2] The crystal growthacetaminophen in different suspensions that were stored twomonths at room temperature was examined by optical micro-scope (Olympus R4 Japan)

23 Rheological Assessment Rheological behavior of theacetaminophen suspensions was determined using a Brook-field viscometer (Dial reading LVT USA with no 3 spindle)Viscosity of samples was determined at 03 06 15 3 6 1230 and 60 rpm after 1min rotation at the room temperatureThe results were plotted as rheograms and their rheological

behaviors were determined by fitting on the correspondingNewtonian and non-Newtonian equations (1)

120591119873

= 1205781015840

120575

Log 120575 = 119873 log 120591 minus log 1205781015840(1)

where 120591 is shear stress 120575 and 1205781015840 are shear rate and viscositycoefficient respectively 119873 is an indicator for defining thetype of flow Since the viscosity of pseudoplastic substancesdecreases with increasing rate of shear the apparent viscosityof the formulations at shear rates corresponding to 30 rpmwas obtained from the slope of the tangent to the curve at thatpointThe area of the hysteresis loop of the rheograms can becalculated from the difference between the areas under theup curve and the down curve by using the trapezoidal rule[4 6 7]

3 Results and Discussion

Comparison of the sedimentation volume in acetaminophensuspension without any suspending agent (formulation 119865

1)

with those suspensions containing one kind of structuralvehicle showed that increasing tragacanth and Veegam couldincrease the sedimentation volume considerably (Table 2)The highest and the lowest sedimentation volumes wereobserved in suspensions containing tragacanth (865 plusmn125) and PVP (13 plusmn 082) respectively So Veegum (2)and tragacanth (075) were used in all blend formulationsbut CMC and PVP in different formulations were changedNag in 2005 studied the stability and flow behavior of bariumsulphate suspensions in the presence of various polymerssuch as PVP Results showed that PVP had no significanteffect on sedimentation volume [10] 119865 and 119899 values of thesuspensions of different structural vehicles and flocculatingagent are shown in Table 2The suspending agents alone werenot able to suspend particles while their combination showedexcellent results According to the results of the ease ofredispersion formulations 119865

8and 11986511with the concentration

of 004 NaCl were not able to disperse ideally

Journal of Drug Delivery 3

Table 2 The value of sedimentation volume (119865) and ease of redis-persion (119899) for acetaminophen suspension in different formulations(mean plusmn SD 119899 = 4)

Formulation 119865 () 119899

1198651

10 plusmn 082 6 plusmn 0001198652

865 plusmn 125 4 plusmn 0001198653

235 plusmn 22 10 plusmn 1401198654

31 plusmn 096 2 plusmn 0001198655

13 plusmn 082 3 plusmn 0001198656

97 plusmn 11 4 plusmn 0821198657

97 plusmn 048 4 plusmn 0501198658

97 plusmn 082 lowast

1198659

99 plusmn 115 4 plusmn 08211986510

98 plusmn 025 4 plusmn 00011986511

98 plusmn 07 lowast

11986512

97 plusmn 175 8 plusmn 16011986513

98 plusmn 082 4 plusmn 00lowastNot dispersed after 20 rotations

The values of 119873 as an indicator for defining the typeof flow for different formulations are presented in Table 3In Newtonian fluids shear stress and shear rate are directlyproportional (119873 = 1) so the rheogram will be a straight linewhile in non-Newtonian fluids there is not a direct relation-ship between them (119873 gt 1) [17] Dilatant systems are inverseof that possessed by pseudoplastic systems (119873 lt 1) [4]According to the values of119873 all formulations showed pseu-doplastic behavior The important parameter for predictingflow behavior of liquid dispersion is the area of the hysteresisloop which is shown in Table 3 Evaluation of hysteresis arearevealed that all of the formulations except formulations 119865

8

and 11986511

had thixotropy behavior It is generally acceptedthat greater hysteresis area leads to stronger thixotropicproperty and a good suspension should have a relatively highpseudoplastic behavior and some degree of thixotropy [18]

In formulations 1198659ndash11986511

all suspending agents were usedThe value of hysteresis loop and apparent viscosity in for-mulation 119865

9without NaCl were 2799 dyne sdot cm sdotminminus1 and

56405 cp respectively (119875 lt 005) At low concentrationsof NaCl (002) the value of hysteresis loop and apparentviscosity of formulation 119865

10increased (Figure 1 and Table 3)

(119875 lt 005) In formulation 11986511

with high concentration ofNaCl (004) the apparent viscosity of suspension was dras-tically rinsed so that the instrument could not show any valuefor torque

Regarding above mentioned results presence of NaCl informulations 119865

10and 119865

11increased the apparent viscosity in

comparison with formulation 1198659(without NaCl) Suspension

1198656is the same as 119865

9 but it did not contain CMC in its

formulation The value of hysteresis loop and apparent vis-cosity of 119865

6was 286 dyne sdot cm sdotminminus1 and 29093 cp respec-

tively But with adding NaCl (002) in formulation 1198657 the

value of hysteresis loop and apparent viscosity increased(984 dyne sdot cm sdotminminus1 and 63530 cp) Formulation 119865

7had

the highest hysteresis loop in comparisonwith other formula-tions (Figure 1(a))Aswith formulation119865

11 in formulation119865

8

Table 3 Indicator for defining the type of rheological behavior(119873) hysteresis loop and pseudoplastic viscosity at 30 rpm (120578

30) in

different formulations

Formulation 119873Hysteresis loop(dynesdotcmmin) 120578

30(cp)

1198656

2039 286 290931198657

2063 984 635301198658

lowast lowast lowast

1198659

1973 2799 5640511986510

2030 3279 6353011986511


11986512

2081 4869 8312311986513

1860 157 67092lowastMore than instrument detection range

with increasing concentration of NaCl (004) the apparentviscosity of the suspension was too high to be detected by theinstrument

Comparison of formulations 1198657and 119865

10showed

when

NaCl was added as flocculating agent presence of CMC (for-mulation 119865

10) caused a decrease in the value of hysteresis

loopThe value of hysteresis loop and apparent viscosity

in formulation 11986512

without NaCl and PVP was4869 dyne sdot cm sdotminminus1 and 83123 cp respectively Butby adding NaCl in formulation 119865

13without PVP the

area of hysteresis loop decreased to 157 dyne sdot cm sdotminminus1(Figure 1(c)) and the value of apparent viscosity was67092 cp In formulation 119865

13without PVP NaCl not only

could not increase the hysteresis loop and viscosity but alsothese values were less than those in formulation 119865

12 The

results of rheological assessment indicated that when NaCl(002) is added as flocculating agent additional PVP maybe necessary for improving thixotropy Flocculating agentsare added to reduce the electrical forces of repulsion betweenparticles and to allow flocks to be formed in order to preventcake formation [9] It can be suggested that enhancementof thixotropy and viscosity in formulations containing NaCland PVP may be related to the cross-linking between thecarbonyl group in the PVP segment and Na+ ions [19] whichpartially prohibits the free mobility of the molecular segmentand finally results in improvement of the apparent viscosityHao et al in 2007 investigated the rheological behavior ofPVP in NN-dimethylformamide solutions containing metalchlorides (LiCl CaCl

2 and CoCl

2) [19] The results showed

the apparent viscosity of the PVP solutions increased withincreasing metal-ion concentration NMR spectroscopyshowed that there were interactions between the metal ionsand the carbonyl groups of the PVP segments in the NN-dimethylformamide solutions which partially prohibits freemobility of the molecular segment Also DSC results indi-cated that the glass transition temperatures of the PVPmetalchloride composites increased with the addition of metalions [19]

In spite of above results it is well known that using hydro-philic gums such as PVP and gelatin and polysorbates leads


0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)

Torque (dynmiddotcm)

(a)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(b)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(c)

Figure 1 Rheograms and thixotropy of acetaminophen suspensions in formulations (a) 1198657 (b) 119865

10 and (c) 119865

13

to their adsorption at particle surface and retards crystalgrowth [9] Nevertheless microscopic observations showedthe growth of crystals in all formulations of acetaminophensuspensions (as shown in suspension 119865

6in Figure 2) It can

be hypothesized that changing the amount of factors such asPVP and polysorbate factors in the formulation of the sus-pensions will prevent crystal growth

4 Conclusion

In this study the combination of the suspending agentsshowed better results in comparison with other formulationsRheological studies showed pseudoplastic behavior for allsuspensions prepared by combination of the suspendingagents NaCl 002 as flocculating agent in presence of PVPimproved the rheological behavior of suspension

Conflict of Interests

The authors do not have a direct financial relation with thecommercial identities mentioned in their paper

Figure 2 Microscopic view of crystal growth in acetaminophensuspension (119865

6) (magnification times40)

Acknowledgment

The paper is issued from Pharm D thesis of Saeed Bahram-pour and financially supported by Ahvaz Jundishapur Uni-versity of Medical Sciences Ahvaz Iran


References

[1] S S Suryawanshi H K Kunjwani V KawadeJayashree AAlkunteMohita and J Yadav Dattatraya ldquoNovel polymericin situ gels for ophthalmic drug delivery systemrdquo Journal ofAdvanced Pharmaceutical Technology amp Research vol 2 pp 67ndash83 2012

[2] V B Junyaprasert and G Manwiwattanakul ldquoRelease profilecomparison and stability of diltiazem-resin microcapsules insustained release suspensionsrdquo International Journal of Pharma-ceutics vol 352 no 1-2 pp 81ndash91 2008

[3] E Behzadfar M H Abdolrasouli F Sharif and H NazockdastldquoEffect of solid loading and aggregate size on the rheologicalbehavior of pdmscalcium carbonate suspensionsrdquo BrazilianJournal of Chemical Engineering vol 26 no 4 pp 713ndash721 2009

[4] P J Sinko Martinrsquos Physical Pharmacy and PharmaceuticalSciences LippincottWilliamsampWilkins Philadelphia Pa USA5th edition 2006

[5] J-C Baudez ldquoAbout peak and loop in sludge rheogramsrdquoJournal of Environmental Management vol 78 no 3 pp 232ndash239 2006

[6] W Khunawattanakul S Puttipipatkhachorn T Rades and TPongjanyakul ldquoChitosan-magnesium aluminum silicate com-posite dispersions characterization of rheology flocculate sizeand zeta potentialrdquo International Journal of Pharmaceutics vol351 no 1-2 pp 227ndash235 2008

[7] T Pongjanyakul and S Puttipipatkhachorn ldquoSodium alginate-magnesium aluminum silicate composite gels characterizationof flow behavior microviscosity and drug diffusivityrdquo AAPSPharmSciTech vol 8 no 3 article E72 2007

[8] B M Berney and P B Deasy ldquoEvaluation of carbopol 934 asa suspending agent for sulphadimidine suspensionsrdquo Interna-tional Journal of Pharmaceutics vol 3 no 2-3 pp 73ndash80 1979

[9] R M Patel ldquoParenteral suspension an overviewrdquo InternationalJournal of Current Pharmaceutical Research vol 2 pp 4ndash132010

[10] A Nag ldquoStability and flow behaviour of barium sulphatesuspension and the preparation of stable barium sulphatesuspension for medical userdquo Journal of Scientific and IndustrialResearch vol 64 no 4 pp 268ndash272 2005

[11] D Gomez-Dıaz and J M Navaza ldquoRheology of aqueous solu-tions of food additives effect of concentration temperature andblendingrdquo Journal of Food Engineering vol 56 no 4 pp 387ndash392 2003

[12] T S Moreira V P de Sousa and M B R Pierre ldquoInfluence ofoleic acid on the rheology and in vitro release of lumiracoxibfrom poloxamer gelsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 13 no 2 pp 286ndash302 2010

[13] D Raj C Sankar C Dilip et al ldquoEvaluation of the suspendingproperties of Leucaena iatisiliqua seed gumrdquo Der PharmaciaLettre vol 2 pp 67ndash74 2010

[14] M Rebelo C Viseras A Lopez-Galindo F Rocha and E Fda Silva ldquoRheological and thermal characterization of peloidsmade of selected Portuguese geological materialsrdquoApplied ClayScience vol 52 no 3 pp 219ndash227 2011

[15] SMohammad S N H Shah B Nasir et al ldquoEfficacious formu-lation of anti-malarial dry suspension for pediatric userdquoAfricanJournal of Pharmacy and Pharmacology vol 6 pp 2629ndash26332012

[16] H Valizadeh A Farajnia and P Zakeri-Milani ldquoFormulationof cefuroxime axetil oral suspension and investigation of its

pharmaceutical propertiesrdquo Advanced Pharmaceutical Bulletinvol 1 pp 93ndash96 2011

[17] M Javanmard and J Endan ldquoA survey on rheological propertiesof fruit jamsrdquo International Journal of Chemical Engineering andApplications vol 1 pp 31ndash37 2010

[18] H-P LiW-GHou andY-Z Zhang ldquoRheological properties ofaqueous solution of new exopolysaccharide secreted by a deep-sea mesophilic bacteriumrdquo Carbohydrate Polymers vol 84 no3 pp 1117ndash1125 2011

[19] C Hao Y Zhao Y Zhou et al ldquoInteractions between metalchlorides and poly(vinyl pyrrolidone) in concentrated solutionsand solid-state filmsrdquo Journal of Polymer Science B vol 45 no13 pp 1589ndash1598 2007

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Autoimmune Diseases


Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of


Pharmaceutics


MEDIATORSINFLAMMATION

of


Table 1 Composition of different formulations of acetaminophen suspensions

Formulation Tragacanth () Veegum () CMC () PVP () NaCl ()1198651

0 0 0 0 01198652

075 0 0 0 01198653

0 0 05 0 01198654

0 2 0 0 01198655

0 0 0 1 01198656

075 2 0 1 01198657

075 2 0 1 0021198658

075 2 0 1 0041198659

075 2 05 1 011986510

075 2 05 1 00211986511

075 2 05 1 00411986512

075 2 05 0 011986513

075 2 05 0 002

fence around the drug [15 16] The objective of this work wasto formulate acetaminophen as a relatively stable liquid formand study the influence of different polymers such as CMCVeegum tragacanth andPVPon its rheologic characteristics

2 Experimental

Polysorbates 80 sodium chloride carboxymethyl cellulose(CMC) polyvinyl pyrrolidone (PVP) tragacanth and mag-nesium aluminum silicate (Veegum) were purchased fromMerck Germany Acetaminophen was kindly donated byChemidarou Pharmaceutical Co Iran

21 Preparation of Suspensions Finely powdered (120 mesh)acetaminophen (32)was used to prepare suspensions usingVeegum (2) CMC (05) PVP (1) or tragacanth (075)alone and their different combinations as structural vehicles(Table 1) Polysorbate 80 (035) and sodium chloride (002and 004) were added as wetting and flocculating agentsrespectively Then physical stability and rheological proper-ties of the formulations were evaluated

22 Physical Stability After preparation sedimentation vol-ume (119865) of the suspensions was measured daily and heightsof sediments were measured when there was no change in 3consecutive readings In order to evaluate the ease of redis-persion suspension samples were rotated periodically at 180degreeThe number of revolutions (119899) was recordedwhen thesuspension restored to homogeneity [2] The crystal growthacetaminophen in different suspensions that were stored twomonths at room temperature was examined by optical micro-scope (Olympus R4 Japan)

23 Rheological Assessment Rheological behavior of theacetaminophen suspensions was determined using a Brook-field viscometer (Dial reading LVT USA with no 3 spindle)Viscosity of samples was determined at 03 06 15 3 6 1230 and 60 rpm after 1min rotation at the room temperatureThe results were plotted as rheograms and their rheological

behaviors were determined by fitting on the correspondingNewtonian and non-Newtonian equations (1)

120591119873

= 1205781015840

120575

Log 120575 = 119873 log 120591 minus log 1205781015840(1)

where 120591 is shear stress 120575 and 1205781015840 are shear rate and viscositycoefficient respectively 119873 is an indicator for defining thetype of flow Since the viscosity of pseudoplastic substancesdecreases with increasing rate of shear the apparent viscosityof the formulations at shear rates corresponding to 30 rpmwas obtained from the slope of the tangent to the curve at thatpointThe area of the hysteresis loop of the rheograms can becalculated from the difference between the areas under theup curve and the down curve by using the trapezoidal rule[4 6 7]

3 Results and Discussion

Comparison of the sedimentation volume in acetaminophensuspension without any suspending agent (formulation 119865

1)

with those suspensions containing one kind of structuralvehicle showed that increasing tragacanth and Veegam couldincrease the sedimentation volume considerably (Table 2)The highest and the lowest sedimentation volumes wereobserved in suspensions containing tragacanth (865 plusmn125) and PVP (13 plusmn 082) respectively So Veegum (2)and tragacanth (075) were used in all blend formulationsbut CMC and PVP in different formulations were changedNag in 2005 studied the stability and flow behavior of bariumsulphate suspensions in the presence of various polymerssuch as PVP Results showed that PVP had no significanteffect on sedimentation volume [10] 119865 and 119899 values of thesuspensions of different structural vehicles and flocculatingagent are shown in Table 2The suspending agents alone werenot able to suspend particles while their combination showedexcellent results According to the results of the ease ofredispersion formulations 119865

8and 11986511with the concentration

of 004 NaCl were not able to disperse ideally



Formulation 119865 () 119899

1198651

10 plusmn 082 6 plusmn 0001198652

865 plusmn 125 4 plusmn 0001198653

235 plusmn 22 10 plusmn 1401198654

31 plusmn 096 2 plusmn 0001198655

13 plusmn 082 3 plusmn 0001198656

97 plusmn 11 4 plusmn 0821198657

97 plusmn 048 4 plusmn 0501198658


1198659

99 plusmn 115 4 plusmn 08211986510

98 plusmn 025 4 plusmn 00011986511

98 plusmn 07 lowast

11986512

97 plusmn 175 8 plusmn 16011986513



8

and 11986511










10and 119865



1198656is the same as 119865






7had



8


30) in



30(cp)

1198656

2039 286 290931198657

2063 984 635301198658


1198659

1973 2799 5640511986510

2030 3279 6353011986511


11986512

2081 4869 8312311986513




10showed

when






13without PVP the




12 The


2 and CoCl





0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(a)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(b)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(c)


10 and (c) 119865

13




4 Conclusion






Acknowledgment



References

























Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of



Formulation 119865 () 119899

1198651

10 plusmn 082 6 plusmn 0001198652

865 plusmn 125 4 plusmn 0001198653

235 plusmn 22 10 plusmn 1401198654

31 plusmn 096 2 plusmn 0001198655

13 plusmn 082 3 plusmn 0001198656

97 plusmn 11 4 plusmn 0821198657

97 plusmn 048 4 plusmn 0501198658


1198659

99 plusmn 115 4 plusmn 08211986510

98 plusmn 025 4 plusmn 00011986511

98 plusmn 07 lowast

11986512

97 plusmn 175 8 plusmn 16011986513



8

and 11986511










10and 119865



1198656is the same as 119865






7had



8


30) in



30(cp)

1198656

2039 286 290931198657

2063 984 635301198658


1198659

1973 2799 5640511986510

2030 3279 6353011986511


11986512

2081 4869 8312311986513




10showed

when






13without PVP the




12 The


2 and CoCl





0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(a)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(b)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(c)


10 and (c) 119865

13




4 Conclusion






Acknowledgment



References

























Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(a)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(b)

0

10

20

30

40

50

60

100 200 300 400

Shea

r rat

e (RP

M)


(c)


10 and (c) 119865

13




4 Conclusion






Acknowledgment



References

























Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


References

























Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of

research article the effect of polymer content on the non...

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