ranitidine loaded biopolymer floats: designing...

Research ArticleRanitidine Loaded Biopolymer Floats DesigningCharacterization and Evaluation

Abdul Karim Muhammad Ashraf Shaheen Tahir Mehmood Abdul Rauf RazaMusadiq Aziz and Badar Din

Department of Chemistry University of Sargodha Sargodha 40100 Pakistan

Correspondence should be addressed to Muhammad Ashraf Shaheen mashaheenuosedupk

Received 17 June 2017 Revised 28 September 2017 Accepted 11 October 2017 Published 14 December 2017

Academic Editor Somdet Srichairatanakool

Copyright copy 2017 Abdul Karim et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

The float formulation is a strategy to improve the bioavailability of drugs by gastroretentive drug delivery system (GRDDS) A drugdelivery model based on swellable and reswellable low density biopolymers has been designed to evaluate its drug release profileusing ranitidine (RNT) as a model drug and formulations have been prepared utilizing 32 factorial designs The drug release (DR)data has been subjected to various kinetic models to investigate the DR mechanism A reduction in rate has been observed byexpanding the amounts of PSG and LSG parts while an expansion has been noted by increasing the concentration of tragacanth(TG) and citric acid (CA) with an increment in floating timeThe stearic acid (SA) has been used to decrease the lag time because adecrease in density of systemwas observedThe kinetic analysis showed that the optimized formulation (S4F3) followed zero-orderkinetics and power law was found to be best fitted due to its minimum lag time and maximum floating ability The resemblance ofobserved and predicted values indicated the validity of derived equations for evaluating the effect of independent variables whilekinetic study demonstrated that the applied models are feasible for evaluating and developing float for RNT

1 Introduction

The control drug delivery has been a critical zone of currentresearch to upgrade the bioavailability of the drug Withphenomenal progress in medical engineering and materialdesign novel materials have been exploited for the improve-ment of drug delivery systems (DDS) Both natural andengineered macromolecules have been extensively utilized asa part of controlled drug delivery to amplify the bioadequacyof the drug and to enhance the patient compliance A fewstrategies are being utilized for effective plan of a GRDDS toimprove the GRT formost extreme assimilation in upper partof gastric system such as floating DDS low density system(LDS) bioadhesive superporous hydrogel and magneticsystem The floating drug delivery is most broadly utilizedamong these methods [1ndash3] The float formulation is anefficient approach to extend the residence time in stomachto increase the absorption of less soluble or less stable drugsin digestive system This system is hydrodynamically well-adjusted having lesser bulk density than GI (gastrointestinal)

fluid As a result system remains floating in the stomachwithout influencing other gastric functions and hence drugdischarges out from float gradually at the coveted ratewith least variance in blood plasma The controlled drugdelivery system (CDDS) has significant advantage for exam-ple patient compliance simple administration and flexibledosage forms [4 5] Psyllium husk and dried seed layer ofPlantago ovata have several pharmaceutical and therapeuticapplications Psyllium husk forms a clear transparent gelon absorbing water which is used as a food supplement[6] Psyllium hydrogel (HG) comprises both dissolvable andinsoluble reswellable polysaccharides Psyllium husk formsthree-dimensional structures in aqueous medium becauseof its gel forming ability [7 8] The HG was utilized forfloat formation due to absence of toxic impurities potentialbiocompatibility and ease of extraction biodegradability andaversion of gastric bothering by forming a coat around thegastric aggravation In addition it has many pharmaceu-tical applications and has been used in the treatment ofnumerous chronic infections [9ndash11] Ranitidine is used for the

HindawiJournal of ChemistryVolume 2017 Article ID 6924601 12 pageshttpsdoiorg10115520176924601

2 Journal of Chemistry

treatment of Zollinger-Ellison Syndrome gastroesophagealreflux duodenal ulcers gastric ulcer and duodenal ulcerThe suggested dose of ranitidine for gastroesophageal refluxillness is 150mg twice a day however for erosive esophagitissame dose is four times a day ormuchmore [12] Studies havedemonstrated that patientrsquos compliances are antagonisticallyinfluenced by increase in number of doses In this waysustained release would be more profitable in decreasing itsfrequency for compelling results [13 14]The gastric residencetime is essential for the drugs which are primarily absorbedthrough stomach or unstable at higher pH In this way thecontrolled drug release in particular area of gastric tractoffers different advantages like enhanced bioavailability andremedial viability [15]

The objective of this study was to prepare ranitidinefloats of controlled drug delivery because of its low bioavail-ability (half) and short organic half-life (2-3 h) [16] In thepresent premises the RNT floats were composed of fractionsdisengaged from Psyllium husk gel and studied for theirgastroretentive profile The regression analysis was utilizedto optimize the formulations similarity (f 2) and differencefactors (f 1) were used to look at the drug release profiles of allhusk fractions with standard tablet accessible in the marketDistinctive kinetic models were connected for example zeroorder first order Higuchi model Power law and H-Crowellcube root law to study the drug release rate and all theseresults demonstrate that the applied methods were sufficientfor designing sustained release floats of RNT having bettertherapeutic and clinical outcomes

2 Materials and Methods

Ranitidine (RNT) was provided by Ferozsons LaboratoriesLimited Pakistan as a gift All other chemicals and solventswere purchased from Sigma Aldrich Pakistan All chemi-cals were of AR grade and used without further purifica-tion

21 Isolation of Hydrogel Psyllium husk (10 g) was immersedin excess distilled water (2 L) and kept overnight Aftercomplete swelling NaOH (04M) solution was added toswelled husk with continuous stirring The solution wasfiltered with muslin cloth to separate insoluble impuritiesThe glacial acetic acid was added gradually with stirring tofiltered solution The gel was decanted off and dried aftercomplete dialysis by distilled water For isolation of differentfractions the dried gel was again swelled in distilled waterand treated with different solvents for example acetonemethanol ethanol and chloroform Different fractions indifferent concentrations were again coagulated using thesaid solvents After separation these fractions were dialyzedthoroughlywith distilledwater to remove separating solventsThe purified gels were dried and ground to fine powder Thepowdered gel was dissolved in drug solution After absorbingthe drug whole mass was dried again The dried mass wasground mixed with excipients and sprayed with isopropylalcohol (iPrOH) and then compressed to form floats Theseparation of different fractions is shown in Figure 1

22 Characterization of ENa

221 Elemental Analysis CHNS analyzer was used to findthe amount of N and C in given sample The elementalanalysis for each sample was performed in triplicate

222 Thermal Analysis (TA) TA of isolated samples wascarried out under N2 atmosphere at multiple heating rate (1015 and 20∘C) using Broidorsquos method and activation energy(119864119886) was calculated from the slope of line by least squaremethods

log( 1119910) = minus(119864119886119877 )(

1119879) + constant (1)

where 119879 is the temperature in Kelvin and 119877 is general gasconstant having value 831 JKndash1molndash1 119910 is ratio of differencein mass before and after heating = (119898119905 minus 119898119891)(1198980 minus 119898119891)where 119898119905 is weight of polymer at temperature 119879 1198980 is themass at initial temperature and 119898119891 is the mass at the finaltemperature of particular decomposition stage so Broidorsquosequation can be represented as 119864119886 = minus (slope times 8314) Thedata was analyzed (TA Instruments USA) using UniversalAnalysis 2000 software version 42E and MS Excel 2007

223 Gel Permeation Chromatography (GPC) GPC analysiswas carried out with Agilent 1200 Series GPC-SEC Systemusing pullulan and dextran as standards The system wasequipped with 2 columns and dimethyl sulphide was used aseluent with flow rate of 05mLminndash1 at 70∘C using injectionsabout 50120583L224 Fourier Transform-Infrared Spectroscopy The absorp-tion bands in FT-IR spectra of ENa were noted to comparewith earlier work for same type of materials [17]

225 Scanning Electron Microscopy (SEM) Pellets of ENafraction were prepared at 3000 psi pressure using hydraulicpress The pellets were mounted with the help of silver painton aluminum stubs and subsequently were coated with goldThe SEM images were taken at different magnification usingJEOL JSM-6480 LV Japan at 10 kV

226 Determination of Water Retention Value (WRV) Thewater retention was calculated by centrifugation methodAbout 10 g dried gel was placed in a beaker containing100mL distilled water at 30∘C for 3 h for complete swellingThe swelled material was filled in 4 fritted glass tubescontaining pores at the bottom The tubes were centrifugedat 2500 rpm for 40min to remove the entrapped water Aftercentrifugation sample material was dried in an oven at 60∘Cfor complete dehydration WRV was calculated as follows

WRV () = (119898119908 minus 119898119889)119898119889 times 100 (2)

where 119898119908 is mass of sample (wet state) and 119898119889 is mass ofsample (dry state)

Journal of Chemistry 3

AcOH(1 30)

Residue discarded

MeOH (1 20)

MNaAANa

Psyllium husk (PH 100 g)

(i) H2O (excess)(ii) aq 04

Filtration

ClfNa

Filtrate

EtOH (1 20)

ENa ANa

Me2CO (1 30)

Acetic acid = AcOH methanol = MeOH ethanol = EtOH acetone = Me2CO chloroform = CHCl3Gel extracted with NaOH and [AcOH(AANa) MeOH(MNa) EtOH(ENa) Me2CO(ANa) (CHCl3(ClfNa)]

M NaOH (to pH 12)

CHCl3 (1 20)

Figure 1 Separation of different fractions of husk gel

Table 1 Formulations design for RNT floats (drug 120mg)

Batches Materials (mg) Low (minus1) Medium (0) High (+1) Constantlowast

1st ENa 100 150 200 NaHCO3 = 10SA 30 60 90 CA = 10

2nd ENa 100 150 200 NaHCO3 = 10Tcanth 30 60 90 CA = 10

3rd ENa 100 150 200 NaHCO3 = 10LSG 30 60 90 CA = 10

4th ENa 100 150 200 NaHCO3 = 15PSG 30 60 90 CA = 10

LSG = linseed gel PSG = psyllium seed gel lowastCHCl3 =iPrOH = 2mL TG = tragacanth gel SA = stearic acid CA = citric acid HPMC hydroxy propyl methyl

cellulose Mg stearate = 5 g to each float

The drug content friability and stability of floats weremeasured as per set criteria by taking 10 floats and aftergrinding concentration of solution was noted by dissolvingin water The friability was checked by the formula

Friability = (Initial mass of sample)(Final mass of sample) times 100 (3)

23 Preparation of Floats For each float a specific quantityof hydrogel along with excipients as per factorial design wastaken and mixed geometrically in plastic bag The mixturewas passed through sieve of mesh size 16 and then pouredinto drug solution The drug loaded mixture was separateddried and ground to fine powder and then sprayed withiPrOH (sim2mL) with rapid geometric mixingThe floats wereprepared by punch machine having punch size 10 times 15mmby direct compression technique with small amount of Mg-stearate as lubricant

24 Preparation of Factorial Formulations Floats were pre-pared as per factorial model (32) as described in Table 1 Fourdifferent batcheswere designed by varying the concentrationsof ENa and SA ENa LSG and PSG as low medium and highas shown in Table 1

25 Dissolution Study All DR profiles were studied usingUSP paddle dissolution apparatus II at 37∘C plusmn 01∘C and50 rpm in buffer solutions of pH 12 (900mL in each beaker)About 5mL sample was taken with syringe After suitabledilution sample was analyzed at 120582max 314 nm After removalof sample same amount of dissolution medium at sametemperature was added to keep the total volume 900mLAccumulative DR percentage was calculated from a standardcurve A calibration graph for RNT was plotted against itsconcentration (ppm) in buffer solution (pH 12) and wasregressed into linear line

26 In Vitro Buoyancy The floating lag time (LT) and thetotal floating time (TFT) were determined for each float inUSP dissolution apparatus II containing simulated gastricfluid at pH 12 at 37 plusmn 05∘C The lag time and TFT for eachdosage form were also calculated

27 Similarity and Difference Factors According to Mooreand Flanner similarity factor (f 2) is actuallymeasurement ofsimilarity in the percent dissolution of drug of sample profileand control profile

1198912 = 50 times log[1 + (1119899)sum100381610038161003816100381610038161198771199052 minus 119879119905210038161003816100381610038161003816

12 times 100] (4)


Table 2 Thermal parameters of ENa gel fractions

Samplecode

Temprange(∘C)

Massloss()

119864119886kJmolminus1

ΔHlowastkJmolminus1

ΔSlowastJKminus1molminus1

Δ119866lowastkJmolminus1 ln119860 IPDT

(∘C) ITSMass at600∘C()

ENa 223ndash315 4924 14668 13976 minus5147 16966 2282 28942 046 0983

The dissolution profiles will be similar to control (stan-dard) profile when f 2 value is gt50 where f 1 measurespercentage difference between test and control dissolutionprofile Its standard values are 0 to 15 for no difference

28 Kinetic Study In vitro DR data was studied by usingdifferent kinetic models to find the mechanism and drugrelease rate

29 Statistical Analysis The drug release percentage at 2 h5 h and 10 h was statistically analyzed by using the DESIGNEXPERT 7150 (STAT-EASE) demo version software Thelinear regression analysis (LRA) was applied to all formula-tions of each batch and an equationwas derived for fixed timeinterval to find the effect of independent variables

3 Results and Discussion

31 Extraction of Hydrogel The ENa fraction extracted byalkali-ethanol method was found to be most suitable dueto its minimum lag time as compared to other fractionsas matrix In present study NaOH solution was used fordissolution of gel Although this is a chemical method itis more economical for production of pure gel The iondipoles interaction between NaOH and hydroxyl (-OH)groups results in cleavage ofmolecularH-bonding among thehydrogel layers and decreases the viscosity of solution hencefiltration becomes easier The separated gels were dialyzedwith distilled water andwashed until the pHwas restored to 7The purified transparent gel was dried and its yield was foundto be 30 relative to weight of husk The extracted materialwas found to be good DR retardant and suitable for floats dueto its low density


321 Elemental Analysis The elemental analysis shows thatENa is free of any nitrogenous matter (proteins) Even withperforming the analysis in triplicate no evidence of nitrogenwas found in all samples The percentage of C and Hwas found to be 402 and 65 against 450 and 60respectively as observed in other natural polysaccharides(pullulan etc) [17]

322 Thermal Analysis The ENa was studied by TGA andDSC from ambient temperature to 600∘C The TGA showedan endothermic weight loss about 10 up to 200∘C whichwas attributed to the loss of absorbed moisture The weightloss of sim45 was observed in range 226ndash326∘C whichwas due to degradation of ENa structure This step was

Table 3 GPC parameters of ENa

Parameters ENa119872119899 (gmolminus1) 3443 times 103119872119908 (gmolminus1) 1344 times 104119872119911 (gmolminus1) 2967 times 104119872119901 (gmolminus1) 8273 times 103119881119901 (cm3) 7497PDI 3724

exothermic in nature The second weight loss of sim24 wasobserved at temperature 452ndash563∘C due to complete degra-dation of ENa leaving behind a carbon rich residue Glasstransition temperature (119879119892) could not be observed in theexperimental range due to presence of carbonThe average119864119886value calculated by Broidorsquos method was 134 kJmolndash1 using10∘Cminndash1 and thermogram was comparable to those ofother commercially available polysaccharides [18]

An overall thermal stability of ENa along with otherfractions was assessed by integral procedural decompositiontemperature (IPDT) and comprehensive index of thermalstability (ITS) values by Doylersquos method The IPDT and ITSvalue were found to be 289∘C and 046 respectively Thesevalues indicate that ENa has good thermal stability [19 20]The apparent119864119886 values formajor stage of decompositionwerealso calculated using Flynn-Wall-Ozawa (FWO)methodThe119864119886 values varied greatly with 120572 indicating a multistep degra-dation The average activation energies by FWO method aregiven in Table 2 and Figure 2

323 Gel Permeation Chromatography (GPC) GPC wasused to determine molar mass distribution 119872119899 (number-average)119872119908 (weight-average)119872119911 (average molar masses)and polydispersity index (PDI) which is the ratio of119872119908119872119899ThePDI value of ENawas to be found as 3724which indicatesthat ENa is polydispersed in nature Table 3

324 Fourier Transform-Infrared Spectroscopy (FT-IR) Theabsorption bands in FT-IR spectra (Figure 3) were assignedtaking two fractions for comparison The absorbance at332335 cmndash1 was due to -OH stretching (broad band) Theabsorbances at 125180ndash132886 cmndash1 were due to deformationcaused by absorbed water A sharp band at 1012ndash10475 cmndash1

was due to beta-glycosidic bond The absorbances at651ndash69062 and 528ndash549 cmminus1 were observed due to polymerbackbone


0

20

40

60

80

100

Wei

ght (

)

0 200 400 600 800

090

095

100

105

110

115

120

125

130

135

Temperature (∘C)

20∘Cmin15∘Cmin10∘Cmin

0

02

04

06

08

1

200 300 400350250

T (∘C)

= 095

= 090 = 085

= 080

= 075

= 070

= 065

= 060

= 055

= 050

= 045

= 040

= 035

= 030

= 025

= 020

log

170 180 190160(1000T) (＋minus1)

Figure 2 Thermogravimetric curves of ENa (L) and representative 120572-T curve and log szlig (R) for ENa (R)

3442

94

3375

4333

2335 29

1637

2353

94

2123

63

1539

49

1552

34

1432

25 1251

80

1051

20

1047

35

1012

63

9933

4

6423

058

057

5497

1

5285

0

6906

2

6519

4

5593

6

6292

1323

95

1251

80

100

95

90

85

80

75

70

4000 3500 3000 2500 2000 1500 1000 500

T

Figure 3 Representative FT-IR graphs of ENa and AANa (compar-ison)

325 SurfaceMorphology of ENa Scanning electronmicros-copy (SEM) of ENa (Figure 4) indicates that its surface ishighly rough which could provide more surface area toadhere with drug for adsorption reported in Iqbal et al [21]

Figure 4 Scanning electron microscopy of ENa

326 Water Retention Value (WRV) The WRV was foundto be 7000 to 7500 to its original volume The H2Oholding capacity decreased on exposure to atmosphere withthe passage of time therefore WRV is not permanent Being


Table 4 Lag time (LT) of all batches

RNT MNa ENa AANa ClfNa ANa Husk 119862stdLT (min) 22 19 27 30 26 24 12Batch-S1 F1 F2 F3 F4 F5 F6 F7 F8 F9LT (sec) 120 100 45 165 145 130 80 70 60Batch-S2 F1 F2 F3 F4 F5 F6 F7 F8 F9LT (sec) 80 125 150 180 200 256 300 325 375Batch-S3 F1 F2 F3 F4 F5 F6 F7 F8 F9LT (sec) 100 150 195 170 225 245 260 285 295Batch-S4 F1 F2 F3 F4 F4 F6 F7 F8 F9LT (min) 07 05 03 08 06 08 11 14 19

MNaENaAANa

ClfNaANaHusk

200 400 600 8000Time (min)

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

CＭＮ＞

Figure 5 Drug release profiles of RNT from isolated fractions

reswellable it can be reused after drying Being highlyhydrophilic it is considered as hydrogel All formulationswere found to be uniform and their drug content ranged from9737 to 10034

327 Dissolution Study and Float Formulations The concen-tration of drug was calculated using the equation 119910 = 0002 timesconcentration + 0003

From above equation and Figure 5 it was found thatDR from all fractions ranged from 835 to 902 wherethe DR by husk and marketed tablets (119862std) was found tobe 933 and 798 respectively On studying the DR ofdifferent formulations it was found that the DR was retardednotably by increasing the amount of husk gel but DR dataindicates that the use of HG by itself as sustained releasematrix is insufficient to achieve the CR (controlled release)profile Figure 5 Therefore different excipients were usedto accommodate balance in DR rates due to difference inswelling from Psyllium polysaccharide ENa was selected asthe main excipient (matrix) due to its better DR retard-ing ability The DR of various batches was calculated atdifferent time intervals and given in Table 4 The rate ofswelling depends upon the amount of H2O taken up by thepolymer which depends upon nature of added excipientsThe hardness of all floats formulations was in the range

60ndash80 kgcm2 The percentage friability of all the floats wasnot found to be more than 07 To increase the wettingability and decrease the lag time NaHCO3 was added inthe matrix which produced CO2 on contact with simulatedgastric fluid which was entrapped within the polymer anddecreased the density of system The drug release of allformulations for 10 h are shown inTables 6ndash9which indicatesthat drug release rate depends upon nature and concentrationof adding excipients and their effect was studied by regressionanalysis By addition of TG DR rate increased due to havingsoluble component TG gum is actually a mixture of solublecomponent tragacanthin (30ndash40) and insoluble componentbassorin (60ndash70) On addition of LSG the DR rate wasdecreased due to its greater retarding ability and it was furtherdecreased by addition of PSG In order to increase the DRrate concentration ofNaHCO3 was increased in 4th batch Soby the adjustment of variables as recommended by regressionanalysis and formulation S4F3 was found to better due to itsminimum lag time and maximum floating ability with bettersustainability (Figure 6)

TA data indicates that ENa is equally stable as otherhydrogel Table 2 The DR of all fractions and designed for-mulations are shown in Table 6 and similarity and differencefactors are shown in Table 7 which are major indicators tounderstand the formulation designThe kinetic study of someselected batches Tables 6ndash9 indicates that as the 119899 value isgreater than 045 the DR behavior is trending towards non-Fickian diffusion In case of optimized formulation S4F3 thevalue of 119899 is 031 indicating that release mechanism is totallyFickian diffusion [22]

328 In Vitro Buoyancy The total floating and lag timeof all formulation were calculated given in Table 4 andminimum lag time andmaximumfloating timewere detectedin formulation S4F3 So this formulation was selected andfound to be best one for floating DDSThe target of this studywas to choose the formulations having maximum GRT withbest bioavailability of drug Among all the fractions ENa hasminimum lag time and maximum floating ability thereforethis fraction was chosen for designing other formulations

329 Similarity and Difference Factors Similarity and dif-ference factors of all the formulations using ENa referencematrix tablet as standard (Table 5) indicate that all formula-tions which have f 2 factor greater than 50 resemble standard


S4F1S4F2S4F3

S4F4S4F5S4F6

S4F7S4F8S4F9

S1F1S1F2S1F3

S1F4S1F5S1F6

S1F7S1F8S1F9

S2F1S2F2S2F3

S2F4S2F5S2F6

S2F7S2F8S2F9

S3F1S3F2S3F3

S3F4S3F5S3F6

S3F7S3F8

0

20

40

60

80

Accu

mul

ativ

e DR

()

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

200 400 600 8000Time (min)

500 10000Time (min)

200 400 600 8000Time (min)

200 400 600 8000Time (min)

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

0

20

40

60

80

100100

Accu

mul

ativ

e DR

()

S3F9

Figure 6 Drug release profiles of four batches (S1 to S4 each containing nine formulations)

Table 5 Similarity (f 2) and difference factor (f 1) for all batches

RNT F1 F2 F3 F4 F5 F6 F7 F8 F9

S1 f 1 2850 1371 1302 1880 1983 2645 2361 2362 2518f 2 5076 6549 6492 5958 5776 5097 5484 5556 5373

119862stdf 1 1302 1367 2077 2333 2998 3626 3251 3252 3421f 2 6293 6422 5595 5251 4482 4019 4533 4395 4210

S2 f 1 2071 927 947 2267 1551 1701 1715 1866 2128f 2 5910 7203 7401 5630 6244 6287 6162 5978 5604

119862stdf 1 1527 1662 2061 1853 2492 2680 2637 2897 3161f 2 6052 5840 5250 5721 5056 4820 4946 4640 4360

S3 f 1 1337 1458 1828 1846 2360 3102 2405 3049 3787f 2 6212 5909 5458 5454 4912 4348 4769 4314 3904

119862stdf 1 2282 2135 2145 2352 2375 2928 2730 3049 3560f 2 5263 5408 5364 5217 4991 4503 4737 4389 4036

S4 f 1 4414 1758 1030 3338 2343 892 1407 0708 0781f 2 4425 6244 7155 5021 5792 7499 6519 7554 7634

119862stdf 1 1834 1579 2019 1487 1545 2578 2284 2425 2739f 2 5576 6088 5518 6065 6057 4901 5245 5038 4730


Table 6 Kinetic study of DR from polymer matrix

RNT S10 hZero order First order Higuchi H-Crowell Power law119896119900 1198772 1198961 1198772 119896H 1198772 119896HC 1198772 119896119875 1198772 119899

MNa 868 0133 0918 minus0004 0985 3922 0968 minus0042 0907 0024 0976 0577ENa 845 0123 0862 minus0004 0957 3659 0962 minus0039 0773 0021 0951 0561AANa 912 0095 0852 minus0004 0967 3061 0942 minus0032 0851 0071 0922 0389ANa 827 0133 0973 minus0004 0977 3775 0958 minus0043 0982 0022 0972 0575ClfNa 841 0128 0982 minus0004 0965 4231 0981 minus0045 0987 0006 0977 0789H 953 0118 0918 minus0004 0828 3272 0885 minus0033 0924 0062 0887 0423119862std 828 0113 0952 minus0004 0918 3241 0985 minus0035 0942 0091 0972 0357

Table 7 DR study for 1st batch matrix tablets

RNT (S1) S10 hZero order First order Higuchi H-Crowell Power law119896119900 1198772 1198961 1198772 119896H 1198772 119896HC 1198772 119896119875 1198772 119899

F1 835 0134 0989 minus0002 0958 4091 0969 minus0044 0989 0003 0978 0832F2 784 0132 0882 minus0003 0949 4295 0953 minus0044 0992 0005 0962 0829F3 744 0132 0857 minus0003 0946 4278 0944 minus0044 0857 0003 0953 0877F4 818 0128 0988 minus0002 0987 3946 0989 minus0042 0988 0003 0995 0852F5 768 0124 0994 minus0002 096 3777 0963 minus0041 0994 0003 0989 0869F6 743 0122 0986 minus0002 0938 3652 0928 minus0042 0986 0004 0978 0858F7 717 0129 0968 minus0002 0932 3864 0912 minus0043 0968 0002 0956 0912F8 684 0118 0962 minus0002 088 3492 0879 minus0039 0962 0003 0956 0849F9 660 0111 0941 minus0001 0841 3252 0852 minus0037 0941 0004 0941 0865

Table 8 DR study for 2nd batch matrix tablets



tablets with respect to the release rate but the formulationhaving lesser f 2 than 50 deviate from resemblance Similarlythe formulations having f 1 0ndash15 resemble 119862std but deviationfrom these values indicates that their release pattern issomewhat different from reference formulation

3210 Kinetic Study The DR data was evaluated by usingdifferent kinetic models By applying Korsmeyer and Peppasequation to DR data of different fractions of Psyllium huskthe diffusion coefficient (119899) was found in the range from0356 to 0799 plusmn 001 with DR from 818 to 943 in10 h These results indicate that the release mechanism was

non-Fickian diffusion as compared to119862std Table 5Thereforenew formulations were designed to find the desired formula-tion Tables 6ndash9

3211 Regression Analysis The equations (see (5)ndash(16))derived by SRA indicate that each factor has either positiveor negative sign The negative sign indicates that its concen-trationmust be decreasedwhile having positive sign indicatesthat concentration must be increased to achieve desired DRprofile The following notations were used for abbreviationfor different variables 1198831 = 119860 1198832 = 119861 11988311198832 = 119862 11988312 = 11986311988322 = 119864


Table 9 DR study for 4th batch matrix tablets



3212 1st Batch

S1 = 009729119905 + 0028367119860 minus 086738119861 + 0001853119862minus 000047119863 + 0010767119864 minus 1565378

(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)

S15 h = 0100789119905 minus 002018119860 minus 106322119861 + 0003319119862minus 000027119860 + 0012404119861 + 243492

(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)

In study the SRA shows that effect of 119861 and 119862 is moresignificant while effect of 119863 is least effective (see (5)) Afterstudy it is found that effect of119861 is most significant while effectof 119860 is negligible (see (6)) and after 10 h it was found that

effect of 119861 and 1198622 is significant while effect of 119863 119860 and 119864is negligible (see (7))

The abbreviated kinetic study of 1st 2nd and 4th batchwith nine formulations each has been discussed to identifythe optimized formulation

3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)

The SRA shows that the effect of 119860 119861 and 119862 is positivewhile effect of119863 and 119864 is negative

S210 h = 0114934119905 + 0098263119860 + 0429285119861 minus 000038119862 minus 000055119863 minus 000226119864 + 820543(CRC = 0969798 1198772 = 0942314 Adj1198772 = 0936522 119899 = 99) (10)

By applying the LRA to DR it was found that impact of119863is most critical while impact of 119864 is minimally noteworthy(see (8)) and then impact of 119863 and 119861 is most huge whileimpact of 119860 is irrelevant (see (9)) Also after 10 h impact of119860 119862 and119863 was observed to be most critical while impact of11988322 is most slightly noteworthyThe relapse examination wasagain led on DR after 10 h and it was found that impact of1198832and11988312 is most critical while impact of C is insignificant (see(10))

3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)

After drug release study SRA shows that effect of 119860 and 119861 ismore significant while effect of 119862 is negligible (see (11)) Theeffect of119860 ismost significant but effect of119864 and119861 is negligible(see (12)) For 10 h study effect of119860 and119863 is significant whileeffect of 119861 and 119862 and 119864 is negligible (see (13))


Table 10 Standard regression analysis (SRA) and effects of variables on DR profiles

Batches Time Effects

1st 10 h119861 (096305) gt 1198632 (060631) gt 119862 (0511874) gt 119864 (0467321) gt 119860 (015455)119861 (048382) gt 119862 (0264335) gt 119863 (02517) gt 119864 (0238427) gt 119860 (005542)119861 (095425) gt 1198632 (060641) gt 119862 (0510984) gt 119864 (0468321) gt 119860 (015445)

2nd 10 h119863 (078219) gt 119860 (0437285) gt 119862 (0319727) gt 119861 (0257393) gt 119864 (019455)119863 (023438) gt 119861 (0208289) gt 119862 (0147678) gt 119864 (010895) gt 119860 (0010716)119861 (0322212) gt 119863 (024913) gt 119864 (020344) gt 119860 (0122779) gt 119862 (007176)

3rd 10 h119860 (068074) gt 119863 (0476) gt 119864 (0316554) gt 119861 (012522) gt 119862 (0055576)119860 (051543) gt 119863 (0320761) gt 119862 (0112551) gt 119864 (0084883) gt 119861 (000452)119860 (036251) gt 119863 (0280217) gt 119861 (0085294) gt 119862 (003699) gt 119864 (0017337)

4th 10 h119861 (037577) gt 119862 (02633) gt 119860 (018647) gt 119863 (004554) gt 119864 (0064829)119861 (024738) gt 119863 (018553) gt 119862 (0120534) gt 119864 (0075439) gt 119860 (001652)119861 (017275) gt 119860 (010162) gt 119864 (0056415) gt 119862 (0054636) gt 119860 (004857)

3215 4th Batch

S4 = 0179377119905 minus 006247119860 minus 041753119861 + 0001268119862 minus 55119864 minus 05119863 + 0001364119864 + 24487(CRC = 0911831 1198772 = 0818584 Adj1198772 = 0778545 119899 = 27) (14)

S4 = 0145528119905 minus 001115119860 minus 046955119861 + 0000945119862 minus 000043119863 + 0002388119864 + 27266(CRC = 0985076 1198772 = 0952796 Adj1198772 = 0945592 119899 = 99) (15)

S410 h = 0121604119905 minus 007896119860 minus 045247119861 + 0001672119862 minus 000025119863 + 0002678119864 + 3727(CRC = 0977618 1198772 = 0954764 Adj1198772 = 0953648 119899 = 99) (16)

In drug release study for 2 h the effects of factors 119861 and119862 are negligible but in case of drug release study for 5 h theeffects of the factors 119861 and 119862 become significant (see (14))Similarly in drug release study for 5 h the effects of 119861 and 119863become prominently significant while in studying the drugrelease for 10 h effects of119864 and119860 are negligible (see (15))Theeffects of all variables are mentioned in Table 10

4 Conclusion

The Psyllium husk is now an established herbal medicinefor colon malignancy and heart ailments The husk and itsfractions are suitable as matrix for designing the floats dueto having desirable pharmaceutical properties for designingcontrolled drug delivery system The 32 full factorial designsreveal that every independent variable of each formula-tion affects drug release rate of floats The SRA (standardregression analysis) indicates that the level of parameters 119860and 119861 in regression equations plays vital role in procuringthe coveted outcomes The sign of variables in equationmight be negative (decrease in the value of that variable)or positive (increase in the value of that variable) so theirsums are adjustable to achieve the desired drug release

profile Excipients used in this work are mostly herbal innature which are enlisted in GRAS (Generally Recognizedas Safe) list and found to be biocompatible The thermalstudy divulges that all polymer fractions are thermally stableand can withstand the environmental changes The GPC(gel permeation chromatography) analysis indicates thatpolydispersity index (PDI) values of the different fractionshave values between 2 and 375 but this difference has nosignificant effects on the drug release rate or disintegrationof floats Due to having tunable drug release profile andtherapeutic significance Psyllium husk and its fractions havepotential utility in biomedical fields and food industriesincluding designing of capsule shells and tablet matrix

Abbreviations

119860 =1198831 Independent factor 1119861 =1198832 Independent factor 2GRAS Generally Recognized as SafeGRDDS Gastroretentive drug delivery systemRNT RanitidineDR Drug releasePSG Psyllium seed gelLSG Linseed gel


TG TragacanthPSG Psyllium seed gelCA Citric acidSA Stearic acidS119899F119898 119899 represents the batch number and119898

represents the formulation number of thatformulation

DDS Drug delivery systemLDS Low density systemGD GastrointestinalHG Husk gel1198911 Difference factors1198912 Similarity factorH-Crowell Hixson CrowellTA Thermal analysisGPC Gel permeation chromatographyFT-IR Fourier transform-infrared spectroscopyENa Ethanol extract gelMNa Methanol extracted gelAANa Acetic acid extracted gelClfNa Chloroform extracted gelANa Acetone extractedH HuskSRA Standard regression analysisLRA Linear regression analysisSEM Scanning electron microscopyWRV Water retention valueiPrOH Isopropyl alcoholLT Lag time119879119892 Glass transition temperature119864119886 Activation energyIPDT Integral procedural decomposition

temperatureITS Index of thermal stabilityFWO Flynn-Wall-OzawaPDI Polydispersity index119872119899 Number-average119872119908 Weight-average119872119911 Average molar massesCstd Standard tabletS4F3 Fourth-batch third formulation

Conflicts of Interest

The authors declare that there are no conflicts of interestregarding the publishing of this paper

References

[1] A Chandel K Chauhan B Parashar H Kumar and SArora ldquoFloating drug delivery systems A better approachrdquoInternational Current Pharmaceutical Journal vol 1 no 5 2012

[2] P Dongare A Darekar S Gondkar and R Saudagar ldquoFloatingdrug delivery system A better approachrdquo International Journalof Pharmacy andBiological Sciences vol 3 no 4 pp 72ndash85 2013

[3] S Shah J Patel and N Patel ldquoStomach specific floating drugdelivery system A reviewrdquo International Journal of PharmTechResearch vol 1 no 3 pp 623ndash633 2009

[4] P Roy and A Shahiwala ldquoStatistical optimization of ranitidineHCl floating pulsatile delivery system for chronotherapy of noc-turnal acid breakthroughrdquo European Journal of PharmaceuticalSciences vol 37 no 3-4 pp 363ndash369 2009

[5] A W Basit and L F Lacey ldquoColonic metabolism of ranitidineImplications for its delivery and absorptionrdquo InternationalJournal of Pharmaceutics vol 227 no 1-2 pp 157ndash165 2001

[6] C L Dikeman M R Murphy and G C Fahey Jr ldquoDietaryfibers affect viscosity of solutions and simulated human gastricand small intestinal digestardquo Journal of Nutrition vol 136 no 4pp 913ndash919 2006

[7] M H Fischer N Yu G R Gray J Ralph L Anderson and JA Marlett ldquoThe gel-forming polysaccharide of psyllium husk(Plantago ovata Forsk)rdquo Carbohydrate Research vol 339 no 11pp 2009ndash2017 2004

[8] B Bakde ldquoFabrication of gastroretentive floating swellablematrices for oral controlled and sustained release of Famoti-dinerdquo International Journal of Advances in Pharmaceutics vol4 no 4 pp 34ndash39 2015

[9] G J Davies P W Dettmar and R C Hoare ldquoThe influence ofispaghula husk on bowel habitrdquo Journal of the Royal Society forthe Promotion of Health vol 118 no 5 pp 267ndash271 1998

[10] C Hallert M Kaldma and B G Petersson ldquoIspaghula huskmay relieve gastrointestinal symptoms in ulcerative colitis inremissionrdquo Scandinavian Journal of Gastroenterology vol 26no 7 pp 747ndash750 1991

[11] Y Nakamura J E Trosko C-C Chang and B L UphamldquoPsyllium extracts decreased neoplastic phenotypes induced bythe Ha-Ras oncogene transfected into a rat liver oval cell linerdquoCancer Letters vol 203 no 1 pp 13ndash24 2004

[12] J R Lightdale D A Gremse L A Heitlinger et al ldquoGastroe-sophageal reflux Management guidance for the pediatricianrdquoPediatrics vol 131 no 5 pp e1684ndashe1695 2013

[13] R Kaza E Usharani R Nagaraju R Haribabu and P V SivaReddy ldquoDesign and evaluation of sustained release floatingtablets for the treatment of gastric ulcersrdquo Journal of Pharma-ceutical Sciences and Research vol 1 no 4 pp 81ndash87 2009

[14] K Kavitha N Chary G Rajesh S Ramesh and S ShivaleelaldquoFormulation and evaluation of ranitidine floating tabletsrdquoInternational Journal of Pharmaceutical Chemical amp BiologicalSciences vol 3 no 3 2013

[15] B Abrahamsson A Pal M Sjoberg M Carlsson E Laurelland J G Brasseur ldquoA novel in Vitro and numerical analysis ofshear-induced drug release from extended-release tablets in thefed stomachrdquo Pharmaceutical Research vol 22 no 8 pp 1215ndash1226 2005

[16] S Jamzad L Tutunji and R Fassihi ldquoAnalysis of macromolecu-lar changes and drug release from hydrophilic matrix systemsrdquoInternational Journal of Pharmaceutics vol 292 no 1-2 pp 75ndash85 2005

[17] J-Y Yin S-P Nie C Zhou Y Wan and M-Y Xie ldquoChemi-cal characteristics and antioxidant activities of polysaccharidepurified from the seeds of Plantago asiatica Lrdquo Journal of theScience of Food and Agriculture vol 90 no 2 pp 210ndash217 2010

[18] A Lazaridou and C G Biliaderis ldquoThermophysical propertiesof chitosan chitosan-starch and chitosan-pullulan films nearthe glass transitionrdquo Carbohydrate Polymers vol 48 no 2 pp179ndash190 2002

[19] S Saghir M S Iqbal A Koschella and T Heinze ldquoEthylationof arabinoxylan from Ispaghula (Plantago ovata) seed huskrdquoCarbohydrate Polymers vol 77 no 1 pp 125ndash130 2009


[20] A X Jin J L Ren F Peng et al ldquoComparative characterizationof degraded and non-degradative hemicelluloses from barleystraw and maize stems Composition structure and thermalpropertiesrdquo Carbohydrate Polymers vol 78 no 3 pp 609ndash6192009

[21] M S Iqbal J Akbar S Saghir et al ldquoThermal studies of plantcarbohydrate polymer hydrogelsrdquo Carbohydrate Polymers vol86 no 4 pp 1775ndash1783 2011

[22] P L Ritger andN A Peppas ldquoA simple equation for descriptionof solute release I Fickian and Non- Fickian release fromswellable devicesrdquo Journal of Controlled Release vol 5 no 1 pp37ndash42 1987

Submit your manuscripts athttpswwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 201

International Journal ofInternational Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal ofInternational Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


Journal of


Quantum Chemistry


Organic Chemistry International

ElectrochemistryInternational Journal of



CatalystsJournal of


treatment of Zollinger-Ellison Syndrome gastroesophagealreflux duodenal ulcers gastric ulcer and duodenal ulcerThe suggested dose of ranitidine for gastroesophageal refluxillness is 150mg twice a day however for erosive esophagitissame dose is four times a day ormuchmore [12] Studies havedemonstrated that patientrsquos compliances are antagonisticallyinfluenced by increase in number of doses In this waysustained release would be more profitable in decreasing itsfrequency for compelling results [13 14]The gastric residencetime is essential for the drugs which are primarily absorbedthrough stomach or unstable at higher pH In this way thecontrolled drug release in particular area of gastric tractoffers different advantages like enhanced bioavailability andremedial viability [15]

The objective of this study was to prepare ranitidinefloats of controlled drug delivery because of its low bioavail-ability (half) and short organic half-life (2-3 h) [16] In thepresent premises the RNT floats were composed of fractionsdisengaged from Psyllium husk gel and studied for theirgastroretentive profile The regression analysis was utilizedto optimize the formulations similarity (f 2) and differencefactors (f 1) were used to look at the drug release profiles of allhusk fractions with standard tablet accessible in the marketDistinctive kinetic models were connected for example zeroorder first order Higuchi model Power law and H-Crowellcube root law to study the drug release rate and all theseresults demonstrate that the applied methods were sufficientfor designing sustained release floats of RNT having bettertherapeutic and clinical outcomes

2 Materials and Methods

Ranitidine (RNT) was provided by Ferozsons LaboratoriesLimited Pakistan as a gift All other chemicals and solventswere purchased from Sigma Aldrich Pakistan All chemi-cals were of AR grade and used without further purifica-tion

21 Isolation of Hydrogel Psyllium husk (10 g) was immersedin excess distilled water (2 L) and kept overnight Aftercomplete swelling NaOH (04M) solution was added toswelled husk with continuous stirring The solution wasfiltered with muslin cloth to separate insoluble impuritiesThe glacial acetic acid was added gradually with stirring tofiltered solution The gel was decanted off and dried aftercomplete dialysis by distilled water For isolation of differentfractions the dried gel was again swelled in distilled waterand treated with different solvents for example acetonemethanol ethanol and chloroform Different fractions indifferent concentrations were again coagulated using thesaid solvents After separation these fractions were dialyzedthoroughlywith distilledwater to remove separating solventsThe purified gels were dried and ground to fine powder Thepowdered gel was dissolved in drug solution After absorbingthe drug whole mass was dried again The dried mass wasground mixed with excipients and sprayed with isopropylalcohol (iPrOH) and then compressed to form floats Theseparation of different fractions is shown in Figure 1


221 Elemental Analysis CHNS analyzer was used to findthe amount of N and C in given sample The elementalanalysis for each sample was performed in triplicate

222 Thermal Analysis (TA) TA of isolated samples wascarried out under N2 atmosphere at multiple heating rate (1015 and 20∘C) using Broidorsquos method and activation energy(119864119886) was calculated from the slope of line by least squaremethods

log( 1119910) = minus(119864119886119877 )(

1119879) + constant (1)

where 119879 is the temperature in Kelvin and 119877 is general gasconstant having value 831 JKndash1molndash1 119910 is ratio of differencein mass before and after heating = (119898119905 minus 119898119891)(1198980 minus 119898119891)where 119898119905 is weight of polymer at temperature 119879 1198980 is themass at initial temperature and 119898119891 is the mass at the finaltemperature of particular decomposition stage so Broidorsquosequation can be represented as 119864119886 = minus (slope times 8314) Thedata was analyzed (TA Instruments USA) using UniversalAnalysis 2000 software version 42E and MS Excel 2007

223 Gel Permeation Chromatography (GPC) GPC analysiswas carried out with Agilent 1200 Series GPC-SEC Systemusing pullulan and dextran as standards The system wasequipped with 2 columns and dimethyl sulphide was used aseluent with flow rate of 05mLminndash1 at 70∘C using injectionsabout 50120583L224 Fourier Transform-Infrared Spectroscopy The absorp-tion bands in FT-IR spectra of ENa were noted to comparewith earlier work for same type of materials [17]

225 Scanning Electron Microscopy (SEM) Pellets of ENafraction were prepared at 3000 psi pressure using hydraulicpress The pellets were mounted with the help of silver painton aluminum stubs and subsequently were coated with goldThe SEM images were taken at different magnification usingJEOL JSM-6480 LV Japan at 10 kV

226 Determination of Water Retention Value (WRV) Thewater retention was calculated by centrifugation methodAbout 10 g dried gel was placed in a beaker containing100mL distilled water at 30∘C for 3 h for complete swellingThe swelled material was filled in 4 fritted glass tubescontaining pores at the bottom The tubes were centrifugedat 2500 rpm for 40min to remove the entrapped water Aftercentrifugation sample material was dried in an oven at 60∘Cfor complete dehydration WRV was calculated as follows

WRV () = (119898119908 minus 119898119889)119898119889 times 100 (2)

where 119898119908 is mass of sample (wet state) and 119898119889 is mass ofsample (dry state)


AcOH(1 30)

Residue discarded

MeOH (1 20)

MNaAANa



Filtration

ClfNa

Filtrate

EtOH (1 20)

ENa ANa

Me2CO (1 30)


M NaOH (to pH 12)

CHCl3 (1 20)




1st ENa 100 150 200 NaHCO3 = 10SA 30 60 90 CA = 10














12 times 100] (4)



Samplecode

Temprange(∘C)

Massloss()






ENa 223ndash315 4924 14668 13976 minus5147 16966 2282 28942 046 0983

















0

20

40

60

80

100

Wei

ght (

)

0 200 400 600 800

090

095

100

105

110

115

120

125

130

135

Temperature (∘C)


0

02

04

06

08

1

200 300 400350250

T (∘C)

= 095

= 090 = 085

= 080

= 075

= 070

= 065

= 060

= 055

= 050

= 045

= 040

= 035

= 030

= 025

= 020

log

170 180 190160(1000T) (＋minus1)


3442

94

3375

4333

2335 29

1637

2353

94

2123

63

1539

49

1552

34

1432

25 1251

80

1051

20

1047

35

1012

63

9933

4

6423

058

057

5497

1

5285

0

6906

2

6519

4

5593

6

6292

1323

95

1251

80

100

95

90

85

80

75

70

4000 3500 3000 2500 2000 1500 1000 500

T








MNaENaAANa

ClfNaANaHusk

200 400 600 8000Time (min)

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

CＭＮ＞










S4F1S4F2S4F3

S4F4S4F5S4F6

S4F7S4F8S4F9

S1F1S1F2S1F3

S1F4S1F5S1F6

S1F7S1F8S1F9

S2F1S2F2S2F3

S2F4S2F5S2F6

S2F7S2F8S2F9

S3F1S3F2S3F3

S3F4S3F5S3F6

S3F7S3F8

0

20

40

60

80

Accu

mul

ativ

e DR

()

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

200 400 600 8000Time (min)

500 10000Time (min)

200 400 600 8000Time (min)

200 400 600 8000Time (min)

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

0

20

40

60

80

100100

Accu

mul

ativ

e DR

()

S3F9




S1 f 1 2850 1371 1302 1880 1983 2645 2361 2362 2518f 2 5076 6549 6492 5958 5776 5097 5484 5556 5373

119862stdf 1 1302 1367 2077 2333 2998 3626 3251 3252 3421f 2 6293 6422 5595 5251 4482 4019 4533 4395 4210

S2 f 1 2071 927 947 2267 1551 1701 1715 1866 2128f 2 5910 7203 7401 5630 6244 6287 6162 5978 5604

119862stdf 1 1527 1662 2061 1853 2492 2680 2637 2897 3161f 2 6052 5840 5250 5721 5056 4820 4946 4640 4360

S3 f 1 1337 1458 1828 1846 2360 3102 2405 3049 3787f 2 6212 5909 5458 5454 4912 4348 4769 4314 3904

119862stdf 1 2282 2135 2145 2352 2375 2928 2730 3049 3560f 2 5263 5408 5364 5217 4991 4503 4737 4389 4036

S4 f 1 4414 1758 1030 3338 2343 892 1407 0708 0781f 2 4425 6244 7155 5021 5792 7499 6519 7554 7634

119862stdf 1 1834 1579 2019 1487 1545 2578 2284 2425 2739f 2 5576 6088 5518 6065 6057 4901 5245 5038 4730



















3212 1st Batch


(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)


(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)




3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)




3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)









3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


AcOH(1 30)

Residue discarded

MeOH (1 20)

MNaAANa



Filtration

ClfNa

Filtrate

EtOH (1 20)

ENa ANa

Me2CO (1 30)


M NaOH (to pH 12)

CHCl3 (1 20)




1st ENa 100 150 200 NaHCO3 = 10SA 30 60 90 CA = 10














12 times 100] (4)



Samplecode

Temprange(∘C)

Massloss()






ENa 223ndash315 4924 14668 13976 minus5147 16966 2282 28942 046 0983

















0

20

40

60

80

100

Wei

ght (

)

0 200 400 600 800

090

095

100

105

110

115

120

125

130

135

Temperature (∘C)


0

02

04

06

08

1

200 300 400350250

T (∘C)

= 095

= 090 = 085

= 080

= 075

= 070

= 065

= 060

= 055

= 050

= 045

= 040

= 035

= 030

= 025

= 020

log

170 180 190160(1000T) (＋minus1)


3442

94

3375

4333

2335 29

1637

2353

94

2123

63

1539

49

1552

34

1432

25 1251

80

1051

20

1047

35

1012

63

9933

4

6423

058

057

5497

1

5285

0

6906

2

6519

4

5593

6

6292

1323

95

1251

80

100

95

90

85

80

75

70

4000 3500 3000 2500 2000 1500 1000 500

T








MNaENaAANa

ClfNaANaHusk

200 400 600 8000Time (min)

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

CＭＮ＞










S4F1S4F2S4F3

S4F4S4F5S4F6

S4F7S4F8S4F9

S1F1S1F2S1F3

S1F4S1F5S1F6

S1F7S1F8S1F9

S2F1S2F2S2F3

S2F4S2F5S2F6

S2F7S2F8S2F9

S3F1S3F2S3F3

S3F4S3F5S3F6

S3F7S3F8

0

20

40

60

80

Accu

mul

ativ

e DR

()

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

200 400 600 8000Time (min)

500 10000Time (min)

200 400 600 8000Time (min)

200 400 600 8000Time (min)

0

20

40

60

80

100

Accu

mul

ativ

e DR

()

0

20

40

60

80

100100

Accu

mul

ativ

e DR

()

S3F9




S1 f 1 2850 1371 1302 1880 1983 2645 2361 2362 2518f 2 5076 6549 6492 5958 5776 5097 5484 5556 5373

119862stdf 1 1302 1367 2077 2333 2998 3626 3251 3252 3421f 2 6293 6422 5595 5251 4482 4019 4533 4395 4210

S2 f 1 2071 927 947 2267 1551 1701 1715 1866 2128f 2 5910 7203 7401 5630 6244 6287 6162 5978 5604

119862stdf 1 1527 1662 2061 1853 2492 2680 2637 2897 3161f 2 6052 5840 5250 5721 5056 4820 4946 4640 4360

S3 f 1 1337 1458 1828 1846 2360 3102 2405 3049 3787f 2 6212 5909 5458 5454 4912 4348 4769 4314 3904

119862stdf 1 2282 2135 2145 2352 2375 2928 2730 3049 3560f 2 5263 5408 5364 5217 4991 4503 4737 4389 4036

S4 f 1 4414 1758 1030 3338 2343 892 1407 0708 0781f 2 4425 6244 7155 5021 5792 7499 6519 7554 7634

119862stdf 1 1834 1579 2019 1487 1545 2578 2284 2425 2739f 2 5576 6088 5518 6065 6057 4901 5245 5038 4730



















3212 1st Batch


(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)


(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)




3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)




3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)









3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



Samplecode

Temprange(∘C)

Massloss()






ENa 223ndash315 4924 14668 13976 minus5147 16966 2282 28942 046 0983

















0

20

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100

Wei

ght (

)

0 200 400 600 800

090

095

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Temperature (∘C)


0

02

04

06

08

1

200 300 400350250

T (∘C)

= 095

= 090 = 085

= 080

= 075

= 070

= 065

= 060

= 055

= 050

= 045

= 040

= 035

= 030

= 025

= 020

log

170 180 190160(1000T) (＋minus1)


3442

94

3375

4333

2335 29

1637

2353

94

2123

63

1539

49

1552

34

1432

25 1251

80

1051

20

1047

35

1012

63

9933

4

6423

058

057

5497

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5285

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6906

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6519

4

5593

6

6292

1323

95

1251

80

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95

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4000 3500 3000 2500 2000 1500 1000 500

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MNaENaAANa

ClfNaANaHusk

200 400 600 8000Time (min)

0

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Accu

mul

ativ

e DR

()

CＭＮ＞










S4F1S4F2S4F3

S4F4S4F5S4F6

S4F7S4F8S4F9

S1F1S1F2S1F3

S1F4S1F5S1F6

S1F7S1F8S1F9

S2F1S2F2S2F3

S2F4S2F5S2F6

S2F7S2F8S2F9

S3F1S3F2S3F3

S3F4S3F5S3F6

S3F7S3F8

0

20

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mul

ativ

e DR

()

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200 400 600 8000Time (min)

200 400 600 8000Time (min)

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S3F9




S1 f 1 2850 1371 1302 1880 1983 2645 2361 2362 2518f 2 5076 6549 6492 5958 5776 5097 5484 5556 5373

119862stdf 1 1302 1367 2077 2333 2998 3626 3251 3252 3421f 2 6293 6422 5595 5251 4482 4019 4533 4395 4210

S2 f 1 2071 927 947 2267 1551 1701 1715 1866 2128f 2 5910 7203 7401 5630 6244 6287 6162 5978 5604

119862stdf 1 1527 1662 2061 1853 2492 2680 2637 2897 3161f 2 6052 5840 5250 5721 5056 4820 4946 4640 4360

S3 f 1 1337 1458 1828 1846 2360 3102 2405 3049 3787f 2 6212 5909 5458 5454 4912 4348 4769 4314 3904

119862stdf 1 2282 2135 2145 2352 2375 2928 2730 3049 3560f 2 5263 5408 5364 5217 4991 4503 4737 4389 4036

S4 f 1 4414 1758 1030 3338 2343 892 1407 0708 0781f 2 4425 6244 7155 5021 5792 7499 6519 7554 7634

119862stdf 1 1834 1579 2019 1487 1545 2578 2284 2425 2739f 2 5576 6088 5518 6065 6057 4901 5245 5038 4730



















3212 1st Batch


(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)


(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)




3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)




3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)









3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


0

20

40

60

80

100

Wei

ght (

)

0 200 400 600 800

090

095

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105

110

115

120

125

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135

Temperature (∘C)


0

02

04

06

08

1

200 300 400350250

T (∘C)

= 095

= 090 = 085

= 080

= 075

= 070

= 065

= 060

= 055

= 050

= 045

= 040

= 035

= 030

= 025

= 020

log

170 180 190160(1000T) (＋minus1)


3442

94

3375

4333

2335 29

1637

2353

94

2123

63

1539

49

1552

34

1432

25 1251

80

1051

20

1047

35

1012

63

9933

4

6423

058

057

5497

1

5285

0

6906

2

6519

4

5593

6

6292

1323

95

1251

80

100

95

90

85

80

75

70

4000 3500 3000 2500 2000 1500 1000 500

T








MNaENaAANa

ClfNaANaHusk

200 400 600 8000Time (min)

0

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Accu

mul

ativ

e DR

()

CＭＮ＞










S4F1S4F2S4F3

S4F4S4F5S4F6

S4F7S4F8S4F9

S1F1S1F2S1F3

S1F4S1F5S1F6

S1F7S1F8S1F9

S2F1S2F2S2F3

S2F4S2F5S2F6

S2F7S2F8S2F9

S3F1S3F2S3F3

S3F4S3F5S3F6

S3F7S3F8

0

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e DR

()

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200 400 600 8000Time (min)

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()

S3F9




S1 f 1 2850 1371 1302 1880 1983 2645 2361 2362 2518f 2 5076 6549 6492 5958 5776 5097 5484 5556 5373

119862stdf 1 1302 1367 2077 2333 2998 3626 3251 3252 3421f 2 6293 6422 5595 5251 4482 4019 4533 4395 4210

S2 f 1 2071 927 947 2267 1551 1701 1715 1866 2128f 2 5910 7203 7401 5630 6244 6287 6162 5978 5604

119862stdf 1 1527 1662 2061 1853 2492 2680 2637 2897 3161f 2 6052 5840 5250 5721 5056 4820 4946 4640 4360

S3 f 1 1337 1458 1828 1846 2360 3102 2405 3049 3787f 2 6212 5909 5458 5454 4912 4348 4769 4314 3904

119862stdf 1 2282 2135 2145 2352 2375 2928 2730 3049 3560f 2 5263 5408 5364 5217 4991 4503 4737 4389 4036

S4 f 1 4414 1758 1030 3338 2343 892 1407 0708 0781f 2 4425 6244 7155 5021 5792 7499 6519 7554 7634

119862stdf 1 1834 1579 2019 1487 1545 2578 2284 2425 2739f 2 5576 6088 5518 6065 6057 4901 5245 5038 4730



















3212 1st Batch


(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)


(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)




3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)




3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)









3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




MNaENaAANa

ClfNaANaHusk

200 400 600 8000Time (min)

0

20

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60

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Accu

mul

ativ

e DR

()

CＭＮ＞










S4F1S4F2S4F3

S4F4S4F5S4F6

S4F7S4F8S4F9

S1F1S1F2S1F3

S1F4S1F5S1F6

S1F7S1F8S1F9

S2F1S2F2S2F3

S2F4S2F5S2F6

S2F7S2F8S2F9

S3F1S3F2S3F3

S3F4S3F5S3F6

S3F7S3F8

0

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mul

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()

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200 400 600 8000Time (min)

200 400 600 8000Time (min)

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mul

ativ

e DR

()

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()

S3F9




S1 f 1 2850 1371 1302 1880 1983 2645 2361 2362 2518f 2 5076 6549 6492 5958 5776 5097 5484 5556 5373

119862stdf 1 1302 1367 2077 2333 2998 3626 3251 3252 3421f 2 6293 6422 5595 5251 4482 4019 4533 4395 4210

S2 f 1 2071 927 947 2267 1551 1701 1715 1866 2128f 2 5910 7203 7401 5630 6244 6287 6162 5978 5604

119862stdf 1 1527 1662 2061 1853 2492 2680 2637 2897 3161f 2 6052 5840 5250 5721 5056 4820 4946 4640 4360

S3 f 1 1337 1458 1828 1846 2360 3102 2405 3049 3787f 2 6212 5909 5458 5454 4912 4348 4769 4314 3904

119862stdf 1 2282 2135 2145 2352 2375 2928 2730 3049 3560f 2 5263 5408 5364 5217 4991 4503 4737 4389 4036

S4 f 1 4414 1758 1030 3338 2343 892 1407 0708 0781f 2 4425 6244 7155 5021 5792 7499 6519 7554 7634

119862stdf 1 1834 1579 2019 1487 1545 2578 2284 2425 2739f 2 5576 6088 5518 6065 6057 4901 5245 5038 4730



















3212 1st Batch


(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)


(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)




3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)




3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)









3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


S4F1S4F2S4F3

S4F4S4F5S4F6

S4F7S4F8S4F9

S1F1S1F2S1F3

S1F4S1F5S1F6

S1F7S1F8S1F9

S2F1S2F2S2F3

S2F4S2F5S2F6

S2F7S2F8S2F9

S3F1S3F2S3F3

S3F4S3F5S3F6

S3F7S3F8

0

20

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80

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mul

ativ

e DR

()

0

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ativ

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()

200 400 600 8000Time (min)

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200 400 600 8000Time (min)

200 400 600 8000Time (min)

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mul

ativ

e DR

()

0

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ativ

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()

S3F9




S1 f 1 2850 1371 1302 1880 1983 2645 2361 2362 2518f 2 5076 6549 6492 5958 5776 5097 5484 5556 5373

119862stdf 1 1302 1367 2077 2333 2998 3626 3251 3252 3421f 2 6293 6422 5595 5251 4482 4019 4533 4395 4210

S2 f 1 2071 927 947 2267 1551 1701 1715 1866 2128f 2 5910 7203 7401 5630 6244 6287 6162 5978 5604

119862stdf 1 1527 1662 2061 1853 2492 2680 2637 2897 3161f 2 6052 5840 5250 5721 5056 4820 4946 4640 4360

S3 f 1 1337 1458 1828 1846 2360 3102 2405 3049 3787f 2 6212 5909 5458 5454 4912 4348 4769 4314 3904

119862stdf 1 2282 2135 2145 2352 2375 2928 2730 3049 3560f 2 5263 5408 5364 5217 4991 4503 4737 4389 4036

S4 f 1 4414 1758 1030 3338 2343 892 1407 0708 0781f 2 4425 6244 7155 5021 5792 7499 6519 7554 7634

119862stdf 1 1834 1579 2019 1487 1545 2578 2284 2425 2739f 2 5576 6088 5518 6065 6057 4901 5245 5038 4730



















3212 1st Batch


(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)


(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)




3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)




3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)









3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



















3212 1st Batch


(CRC = 0903129 1198772 = 0813737 Adj1198772 = 0757978 119899 = 27)(5)


(CRC = 0969284 1198772 = 0939511 Adj1198772 = 0931789 119899 = 99)(6)


(CRC = 0992215 1198772 = 0983514 Adj1198772 = 0982528 119899 = 99) (7)




3213 2nd Batch

S22 h = 0221171119905 + 0182557119860 + 0178385119861 + 0000876119862minus 000118119863 minus 000112119864 + 482514

(CRC = 0942855 1198772 = 0887506 Adj1198772 = 0855448 119899 = 27)(8)

S25 h = 0154039119905 + 0006524119860 + 0210632119861 + 00015119862minus 000157119863 minus 000082119864 + 1087422

(CRC = 0971366 1198772 = 0944552 Adj1198772 = 0946346 119899 = 54) (9)




3214 3rd Batch

S3 = 0256874119905 minus 026814119860 minus 016514119861 + 0000262119862+ 0000548119863 + 0006923119864 + 3592275

(CRC = 0976225 1198772 = 0957119 Adj1198772 = 0944255 119899 = 27)(11)

S3 = 0162851119905 minus 031975119860 minus 000574119861 + 000088119862+ 000053119863 + 0002823119864 + 4442843

(CRC = 0976629 1198772 = 0961753 Adj1198772 = 0954716 119899 = 54)(12)

S310 h = 0093693119905 minus 024862119860 + 0196631119861 minus 000024119862+ 0000654119863 + 0000376119864 + 4655

(CRC = 0951827 1198772 = 0906334 Adj1198772 = 0901202 119899 = 99) (13)









3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of








3215 4th Batch





4 Conclusion



Abbreviations









References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of








References

































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of














Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

ranitidine loaded biopolymer floats: designing...

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