formulation and evaluation of fast dissolving tablets of carbamazepine using solid dispersion

Int. J. Pharm. Res. Sci., 2014, 02(1), 47-59. www.ijprsonline.com ISSN: 2348 –0882==========================================================================

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Formulation and Evaluation of Fast Dissolving Tablets of CarbamazepineUsing Solid Dispersion.

Metkari VB1,*, Kulkarni LV1, Patil PS1, Jadhav PA1, Jadhav PH1, Yadav PS1.

1College of pharmacy Medha Satara, Maharashtra, India.Corresponding author email: [email protected]

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Abstract:The purpose of present research work was tooptimize the formulation of fast dissolving tabletof carbamazepine. Carbamazepine is one the mostprescribed antiepileptic drug. Fast dissolvingtablets of carbamazepine were prepared by usingdifferent types of superdisintegrants likecroscarmellose sodium and sodium starchglycolate. Fast dissolving tablet is prepared bydirect compression method. The formulationswere evaluated for wetting time, hardness,friability, content uniformity, invitrodisintegration time, release profile. The resultrevealed that the formulation F5 which containingthe 5% croscarmellose sodium as asuperdisintegrant have good dissolution profilewith shortest Disintegration time. It can beconcluded that the tablet of carbamazepine withbetter pharmaceutical properties than conventionaltablets could be obtained using formulation F5.Keywords: Fast dissolving tablet, Croscarmellosesodium, sodium starch glycolate, Directcompression.Introduction:Oral route has been one of the most of popularroutes of drug delivery due to its ease ofadministration, patient compliance, least sterilityconstraints and flexible design of dosage forms(Brahmankar et al., 2005).Many patient ofdifferent age group like geriatric and pediatriccomplaint of some solid dosage form because ofdifficulty in swallowing. So to solve this problemand increase patient compliance fast dissolvingtablet is prepared. Fast dissolving tablets are those

when put on tongue disintegrating instantaneouslyreleasing the drug which dissolves or disperses inthe saliva. Fast dissolving tablets are also called asmouth dissolving tablets, orodispersible tablets,rapi melts, porous tablets, quick dissolving etc.The faster the drug into solution, quicker theabsorption and onset of clinical effects. Somedrugs are absorbed from mouth, pharynx andesophagus as the saliva passes down into thestomach. In such cases bioavailability of drug issignificantly greater than those observed fromconventional tablets dosage form. According toEuropean pharmacopoeia, the ODT shoulddisintegrate in less than three minutes. The basicapproach in development of fast dissolving tabletsis the use of the superdisintegrants likecrosscarmellose sodium and sodium starchglycolate. Which provide instaneousdisintegration of the tablets after putting ontounge, their by release the drug in saliva. Thebioavailability of some drug may be increased dueto absorption of drug in oral cavity and also due topregastric absorption of saliva containingdispersed drugs that pass down into stomach(Abed et al., 2010). Fast dissolving tablets arethose when put on tongue disintegratinginstantaneously releasing the drug which dissolvesor disperses in the saliva. Fast dissolving tabletsare also called as mouth dissolving tablets,orodispersible tablets, rapi melts, porous tablets,quick dissolving etc.The faster the drug intosolution, quicker the absorption and onset ofclinical effects. Some drugs are absorbed frommouth, pharynx and esophagus as the saliva


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passes down into the stomach. In such casesbioavailability of drug is significantly greater thanthose observed from conventional tablets dosageform. According to European pharmacopoeia, theODT should disintegrate in less than threeminutes. The basic approach in development offast dissolving tablets is the use of thesuperdisintegrants like crosscarmellose sodiumand sodium starch glycolate. Which provideinstaneous disintegration of the tablets afterputting on tounge, their by release the drug insaliva.The bioavailability of some drug may beincreased due to absorption of drug in oral cavityand also due to pregastric absorption of salivacontaining dispersed drugs that pass down intostomach (Madhusudan et al.,).2. MATERIAL AND METHODS:2.1 Material:Carbamazepine is obtained as a gift sample fromAbbott pvt ltd, Mumbai. Croscarmellose sodiumis obtained from Fine chem industry Mumbai.Sodium starch glycolate is obtained fromChemika Biochemika Reagents. All otherchemicals used were of analytical grade.2.2 Methods:2.2.1 Preparation of solid dispersion ofCarbamazepineCarbamazepine solid dispersions were preparedby solvent evaporation, melting and kneadingmethods using drug: polyethylene oxide N10 inproportion, viz. 1:1, 1:1.25, 1:1.5, 1:2. (Drug:Carrier). Methanol and isopropyl alcohol wereselected as common solvents for solid dispersion.2.2.1.1 Solvent evaporation method:The 100 mg of carbamazepine was dissolved in 20ml of methanol in beaker and weighed amount ofpolyethylene oxide N 10 was added and stirred todissolve both drug and carrier to get clearsolution. Solution was poured on Petri plate andallowed to evaporate the solvent. The process ofevaporation was operated until all methanols getevaporated. Solid dispersion prepared was thendried at room temperature and stored indesiccators for further study (Lewis et al., 2009).

2.2.1.2 Kneading methodAccurate weighed amount of Carbamazepine andpolyethylene oxide N 10 were taken into glassmortar and then methanol was added in smallquantity to make paste. The paste was allowed tostand for 45 mins and then dried in oven at 400c.The product obtained was pulverized and passedthrough mesh (#) 80 and stored in desiccator forfurther study (Madhavi et al., 2011).2.2.1.3 Physical mixture:Accurate weighed amount of Carbamazepine andpolyethylene oxide N 10 were taken into glassmortar and then mixed for 10 minutes to get goodmixture of drug and polymer. Then product wasstored in the desiccator for further study(Kahkeshan et al., 2012).2.2.1 Formulation of fast dissolving tablets:Fast dissolving tablets containing optimizedsolid dispersion were prepared by directcompression method using single punch tabletmachine to produce convex faced tabletsweighing 500 mg each with a diameter of 12mm. A minimum of 40 tablets were preparedfor each batch (Solanki et al.,2011).2.2.2 By direct compression techniqueThe direct compression technique was selected fordeveloping novel fast dissolving tablets. In directcompression technique all materials accuratelyweighed like solid dispersion complex,microcrystalline cellulose, sodium saccharine,talc, magnesium state, and mannitol passedthrough a 40 mesh prior to mixing. The soliddispersion complex was properly mixed withsuperdisintegrant, and then with diluents MCC.The mixture was mixed with talc, sodiumsaccharine, magnesium state and mannitol. Thenmixture was subjected to compression usingsingle punch tablet machine (Solanki et al.,2011).

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Table 1. Formulation of fast dissolving tablets using croscarmellose sodium

Table 2. Formulation of fast dissolving tablets using sodium starch glycolateIngredients in (mg) F1 F2 F3SD complex 250 250 250Sodium starch glycolate 10 20 30Microcrystalline cellulose 145 135 125Mannitol 75 75 75Magnesium state 5 5 5Sodium saccharine 10 10 10talc 5 5 5Total weight 500 500 500

2.2.3 Characterization of blends:The quality of tablet, once formulated by rule,is generally dictated by the quality ofphysicochemical properties of blends. There aremany formulations and process variablesinvolved in mixing step and all these can affectthe characteristics of blend produced. Thecharacterization of mixed blend done for theflow property of powder that are bulk density,tapped density, Hausner’s ratio, Compressibilityindex, angle of repose. The variouscharacteristics of blends tested are given belowand results were shown in Table below (Kakde etal.,2010).Bulk densityBulk density of powder blend is always less thanthe true density of its component particles becausethe powder contains interparticulate pores orvoids. The bulk density of powder is dependent onparticle packing and changes as powderconsolidates. A consolidated powder is likely tohave a greater arch strength than a lessconsolidated one and may therefore be more

resistant to powder flow. However, a high bulkdensity does not necessarily imply a close-packedlow-porosity bed, as bulk density is directlyproportional to true density. Bulk density can bedefined as the mass of powder divided by the bulkvolume. Bulk density of powder blends wasdetermined using 25ml calibrated plasticmeasuring cylinder, in which powder blends weresimply poured and bulk density was measured inunit gm/ml. Bulk density is also known as fluff orpoured bulk density. It can be calculated byfollowing equation,Bulk Density = Mass/volume

ρb = M/Vb

Tapped densityAs stated above that due to interparticulate voidsbulk density of a powder is always less than truedensity. This statement reveals that whereas as apowder can only possess a single true density, itcan have many different bulk densities, dependingon the way in which the particles are packed andthe bed porosity. For powders having comparabletrue densities, an increase in bulk density causes

Ingredients in (mg) F1 F2 F3 F4 F5 F6SD complex 250 250 250 250 250 250Croscarmellose sodium 10 20 30 40 50 75Microcrystalline cellulose 145 135 125 115 105 80Mannitol 75 75 75 75 75 75Magnesium state 5 5 5 5 5 5Sodium saccharine 10 10 10 10 10 10talc 5 5 5 5 5 5Total weight 500 500 500 500 500 500

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decrease in porosity. This increases the number ofinterparticulate contacts and contacts areas andcauses an increase in cohesion. In very coarseparticles this may still be insufficient to overcomethe gravitational influence on particles. Tappeddensity is defined as the mass of a powder dividedby the tapped volume. Tapped density of powderblends was performed for 100 taps by usingdigital bulk density equipment and was measuredin unit of gm/ml. True density is also known asequilibrium, tapped or consolidated bulk density.It can be calculated by following equation,

Tapped Density = Mass/ Tappedvolume

ρt = M/Vt

Carr’s Compressibility indexThe simplex way of measurement of the free flowof powder is compressibility, an indication of easewith which a material can be induced to flow isgiven by compressibility index of the granuleswas determined by Carr’s compressibility index (I)which is calculated by using the formula(Rockville et al.,2000).Compressibility index = Bulk volume – Tappedvolume/Bulk volume × 100

Table 3. Compressibility Index as an Indication of Powder Flow Properties

Carr ̀̀̀,s Index (%) Type of Flow>12 Excellent

12-16 Good18-21 Fair to passable23-35 Poor33-38 Very poor>40 Extremely poor

Hausner ratioHausner ratio is an indirect index of ease ofpowder flow. It is calculated by the followingformulHausner ratio = tapped density/ bulk density

Hausner ratio = ρt/ ρb

Angle of reposeAngle of repose was determined using fixedfunnel method. The blend was poured through a

funnel that can be raised vertically until amaximum cone height (h) was obtained. Radius ofheap (r) was measured and angle of repose wascalculated using formula

Ө = tan-1h/r

Where, Ө is angle of repose, h is height ofpile and r is radius of base pile.

Table 4. Angle of Repose as an Indication of Powder Flow Properties

Angle of repose (o) Type of flow

<25 Excellent25-30 Good30-40 Passable>40 Very poor

2.2.2.4 Characterization of fast dissolvingtablets:After compression of powder, the tablets wereevaluated for diameter, thickness and physicalcharacteristics like hardness, friability,

disintegration time, wetting time, dispersiontime and dissolution studies. The results wereshown in Table below.

Tablet Thickness

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Ten tablets from each batch formulation wereselected randomly and their thickness wasmeasured with a screw gauge for calculatingthickness variation (Shirsand et al.,2010).Uniformity of weightAs per IP twenty tablets were taken randomly

from each formulation and weighed collectivelyand average weight was calculated using digitalbalance. The individual weights were comparedwith the average weight for obtaining weightvariation.

Table 5. Weight Variation Limits for Tablets as per IP.Average of Tablets (mg) Maximum% difference allowed130 or less 10130-324 7.5More than 324 5

HardnessHardness of the tablet was measured using theMonsanto hardness tester (soumya et al.,2013).FriabilityFriability of the tablets was determined usingRoche friabilator. This device subjects thetablets to the combined effect of abrasions andshock in a plastic chamber revolving at 25 rpmand dropping the tablets at a height of 6 inch ineach revolution. Pre-weighed sample of tabletswas placed in the friabilator and were subjectedto 100 revolutions. Tablets were dusted using asoft muslin cloth and reweighed. The friability(F %) is determined by the formula (Rangole etal., 2008).

% friability = loss in weight/initialweight×100

Drug content uniformityDrug content of fast dissolving tablets ofcarbamazepine was calculated by weighing tentablets of each formulation, pulverizing to a finepowder. A quantity of powder equivalent to 10 mgof carbamazepine dissolved in methanol andsolution was filtered through a 0.45 μm whatmannfilter paper. Carbamazepine content wasdetermined by measuring the absorbance at 285nm at UV visible spectrophotometer afterappropriate dilution with methanol. The drugcontent was determined using calibration curve.The mean percent drug content was calculated asan average of three dimensions(Masareddy etal.,2008).

In Vitro dispersion time

The In vitro dispersion time of fast dissolvingtablets of carbamazepine was determined byplacing one tablet in a beaker containing 100 mlof phosphate buffer and time required forcomplete dispersion was determined.Wetting timeWetting time of fast dissolving tablets ofcarbamazepine was determined by carefullyplacing tablets on to a twice folded circular tissuepaper placed in a Petri-dish having the internaldiameter of 5 cm containing 6 ml of water. Thetime required for water to reach the upper surfaceof the tablet and to completely weight the tabletwas noted as wetting time(Rangole et al.,2008).Water absorption ratioThe weight of the tablets prior to placing in Petridish was noted (wb) using the digital balance. Theweighted tablet was removed and reweighed (wa).Water absorption ratio(R) was then determinedaccording to the following equation.

R = 100× (wa-wb)Where, wb and wa were tablet weights before andafter water absorption respectively.In-vitro dissolution studyIn-vitro dissolution study of fast dissolving tabletsof carbamazepine was performed according toUSP type-II dissolution apparatus employing apaddle stirrer at 50 rpm using 900 ml of phosphatebuffer of pH 6.8 at 37±0.5 as dissolution medium.One tablet was used in each test. Aliquots of thedissolution medium 5 ml were withdrawn atspecific time interval 5, 10, 15,20,25,30 minutesand replaced with the equal volume of freshmedium. The samples were filtered through 0.45μm whatman analyzed by measuring the

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absorbance at 285 nm. Drug concentration wascalculated from the standard calibration curve andexpressed as cumulative percent drug dissolved.The release studies were performed in triplicate(Arora et al.,2010).In-vitro Disintegration timeDisintegration of FDT was generally occurringdue to water uptake by superdisintegrant viacapillary action, which results in swelling ofsuperdisintegrants and tablet get disintegrated. Itwas also reported that increased compaction forcemay increase or decrease disintegration time. Inthe present study disintegration test was carriedout on six tablets using the apparatus specified inUSP (Electrolab disintegration apparatus USP).The distilled water at 370C ± 20C was used as adisintegration media and time in second taken forcomplete disintegration of the tablet with nopalpable mass remaining in the apparatus wasmeasured in seconds (Pandit et al., 2012).

IR Spectrum of CarbamazepineIR spectrophotometer was used for infraredspectroscopy analysis of carbamazepine. Thesamples were prepared in KBr disk by means of ahydrostatic press. The scanning range was 400-4000 cm-1 (Wan et al., 2012).DSC of CarbamazepineDifferential scanning calorimetry (DSC)measurements were performed on SDT Q600Differential scanning calorimeter. The accuratelyweighed sample was placed in an aluminium panand an empty aluminium pan was used as areference (Wan et al.,2012).XRD of carbamazepineXRD of carbamazepine was carried out by usingthe Philips PW 1729 X-ray generator (Wan etal.,2012).3. RESULT AND DISSCUSION:

Table.6. Solubility of PM and SD in water:Drug: Polymer ratio Solubility (mg/ml)

PM SE KM1:1 0.13 0.16 0.27

1:1.25 0.14 0.18 0.291:1.5 0.15 0.19 0.351:2 0.14 0.17 0.26

From table 6 it is know that Solubility ofcarbamazepine is increased by different methodsof solid dispersion like physical mixture, solvent

evaporation and kneading method. Kneadingmethod is only method which gives the highsolubility than other method i.e. 0.35 mg/ml.

Table.7.Solubility data of SD prepared by KM in water:Drug: Polymer ratio Solubility (mg/ml)

1:1 0.271:1.25 0.291:1.5 0.351:1.75 0.29

1:2 0.261:3 0.231:4 0.23

From table 7 it is clear that proportion of drug topolymer ratio 1:1.5 give the high solubility i.e.0.35 mg/ml that’s why 1:1.5 proportion is used forpreparing fast dissolving tablets which gives highdrug release with in 30 mins i.e. 87.5±1.5.

3.1Drug polymer interaction studies:Drug and polymer interaction study was

carried out by doing the different analysis of pure

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carbamazepine, physical mixture, solid dispersion, polymer and the formulation.Fourier Transform Infrared Spectroscopy

Figure 1. IR spectra of A) Pure carbamazepine, B) polyox N 10 C) Physical Mixture D) SolidDispersion E) Formulation F.

IR spectrum of pure carbamazepine,polyox N 10, Physical Mixture and Soliddispersion are shown in figure 1. The IR spectraof pure carbamazepine showed peak at 3458.37,3153.61, 3032.10, 1666.50, 1595.13, 1477.47,1377.17 cm-1 indicating stretching of N-H, C-H,C-H aromatic, amide, C-N , N-H deformationrespectively. These peaks seemed to be retained at

almost the same wave number with same intensityin the spectra of physical mixture solid dispersionwhich indicate that the absence of any potentialphysical or chemical interaction between drug andpolymer and other additives, Hence drug nadpolymer were found to be compatible with thedrug.

Differential Scanning Colorimetry Analysis

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Figure 2. DSC thermogram of A) Pure carbamazepine, B) polyox N 10 C) Physical Mixture D) SolidDispersion E) Formulation F5

One of the most classic application of DSCanalysis is the determination of the possibleinteraction between the drug and excipients in theformulation supporting evidence for compatiblebetween drug and excipients was obtained fromDSC analysis studies. As shown in the figure 2 theDSC thermogram of carbamazepine showed sharpendothermic peak at 193.930c which is near tomelting point of carbamazepine.DSC thermogramof polyox N 10 showed sharp melting at 73.440cwhich also observed in DSC thermogram of

physical mixture, solid dispersion and formulationF5.Endothermic peak of caarbamazepine was notobserved in Physical mixture, solid dispersion andformulation F 5 because carbamazepine isdispersed in the polyox N10 at molecular level.

This indicate the absence of anyinteraction between drug and excipients, Hencefrom above DSC thermogram, it was found thatthere was compatibility between drug andexcipients.

X- Ray Diffraction (XRD)XRD pattern were recorded using Philips 1729 X-ray generator. Powder X-ray diffraction patterns

were recorded for drug, physical Mixture, solid dispersion and polymer.

Figure 3 . XRD pattern of A) Pure carbamazepine, B) polyox N 10 C) Physical Mixture D) SolidDispersion

Figure 3 shows the diffraction pattern ofpure carbamazepine which shows its crystallinenature that was demonstrated by numerous sharp,highly intense and less diffused peaks. These

peaks were observed at 2θ values of 10.32, 13.32,16.16, 19.76, 25.14, 27.88, and 32.33 infingerprint regions referring to its crystallinity.

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Peak height of pure carbamazepine wasselected to calculate the RDC of CBZ, bestphysical mixture and solid dispersion. When pureCBZ was considered as a reference sample, asignificant decrement in crystallinity of thecharacterized solid dispersion was observed (˂0.1).RDC values were 1, 0.9 and 0.6. For puredrug, physical mixture and solid dispersion

respectively indicating the amorphousness ofdrug, polymer.

3.2 Characterization of blend for fastdissolving tablets:The data for evaluation of powder blends ofrapidly disintegrating tablets of carbamazepine isas shown below.

Table 7. Characterization of blends:Formulation code Bulk density

(gm/cm3)Tapped density

(gm/cm3)Hausner’s ̀̀́́̀̀ ratio Carr’s index

(%)Angle of repose

(Ө)F1 0.33±0.007 0.37±0.01 1.14±0.008 12.68±0.01 29.7±0.43F2 0.33±0.01 0.40±0.012 1.20±0.005 16.62±0.69 29.57±0.33F3 0.31±0.01 0.36±0.010 1.12±0.005 12.93±0.34 26.33±0.39F4 0.31±0.01 0.39±0.013 1.17±0.008 17.30±0.21 25.38±0.25F5 0.32±0.01 0.37±0.016 1.12±0.008 11.62±0.25 24.29±0.05F6 0.33±0.01 0.40±0.007 1.16±0.005 13.27±0.38 28.38±0.21F7 0.34±0.01 0.40±0.008 1.17±0.008 14.22±0.34 27.46±0.57F8 0.30±0.01 0.34±0.008 1±0.007 12.39±0.26 25.19±0.10F9 0.29±0.01 0.35±0.01 1.18±0.03 17.57±0.27 27.45±0.17

Bulk density of powder blends of differentformulation was found to be in the range of 0.29to 0.34 gm/cm3 whereas the tapped density wasfound to be in the range of 0.35 to 0.40 gm/cm3.

Angle of repose was found to be less than 300

which indicate good flow characteristics of thepowder blends. Carr’s index was found to be inthe range of 11.62 to 17.57 whereas the Hausnerratio was found to be less than 1.25. Both this

values indicate good flow property and goodcompression characteristics.3.3 Evaluation of fast dissolving tablets3.3.1 Evaluation of physical parameter oftabletsThe data for evaluation of physical parameters offast dissolving tablets of carbamazepine is asshown below.

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Table 8. Evaluation of fast dissolving tablets.

Formulation code Weight variation(mg)

Diameter(mm)

Thickness(mm)

Hardness(Kg/cm2)

Friability(%)

F1 Passes 12.00±0.007 4.326±0.019 3.14±0.054 0.65±0.11F2 Passes 12.02±0.007 4.4±0.035 3.22±0.10 0.63±0.11F3 Passes 12.024±0.005 4.368±0.024 3.04±0.11 0.54±0.14F4 Passes 12.024±0.005 4.472±0.035 3.02±0.10 0.59±0.07F5 Passes 12.036±0.011 4.362±0.019 3.1±0.1 0.63±0.06F6 Passes 12.054±0.018 4.338±0.039 3.24±0.26 0.74±0.07F7 Passes 12.054±0.015 4.342±0.04 3.04±0.11 0.62±0.08F8 Passes 12.042±0.017 4.342±0.052 2.94±0.15 0.72±0.10F9 Passes 12.064±0.023 4.332±0.016 3.12±0.17 0.59±0.09

During weight variation test none of the tablet wasfound to be deviate by permissible percentage asper Indian pharmacopoeia 5% from the meanvalue of 20 tablets. Thus it was found that all theformulations complied with weight variation test.Hardness of the tablet was found to be in therange of 2.94 to 3.24, which was found to wellwithin the required hardness for the fast dissolvingtablets (3 to 4 kg/cm2). Diameter of the tabletswas found to be in the range of 12 to 12.064 mm

while thickness was found to be in the range of4.32 to 4.4 mm. Percentage friability was found tobe in the range of 0.49 to 0.74 which is withinlimit <1%.

3.3.2 Wetting time and water absorption ratioThe data for wetting time and water

absorption ratio of fast dissolving tablets ofcarbamazepine is as shown below.

Table 9. Data for wetting time and water absorption ratio.Formulation code Wetting time

(sec)Water absorption ratio

(%)F1 130.2±0.44 71.14±0.53F2 116.4±0.89 72.50±0.47F3 105.2±0.83 77.14±0.03F4 106.2±0.83 83.35±0.68F5 97±0.70 97.03±0.01F6 101±0.70 87.34±0.38F7 110.6±0.89 82.38±0.66F8 102.8±0.44 86.26±0.39F9 113.4±0.89 75.73±0.10

Wetting time was found to be in the range of 97.00 to 130.2. Water absorption ratio was found to bein the range of 71.14 to 97.03. It may be due to the hydrophilic nature of carriers used. This thing mightresult into increased capillary action which has resulted into decreasing the wetting time and increasing thewater absorption ratio.3.3.3 Disintegration time, uniformity of content and Disintegration time:The data for disintegration time, uniformity of content and Disintegration time of fast dissolving tablets ofcarbamazepine is as shown below.

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Table 10. Data for disintegration time, drug content and Disintegration time of fast dissolving tabletsof carbamazepine.

Formulation code Disintegration time(sec)

Drug content(%)

Dispersiontime (Sec)

F1 85.33±1.52 95.43±0.91 91.10±0.7F2 80±1.0 98.23±0.96 83.20±1.20F3 76±1.0 101.84±1.11 81.46±0.5F4 65±2.0 99.88±0.511 71±1.5F5 57±1.0 98.85±1.04 62.20±0.6F6 61.66±1.52 98.39±1.20 67.16±1.2F7 71.66±1.52 96.22±0.80 75.87±1.4F8 61±1.0 98.46±0.61 65.57±0.4F9 63±1.0 102.08±1.09 64±0.5

3.3.4 Disintegration time:In vitro disintegration times of all

formulations were found to be in the range of 57to 85.33 Sec, this was found to be well within theacceptable limit for fast dissolving tablet (≤ 3min). In vitro disintegration time of all theformulations was found to decrease withcorrespondent increase in the concentration ofboth croscarmellose sodium and sodium starchglycolate. It may be due to the hydrophilic natureof sodium starch glycolate and croscarmellosesodium which attracts water and may increase thecapillary action of the tablet matrices which resultinto decreasing the disintegration time.3.3.5 Uniformity of content:All the formulations upon spectroscopic analysiswere found to contain carbamazepine in the rangeof 95.43 to 102.08 which complies with thestandard for uniformity of content laid down forcarbamazepine in official compendia.3.3.6 In vitro Dispersion time:

In vitro dispersion time of all formulationwas found to be in range of 62.20 to 91.10 sec,this was found to be well within acceptable range.3.3.7 In vitro Dissolution study:During in vitro dissolution study, it is found thatwithin 30 minutes drug release was found to be

62% to 83% from F1 to F9 formulation. The F5formulation which contain 10% of thecroscarmellose sodium which shows 83.6% ofdrug release. It was also observed that as theconcentration of the croscarmellose increases drugrelease increases upto 10% and then getdecreased. In case of the sodium starch glycolateconcentration used were 2, 4 and 6%. From that4% concentration of SSG shows 80.2% and othershows less.

This may also attribute to croscarmellosesodium and sodium starch glycolate. Withincrease in concentration of this polymer capillaryaction might have increased which in turn resultedin reducing the time required for wetting anddisintegration of tablets and finally the dissolutionof drug.

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Table 11. In vitro dissolution profile of formulationF1- F9.

Figure 4. In vitro dissolution profile of formulationF1- F9.

Conclusion:The oral fast dissolving tablet of carbamazepinewere formulated and evaluated for variousparameters from the compatibility studies byDSC, FTIR and XRD of drug it was found to becompatible with other formulation excipients. Allevaluation parameter were within specification.The release of drug from the tablet was increasedas the concentration of superdisintegrants wasincreased. The croscarmellose sodium shownfaster drug release than sodium starch glycolate.Formulation F5 release maximum drug within the30 mins.i.e.83.6% and shown minimumdisintegration time i.e. 57 sec than other

formulation and hence considered bestformulation.It is concluded that fast dissolving tablets ofcarbamazepine could be prepared by usingcroscarmellose sodium and sodium starchglycolate. In which croscarmellose sodium showsgood result as compared to the sodium starchglycolate.Acknowledgement:We wish to thank Abbott healthcare Pvt.Ltd forproviding carbamazepine as a gift sample.We also wish to thank Yashoda technical campusSatara for providing instruments and facilitiesrequired for research work.

0

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0 5 10 15 20 25 30 35

Cum

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rele

ase

Time (min)

F1

F2

F3

F4

F5

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F7

F8

F9

Time(min)

Cumulative drug release (%)

F1 F2 F3 F4 F5 F6 F7 F8 F9

0 0 0 0 0 0 0 0 0 0

5 20.3±1.5 24.0±1.5 27.2±2.4 38.0±1.2 40.2±2.3 29.2±1.1 29.2±1.1 39.5±1.8 25.4±1.610 24.7±2.5 29.5±0.7 33.5±1.4 41.1±3.2 47.3±2.2 34.9±0.9 34.9±0.9 40.0±2.5 31.4±0.815 32.5±2.1 35.7±1.0 39.3±2.4 46.5±2.2 52.0±1.5 41.5±1.4 40.3±0.7 48.8±1.2 38.4±1.420 40.1±1.2 47.5±1.8 49.2±2.4 57.1±1.6 59.7±0.4 50.8±1.8 51.3±1.2 57.8±0.4 54.9±1.325 51.2±1.2 59.4±2.8 62.4±0.7 65.6±2.3 69.4±1.4 65.9±1.4 61.3±2.0 67.8±2.0 59.3±3.330 62.7±2.0 66.5±2.5 70.2±1.4 78.5±2.7 83.6±2.3 71.2±2.0 70.2±1.1 80.2±0.6 70.7±1.3

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References:1. Brahmankar DM, Jaiswal SB, 2005.Biopharmaceutics and pharmacokinetics: atreatise. 4th ed.: Delhi: Vallabh prkashan.5-6, 27.2. Abed KK, Hussein AA, Abdulrasol AA, 2010.Formulation and optimization of orodispersibletablets of diazepam.AAPS. Pharm. Sci. Tech. 11,356-361.3. Madhusudan RY, Jithan AV, Advances in drugdelivery. 2, 57-111.4.Dhirendra K, Lewis S, Udupa N, Atin K, 2009.Solid dispersion: A review.Pak.J.Pharma. Sci.22,234-246.5.Madhavi BB, Kusum B, Chatanya CK, Madhu,MN., Harsha,VS., Banji, D.,2011.Dissolutionenhancement of efavirenj by solid dispersion andPEGyalation techniques.Int.J. Pharma.Invest.1,29-32.6. Nikghalb LA, Singh G, Singh G., KahkeshanKF, 2012.Solid dispersion: methods and polymerto increase the solubility of poorly water solubledrug.J.Applied Pharm.Sci.2, 170-175.7. Solanki SS, Dahima R, 2011. Formulation andevaluation of aceclofenac mouth dissolvingtablets. J. Adv. Pharm. Tech. Res. 2, 128-131.8.Kakde SM, Mannur VS, Ramani KB, DhadaAA, Naval CV, Bhagvat A.Formulation andevaluation of mouth dissolving tablets of losartanpotassium by direct compression technique.Int JRes Pharm Sci.2010; 1: 290-295.9. Bulk density and Tapped density. The UnitedStates Pharmacopoeia. 24th Ed. United states:Rockville. Pharmacopoeial Convention Inc.: 2000.

10. Shirsand SB, Sarasjia S, Jodhana LS, SwamyPV, 2010. Formulation design and optimization offast disintegrating lorazepam tablets byeffervescent method. Ind. J. Pharm. Sci. 72,431-436.11.Soumya M, Chowdary YA, Madhuri A,Sindhusha MD, Nagarani T, Aruna B, Manasa V,2013.Formulation and in vitro evaluation of fastdissolving tablets of flecainide acetate. Int. J.Pharma. Pharma. Sci.5,555-560.12.Rangole US, Kawitkwar PS,SakarkarDM,2008.Formulation and in-vitro evaluation ofrapidly disintegrating tablet usinghydrochlorothiazide as a modeldrug.Res.J.Pharma. Tech.1,349-352.13. Masareddy RS, Kadia RV, ManviFV,2008.Devlopment of mouth dissolving tabletof clozapine cusing two different techniques.Ind.J. Pharma. Sci.570,526-528.14.Arora SC, Sharma PK, Irchhaiya R, Khatkar A,Singh N, Gagoria J,2010.Devlopment .Characterization and solubility study of soliddispersion of cefuroxime axetil by solventevaporationmethod.J.Adv.Pharma.Tech.res.1,326-329.15.Pandit V, Sai RS, Devi K, Sarasija S,2012.In-vitro in-vivo evaluation of fast dissolving tabletcontaining solid dispersion of pioglitazone.16.Wan S, Sun Y, Qi X, Tan F, 2012.Improvedbioavailability of poorly water soluble drugcurcumin in cellulose acetate soliddispersion.AAPS. Pharma. Sci. Tech.13,159-166.

formulation and evaluation of fast dissolving tablets of carbamazepine using solid dispersion

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