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Research ArticleFast Disintegrating Combination Tablet of Taste MaskedLevocetrizine Dihydrochloride and Montelukast SodiumFormulation Design Development and Characterization

M M Gupta12 Niraj Gupta2 Bhupendra S Chauhan2 and Shweta Pandey2

1 School of Pharmacy Faculty of Medical Sciences The University of the West Indies St Augustine Trinidad and Tobago2Department of Pharmaceutics Jaipur College of Pharmacy Sitapura Tonk Road Jaipur Rajasthan 302022 India

Correspondence should be addressed to M M Gupta mminguptagmailcom

Received 16 November 2013 Revised 26 February 2014 Accepted 27 February 2014 Published 30 March 2014

Academic Editor Sumio Chono

Copyright copy 2014 M M Gupta 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 aim of this study was to prepare fast disintegrating combination tablet of taste masked Levocetrizine dihydrochloride andMontelukast sodium by using direct compression method To prevent bitter taste and unacceptable odour of the Levocetrizinedihydrochloride drug the drugwas tastemaskedwith ion exchange resins like Kyron-T-104 and Tulsion-412 Among the two resinsKyron-T-104 was selected for further studies because of high drug loading capacity low cost and better drug release profile An ionexchange resin complex was prepared by the batch technique and various parameters namely resin activation drug resin ratio pHtemperature and stirring time and swelling time were optimized to successfully formulate the tasteless drug resin complex (DRC)The tablets were prepared using microcrystalline cellulose (MCC) PH 102 as diluent along with crospovidone (CP) croscarmellosesodium (CCM) and sodium starch glycolate (SSG) as a superdisintegrantsThe tabletswere evaluated forweight variation hardnessfriability wetting time water absorption ratio disintegration time (DT) and dissolution study and it was concluded that the tabletformulation prepared with 2 SSG + CCS showed better disintegration time in comparison with other formulation and good drugrelease The stability studies were carried out for the optimized batch for three months and it showed acceptable results

1 Introduction

Various physiological and neurological conditions like dys-phagia motion sickness and hand tremors lead to noncom-pliance of conventional oral dosage forms Mouth dissolvingdrug delivery systems (MDDDS) orally disintegrating sys-tem (ODT) and fast disintegrating tablet (FDT) are espe-cially designed for dysphagic geriatric pediatric bed-riddentravelling and psychotic patients who are unable to swallowor refuse to swallow conventional oral formulations As theydissolvedisintegrate very fast when placed in the mouthFDT are the most convenient dosage forms for dysphagicpediatric and geriatric patients with swallowing problem [1ndash3] They do not require water for administration and thus area good alternative for travelers and for bed ridden patientsThey simply vanish when placed in the mouth and so cannotbe hidden in mouth by psychotic patients These productsnot only increase the patientrsquos compliance but also fetch

large revenues to manufacturers due to line extension of theexisting formulation [4ndash6]

FDT or MDDDS display a fast and spontaneous deaggre-gation in themouth soon after it comes in contact with salivadissolving the active ingredient and allowing absorptionthrough all possible membranes it comes in contact withduring deglutition [7ndash9]

Recently several new advanced technologies lyophiliza-tion moulding direct compression cotton candy processspray drying sublimation mass extrusion nanonizationand quick dissolve film formation have been introducedfor the formulation of mouth dissolving tablets (MDTs) orfast disintegrating system with very interesting features likeextremely low disintegration time exceptional taste maskingability pleasant mouth feel and sugar free tablets for diabeticpatients [10 11] These techniques are based on the principlesof increasing porosity andor addition of superdisintegrantsand water soluble excipients in the tablets [12ndash14]

Hindawi Publishing CorporationJournal of PharmaceuticsVolume 2014 Article ID 568320 15 pageshttpdxdoiorg1011552014568320

2 Journal of Pharmaceutics

Table 1 Details of formulations (K1ndashK6) of batch formulation

Batch-1Levocetrizine dihydrochloride Kyron-T-104 (1 4)

Ingredients K1 K2 K3 K4 K5 K6Montelukast sodium 10mg 10mg 10mg 10mg 10mg 10mgMCC 176mg 176mg 176mg 176mg 176mg 176mgSSG 4mg mdash mdash mdash mdash mdashCCS mdash 4mg mdash mdash mdash mdashCP mdash mdash 4mg mdash mdash mdashSSG + CCS mdash mdash mdash 4mg mdash mdashSSG + CP mdash mdash mdash mdash 4mg mdashCCS + CP mdash mdash mdash mdash mdash 4mgMg stearate 2mg 2mg 2mg 2mg 2mg 2mgTalc 3mg 3mg 3mg 3mg 3mg 3mgMCC microcrystlline cellulose SSG sodium starch glycolate CCG Crosscarmellose sodium CP crosspovidone

Ion exchange resins have been increasingly used for thetaste masking of bitter taste drugs and help to prepare fastdisintegrating tablets Thus the taste masking of bitter activesubstances is a critical hurdle to overcome for the success-ful development of oral formulations [15ndash17] Levocetrizinedihydrochloride is an orally active and R-enantiomer ofcetrizine and is a third generation nonsedating selectiveperipheral H1-receptor antagonist used in seasonal allergicrhinitis perennial allergic rhinitis and chronic urticaria [1819] Allergy is a common problem among all age groupsLevocetrizine dihydrochloride is rapidly absorbed after oraladministration and half-life is 83 hr which makes it suitablefor once a day formulationThese diseases require rapid onsetof action in order to provide fast relief Unfortunately it isaccompanied with a very unpleasant bitter taste so it requirestaste masking [20ndash22]

Montelukast sodium is a leukotriene receptor antag-onist (LTRA) used in maintenance treatment of asthmaand to relieve symptoms of seasonal allergies It is usuallyadministered orally [23ndash25] In the present study an attempthad been made to prepare fast disintegrating combinationtablets of Montelukast sodium and taste masked Levo-cetrizine dihydrochloride for the treatment of allergic rhinitisusing coprocessed superdisintegrants containing crospovi-done croscarmellose sodium and sodium starch glycolateThe coprocessed superdisintegrants help to increase thewateruptake with shortest wetting time and thereby decreasethe disintegration time of the tablets These systems mayoffer superior profile with potential mucosal absorptionthus increasing the drug bioavailability These systems arealso called mouth dissolving tablets melt-in-mouth tabletsreprimelts porous tablets orodispersible quick dissolving orrapidly disintegrating tablets

2 Materials and Methods

21 Materials Montelukast sodium sodium starch glycolatecroscarmellose sodium and crospovidone were procured asgift sample from MMC Health care pvt Ltd Baddi IndiaLevocetrizine dihydrochloridewas a generous gift fromAmol

Pharmaceuticals Jaipur India Tulsion-412 and Kyron-T-104were obtained as gift samples from Cadila PharmaceuticalsAhemdabad India All other materials (microcrystalline cel-lulose PH 102 Magneshium stearate and Talc) and chemicalsused were of analytical reagent grade

22 Analysis of Levocetrizine Dihydrochloride and Mon-telukast Sodium The solution containing 20 120583gmL of Levo-cetrizine dihydrochloride and Montelukast sodium in phos-phate buffer (pH 68) was prepared and scanned over rangeof 200ndash400 nm against phosphate buffer (pH 68) as ablank using double beam UV spectrophotometer The max-imum wavelength was found to be 2310 nm and 35220 nmfor Levocetrizine dihydrochloride and Montelukast sodiumrespectively which confirmed to the reported value

23 Formulation of Drug (Levocetrizine Dihydrochloride)Resin Complex Formulation of drug resin complex (DRC) ofLevocetrizine dihydrochloridewas done by the batch processdifferent amounts of resin Kyron-T-104 and Tulsion-412 wereplaced in beakers containing 100mL of deionized water andallowed to swell for a definite period of time Accuratelyweighed amount of Levocetrizine dihydrochloride (as per1 1 1 2 1 3 1 4 1 5 1 6 and 1 7 drug resin ratio) wasadded and stirred for desired period of timeThemixture wasfiltered and residue was washed with deionized water Filtratewas analyzed by UV spectrophotometer at 231 nm for theunbound drug and percentage drug loading was calculated[26ndash28]

24 Formulation Development of FDTS All formulations ofFDTs were prepared by direct compression technique forbatch by taking DRC equivalent to 5mg of Levocetrizinedihydrochloride Montelukast sodium (10mg) MCC wasused as diluent talc as an antiadherent and magnesiumstearate as a lubricant All the ingredients were accuratelyweighed and blended together to get uniform mixture Thenthe blend was compressed to get tablets using rotary tabletmachine The formulations are shown in Table 1

Journal of Pharmaceutics 3

995

990

985

980

Tran

smitt

ance

()

Wavenumber (cmminus1)3500 3000 2500 2000 1500 1000

393741

381661

374039

357411

338080

322553

297877

288440

276297

263053

238059

230800

174087

164730

149264

143487

131626

126879

113313

102077

89143

84303

75503

Figure 1 Fourier transform infrared spectra of Levocetrizinedihydrochloride

996

994

992

990

988

385394

375026

349585

336811

318392

300506

282460

272506

268025

236544

226783

218329

204893

193348

174999

165176

155888

154351

149031

140249

113374

106443

93123

80916

74917

Tran

smitt

ance

()

Wavenumber (cmminus1)3500 3000 2500 2000

307217

1500 1000

Figure 2 Fourier transform infrared spectra of Montelukastsodium

3 Result and Discussion

31 Characterizations of Drugs DRC and Final Blend TheFTIR (Fourier transmission Infrared) spectroscopy study ofLevocetrizine dihydrochloride Montelukast sodium (mixedand separate) drug-resin complex blend containing boththe drug resin and other excipients used in the formulationdevelopment was carried out to check the compatibility toeach other (Figures 1 2 3 and 4)

The spectra indicated that there was no drug-drug anddrug-excipients interaction as the peaks of the drug andother excipients were seen the same in the drug-excipientsmixture indicating that the drug molecule was present in anunchanged state in the formulation

32 Precompression Evaluation

321 Optimization of Various Conditions for Maximum DrugLoading Drug loading process was optimized for maximumdrug loading considering conditions like effect of resinactivation drug resin ratio pH temperature resin swellingtime and stirring time [18 28ndash30]

Optimization of Resin Activation Changing the ionic formof ion exchange resin (IER) might occasionally be requiredto convert a resin from one form to another if it doesnot have the desired counter ions Strongly acidic cation

998

996

994

992

990

988

986

378643

363337

340714

330427

297297

277775

266705

254556

240380

231133

218378

197554

181782

170490

163042

148419

126745

116576

91084

79739

Tran

smitt

ance

()


Figure 3 Fourier transform infrared spectra of Levocetrizinedihydrochloride and resins (Kyron-T-104 Tulsion 412)

994

992

990

988

986

984

982

980385614

375598

367125

352621

342774

331132

318461

304855

297245

263399

250738

239244

229045

218755

210788

195489

174104

158954

149082

143547

138399

135524

131575

126846

117996

113278

109933

101792

92103

80115

75531

Tran

smitt

ance

()


Figure 4 Fourier transform infrared spectra of Levocetrizinedihydrochloride Montelukast sodium resins and other excipients

exchange resins are usually marketed in Na+ form andstrongly basic anion exchange resins in Clminus form Theyare generally converted into hydrogen and hydroxide formsrespectively The conversion could be achieved by soakingthe resins with acid or alkali solutions respectively Afterchanging the ionic form the resin was subjected to washingwith distilled water until elute becomes neutral in reactionand finally dried at 50∘C The effect of activation of resinon drug loading was studied 100mg of resin placed on aWhatman filter paper in a funnel was washed with deionizedwater and subsequently with 1N HCl (100mL) The resinswere rewashed with deionized water until neutral pH wasreached DRC was prepared in the same way as discussedearlier using 100mg each of Levocetrizine dihydrochlorideand acid activated resins Similarly alkali activation of resinwas done replacing 1N HCl with 1N NaOH Finally KyronT-104 and Tulsion-412 were also activated with combinedtreatment of 1 N HCl and 1N NaOH solutions Drug loadingefficiency in each case was determined

In the case of Kyron-T-104 the acid treated resin loadedmaximum drug that is 6724 whereas 6387 drug wasloadedwhenTulsion-412 usedThe resin so activated exposedthe exchangeable groups producing rapid ion exchange hencehighest drug binding Highest percentage drug loading wasfound for acid activated resin but as compared to inactivated


Table 2 Effect of resin activation on drug loading

Optimized ratio ofdrug and resin

Drug loading by resin activationAcid Alkali Acid-alkali

Kyron-T-104 (1 4) 6724 4832 5763Tulsion-412 (1 5) 6387 4319 5684

Table 3 Effect of pH on drug loading

pH Drug loadingKyron-T-104 (1 4) Tulsion-412 (1 5)

2 3925 36643 4578 44734 4843 50195 7659 74616 6208 63387 6417 6825

resin no major effect was found on percentage drug loadingThus trials were made with inactivated resin The results areshown in Table 2

Optimization of Drug Resin Ratio 100mg of Levocetrizinedihydrochloride was added to each of the fourteen beakerscontaining 100 200 300 400 500 600 and 700mg of resinsseparately swelled in 100mL of deionized water The mixturewas stirred for 4 hrs DRC was collected by filtration washedwith deionized water and evaluated for drug content

Optimization of pHThe studywas carried out at six pHvalues2 3 4 5 6 and 7The pH was adjusted to desired value usingstandard solutions of HCl and NaOH Loading efficiency wasdetermined at these conditions

The pH affects the extent of drug loading process It wasobserved that optimum drug loading was achieved at pH50 and was not much increased at pH higher than this Theresults are shown in Table 3

Optimization of Temperature Temperature was optimized bypreparing DRC using 100mg Levocetrizine dihydrochlorideand 300mg resins in 100mL of deionized water and settemperature at 20∘C 30∘C 40∘C 50∘C and 60∘C usingtemperature controlled magnetic stirrer

The Efficient drug loading on Kyron T-104 and Tulsion-412 occurred uniformly in the experimental temperature30∘C and the effect of temperature on drug loading is shownin Table 4

Optimization of Resin Swelling Time Optimization of resinsswelling time was carried out by keeping 400mg of resinKyron T-104 and 500mg of resin Tulsion-412 in each ofthe beakers containing 100mL of deionized waterfor 30 6090 and 120min respectively on magnetic stirrer DRC wasprepared as described above using 100mg of Levocetrizinedihydrochloride and percent drug loading was estimated

It was noted that the resin requires proper swelling timefor maximum drug loading Swelling and hydration increase

Table 4 Effect of temperature on drug loading

Temperature (∘C) Drug loadingKyron-T-104 (1 4) Tulsion-412 (1 5)

20 5824 561530 7935 723140 7416 604650 4793 491660 3842 3481

Table 5 Effect of swelling time on drug loading

Swelling time (min) Drug loadingKyron-T-104 (1 4) Tulsion-412 (1 5)

30 7136 741860 8638 844290 8813 8775180 7469 7418

the rate and extent of ion exchange process In unswollenresin matrix the exchangeable groups are latent and coiledtowards the backbone Swelling increases the surface area andthese groups get oriented towards outside Loading that wasconsiderably increased at 90 minutes was considered as theoptimum swelling time The effect of swelling time on drugloading is shown in Table 5

Optimization of Resin Stirring Time For optimizing stirringtime DRC was prepared by stirring 100mg of Levocetrizinedihydrochloride with 400mg of resin Kyron T-104 and500mg of resin Tulsion-412 in 100mL of deionized waterseparately for 60 90 120 180 240 and 300min and percentdrug loading was evaluated

Stirring time affects the ion exchange equilibrium processas it is stoichiometric process This may indicate the signifi-cant involvement of Van-der Waals forces or chemisorptionstaking place along with drug exchange during complexationLoading was not considerably increased after 240 minutesso it was considered as the optimum contact time betweenLevocetrizine dihydrochloride and Kyron T-104 and Tulsion-412 The effect of stirring time on drug loading is shown inTable 6

322 Evaluation of Taste of Resinate Taste of resinate waschecked by time intensity method For this purpose humanvolunteers were selected In this method a sample equivalentto a normal dose was held in mouth for 10 seconds andvolunteers were asked to evaluate the taste of resinate Bitter-ness levels were recorded immediately according Strong BiterModerate Bitter Slight Bitter and Tasteless These volunteerswere instructed not to swallow resinate whichwere placed onthe tongue They were instructed to thoroughly gargle theirmouth with distilled water after the completion of test [31]

Optimization of drug resin ratio had shown that com-plete taste masking was achieved in ratio 1 4 to 1 7 in case


Table 6 Effect of stirring time on drug loading

Stirring time (min) Drug LoadingKyron-T-104 (1 4) Tulsion-412 (1 5)

60 7863 7452120 7958 8069180 8418 8166240 8937 8624300 8374 8291

Table 7 Scale for bitterness evaluation

Drug (Levocetrizinedihydrochloride) resin

Kyron-T-104 Tulsion-412Bitterness evaluation

1 1 Strongbitterness

Strongbitterness

1 2 Moderate tostrong bitterness

Moderate tostrong bitterness

1 3Slightly tomoderately

bitter

Slightly tomoderately

bitter1 4 Tasteless Tasteless1 5 Tasteless Tasteless1 6 Tasteless Tasteless1 7 Tasteless Tasteless

Table 8 Effect of drug-resin ratio on drug loading

Resin Drug loading in different ratios of drug (Levocetrizine dihydrochloride) resin1 1 1 2 1 3 1 4 1 5 1 6 1 7

Kyron-T-104 5472 6039 6428 8526 7322 7011 7149Tulsion-412 5643 6256 6538 7439 8093 7543 7728

Table 9 Relation between drug-resin ratio and drug loading

Optimized ratio of drug and resin Drug loadingKyron-T-104 (1 4) 8526 plusmn 132Tulsion-412 (1 5) 8093 plusmn 148

of both the resins The scale of bitterness is represented inTable 7

Optimization of drug resin ratio was done by takinginactivated resins in ratio 1 1 to 1 7 with drug (Levocetrizinedihydrochloride) Maximum drug loading was found inratios 1 4 (kyron-T-104) and 1 5 (Tulsion-412) so furtheroptimizations was done with this ratio The effect of drug-resin ratio on drug loading and relation between drug-resinand drug loading is represented in Tables 8 and 9

323 Micromeritic Properties Prior to compression theblend was evaluated for their micromeritic properties such asangle of repose bulk density tapped density compressibilityindex and Hausnerrsquos ratio

Angle of repose was determined by fixed funnel method(static method) the powder was poured in the funnel and thecircumference of powder pile was drawn with a pencil on thegraph paper and the radius of base of a pile was measuredat five different points and average was taken for calculatingangle of repose

Both bulk and tapped density are determined in USPspecification density apparatus by pouring the blend into agraduated cylinder via a large funnel andmeasure the volumeand weight and tapped density was measured by operatingthe instrument for a fixed number of taps until powder hasreached a minimum volume

Hausnerrsquos ratio indicates the flow ability and packingability When Hausnerrsquos ratio is close to 1 materials haveacceptable flow and packing ability

From the results of precompression studies of the batchK1ndashK6 it was concluded that powder mixtures has good flowand compressibility property The bulk density of powdermixtures was found in the range of 0438ndash0465 gcm3 Thevalues of Carrrsquos index were in the range of 1289ndash1349 andHausnerrsquos ratio was in the range of 1142ndash1156 suggested that


Table 10 Precompression evaluation of Levocetrizine dihydrochloride and Montelukast sodium blend

Formulation batch Precompression parametersAngle of Repose Bulk density Tapped density Hausner ratio Carrrsquos index compressibility

K1 3468 0465 0536 1152 1319 1324K2 3225 0448 0512 1142 1243 1250K3 3272 0453 0524 1156 1349 1354K4 3357 0438 0503 1148 1289 1292K5 3426 0453 0521 1150 1304 1305K6 3148 0435 0502 1154 1334 1335

Table 11 Postcompression evaluation of developed formulations

Formulation Postcompression evaluation parametersThickness (mm) Diameter (mm) Hardness (Kgcm2) Wt variation Friability

K1 312 plusmn 017 30 plusmn 038 31 plusmn 068 21903 plusmn 108 049 plusmn 0082K2 313 plusmn 014 30 plusmn 027 32 plusmn 073 21859 plusmn 094 052 plusmn 0068K3 312 plusmn 019 31 plusmn 028 34 plusmn 069 21913 plusmn 111 057 plusmn 0072K4 311 plusmn 013 30 plusmn 024 32 plusmn 047 21944 plusmn 092 047 plusmn 0069K5 313 plusmn 011 30 plusmn 033 33 plusmn 081 22019 plusmn 091 053 plusmn 0036K6 312 plusmn 017 30 plusmn 036 30 plusmn 071 21831 plusmn 089 037 plusmn 0074

blend having fairly good flow The results of precompressionevaluation are shown in Table 10

33 Postcompression Evaluation The weight variation testwas carried out in order to ensure uniformity in the weightof tablets in a batch The total weight of randomly selected20 tablets was determined and the average was calculatedThe individual weight of the tablets was also determinedaccurately and the weight variation was calculated

The permissible limit for hardness is 3ndash12 kgcm2 Thehardness test was performed by using Pfizer hardness tester

The thickness and diameter of the tablets were deter-mined by using vernier calipers Randomly 10 tablets selectedwere used for determination of thickness that expressed inmean plusmn SD and unit is millimeter (mm)

The pharmacopoeia limit of friability is 1 and friabilitywas measured using a Roche friability apparatus carried outat 25 rpm for 4min (100 rotations) However it becomes agreat challenge for a formulator to achieve friability withinthis limit for MDT product keeping hardness at its lowestpossible level in order to achieve a minimum possible disin-tegration time The friability (119865) is given by the followingformula

119865 = (1 minus1198820

119882) times 100 (1)

where1198820is weight of the tablets before the test and119882 is the

weight of the tablets after testTablets prepared by direct compression method were

found to be goodwithout any chipping capping and stickingVarious physical parameters like thickness hardness weightvariation friability hardness and disintegration time weremeasured to evaluate tablets It was found that the averagethickness of the tablets also ranged between 311 and 313mm

however the variations were not alarming and remainedwithin the acceptable range Hardness of tablets of thedifferent formulations varied widely ranging from 30 to34 kgcm2 The loss in friability was ranged from 037 to057 so all the postcompression parameters were in the limitand results are shown in Table 11 [32ndash36]

331 Wetting Time The wetting time of the tablets wasmeasured using a simple procedure Five circular tissuepapers of 10 cm diameter were placed in a Petri dish con-taining 02wv solution of amaranth (10mL) One tabletwas carefully placed on the surface of the tissue paper Thetime required to develop blue color due to amaranth watersoluble dye on the upper surface of the tablets was noted asthe wetting time [37]

332 Water Absorption Ratio A small piece of tissue paperfolded twice was placed in a small Petri dish containing 6mLof water A tablet was put on the paper for water absorption(Figure 5)

The wetted tablet was then weighed Water absorptionratio 119877 was determined by using following formula

119877 =(119882119886minus119882119887)

119882119887

times 100 (2)

Here 119877 is the water absorption ratio119882119887is the weight of

tablet before water absorption and119882119886is the weight of tablet

after water absorption [38]The water absorption ratio was found to be in range

from 8338 to 9318 whereas the wetting time of batchK1 to K6 was found from 1949 to 2832 and wetting timewas significantly lower in K4 due to highly water absorptioncapacity (Table 12)


(a) (b)

(c) (d)

Figure 5 Water absorption by fast disintegrating combination tablets

Table 12 Determination of wetting time and water absorption ofdeveloped formulations

Formulation batch Wetting time (sec) Water absorptionK1 2832 plusmn 0524 8816 plusmn 0985K2 2441 plusmn 0331 8338 plusmn 0886K3 2362 plusmn 0632 9043 plusmn 0894K4 1949 plusmn 0309 9318 plusmn 0734K5 2176 plusmn 0412 9057 plusmn 0759K6 2213 plusmn 0476 9179 plusmn 0804

333 Drug Content Ten tablets were powdered and 10mgdrug equivalent powder dispersed in phosphate buffer pH68 Volume of the solution made up to 10mL by media Themixture was filtered and 1mL of the filtrate was diluted to10mL using phosphate buffer pH 68 The absorbance of thesample preparations was measured at 120582max 2310 nm for Lev-ocetrizine dihydrochloride and 35220 nm for Montelukastsodium

Another method (Petri dish method) was used to calcu-late drug content in which 10mL phosphate buffer pH 68 wastaken in Petri dish and then a tablet was dipped in it andafter 30 sec media was filtered (process repeated at least for3 times) and the absorbance of the sample preparations wasmeasured at 120582max 2310 nm for Levocetrizine dihydrochlorideand 35220 nm for Montelukast sodium [39]

Uniformity of Drug Content Ten tablets were selected ran-domly and average weight was calculated for both Levo-cetrizine dihydrochloride and Montelukast sodium Tablets

were crushed in a mortar and accurately weighed amount ofdrug was taken from the crushed blend Then the sampleswere transferred to 100mLvolumetric flasks and diluted up tothemarkwithmethanolThe content was shaken periodicallyand kept for one hour to dissolve the drug completely Themixtures were filtered and appropriate dilutions were madeseparately for both drugsThe drug content in each tablet wasestimated at 120582max against blank reference and reported

In the case of Levocetrizine dihydrochloride the drugcontent was found in the range of 9465ndash9874 whereas9298ndash9578 drug was found in case ofMontelukast sodium(Table 13)

334 Disintegration Time

By Disintegration Test Apparatus Disintegration time is con-sidered to be one of the important criteria in selection the bestformulation To achieve correlation between disintegrationtimes in vitro and in vivo several methods were proposeddeveloped and followed at their convenience [40ndash43] Onetablet was placed into each tube and the assembly wassuspended into the 1000mL beaker containing phosphatebuffer pH68maintained at 37∘CThe apparatus was operatedand time was taken as disintegration time when no particleof tablet remains on the mesh when it is at up position Theassembly was removed from the liquid and the tablets wereobserved

Disintegration Time in the Oral CavityThe healthy volunteersof either sex (age 18ndash25) were selected trained and then DT


Table 13 Determination of drug contents by different methods

Formulation Dispersion time (sec) Drug content () by dilution method Drug content () by Petri dish methodLevocetrizine dihydrochloride Montelukast Levocetrizine dihydrochloride Montelukast

K1 3141 plusmn 041 9465 plusmn 108 9353 plusmn 115 9602 plusmn 126 9514 plusmn 114K2 3015 plusmn 053 9638 plusmn 113 9417 plusmn 106 9528 plusmn 123 9304 plusmn 119K3 2632 plusmn 064 9668 plusmn 105 9388 plusmn 098 9741 plusmn 119 94 53 plusmn 126K4 1979 plusmn 059 9814 plusmn 097 9563 plusmn 092 9874 plusmn 116 9578 plusmn 116K5 2262 plusmn 047 9746 plusmn 116 9405 plusmn 102 9810 plusmn 124 9392 plusmn 128K6 2458 plusmn 068 9822 plusmn 114 9298 plusmn 113 9668 plusmn 118 9511 plusmn 117

100 rpm

Hook

Sinker

Tablet

900mL water (37∘C)

85

cm

Paddle

(a) (b)

Figure 6 Schematic view of modified dissolution apparatus for disintegration test (from reference)

of each tablet for complete disintegration in the mouth wasmeasured The time when the tablet placed on the tonguedisintegrated without leaving any lumps was taken as endpoint After disintegration of tablet in the oral cavity the tabletcontents were spit out and the oral cavity was rinsed withwater DT of six tablets per batch (three tablets per trainedvolunteer or total of two volunteers per batch) was recordedand the average was reported

Disintegration Test Using Modified Dissolution Apparatus Biet al suggested the use of a modified dissolution apparatusfor disintegration (Figure 6) instead of the traditional disin-tegration apparatus In this experiment 900mL of phosphatebuffer (pH 68) was maintained at 37∘C as the disintegrationfluid and a paddle at 100 rpm as stirring element was usedDisintegration time was noted when the tablet disintegratedand passed completely through the screen of the sinker (3ndash35mm in height and 35ndash4mm in width immersed at adepth of 85 cm from the top with the help of a hook)This method was useful in providing discrimination amongbatches which was not possible with the conventional disin-tegration apparatus (Figure 7)

Disintegration by Petri Dish Method Petri dish method wasused to calculate drug content in which 10mL phosphatebuffer pH 68 was taken in Petri dish then a tablet was dippedin it (Figure 8) Disintegration timewas notedwhen the tabletdisintegrated (process repeated at least for 3 times)

As per the pharmacopoeia requirement formulation offast disintegrating tablet should exhibit disintegration timein le60 seconds K1 to K6 batches pass the disintegrationtime requirement From the above it is observed that allthe prepared formulations batches exhibited disintegrationtime less than 60 seconds and out of these K4 and K5 batchexhibited the least disintegration time (Table 14)

In all observations K4 and K5 were found suitable forfurther dissolution study as an optimized batch

34 In Vitro Drug Release Study K4 and K5 batch for-mulations were selected for drug release study The Levo-cetrizine dihydrochloride and Montelukast sodium releasesfrom different FDTs were evaluated by using the USP30NF25pharmacopoeia dissolution apparatus IImdashpaddle at 37 plusmn05∘C using 900mL of phosphate buffer (pH 68) as


(a) (b)

Figure 7 Experimental view of modified dissolution apparatus for disintegration test

(a) (b)

(c) (d)

Figure 8 Experimental view of modified disintegration test (Petri dish method)

a dissolutionmediumwith stirring speed of 50 rpm Aliquots(5mL) withdrawn at various time intervals were immediatelyfiltered through Whatman filter paper diluted suitably andanalyzed at 120582max 2310 nm for Levocetrizine dihydrochlorideand 35220 nm for Montelukast sodium [44]

The highest drug release was obtained with the formu-lation K4 containing super disintegrants SSG + CP in ratioof 2 (Levocetrizine dihydrochloride Kyron-t-104 is 1 4)Hence batch K4 was selected as optimized batch

The results of dissolution are shown in Tables 15 and 16and Figures 9 and 10

35 Stability Studies of Optimized Batch The optimizedformulations (K4 and K5) were stored in aluminum cappedclear glass vials and were subjected to a storage conditionof 40∘C plusmn 2∘C75 plusmn 5 RH for 3 months in humiditychamber The samples were withdrawn at time intervals of0 1 2 and 3 months and evaluated for hardness friability

dispersion time disintegration time drug content and invitro dissolution study [45]

Stability study revealed (Tables 17 18 and 19) that all theformulations were physically stable when stored at 40 plusmn 20∘Cand 75 plusmn 5 RH till 3 months and there was no significantdifference in dissolution for optimized formulation (Figures11 12 13 and 14)

36 Determination of Similarity and Dissimilarity FactorsA model independent approach was used to estimate dis-similarity factor (119891

1) and a similarity factor (119891

2) to com-

pare dissolution profile of optimized calculated FDTs withFDTs containing superdisintegrants The FDA and SUPAC-IR guidelines define difference factor (119891

1) as the calculated

percent () difference between the reference and test curvesat each time point and are ameasurement of the relative errorbetween the two curves


Table 14 Determination of disintegration time by different methods

FormulationDisintegration by

disintegration apparatus(sec)

Disintegration Time in theOral Cavity (DT)

Disintegration by Petri dishmethod (sec)

Disintegration by dissolutionapparatus with basket (sec)

K1 23 plusmn 076 24 plusmn 016 31 plusmn 089 28 plusmn 043K2 20 plusmn 063 26 plusmn 024 32 plusmn 072 29 plusmn 051K3 19 plusmn 058 22 plusmn 019 30 plusmn 094 26 plusmn 047K4 16 plusmn 055 21 plusmn 025 21 plusmn 067 20 plusmn 039K5 16 plusmn 061 22 plusmn 021 23 plusmn 074 21 plusmn 044K6 20 plusmn 051 24 plusmn 018 26 plusmn 069 24 plusmn 053

Table 15 In vitro drug release study of K4 batch (Kyron-T-104) inphosphate buffer (pH 68)

Dissolution media rarr Phosphate buffer pH 68Time (min) darr L M0 0 05 2734 263110 4146 394615 6257 506220 8373 677425 9583 838730 9292L Levocetrizine dihydrochloride M Montelukast sodium


Dissolution media rarr Phosphate buffer pH 68Time (min) darr L M0 0 05 2616 241810 3735 382615 5146 513720 6954 684925 8167 826430 9482 9174L Levocetrizine dihydrochloride M Montelukast sodium

The similarity factor (1198912) is given by the following

equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)

The dissimilarity factor (1198911) is given by the following

equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)

where 119899 is the number of pull points 119877119905is the reference batch

profile at time point 119905 and 119879119905is the test batch profile at the

same time 119905 For in vitro dissolution curves to be considered

0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)

Comparison of CDR of Levocetrizine dihydrochloride

K4 batchK5 batch

with Kyron-t-104 in pH 68 buffer

Figure 9 Comparison of in vitro drug release study of Levocetrizinedihydrochloride in K4 and K5 batch in phosphate buffer (pH 68)

0

10

20

30

40

50

60

70

80

90

100

40

CDR of Montelukast sodium in PBS of K4 and K8

0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R

Figure 10 Comparison of in vitro drug release study ofMontelukastsodium in K4 and K5 batch in phosphate buffer (pH 68)

similar 1198911values should be in the range of 0ndash15 while values

of 1198912should lie within 50ndash100 [46ndash49]

Similarity (1198912) and dissimilarityfactors (119891

1) for K4 andK5

are shown in Tables 20 and 21 All formulations showed (1198912)

value between 50 and 100 and (1198911) value below 15 indicating


Table 17 Stability study data for optimized formulation K4 and K5

Formulation batch Parameters evaluated Time interval (months)0 1 2 3

K4

Hardness (kgcm2) 31 plusmn 047 32 plusmn 038 31 plusmn 024 33 plusmn 042Friability () 049 plusmn 0089 051 plusmn 0072 043 plusmn 0091 039 plusmn 0103

Dispersion time (sec) 2037 plusmn 016 1978 plusmn 021 1964 plusmn 039 2131 plusmn 025

Drug content () L M L M L M L M976 932 963 947 969 936 982 925

Disintegration time (sec) 18 plusmn 012 20 plusmn 016 18 plusmn 007 19 plusmn 021

K5




Disintegration time (sec) 20 plusmn 006 21 plusmn 015 21 plusmn 011 19 plusmn 018L Levocetrizine dihydrochloride M Montelukast sodium

Table 18 Dissolution profile of stability study batch K4

Cumulative drug release in phosphate buffer (pH 68)mdashKyron-T-104 (SSG + CP)Month batch rarr 0 1 2 3Time (min) darr L M L M L M L M5 2443 2138 2562 1938 2651 2543 2523 231010 4357 3479 4337 3489 4278 3792 4342 402515 6313 4362 5882 5266 6148 5107 5968 523120 8168 6491 8136 6623 8239 6661 8191 664725 9486 8241 9371 8156 9572 8239 9386 805430 9306 9149 9198 9123L Levocetrizine dihydrochloride M Montelukast sodium


Cumulative drug release in phosphate buffer (pH 68)mdashKyron-T-104 (SSG + CCS)Month batch rarr 0 1 2 3Time (min) darr L M L M L M L M5 2372 2261 2423 2132 2773 2564 2623 211310 3428 3456 3169 3558 3949 4011 4342 352015 4815 5223 4901 5473 5072 5387 5968 493220 6529 6479 6172 6329 6787 6891 8191 654425 8038 8473 8044 7948 8213 8117 9386 795430 9589 9219 9411 9108 9437 9054 9178 8862L Levocetrizine dihydrochloride M Montelukast sodium

Table 20 Similarity factor and dissimilarity factors of Levocetrizine dihydrochloride in K4 and K5 before and after stability study

Time (min) Cumulative drug release of before

stability study (119877119905)

Cumulative drug release of afterstability study (119879

119905)

L with(SSG + CCS)

L with(SSG + CP)

L with (SSG + CCS) L with (SSG + CP) L with (SSG + CCS) L with (SSG + CP) 1198911119891211989111198912

5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine


Table 21 Similarity factor and dissimilarity factors of Montelukast sodium in K4 and K5 before and after stability study

Time (min) Drug release of before stability study

(119877119905)

Drug release of after stability study(119879119905)

M with(SSG + CCS)

M with(SSG + CP)

M with (SSG + CCS) M with (SSG + CP) M with (SSG + CCS) M with (SSG + CP) 1198911119891211989111198912

1 2418 2631 2113 2310

412 7717 305 8259

2 3826 3946 3520 40253 5137 5062 4932 52315 6849 6774 6544 66478 8264 8387 7954 805412 9174 9292 8862 9123M Montelukast sodium

0

20

40

60

80

100

120

0 5 10 15 20 25 30

Stability study of Levocetrizine of batch K4

0L1L

2L3L

Time (min)

CD

R

Figure 11 Comparative in vitro drug release profile of stability studybatches of Levocetrizine dihydrochloride (K4 batch) in phosphatebuffer (pH 68)

0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R

Figure 12 Comparative in vitro drug release profile of stability studybatches of Levocetrizine dihydrochloride (K5 batch) in phosphatebuffer (pH68)

similar release profiles of the formulations before and afterstability studies

4 Conclusion

In the present work an attempt was made to use ion exchangeresins (Kyron-T-104 and Tulsion-412) as taste masking agents

0

10

20

30

40

50

60

70

80

90

100Stability study of Montelukast sodium of batch K4

350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R

Figure 13 Comparative in vitro drug release profile of stabilitystudy batches ofMontelukast sodium (K4 batch) in phosphate buffer(pH68)

0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R

Figure 14 Comparative in vitro drug release profile of stability studybatches of Montelukast sodium (K5 batch) in phosphate buffer (pH68)

for Levocetrizine dihydrochloride Combinations of threesuperdisintegrants (separately and in ratio) were used inthe formulation of fast disintegrating combination tablet ofLevocetrizine dihydrochloride andMontelukast sodiumThepurpose was to enhance patient compliance and provide


fast onset of action Kyron T-104 and Tulsion-412 were usedas ion exchange resins and it was mixed with the drug indifferent ratios and evaluated for the extent of complexationResults have shown that with Kyron T-104 drug to resinratio of 1 4 and with Tulsion-412 drug to resin ratio of 1 5gave maximum amount of drug loading These drug-resincomplexes further evaluated for taste masking and differentconditions of drug loading and after optimization Kyron T-104 resinate with drug in ratio 1 4 selected for formulationdevelopment on the basis of maximum drug loading andcost effectiveness All the blends (K1 K2 K3 K4 K5 andK6) for formulation exhibited satisfactory values for angleof repose bulk density Tapped density Hausner ratio andCarrrsquos index and shown good flow properties All the tabletspassed the weight variation test friability test hardnesstest and variation and were found within the pharma-copoeia limit Drug content estimation showed that morethan 90 of the drugs (Levocetrizine dihydrochloride andMontelukast sodium) was present The dispersion producedwas smooth with pleasant mouth feel and the bitter tastewas totally masked in all formulations The disintegrationtests conducted on all these formulations showed that therewas faster disintegration of the tablets taking 16 to 31seconds which was much less than the official limit forfast disintegrating tablets (1 minutes) Minimum time fordisintegration was shown by the formulations K4 and K5so these two formulations finally selected for drug releasestudy In vitro drug release profile of tablet shown above90 drugs (Levocetrizine dihydrochloride and Montelukastsodium) in 25ndash35 minutes in phosphate buffer (pH 68)indicating that the drug will be absorbed faster in the mouthpharynx and oesophagus and thus chances of enhancementthe bioavailability by pregastric absorption through mouthpharynx and oesophagus Stability study was conductedfor 3 months Similarity (119891

2) and dissimilarity factors (119891

1)

for K4 and K5 were calculated All formulations showed(1198912) values between 50 and 100 and (119891

1) value below 15

indicating similar release profiles of the formulations beforeand after stability studies There was no significant changein taste and color at optimized temperature There was nosignificant variation in the disintegration time hardnessfriability and in vitro dissolution profiles for the optimizedformulations K4 and K5 On the basis of drug release K4was the optimized formulation but as there was no significantdifference between drug release profiles and other parametersof K4 and K5 and on the basis of cost effectiveness K5 mayalso be considered as optimized formulation

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

[1] Y Bircan and T Comoglu ldquoFormulation technologies of orallyfast disintegrating tabletsrdquo Marmara Pharmaceutical Journalvol 16 pp 77ndash81 2012

[2] V N Deshmukh ldquoMouth dissolving drug delivery system areviewrdquo International Journal of PharmTech Research vol 4 no1 pp 412ndash421 2012

[3] S Prateek G Ramdayal S U Kumar C Ashwani G Ashwiniand S Mansi ldquoFast dissolving tablets a new venture in drugdeliveryrdquo American Journal of PharmTech Research vol 2 no4 pp 252ndash279 2012

[4] D Sharma D K Singh G M Singh and M S Rathore ldquoFastdisintegrating tablets a new era in novel drug delivery systemand new market opportunitiesrdquo Journal of Drug Delivery ampTherapeutics vol 2 no 3 pp 74ndash86 2012

[5] P Ashish M S Harsoliya J K Pathan and S Shruti ldquoA review-formulation ofmouth dissolving tabletrdquo International Journal ofPharmaceutical and Clinical Science vol 1 no 1 pp 1ndash8 2011

[6] P Nagar K Singh I Chauhan et al ldquoOrally disintegratingtablets formulation preparation techniques and evaluationrdquoJournal of Applied Pharmaceutical Science vol 1 no 4 pp 35ndash45 2011

[7] P B PawarAGMansukKHRamteke Y P Sharma and SNPatil ldquoMouth dissolving tablet a reviewrdquo International Journalof Herbal Drug Research vol 1 no 2 pp 22ndash29 2011

[8] A K Gupta A Mittal and K K Jha ldquoFast dissolving tablet- areviewrdquoThe Pharma Innovation vol 1 no 1 pp 2ndash8 2011

[9] A Kumar V Bhushan M Singh and A Chauhan ldquoA reviewon evaluation and formulation of fast dissolving tabletsrdquo Inter-national Journal of Drug Research and Technology vol 1 no 1pp 8ndash16 2011

[10] V A Agrawal R M Rajurkar S S Thonte and R G IngaleldquoFast disintegrating tablet as a new drug delivery system areviewrdquo Pharmacophore vol 2 no 1 p 108 2011

[11] A K Nayak and K Manna ldquoCurrent developments in orallydisintegrating tablet technologyrdquo Journal of PharmaceuticalEducation and Research vol 2 no 1 pp 21ndash34 2011

[12] S S Olmez and I Vural ldquoAdvantages and quality control oforally disintegrating tabletsrdquo Journal of Pharmaceutical Sciencesvol 34 no 3 pp 167ndash172 2011

[13] H Jagani R Patel P Upadhyay J Bhangale and S KosalgeldquoFast dissolving tablets present and future prospectusrdquo Journalof Advances in Pharmacy and Healthcare Research vol 2 no 1pp 57ndash70 2011

[14] A Gupta A K Mishra V Gupta P Bansal R Singh and A KSingh ldquoRecent trends of fast dissolving tabletmdashan overview offormulation technologyrdquo International Journal of Pharmaceuti-cal amp Biological Archives vol 1 no 1 pp 1ndash10 2010

[15] P Datrange S Kulkarni and R R Padalkar ldquoDevelopment oftaste masked formulation for bitter drugrdquo Research Journal ofPharmaceutical Biological and Chemical Sciences vol 3 no 3pp 727ndash753 2012

[16] J Wadhwa and S Puri ldquoTaste masking a novel approach forbitter and obnoxious drugsrdquo International Journal of Biophar-maceutical amp Toxicological Research vol 1 no 1 pp 47ndash60 2011

[17] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud University Science vol 22 no 4 pp 229ndash240 2010


[18] V Sharma andH Chopra ldquoFormulation and evaluation of tastemasked mouth dissolving tablets of levocetirizine hydrochlo-riderdquo Iranian Journal of Pharmaceutical Research vol 11 no 2pp 457ndash463 2012

[19] MDekivadia A Gudigennavar C Patil and BUmarji ldquoDevel-opment amp optimization of fast dissolving tablet of levocetirizineHClrdquo International Journal of Drug Development amp Researchvol 4 no 2 pp 237ndash246 2012

[20] S Kanungo S M A Ali A Samanta and S M A AllildquoCrosslink polyacrilic resin based levocetirizine melt-in-mouthtabletsrdquo International Journal of Pharma Sciences and Researchvol 2 no 11 pp 196ndash204 2011

[21] M Moiz M P Srinivas and M Sadanandam ldquoFormulationand evaluation of bilayered tablets of montelukast and lev-ocetrizinedihydrochloride using natural and synthetic poly-mersrdquo International Journal of Drug Delivery vol 3 no 4 pp597ndash618 2011

[22] S Reddy C S Gonugunta and P R Veerareddy ldquoFormulationand evaluation of taste-masked levocetirizine dihydrochlorideorally disintegrating tabletsrdquo Journal of Pharmaceutical Scienceand Technology vol 63 no 6 pp 521ndash526 2009

[23] PMadhuri S SrikrishnaM S Kumar KV Subramanyam andLMatsyagiri ldquoFormulation and evaluation of sublingual tabletsof an antiasthmatic drugrdquo International Journal of PharmaWorld Research vol 3 no 3 pp 2ndash17 2012

[24] E Mahesh G B K Kumar M G Ahmed and K kumarldquoFormulation and evlaution of montelukast sodium fast dis-solving tabletsrdquoAsian Journal of Biomedical and PharmaceuticalSciences vol 2 no 14 pp 75ndash82 2012

[25] M Sivakranth A S Althaf and S Rajasekhar ldquoFormulationand evaluation of oral fast dissolving tablets of sildenafilcitrarterdquo International Journal of Pharmacy and PharmaceuticalSciences vol 3 no 2 pp 112ndash121 2011

[26] G S Gandhi D R Mundhada and S Bhaskaran ldquoLevoce-tirizine orodispersible tablet by direct compression methodrdquoJournal of Applied Pharmaceutical Science vol 1 no 5 pp 145ndash150 2011

[27] S K Shilpa M A Kumar and P Garigeyi ldquoFormulation andoptimization of clopidogrel bisulfate immediate release tabletrdquoInternational Journal of Pharmaceutical Frontier Research vol 1no 3 pp 56ndash72 2011

[28] P N Kadliya K V Chauhan K N Patel and P A Patel ldquoCom-parison and evaluation of bitter taste masked levocetrizine dihydrochloride using 120573-cyclodextrin and kyron T-114rdquo Interna-tional Journal for Pharmaceutical Research Scholars vol 2 no2 pp 114ndash124 2013

[29] N M Ghuge A Bhople A R Thakre et al ldquoFormulation andevaluation of taste masked fast dissolving tablets of risperidoneby using kyron T-104rdquo Indo American Journal of PharmaceuticalResearch vol 2 no 9 2012

[30] M M Gupta and V Patel ldquoFormulation and evaluation oraldispersible tablet of cinnarizinerdquo Journal of Drug Delivery ampTherapeutics vol 3 no 2 pp 12ndash17 2013

[31] A Garg and M M Gupta ldquoTaste masking and formula-tion development amp evaluation of mouth dissolving tabletsof levocetrizine hydrochloriderdquo Journal of Drug Delivery ampTherapeutics vol 3 no 3 pp 123ndash130 2013

[32] B S Chauhan L S Chauhan A Chatterjee G Niraj S Pandeyand U S Baghel ldquoAn approach based on advantages over

conventional systemrdquo Journal of Biomedical and PharmaceuticalResearch vol 2 no 1 pp 41ndash51 2013

[33] K Saroha G Kumar and Y Paul ldquoFormulation and evaluationof fast dissolving tablets of amoxicillin trihydrate using syn-thetic superdisintegrantsrdquo International Journal of Pharma andBio Sciences vol 4 no 1 pp 254ndash262 2013

[34] S Dhiman and S Verma ldquoOptimization of melt-in-mouthtablets of levocetirizine dihydrochloride using response surfacemethodologyrdquo International Journal of Pharmacy and Pharma-ceutical Sciences vol 4 no 1 pp 176ndash184 2012

[35] A Modi A Pandey V Singh C G Bonde D Jain and SShinde ldquoFormulation and evaluation of fast dissolving tablets ofdiclofenac sodium using different superdisintegrants by directcompression methodrdquo Pharmacia vol 1 no 3 pp 95ndash101 2012

[36] U Kulkarni and N G R Rao ldquoDesign and development of ace-clofenac fast dissolving tablets by amorphous solid dispersiontechnique using modified aeglemarmelos gumrdquo InternationalJournal of Pharmaceutical Research and Development vol 3 no6 pp 201ndash210 2011

[37] R K Nayak V B N Swamy A Senthil T Hardikkumar DM Kumar and R Mahalaxmi ldquoFormulation and evaluation offast dissolving tablets of lornoxicamrdquo Pharmacologyonline vol2 pp 278ndash290 2011

[38] S Kumari S Visht and P K Sharma ldquoPreparation and evalua-tion of fast disintegrating tablets of dicyclomine hydrochloriderdquoScholars Research Library Der Pharmacia Lettre vol 2 no 3 pp342ndash351 2010

[39] P S Mohanachandran P R K Mohan F Saju K B Bini BBabu and K K Shalina ldquoFormulation and evaluation of mouthdispersible tablets of amlodipine besylaterdquo International Journalof Applied Pharmaceutics vol 2 no 3 pp 1ndash6 2010

[40] R Kannuri T Challa and H Chamarthi ldquoTaste masking andevaluation methods for orodispersible tabletsrdquo InternationalJournal of Pharmacy amp Industrial Research vol 1 no 3 pp 201ndash210 2011

[41] V Lalji and M M Gupta ldquoOral disintegrating tablet of antihy-pertensive drugrdquo Journal of Drug Delivery amp Therapeutics vol3 no 1 pp 85ndash92 2013


[43] D Shukla S Chakraborty S Singh and B Mishra ldquoMouth dis-solving tablets an overview of evaluation techniquesrdquo ScientiaPharmaceutica vol 77 no 2 pp 327ndash341 2009

[44] K Kavitha D S Sandeep M Yadawad and M MangeshldquoFormulation and evaluation of oral fast dissolving tabletsof promethazine HCL by sublimation methodrdquo InternationalJournal of PharmTech Research vol 3 no 2 pp 659ndash663 2011

[45] N G R Rao K Venkatesh U Kulkarni M S Reddy and CKistayya ldquoDesign and development of fast dissolving tabletscontaining baclofen by direct compression methodrdquo Interna-tional Journal of Pharmaceutical and Biomedical Research vol3 no 4 pp 216ndash221 2012

[46] J W Moore and H H Flanner ldquoMathematical comparison ofdissolution profilesrdquo Pharmaceutical Technology vol 20 no 6pp 64ndash74 1996


[47] M M Gupta M Kedawat and S Maharaj ldquoReproducibilitydetermination of optimized batches of aceclofenac and queti-apinefumarate spherical crystals by comparing the dissolutionprofile employing the similarity and dissimilar factorsrdquo Interna-tional Journal of Pharmaceutical Research andDevelopment vol5 no 12 pp 27ndash32 2014

[48] H Goel N Vora and V Rana ldquoA novel approach to optimizeand formulate fast disintegrating tablets for nausea and vomit-ingrdquo AAPS PharmSciTech vol 9 no 3 pp 774ndash781 2008

[49] N Patel N Chotai J Patel T Soni J Desai and R PatelldquoComparison of in vitro dissolution profiles of oxcarbazepine-HP 120573-CD tablet formulations with marketed oxcarbazepinetabletsrdquoDissolution Technologies vol 15 no 4 pp 28ndash34 2008

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of


StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of



Advances in Pharmacological Sciences

Tropical MedicineJournal of


Medicinal ChemistryInternational Journal of


AddictionJournal of



BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Autoimmune Diseases


Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of


Pharmaceutics


MEDIATORSINFLAMMATION

of


Table 1 Details of formulations (K1ndashK6) of batch formulation

Batch-1Levocetrizine dihydrochloride Kyron-T-104 (1 4)

Ingredients K1 K2 K3 K4 K5 K6Montelukast sodium 10mg 10mg 10mg 10mg 10mg 10mgMCC 176mg 176mg 176mg 176mg 176mg 176mgSSG 4mg mdash mdash mdash mdash mdashCCS mdash 4mg mdash mdash mdash mdashCP mdash mdash 4mg mdash mdash mdashSSG + CCS mdash mdash mdash 4mg mdash mdashSSG + CP mdash mdash mdash mdash 4mg mdashCCS + CP mdash mdash mdash mdash mdash 4mgMg stearate 2mg 2mg 2mg 2mg 2mg 2mgTalc 3mg 3mg 3mg 3mg 3mg 3mgMCC microcrystlline cellulose SSG sodium starch glycolate CCG Crosscarmellose sodium CP crosspovidone

Ion exchange resins have been increasingly used for thetaste masking of bitter taste drugs and help to prepare fastdisintegrating tablets Thus the taste masking of bitter activesubstances is a critical hurdle to overcome for the success-ful development of oral formulations [15ndash17] Levocetrizinedihydrochloride is an orally active and R-enantiomer ofcetrizine and is a third generation nonsedating selectiveperipheral H1-receptor antagonist used in seasonal allergicrhinitis perennial allergic rhinitis and chronic urticaria [1819] Allergy is a common problem among all age groupsLevocetrizine dihydrochloride is rapidly absorbed after oraladministration and half-life is 83 hr which makes it suitablefor once a day formulationThese diseases require rapid onsetof action in order to provide fast relief Unfortunately it isaccompanied with a very unpleasant bitter taste so it requirestaste masking [20ndash22]

Montelukast sodium is a leukotriene receptor antag-onist (LTRA) used in maintenance treatment of asthmaand to relieve symptoms of seasonal allergies It is usuallyadministered orally [23ndash25] In the present study an attempthad been made to prepare fast disintegrating combinationtablets of Montelukast sodium and taste masked Levo-cetrizine dihydrochloride for the treatment of allergic rhinitisusing coprocessed superdisintegrants containing crospovi-done croscarmellose sodium and sodium starch glycolateThe coprocessed superdisintegrants help to increase thewateruptake with shortest wetting time and thereby decreasethe disintegration time of the tablets These systems mayoffer superior profile with potential mucosal absorptionthus increasing the drug bioavailability These systems arealso called mouth dissolving tablets melt-in-mouth tabletsreprimelts porous tablets orodispersible quick dissolving orrapidly disintegrating tablets

2 Materials and Methods

21 Materials Montelukast sodium sodium starch glycolatecroscarmellose sodium and crospovidone were procured asgift sample from MMC Health care pvt Ltd Baddi IndiaLevocetrizine dihydrochloridewas a generous gift fromAmol

Pharmaceuticals Jaipur India Tulsion-412 and Kyron-T-104were obtained as gift samples from Cadila PharmaceuticalsAhemdabad India All other materials (microcrystalline cel-lulose PH 102 Magneshium stearate and Talc) and chemicalsused were of analytical reagent grade

22 Analysis of Levocetrizine Dihydrochloride and Mon-telukast Sodium The solution containing 20 120583gmL of Levo-cetrizine dihydrochloride and Montelukast sodium in phos-phate buffer (pH 68) was prepared and scanned over rangeof 200ndash400 nm against phosphate buffer (pH 68) as ablank using double beam UV spectrophotometer The max-imum wavelength was found to be 2310 nm and 35220 nmfor Levocetrizine dihydrochloride and Montelukast sodiumrespectively which confirmed to the reported value

23 Formulation of Drug (Levocetrizine Dihydrochloride)Resin Complex Formulation of drug resin complex (DRC) ofLevocetrizine dihydrochloridewas done by the batch processdifferent amounts of resin Kyron-T-104 and Tulsion-412 wereplaced in beakers containing 100mL of deionized water andallowed to swell for a definite period of time Accuratelyweighed amount of Levocetrizine dihydrochloride (as per1 1 1 2 1 3 1 4 1 5 1 6 and 1 7 drug resin ratio) wasadded and stirred for desired period of timeThemixture wasfiltered and residue was washed with deionized water Filtratewas analyzed by UV spectrophotometer at 231 nm for theunbound drug and percentage drug loading was calculated[26ndash28]

24 Formulation Development of FDTS All formulations ofFDTs were prepared by direct compression technique forbatch by taking DRC equivalent to 5mg of Levocetrizinedihydrochloride Montelukast sodium (10mg) MCC wasused as diluent talc as an antiadherent and magnesiumstearate as a lubricant All the ingredients were accuratelyweighed and blended together to get uniform mixture Thenthe blend was compressed to get tablets using rotary tabletmachine The formulations are shown in Table 1


995

990

985

980

Tran

smitt

ance

()


393741

381661

374039

357411

338080

322553

297877

288440

276297

263053

238059

230800

174087

164730

149264

143487

131626

126879

113313

102077

89143

84303

75503


996

994

992

990

988

385394

375026

349585

336811

318392

300506

282460

272506

268025

236544

226783

218329

204893

193348

174999

165176

155888

154351

149031

140249

113374

106443

93123

80916

74917

Tran

smitt

ance

()


307217

1500 1000








998

996

994

992

990

988

986

378643

363337

340714

330427

297297

277775

266705

254556

240380

231133

218378

197554

181782

170490

163042

148419

126745

116576

91084

79739

Tran

smitt

ance

()



994

992

990

988

986

984

982

980385614

375598

367125

352621

342774

331132

318461

304855

297245

263399

250738

239244

229045

218755

210788

195489

174104

158954

149082

143547

138399

135524

131575

126846

117996

113278

109933

101792

92103

80115

75531

Tran

smitt

ance

()









Kyron-T-104 (1 4) 6724 4832 5763Tulsion-412 (1 5) 6387 4319 5684



2 3925 36643 4578 44734 4843 50195 7659 74616 6208 63387 6417 6825











20 5824 561530 7935 723140 7416 604650 4793 491660 3842 3481



30 7136 741860 8638 844290 8813 8775180 7469 7418









60 7863 7452120 7958 8069180 8418 8166240 8937 8624300 8374 8291





Strongbitterness




bitter





Kyron-T-104 5472 6039 6428 8526 7322 7011 7149Tulsion-412 5643 6256 6538 7439 8093 7543 7728













K1 3468 0465 0536 1152 1319 1324K2 3225 0448 0512 1142 1243 1250K3 3272 0453 0524 1156 1349 1354K4 3357 0438 0503 1148 1289 1292K5 3426 0453 0521 1150 1304 1305K6 3148 0435 0502 1154 1334 1335









119865 = (1 minus1198820

119882) times 100 (1)








119877 =(119882119886minus119882119887)

119882119887

times 100 (2)






(a) (b)

(c) (d)
















100 rpm

Hook

Sinker

Tablet


85

cm

Paddle

(a) (b)









(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


995

990

985

980

Tran

smitt

ance

()


393741

381661

374039

357411

338080

322553

297877

288440

276297

263053

238059

230800

174087

164730

149264

143487

131626

126879

113313

102077

89143

84303

75503


996

994

992

990

988

385394

375026

349585

336811

318392

300506

282460

272506

268025

236544

226783

218329

204893

193348

174999

165176

155888

154351

149031

140249

113374

106443

93123

80916

74917

Tran

smitt

ance

()


307217

1500 1000








998

996

994

992

990

988

986

378643

363337

340714

330427

297297

277775

266705

254556

240380

231133

218378

197554

181782

170490

163042

148419

126745

116576

91084

79739

Tran

smitt

ance

()



994

992

990

988

986

984

982

980385614

375598

367125

352621

342774

331132

318461

304855

297245

263399

250738

239244

229045

218755

210788

195489

174104

158954

149082

143547

138399

135524

131575

126846

117996

113278

109933

101792

92103

80115

75531

Tran

smitt

ance

()









Kyron-T-104 (1 4) 6724 4832 5763Tulsion-412 (1 5) 6387 4319 5684



2 3925 36643 4578 44734 4843 50195 7659 74616 6208 63387 6417 6825











20 5824 561530 7935 723140 7416 604650 4793 491660 3842 3481



30 7136 741860 8638 844290 8813 8775180 7469 7418









60 7863 7452120 7958 8069180 8418 8166240 8937 8624300 8374 8291





Strongbitterness




bitter





Kyron-T-104 5472 6039 6428 8526 7322 7011 7149Tulsion-412 5643 6256 6538 7439 8093 7543 7728













K1 3468 0465 0536 1152 1319 1324K2 3225 0448 0512 1142 1243 1250K3 3272 0453 0524 1156 1349 1354K4 3357 0438 0503 1148 1289 1292K5 3426 0453 0521 1150 1304 1305K6 3148 0435 0502 1154 1334 1335









119865 = (1 minus1198820

119882) times 100 (1)








119877 =(119882119886minus119882119887)

119882119887

times 100 (2)






(a) (b)

(c) (d)
















100 rpm

Hook

Sinker

Tablet


85

cm

Paddle

(a) (b)









(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





Kyron-T-104 (1 4) 6724 4832 5763Tulsion-412 (1 5) 6387 4319 5684



2 3925 36643 4578 44734 4843 50195 7659 74616 6208 63387 6417 6825











20 5824 561530 7935 723140 7416 604650 4793 491660 3842 3481



30 7136 741860 8638 844290 8813 8775180 7469 7418









60 7863 7452120 7958 8069180 8418 8166240 8937 8624300 8374 8291





Strongbitterness




bitter





Kyron-T-104 5472 6039 6428 8526 7322 7011 7149Tulsion-412 5643 6256 6538 7439 8093 7543 7728













K1 3468 0465 0536 1152 1319 1324K2 3225 0448 0512 1142 1243 1250K3 3272 0453 0524 1156 1349 1354K4 3357 0438 0503 1148 1289 1292K5 3426 0453 0521 1150 1304 1305K6 3148 0435 0502 1154 1334 1335









119865 = (1 minus1198820

119882) times 100 (1)








119877 =(119882119886minus119882119887)

119882119887

times 100 (2)






(a) (b)

(c) (d)
















100 rpm

Hook

Sinker

Tablet


85

cm

Paddle

(a) (b)









(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




60 7863 7452120 7958 8069180 8418 8166240 8937 8624300 8374 8291





Strongbitterness




bitter





Kyron-T-104 5472 6039 6428 8526 7322 7011 7149Tulsion-412 5643 6256 6538 7439 8093 7543 7728













K1 3468 0465 0536 1152 1319 1324K2 3225 0448 0512 1142 1243 1250K3 3272 0453 0524 1156 1349 1354K4 3357 0438 0503 1148 1289 1292K5 3426 0453 0521 1150 1304 1305K6 3148 0435 0502 1154 1334 1335









119865 = (1 minus1198820

119882) times 100 (1)








119877 =(119882119886minus119882119887)

119882119887

times 100 (2)






(a) (b)

(c) (d)
















100 rpm

Hook

Sinker

Tablet


85

cm

Paddle

(a) (b)









(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




K1 3468 0465 0536 1152 1319 1324K2 3225 0448 0512 1142 1243 1250K3 3272 0453 0524 1156 1349 1354K4 3357 0438 0503 1148 1289 1292K5 3426 0453 0521 1150 1304 1305K6 3148 0435 0502 1154 1334 1335









119865 = (1 minus1198820

119882) times 100 (1)








119877 =(119882119886minus119882119887)

119882119887

times 100 (2)






(a) (b)

(c) (d)
















100 rpm

Hook

Sinker

Tablet


85

cm

Paddle

(a) (b)









(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


(a) (b)

(c) (d)
















100 rpm

Hook

Sinker

Tablet


85

cm

Paddle

(a) (b)









(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





100 rpm

Hook

Sinker

Tablet


85

cm

Paddle

(a) (b)









(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of


(a) (b)


(a) (b)

(c) (d)










2) to com-

















equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of














equation

1198912= 50 times log[1 + (1

119899) 119878119899

119905=1(119877119905minus 119879119905)2

]

minus05

times 100 (3)


equation

1198911= [119878119899

119905=1

1003816100381610038161003816119877119905 minus 1198791199051003816100381610038161003816]

[119878119899

119905=1119877119905] times 100 (4)




0

20

40

60

80

100

120

0 5 10 15 20 25 30 35

CD

R

Time (min)


K4 batchK5 batch



0

10

20

30

40

50

60

70

80

90

100

40


0 5 10 15 20 25 30 35

Time (min)

K4 batchK5 batch

CD

R





1) for K4 andK5






K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




K4





K5













119905)

L with(SSG + CCS)

L with(SSG + CP)


5 2616 2734 2418 2923

364 7960 198 8590

10 3735 4146 3523 434215 5146 6257 4852 596820 6954 8373 6558 819125 8167 9583 7860 938630 9482 9178L Levocetrizine




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




(119877119905)


M with(SSG + CCS)

M with(SSG + CP)


1 2418 2631 2113 2310

412 7717 305 8259


0

20

40

60

80

100

120

0 5 10 15 20 25 30


0L1L

2L3L

Time (min)

CD

R


0

20

40

60

80

100

120

35


0 5 10 15 20 25 30

0L1L

2L3L

Time (min)

CD

R



4 Conclusion


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R


0

10

20

30

40

50

60

70

80

90


350 5 10 15 20 25 30

0M1M

2M3M

Time (min)

CD

R






1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of




1)


1) value below 15




References

























































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of








































Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of









Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of





Volume 2014

ToxinsJournal of

VaccinesJournal of















AddictionJournal of






Autoimmune Diseases




Journal of


Pharmaceutics



of

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