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1/16

Experimental

5. EXPERIMENTAL5.1 MATERIALS USED

Table No. 5.1: List of materials used and their suppliers

SR.NO.

CHEMICALS & REAGENTS MANUFACTURES

1

Tramadol HCL Linchon Pharma Ltd., Ahmadabad

2 Sodium starch glycolateLoba Chemie Laboratory Chemicals

Ltd.

Cosscaremellose sodium !aple "iotech P#t. Ltd

$ %ndion 2$ %on &'change (esin Ltd.

!umbai.) %ndion $1$

*!icrocrystalline cellulose

+A#icel PH1-2Samar Chemicals +%ndia

/ !agnesium Stearate Loba Chemie Laboratory ChemicalsLtd.

0 Hydrochloric acid !erc Chemicals

Sodium hydro'ide pellets (3CL LT4 5e6 4elhi

1-Potassium dihydrogen

7rthophosphate

8ual9gens 3ine Chemicals,

5a#i !umbai

11 Potassium chloride(anba'y 3ine Chemicals Ltd.,

5e6 4elhi

12Potassium bromide +%( 8ualigence Laboratories,

5a#i !umbai.

1 7range 3la#our Sapphire Life ScienceP#t. Ltd.

[Formulation development and evaluation of oro-dispersible tablet by directcompression Method] Page 44


2/16

Experimental

5.1 INSTRUMENTS USED

Table No. 5.2: List of instruments used and their manufacturer

SR.NO.

INSTRUMENTS/EUIPMENTS

MANUFACTURES

1(otary Press Tablet

Compression !achine

(%!&: !inipress%,

:arna#ati &ngineering Ltd.,

!ehsana, ;u9arat.

2 4hona "alance 4hona %nstruments P#t. Ltd., :olata.

4igital pH meter !odel 5o. 5%; ,

5aina Solaris Ltd. %ndia.

$ !onsanto Hardness tester Cadmach !achinery P#t. Ltd.,

Ahmedabad.

) (oche 3riabilator %%%

!odel 5o. &31?,

&lectrolab P#t. Ltd., ;oregaon +&,

!umbai.

* Sie#es Sethi Standard Test Sie#es

/4ouble "eam

SpectrophotometerTechcomp 2--

0 4issolution Apparatus %%%!odel 5o. T4T @ -*P,

&lectrolab P#t. Ltd., ;oregaon +&,

!umbai.

3T%( Spectrophotometer

!odel 5o. 0$-- S,

Shimadu Asia Pacific P#t. Ltd.,

Singapore.

1- 4igital >ernier Caliper ASAH%, %ndia.

11 +Poona College of Pharmacy, Pune.



3/16

Experimental

;raph Pad Prism +>ersion ).-

!icrosoft 7ffice 2--/

5!PREFORMULATION STUDIES5.1.1 I"e#$%%'a$%o# $e($ o) T)a*a"ol HCl

a+ Mel$%#, -o%#$: The melting point of Tramadol HCl 6as determined by capillary

method and checed, 6hether it complies 6ith the reported ones or not.

b+ I#)a)e" ab(o)-$%o# (-e'$)o-o$o*e$):Tramadol HCl 6as dried in hot air o#en

at )--C for 2 hours. The sample 6as prepared by mi'ing it thoroughly 6ith

potassium bromide. This sample 6as compressed under pressure of 1- TonBnm2and

con#erted in a circular disc. This disc 6as then placed in the scanning slot of 3ourier

Transform %nfrared +3T%( Spectrophotometer and scanned at range from $-- to

$--- cm1 to obtain the 3T%( of Tramadol HCl.

5.1.1 P)e-a)a$%o# o ($o'0 (ol$%o# o T)a*a"ol HCl

Accurately 6eighed 1--.- mg of tramadol HCl and dissol#ed in 1--.-mL of

dilution media +respecti#e buffer solution. The strength of solution 6as found to be 1

mgBmL. (especti#e dilutions 6ere prepared using stoc solution +A.

Then 1- mL of stoc solution +A 6as accurately pipetted into a 1-- mL of

#olumetric flas and #olume 6as made 6ith the dilution media to get stoc solution

+" of strength 1-- gBmL. (especti#e dilutions 6ere prepared using stoc solution +".

5.1.2 P)e-a)a$%o# o ($a#"a)" 'al%b)a$%o# ')e

To mae dilutions of Tramadol HCl ranging from ) gBmL to - gBmL

appropriate #olumes of stoc solution +" i.e. ), 1-, 1), 2- ,2) and - mL 6as pipette

and #olume 6as made up to 1--.- mL 6ith the dilution media. The absorbance 6as

measured of the prepared dilution in >isible spectrophotometer at 2/1 nm

6a#elength and Calibration cur#e bet6een absorbance and concentration 6as plotted.

Same procedure 6as repeated for acidic buffer PH1.2 and phosphate buffer

PH*.0 to prepare standard cur#e.

The reagents reuired for preparation of pH 1.2 hydrochloric acid buffer and pH

*.0 phosphate buffer are gi#en as follo6sD

[Formulation development and evaluation of oro-dispersible tablet by directcompression Method] Page 4"


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Experimental

5.1.3 P)e-a)a$%o# o Rea,e#$(

The reagents 6ere prepared as per %P.

a+ P)e-a)a$%o# o 4.2M ")o'lo)%' a'%" HCl+ (ol$%o#: Conc. HCl diluted 6ith

distilled 6ater so that final solution contains /.22 g of hydrochloric acid in 1---.-

mL to obtain -.2! hydrochloric acid solution.

b+ P)e-a)a$%o# o 4.2M -o$a((%* 'lo)%"e 6Cl+ (ol$%o#:4issol#ed 1$.11 g of

potassium chloride in distilled 6ater and diluted to 1---.- mL 6ith distilled 6ater

to obtained -.2! potassium chloride solution.

'+ P)e-a)a$%o# o "%l$%o# *e"%a -H 1.2 ")o'lo)%' a'%" be)+: ?eighed

accurately 2)-.- mL of -.2! potassium chloride solution 6as placed in a 1---.-

mL #olumetric flas. To this, about $2).- mL of -.2! hydrochloric acid 6as added

and then #olume 6as ad9usted to 1--- mL 6ith distilled 6ater. Then prepared

solution 6as tested using pH meter. The pH of solution 6as ad9usted to pH 1.2 6ith

the help of -.2! hydrochloric acid.

"+ P)e-a)a$%o# 4.2M -o$a((%* "%")o,e# -o(-a$e (ol$%o#: 2/.210 g of

potassium dihydrogen phosphate 6as dissol#ed in distilled 6ater and the #olume6as then made up to 1---.- mL 6ith distilled 6ater. This gi#es solution of strength

-.2! of potassium dihydrogen phosphate.

e+ P)e-a)a$%o# 4.2M (o"%* ")o7%"e (ol$%o#: Accurately 6eighed 0.- g of

sodium hydro'ide pellets 6as dissol#ed in distilled 6ater and the #olume 6as then

made up to 1---.- mL 6ith distilled 6ater to obtain the -.2! sodium hydro'ide

solution.

+ P)e-a)a$%o# o "%l$%o# *e"%a -H 8.9 -o(-a$e be)+: 2)-.- mL of -.2!

Potassium dihydrogen phosphate solution 6as placed in a 1--- mL #olumetric

flas. To this, about 112.- mL of -.2! Sodium hydro'ide solution 6as added and

then #olume 6as ad9usted to 1--- mL 6ith distilled 6ater. Then prepared solution

6as tested using pH meter. The pH of solution 6as ad9usted to *.0 6ith the help of

-.2! Sodium hydro'ide solution.

[Formulation development and evaluation of oro-dispersible tablet by directcompression Method] Page 4#


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Experimental

5.2+ TASTE MAS6ING ; USING ION EXCHANGE RESINS

5.2.1. Mo%($)e 'o#$e#$ "e$e)*%#a$%o# o $e )e(%#

Accurately ?eighed 1 gm resin sample +%ndion 2$ 6as ept in o#en

+pre#iously heated to 1---C for 2$ hours and 6eighed. The difference in the 6eight

before and after drying gi#es moisture content.

5.2.2. P)e


6/16

Experimental

slurry of resin that 6ere resulted in 1D1, 1D2 and 1D ratio of drug to resin. The percent

comple'ation 6as estimated at 2/1 nm. 4ata obtained is as sho6n in Table No. 6.6

5.3. b+. Ee'$ o A'$%a$%o# o %o# e7'a#,e )e(%# o# -e)'e#$ "), 'o*-le7a$%o#:

"y eeping drugD resin ratio +1D constant, %ndion 2$ 6as placed on a

?hatman filter paper in a funnel, 6as 6ashed 6ith distilled 6ater and subseuently

6ith 15 HCl +1-- mL. The resin 6as re6ashed 6ith 6ater until neutral pH 6as

reached and then resin 6as dried. 4rug resin comple' 6as prepared by placing 1--

mg to -- mg of acidacti#ated resin in a beaer containing 2) mL distilled 6ater.

Accurately 6eighed 1-- mg of Tramadol HCl 6as added to resin slurry 6ith

magnetic stirring.7n filtration, the residue 6as 6ashed 6ith /) mL of distilled

6ater. Percent comple'ation 6as estimated at 2/1 nm using Spectrophotometer.

Similarly, alali acti#ation of %ndion 2$ 6as performed, replaced 1 5 HCl

6ith 1 5 5a7H. The percent comple'ation 6as calculated at 2/1 nm using

Spectrophotometer. The data obtained is sho6n in theTable No. 6.7

5.3. '+. Ee'$ o 'o#'e#$)a$%o# o loa"%#, (ol$%o# o# 'o*-le7a$%o#:

"y eeping drugD resin ratio +1D constant, different uantities of drug resin

solution 6as prepared in beaer by using the concentration of loading solution 6ere

#aried from 2.) mgBmL, ).- mgBmL, /.) mgBmL, 1- mgBmL and 12.) mgBmL The

drugD resin slurry 6as stirred for one hour inter#al on magnetic stirrer. The percent

comple'ation 6as estimated by using Spectrophotometer at 2/1 nm. Similar

procedure 6as carried out 6ith different ratios. 4ata obtained is as sho6n in Table

No.6.8

5.3. "+. Ee'$ o *%7%#, $%*e o# -e)'e#$ "), 'o*-le7a$%o#:"y eeping drugD resin ratio +1D constant, -- mg of resin 6as stirred in 2) ml

of distilled 6ater for - min then add 1-- mg of Tramadol Hcl 6as added to it. Then

4rugD resin slurry 6as ept for 1), -, $), *-, - and 12- minutes inter#al on magnetic

stirrer. The percent comple'ation 6as estimated by using Spectrophotometer at 2/1

nm. 4ata obtained is as sho6n in Table No. 6.9

[Formulation development and evaluation of oro-dispersible tablet by directcompression Method] Page 4%


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Experimental

5.3. e+. Ee'$ o $%*e o (>ell%#, o )e(%# o# 'o*-le7a$%o#:

"y eeping drugD resin ratio +1D constant, -- mg of resin +%ndion 2$ 6as s6elled

in 2) mL of distilled 6ater in a beaer for 1-, 2-, - and $- minutes on

magnetic stirrer. 1-- mg of Tramadol Hcl 6as added to the slurry of resin during

stirring. 4rugD resin slurry 6as stirred for *- minutes on magnetic stirrer. The

percent comple'ation 6as estimated by using Spectrophotometer at 2/1 nm.

4ata obtained is as sho6n in Table No. 6.10

5.? Eala$%o# ($"%e( o (ol%" "),: )e(%# 'o*-le7

5.?.1. FT


8/16

Experimental

ratio of comple' 6ith that of the control and indicate the le#el of bitterness percei#ed by

them. The members of the panel 6ere ased to gargle. After complete remo#al of taste

sense of pre#ious sample then only the ne't sample 6as gi#en for taste analysis. The

a#erage bitterness #alue of each of the ratio 6as 6ored out based upon the le#el of

bitterness percei#ed by indi#idual member of the panel.

The a#erage bitterness #alue of each of the ion e'change resin comple' 6ith the

drug is sho6n in Table No. 5.12

5.?.3. A((a o D),: Re(%# Co*-le7e(:

A comple' eui#alent to )- mg 6as accurately 6eighed, in that 1- mL of 15 HCl

6as added to brea the drugD resin comple'. This 6as stirred on magnetic stirrer for

-min. Solution 6as filtered E dilutions 6ere made, and absorbance 6as measured at

2/1 nm using Spectrophotometer. The data obtained is sho6n inTable No. 6.13

5.5+ Fo)*la$%o# De(%,# :

Sele'$%o# o (-e)"%(%#$e,)a#$

A disintegrant is included in the formulation to ensure that the tablet, 6hen in

contact 6ith a liuid, breas up into small fragments, 6hich promotes rapid drug

dissolution. %deally, the tablet should brea up into indi#idual drug particles in order to

obtain the largest possible effecti#e surface area during dissolution.

The disintegration process for tablet occurs into t6o steps. 3irst, the liuid 6ets

the solid and penetrates the pores of the tablet. Thereafter, the tablet breas into smaller

fragments. A disaggregation directly into primary po6der particles 6ill set up

conditions for the possible dissolution of the drug.

The disintegration times of these tablets depend largely on the sie of the dosage

form and hardness parameter. The basic approach used in the de#elopment of the

7rodispersible tablet is the use of superdisintegrants.

Preliminary study 6as carried out for screening of three superdisintegrants namely,

1 Sodium starch glycolate

[Formulation development and evaluation of oro-dispersible tablet by directcompression Method] Page 5!


9/16

Experimental

2 Croscarmellose sodium

%ndion $1$

4rug, mannitol, aspartame, orange fla#or, magnesium stearate,aerosil, microcrystalline cellulose and #arious concentrations of superdisintegrants 6ere

taen and compressed. The 6eight of tablet in all batches 6as ept constant. All the

batches of tablets 6ere prepared by direct compression using 11 station rotary tablet

machine +(ime machineries Ltd.&feect of disintegrating agents and their

concentrations on #arious table properties and in #itro dissolution characteristics 6ere

studied and discussed.

[Formulation development and evaluation of oro-dispersible tablet by directcompression Method] Page 5'


10/16

Experimental

Na*e o

%#,)e"%e#$(

a#$%$ %# *,

F1

1F

F2

2F

F3

$F

F?

1F

F5

2F

F8

$F

F@

1F

F9

2F

F

$F

F14

ab%l%$

A#,le o Re-o(e + Flo>ab%l%$

2- &'cellent

2-- ;ood

-$ Acceptable


?eight of sample in gm

"ul density +gBmL K

>olume occupied by the sample

?eight of sample in gm

Tapped density +gBmL K

>olume occupied by the sample


13/16

Experimental

M $- >ery poor

5.@. "+ Co*-)e((%b%l%$ Ca))( %#"e7+:

%t is also one of the sample methods to e#aluate flo6 property of a po6der by

comparing the bul density and tapped density. A useful empirical guide is gi#en by the

CarrIs compressibility.

1--densityTapped

density"ul,densityTappedilityCompressibF =

Table 5.5: Rela$%o#(%- be$>ee# 'o*-)e((%b%l%$ a#" Flo>ab%l%$.

Co*-)e((%b%l%$ Flo>ab%l%$

)1) &'cellent

121* ;ood

1021 3airly acceptable

2) Poor

0 >ery poor

$- >ery #ery poor.

5.9+ Po($


14/16

Experimental

134 o) le(( 94 o) le(( 14

F)o* 134 $)o, 32? 94 *, 7 254 *, @.5

*o)e $a# 32? 254 *, o) *o)e 5

b+ Ha)"#e(( :

3or each formulation, the hardness of * tablets 6as determined using Thermoni

tablet tester +Campbell &lectronics !odel 5o. 4HT2)-. Tablet 6as ept diagonally

bet6een the t6o plungers and a pressure 6as applied to it until the tablet broe do6n

into t6o parts completely and the reading on the scale 6as noted do6n in gBcm2.

'+ F)%ab%l%$ :

(oche friabilator +&lectrolab 3riabilator @


15/16


16/16

Experimental

3ig 5o ).D method for measuring the 6etting time and 6ater absorption ratio

e+ In-vitro D%((ol$%o# ($"%e(:

The dissolution test has been carried out for all the formulations .The in #itro drug

released 6as performed using isible spectrophotometer.

5. + Co*-a)%(o# O O-$%*%Ke" Fo)*la$%o# !%$ Ma)0e$e" Table$

%n #itro 4issolution studies for optimied formulation and uncoated

con#entional tablet +Contramol 4T, Piramal Pharma LT4., !umbai. 4ose )- mg 6ere

carried out using

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