Cachet Pharmaceuticals Pvt.

Ltd

Submitted By: Pankaj Gupta

FORMULATION AND EVALUATION OF PARACETAMOL TABLET (A SOLID DOSAGES FORM)

Dissertation submitted to Rajasthan University of Health Sciences, Jaipur,

in the partial fulfillment of the requirements For the degree of

!"H#$%R %F &H!R'!"(

Submitted by
'r) &!*+!J ,U&-! )&H!R'!"( &!R-. /0 1#nrollment *o) 10/282

Under the ,uidance of

Dr) ,) J!(! !$!*
')&harm, &)hd 1&rincipal2 !l3ar &harmacy "oll4ge

5678.5679
!$:!R &H!R'!"( "%$$#,# *%R-H #;-#*S/%*, ')/)!) !$:!R.867686 1R!J!S-H!*2

CERTIFICATE

It is certified that Pankaj Gupta has carried out the project work presented in this report entitled Formulation and evaluation of paracetamol tablets for the award of Bachelor of pharmacy from Alwar Pharmacy College, Rajasthan University of ealth ! "ciences, #aipur under my supervision$ %he report em&odies original work, and studies are carried out &y the student$

"ignature 'r$ A$P$ (upta Cachet Pharmaceuticals Pvt$ )td$, Bhiwadi

*ate +

Acknowledgement
Words are few to express the feeling of thanks and gratitude to the following persons.
t is a great pleasure and honour to thank Plant !ead "

Mr. A.P. Gupta

G.#. ($achet Pharmaceuticals Pvt. %td.) would like to grab the opportunit& to thank m& guide

Mr. B.K. Dubey

!ead of '.$. ($achet Pharmaceuticals Pvt. %td.) for his immense support for the project. (ir &ou have been a great support for me" enlightening m& path of education and knowledge. am thankful to all the )ther (taffs

Mr. Abhishek Sir, Mr. Shukla Sir, Mr. Vipin Sir, Mr. Santosh Sir & Ms. Shubham Mam
for providing me all the help and support during m& work.

PA KA! G"P#A Date$% Al&ar

This treatise is Dedicated to My amily member ! my project guide "ho #ncouraged and lared Passion in me to learn more always And My pro ession $Pharmacist is the ounder stone o the medicine%

PA&'A( G)PTA

"r$ ,o$ /$ 0$ 1$ 3$ 5$ 6$ 7$ Introduction *rug Profile Plan of 2ork

%I%A)

PA(- ,.$

)ists of e4uipment used Process of manufacturing and its evaluation "ummary and Conclusion References

CONTENTS:

INTRODUCTION:A ta&let is a pharmaceutical dosage form$ It comprises a mi8ture of active su&stances ande8cipients, usually in powder form, pressed or compacted from a powder into a solid dose$ %he e8cipients can include diluents, &inders or granulating agents, glidants 9flow aids: and lu&ricants to ensure efficient ta&letting; disintegrants to promote ta&let &reak<up in the digestive tract; sweeteners or flavours to enhance taste; and pigments to make the ta&lets visually attractive$ A polymer coating is often applied to make the ta&let smoother and easier to swallow, to control the release rate of the active ingredient, to make it more resistant to the environment 9e8tending its shelf life:, or to enhance the ta&let=s appearance$ Advantages of tab ets : %a&lets are simple and convenient to use$ %hey provide an accurately measured dosage of the active ingredient in a convenient porta&le package$ %hey can &e designed to protect unsta&le medications or disguise unpalata&le ingredients$ Colored coatings, em&ossed markings and printing can &e used to aid ta&let recognition$ 'anufacturing processes and techni4ues can provide ta&lets special properties, for e8ample, sustained release or fast dissolving formulations$ Disadvantages of tab ets :

"ome drugs may &e unsuita&le for administration &y the oral route$ >or e8ample, protein drugs such as insulin may &e denatured &y stomach acids$ "ome drugs may &e deactivated &y the liver when they are carried there from the gastrointestinal tract &y the hepatic portal vein$ %he oral &ioavaila&ility of some drugs may &e low due to poor a&sorption from the gastrointestinal tract$ "uch drugs may need to &e given in very high doses or &y injection$

!ene"a #"o$ess of tab ets : /: Raw material ?: 'i8ing 0: Blending @: (ranulation 2et granulation *ry granulation Active pharmaceutical ingredients -8cipients

1: (ranule lu&rication 3: "ieving 5: Compression 6: Coating 7: Packing

DRU! %ROFI&E:
%a"a$eta'o St"($t("e :

Catego") : Analgesic IU%AC na'e : , <9@<hydro8yphenyl:acetamide *o e$( a" weight : /1/$/3? gAmol *o e$( a" fo"'( a + C6 Bioavai abi it) : B/CCD Des$"i#tion - Paracetamol is classified as a mild analgesic$ It is commonly used for the relief of headaches and other minor aches and pains and is a major ingredient in numerous cold and flu remedies$ In com&ination with opioid analgesics, paracetamol can also &e used in the management of more severe pain such as post<surgical pain and providing palliative care in advanced cancer patients$%hough paracetamol is used to treat inflammatory pain, it is not generally classified as an ,"AI* &ecause it e8hi&its only weak anti<inflammatory activity$ ,.?

%&AN OF ,OR-:
*ispensing 9 weighing of each ingredient in the mi8ture is determined according to dose$:

"iEing 9"iEe reduction, milling, crushing$:

Blending

2et granulation 9involves wet massing of powder &lend with granulating agent:

*rying 9keeping the residual moisture low enough to prevent product deterioration and ensure free flowing properties:

Compression of granules

-valuations >ollowings are the tests to &e performed with final product$ /$ ?$ 0$ @$ *escription *isintegration time 'oisture content 92ater &y F>: Average weight

1$ 3$ 5$ 6$ 7$

>ria&ility ardness *etermination of thickness Assay Content uniformity

/C$ *issolution

&IST OF E.UI%*ENTS USED:

"r$ ,o$ / ? 0 @ 1 3 5 6 7 /C // /? /0 /@ /1

-4uipment Gi&ro sifter >luid Bed -4uipment Huadro co<mill Bin &lender Gi&ro sifter Bilayer Compression 'achine 'etal *etecter *eduster *issolution Apparatus U"P<II Analytical &alance *isintegration apparatus >ria&ility test apparatus ardness tester Farl I >ischer Gernier calipers

>unction "ifting (ranulation 'illing Blending "ifting Compression *etection of metal *edusting of ta&lets *issolution studies 2eighing of materials >or disintegration time >or fria&ility of ta&let >or hardness of ta&let 'oisture content *etermination of thickness

TAB&ETIN! *ET/ODS:

Co'#"ession $)$ e (ranules from hopper empty in the feed frame 9A: containing several interconnected compartments$ %hese compartments spread the granulation over a wide area to provide time for the dies 9B: to fill$ %he pull down cam 9C: guides the lower punches to the &ottom, allowing the dies to overfill %he punches then pass over a weight<control cam 9-:, which reduces the fill in the dies to the desired amount A swipe off &lade 9*: at the end of the feed frame removes the e8cess granulation and directs it around the turret and &ack into the front of the feed frame

%he lower punches travel over the lower compression roll 9>: while simultaneously the upper punches ride &eneath the upper compression roll 9(:

%he upper punches enter a fi8ed distance into the dies, while the lower punches are raised to s4ueeEe and compact the granulation within the dies

After the moment of compression, the upper punches are withdrawn as they follow the upper punch raising cam 9 : %he lower punches ride up the cam 9I: which &rings the ta&lets flush with or slightly a&ove the surface of the dies

%he ta&lets strike a sweep off &lade affi8ed to the front of the feed frame 9A: and slide down a chute into a receptacle

At the same time, the lower punches re<enter the pull down cam 9C: and the cycle is repeated

%he principle modification from earlier e4uipment has &een an increase in production rate which is regulated &y ,um&er of tooling sets ,um&er of compression stations Rotational speed of the press

%"o$essing #"ob e's Ca##ing is the partial or complete separation of the top or &ottom crowns of a ta&let from the main &ody of the ta&let$ &a'ination is separation of a ta&let into two or more distinct layers$ Both of these pro&lems usually result from air entrapment during processing$ %i$0ing is removal of a ta&letJs surface material &y a punch$ Sti$0ing is adhesion of ta&let material to a die wall$ %hese two pro&lems result from e8cessive moisture or su&stances with low melting temperatures in the formulation *ott ing is an une4ual color distri&ution on a ta&let, with light or dark areas standing on otherwise uniform surface$ %his results from use of a drug with a color different from that of the ta&let e8cipients or from a drug with colored degradation products$

2eight variation<granule siEe distri&ution, poor fiow, punch variation ardness variation *ou&le impression<monograms or engraving on punch

DT A##a"at(s:- 'esh Apperture+< ?mm 9K/C:, Cycles+< ?6 I 0? cyclesAmin, 1C I 3C mm distance from &ottom ! top, %emp of water 05CC L ?CC$ If / or ? ta&s fail, repeat for /? ta&s$ %ARA*ETER 1ARIAB&ES )imits on ta&let weight are generally set as 0 to 1D of a formulation Tab et ,eight specific target weight "ome issues that may cause weight variation are powder flow pro&lems, improper die fill, and powder siEe distri&ution -8presses as load re4uired to crush a ta&let on end$ 'easured using a ta&let hardness tester$ (enerally, the larger the ta&let, the higher the hardness$ "maller ta&lets Tab et /a"dness 9/A@M round: usually have a hardness N1 kp$ )arger ta&lets usually have a hardness N?C kp$ "ome issues that may cause variations in ta&let hardness are inconsistent ta&let weight, particle siEe variations, poor powder compressi&ility, insufficient &inder level Tab et Thi$0ness Uniform compression force and volume of die fill, leads to uniform thickness %he time it takes for the ta&let to &reak up into individual granules or Disinteg"ation Ti'e particles$ Poor disintegration can come from ta&lets which are compressed too hard, insufficient disintegrant levels, or too much &inder$ F"iabi it) >ria&ility is the tendency of a ta&let to crum&le, chip or &reak$ It is measured &y ta&let weight loss after rotation on a fria&ilator 9i$e$ /CC revolutions or @ minutes at ?1 RP':$ %ypically D loss is NC$1D, &ut can &e up to ?D for very large ta&lets$

>ria&le ta&lets can &e caused &y low moisture content, insufficient &inder, ta&let configuration 9e$g$ sharp versus &eveled edges:$

,eight 1a"iation:
23 Content of A$tive Ing"edient: - /: Assay of Active ?: ?C ta&s+ < )imits 7CD to //CD 43 Unifo"'it) of ,eight5,t 1a"iation:?C ta&s, calculate avg$ wt ,'% ? deviate, none twice the limits$ ,eight 1a"iation &i'its:23 Fo" Tab ets I%5B% 6C mg or less &i'it /CD US% /0Cmg or less /0Cmg to 0?@mg 43 Fo" Ca#s( e:-

'ore than 6Cmg or 5$1D )ess than ?1Cmg

?1Cmg or more

1D

'ore than 0?@mg

F"iabi it) Test:- %his test is additional to check crushing strength of ta&let &y this test one can I% )ess than 0CCmg 0CCmg or 'ore &i'it /CD 5$1D

check Capping !Aor )amination$ U"P limit is C$1 to /D$ Rotation+ < ?1 rpm or /CC rotations in @ min$

Unifo"'it) of Content o" Content Unifo"'it):I%: - Active less than /Cmg or /CD, B%:- Active less than ? mg or ?D, US%:- Active less than ?1mg or ?1D$ </C ta&s limit ,'% / ta& deviate 61 I //1D ! none outside 51 I /?1D of the Avg valueAIPABPAU"P 9Relative "tandard *eviation less than or e4ual to 3D:, < If ? or 0 individual values are outside the limits 61 I //1D of the Avg value, ! none outside 51 I /?1D repeat for ?C ta&s$ < Complies when 0C ta&s ,'% 0 of the individual values are outside the limit 61 I //1D of the Avg value, and none outside 51 I /?1D$ Disinteg"ation Ti'e:Un$oated Tab et Coated Tab et ,'% /1 min, in water with *isc 05CC L ?CC ,'% 0C min, In water with *isc for Fi ' Coated Tab, and ,'% 3C min .ther than >ilm coated ta&let Ente"i$ Coated Tab Intact for / hr in C$/ , Cl ! disintegrate within ? hr in 'i8ed 3$6 Phosphate &uffer$ According to U"P / hr in "imulated gastric fluid, then in "imulated Intestinal >luid$ Dis#e"sib e5So (b e O"odis#e"sib e Effe"ves$ent Tab 2ithin 0 min in water at ?1CC L /CC 9I%: ! /1 I ?1CC 9B%: 2ithin / min 1 min in ?1C ml water at ?C I 0CCC 9I%: ! 1 min in ?CC ml water

at /1<?1CC 9B%: B($$a 6 S(b ing(a ,ot Applica&le &ut dissolve within /1 I 0C min$

,ET !RANU&ATION:

DISINTE!RATORS:
O %he &reakup of the ta&lets to smaller particles is important for dissolution of the drug and su&se4uent &ioavaila&ility$ *isintegrators promote such &reakup$ %o rupture or &reakup of ta&lets, disintegrating agents must swell or e8pand on e8posure to a4ueous solution$ %hus, the most effective disintegrating agents in most ta&let systems are those with the highest water uptake property$ In general, the more hydrophilic, the &etter disinter<grating agents are therefore highly hydrophilic$ A list of typical disinter<grants is ta&ulated in %a&le

.UA&IT7 CONTRO& Disso (tion

%he pharmaceutical scientist would like to find a relationship &etween an in vitro characteristic of a dosage form, and its in vivo performance$ *isintegration was originally thought to &e this characteristic$ %he U"P introduced its disintegration test in /71C$ 2ith advances in methodology, the disintegration test was found to &e too insensitive, and dissolution test methods were introduced in the U"P in /736$ *issolution is principally useful as a HC test$ It $an be predictive of in vivo &ehavior, &ut this must &e demonstrated &y an in<vivo in<vitro correlation study 9IGIGC:$ US% 829::;: P,o product, including suspensions and chewa&le ta&lets, should &e developed without dissolution or drug release $ha"a$te"i<ation where a solid phase e8ists$ Pand P*issolution testing is re4uired for all solid oral Pharmacopeia dosage forms in which a&sorption of the drug is necessary for the product to e8ert the desired therapeutic effect$ -8ceptions are for ta&lets meeting a re4uirement for completeness of solution or for rapid 9/C to /1 minutes: disintegration for solu&le or radio la&eled drugs$Q Disso (tion Re=(i"e'ents Artemether capsules < *issolution$ Carry out the test as descri&ed under 1$1 *issolution test for solid oral dosage forms$ Artemether ta&lets I as a&ove Artesunate ta&lets I as a&ove

ArtemetherAlumefantrine ta&lets I no reference to dissolution ArtemetherAlumefantrine oral suspension I no reference to dissolution, including in the referenced general monograph+

P)i4uid

preparations

for

oral

useQ

under

the

section,

PPowders

for

oral

solutionsAsuspensionsAdropsQ Availa&ility in .ther Pharmacopeia BP ?CC6+ no monographs$ U"P ?CC7+

A%I>s: a'odia=(ine, a'odia=(ine /C , 'ef o=(ine Dosage Fo"'s: Amodia4uine Cl %a&lets "ulfado8ineAPyrimethamine %a&lets

>or &oth of the a&ove, dissolution limits are included$ US% *onog"a#h Disso (tion *ethods5&i'its A'odia=(ine /C Tab ets 'edium+ water; 7CC m)$ Apparatus ?+ 1C rpm$ ,)% 51D 9H: in 0C minutes

S( fado?ine5%)"i'etha'ine Tab ets 'edium+ p 3$6 phosphate &uffer, prepared as directed under Buffer "olutions in the section Reagents, Indicators, and "olutions; /CCC m)$ Apparatus ?+ 51 rpm$ ,)% 3CD 9H: each API in 0C minutes$

Disinteg"ation @DT3 Testing ,ote that disintegration is generally an in<process test when the API is not highly solu&le$ *isintegration is indicated in the PhInt (eneral Chapter on ta&lets for various ta&let types 9uncoated, solu&le ta&lets, effervescent ta&lets, coated ta&lets:$ owever+ a statement is

included regarding all ta&lets+ P2here a re4uirement for the P*issolution testQ is specified in the individual monograph, the 1$0 *isintegration test for ta&lets and capsules is not re4uiredQ$

Disinteg"ation vs Disso (tion IC H3+ *isintegration may &e su&stituted for dissolution when+ <rapidly dissolving >PPJs 9dissolution R6CD in /1 minutes at p volume N ?1C m) from p /$? to 3$6: *ost a##"o#"iate when: relationship &etween *% and dissolution is esta&lished, or *% shown to &e more discriminating than dissolution$ /$?, @$C and 3$6: and >PPJs containing APIJs which are highly solu&le throughout the physiological range 9doseAsolu&ility

In these cases development information should &e provided to support the ro&ustness of the formulation and manufacturing process with respect to the selection of dissolution vs$ disintegration testing 9see *ecision %ree K59/::$ *ethod Des$"i#tion %he written procedure should include+ Apparatus "tandard and sample preparation 'ethod of analysis 9eg UG, P)C: "ampling procedure 9intervals, filtrationS, handling of samples, dilutions: Calculations Acceptance Criteria

S#e$t"o#hoto'ete":-

S#e$t"o#hoto'ete"s in the %ha"'a$e(ti$a Ind(st")

Color is a main component in the production of pharmaceutical and personal care products$ Color can &e used for many reasons such as to ensure that a product adheres to 4uality standards, or enhance a productJs appearance$ If a color is not e8act, it can alter the outcome of the final product and cause waste on the production line$

*eas("ing Co o" with A$$("a$) "pectrophotometers ensure that a productJs color matches specifications &y evaluating and e8pressing it in numerical terms$ 'anufacturers can control pigments and hues in pills, powders, li4uids, and other pharmaceutical products more easily with the color information provided &y the spectrophotometer$ %his e8treme accuracy reduces waste and outputs higher 4uality items with greater efficiency, which will increase profits$ S#e$t"o#hoto'ete" So (tions fo" the %ha"'a$e(ti$a Ind(st"): C*-A Ben$h-to# S#e$t"o#hoto'ete"

%his 4uick and simple &ench top spectrophotometer can ensure that color stays uniform throughout development of c

-e) Feat("es:

'easures in 0 simple steps Integrated software and )C* screen eliminates need for a separate computer PA""A>AI) grading for 4uick readings Gersatility to measure a different sample siEes and forms

C* BC99A %his spectrophotometer provides a level of accuracy that e8ceeds most re4uirements in the color industry$ Its versatility makes it suita&le for virtually any color measurement need$ -e) Feat("es:

-asily measures reflective and fluorescent colors Gersatile measurement area for various sample siEes and wide range of materials 2indows compati&le for easy control and editing Tenon flash for accurate measurement of very dark shades

/igh-#e"fo"'an$e i=(id $h"o'atog"a#h) @/%&C3:-

igh<performance

li4uid

chromatography 9formerly

referred

to

as high<pressure

li4uid

chromatography:, P)C, is a chromatographic techni4ue used to separate the components in a mi8ture, to identify each component, and to 4uantify each component$ Chromatography can &e descri&ed as a mass transfer process involving adsorption$ P)C relies on pumps to pass a pressuriEed li4uid and a sample mi8ture through a column filled with a sor&ent, leading to the separation of the sample components$ %he active component of the column, the sor&ent, is typically a granular material made of solid particles 9e$g$ silica, polymers, etc$:, ?I1C micrometers in siEe$ P)C is distinguished from traditional 9Mlow pressureM: li4uid chromatography &ecause operational pressures are significantly higher 91CI01C &ar:, while ordinary li4uid chromatography typically relies on the force of gravity to pass the mo&ile phase through the column$ *ue to the small sample amount separated in analytical P)C typical column dimensions are ?$/I@$3 mm diameter, and 0CI ?1C mm length$ Also P)C columns are made with smaller sor&ent particles 9?I1C micrometer in average particle siEe:$ %his gives P)C superior resolving power when separating mi8tures, which is why it is a popular chromatographic techni4ue$

A digital microprocessor and user software control the P)C instrument and provide data analysis$ "ome models of mechanical pumps in a P)C instrument can mi8 multiple solvents together in ratios changing in time, generating a composition gradient in the mo&ile phase$ Garious detectors are in common use, such as UGAGis, photodiode array 9P*A: or &ased on mass spectrometry$ 'ost P)C instruments also have a column oven that allows for adjusting the temperature the separation is performed at$

O#e"ation:

S$he'ati$ "e#"esentation of an /%&C (nit 9/: "olvent reservoirs, 9?: "olvent degasser, 90: (radient valve, 9@: 'i8ing vessel for delivery of the mo&ile phase, 91: igh<pressure pump, 93: "witching valve in Minject positionM, 93=: "witching valve in Mload positionM, 95: "ample injection loop, 96: Pre<column 9guard column:, 97: Analytical column, 9/C: *etector 9i$e$ IR, UG:, 9//: *ata ac4uisition, 9/?: 2aste or fraction collector$ A typical gradient profile in reversed phase chromatography might start at 1D acetonitrile 9in water or a4ueous &uffer: and progress linearly to 71D acetonitrile over 1I?1 minutes$ Periods of constant mo&ile phase composition may &e part of any gradient profile$ >or e8ample, the mo&ile phase composition may &e kept constant at 1D acetonitrile for /I0 min, followed &y a linear change up to 71D acetonitrile$ %he chosen composition of the mo&ile phase 9also called eluent: depends on the intensity of interactions &etween various sample components 9ManalytesM: and stationary phase 9e$g$ hydropho&ic interactions in reversed<phase P)C:$ *epending on their affinity for the stationary and mo&ile phases analyses partition &etween the two during the separation process taking place in

the column$ %his partitioning process is similar to that which occurs during a li4uidIli4uid e8traction &ut is continuous, not step<wise$ In this e8ample, using a waterAacetonitrile gradient, more hydropho&ic components will elute 9come off the column: late, once the mo&ile phase gets more concentrated in acetonitrile 9i$e$ in a mo&ile phase of higher eluting strength:$

A## i$ation:-

After having gained e8posure to

igh Performance )i4uid Chromatography systems and their

components we now introduce to typical applications$ P)C has contri&uted to analytical solutions in diverse fields such as pharmaceuticals, foods, life sciences, environment, forensics, etc$ In the present module we shall discuss some application areas in pharmaceuticals and foods$ %ha"'a$e(ti$a s igh Performance )i4uid Chromatography provides relia&le 4uantitative precision and accuracy along with a high linear dynamic range to allow determination of API and related su&stances in a single run$ A convenient method for sample preparation for solid dosage forms is dispersion in water or a4ueous media modified with acetonitrile or methanol $ P)C offers several possi&ilities for separation of chiral molecules into their respective enantiomers$ %hese include precolumn derivatiEation to form diastereomers$ Alternately, specialty columns prepared with cyclode8trins or special chiral moieties as stationary phases may&e used $In short P)C, particularly reverse phase P)C is the most popular choice for 4uantitative analysis in the pharmaceutical industry$

Co''on a## i$ation a"eas in #ha"'a$e(ti$a ana )sis a"e:

Assay Related "u&stances Analytical 'ethod Galidation "ta&ility "tudies Compound Identification 2orking "tandards

.(antitative Esti'ation of Te 'isa"tan In B( 0 D"(g And Tab ets B) U1 S#e$t"os$o#):A sensitive and rapid e8tractive spectrophotometer method has &een developed for the assay of telmisartan in &ulk drug and ta&lets$ %elmisartan shows ma8imum a&sor&ance at ?/3 nm$ BeerJs law was o&eyed in the concentration range of in the range of 1<?1 UgAml$ Beers law was o&eyed in this concentration range with correlation coefficient of C$777$ %he concentrations of this drug were evaluated in la&oratory mi8ture and marketed formulation$ Accuracy was determined &y recovery studies from ta&let dosages forms and ranges from 77$C/ to /CC$/?/D$ Precision of method was find out as repeata&ility, day to day and analyst to analyst variation and shows the values within accepta&le limit 9R$"$* V ? percentage:$ *ate"ia and *ethods All spectral measurements were made on a "ystronic UG<Gisi&le recording dou&le &eam spectrophotometer 9model ?/C/: with a / cm matching 4uartE cell$ %elmisartan drug sample was supplied as gift sample &y .asis %est )a&oratory #aipur$ Commercial ta&lets of %elmisartan were procured from the market 9%-%A,<?C mg from Alem&ic )td$, %-)*AW<@C mg from %orrent )a&$ )td$, and %-)"AR<6C mg from Unichem )a&: All other chemicals used were of analytical grade$ Ana )sis of Te 'isa"tan in tab ets (sing 29 * ("ea so (tion %wenty ta&lets of formulation<I 9%-%A,: were weighed and powdered$ Powder e4uivalent to ?C mg %elmisartan was transferred to a 1C ml volumetric flask containing @C ml of /C ' urea solution$ %he flask was shaken for a&out 1 min to solu&iliEe the drug$ %hen volume was made upto the mark with distilled water$ "olution was filtered through 2hatman filter paper K @/$ filtrate was divided in two parts, A and B$ part A was kept at room temperature for @6 hours to check the effect on sta&ility of drug in presence of urea and also to note precipitation, if any, during this period$ Part B filtrate was appropriately diluted with

distilled water and a&sor&ance was noted at 0/1 nm 9Xma8: against solvent &lank and the drug content was calculated 9%a&le</:$ After @6 hours, filtrate of part B was also appropriately diluted with distilled water and analyEed for drug content$ %here was no precipitation in the filtrate in @6 hours$ "imilar procedures were adopted in cases of formulation<II 9%-)*AW: and formulation<III 9%-)"AR:$ Res( t and Dis$(ssion %he mean percent la&el claims estimated &y proposed method for ta&let formulations I, II and III were 77$C/, /CC$@7@ and /CC$/?/ respectively which are very close to /CC, indicating the accuracy of the method$ %his also indicates that there was no interference of urea and the commonly used additives present in the ta&let formulation in the estimation &y the proposed method$ Galidation of the proposed method is further confirmed &y the low values of standard deviation, percent coefficient of variation and standard error 9%a&le /:$ %he mean percent recovery values ranged from 77$/0 to /CC$C3 and were very close to /CC$ Also the values of statistical parameters viE$ standard deviation, percent coefficient of variation and standard error were significantly low 9%a&le ?:$ %hus, the proposed method of analysis was very well validated$ Tab e 2: Res( ts of ana )sis of $o''e"$ia tab ets of Te 'isa"tan

Tab e 4: Re$ove") st(dies of $o''e"$ia tab ets of Te 'isa"tan

Tab e B: Statisti$a Data 6 Reg"ession E=(ation fo" Te 'isa"tan

St"($t("e of te 'isa"tan

CONC&USION %hus, it may &e concluded that the proposed method of analysis, using urea as the hydrotropic solu&iliEing agent is new, simple, cost<effective, environmentally friendly, safe, accurate and reproduci&le$ Urea and the commonly used ta&let e8cipients did not interfere in "pectrophotometric estimation at 0/1 nm$ *ecided advantage is that organic solvents are precluded &ut not at the e8pense of accuracy$ %he proposed method is worth adopting in pharmacopoeia$ By proper choice of hydrotropic agents, the use of organic solvents in analysis may &e discouraged to a large e8tent$ %he proposed method shall prove e4ually effective to analyEe %elmisartan in the corresponding drug sample and may prove to &e of great importance in pharmaceutical analysis$

REFERENCES
/$ %he theory and practice of industrial pharmacy &y )eon )achman, A$ lie&erman
2. #oseph Price Remington 9?CC3:$ Remington+ %he "cience And Practice .f Pharmacy$

)ippincott 2illiams ! 2ilkins$ I"B, C56/5@3503$ 0$ Pharmaceutical dosage forms vol</ 9unit operations and mechanical properties: &y Augs&urger and oag$ @$ M%a&let hardness testingM$ "ota8$ Retrieved /3 >e&ruary ?C/0$
5. M"ome Information on %a&let

ardness %estingM$ -ngineering "ystems$ Retrieved /3 ardness %esting 'achineM$ United "tates Patent

>e&ruary ?C/0$
6. Ro&ert Al&recht 9#ul ?/, /710:$ M%a&let

.ffice$ Retrieved /3 >e&ruary ?C/0$ U" ?3@1703

7. MHuality control of solid dosage formM$ "cri&d$ Retrieved /3 >e&ruary ?C/0$ 8. 'cCallum, A$, Buchter, #$ and Al&recht, R$ 9/711:$ MComparison and correlation of the

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?/$ Chanton, #$, Bryskier, A$ and (asc, #$C$, #$ Anti&iotics , /763, 07, 33C$ ??$ %he 'erck Inde8, /@th -d$, 'erck Research )a&oratories, *ivision of 'erck ! Co, Inc$ 2hitehouse "tation ,# U"A, /137$ ?0$ 'artindale 9?CC7:, [%he Complete *rug ReferenceJ, 03th -d$, %he Pharmaceutical Press, )ondon, Gol$/, /@C7$ ?@$ Chitra, P; (anesa, ""; Arumugam, F; "uvarna, F and 'allayasamy, "R 9?CC5:, P*etermination of telmisartan &y P%)C<A sta&ility indicating assayQ, Indian #ournal of Pharmaceutical science, ?C, @55<@6/$ ?1$ '", Palled; P ',, Rajesh et al$9?CC1:, PRP< P)C determination of %elmisartan in ta&let dosage formsQ, Indian #ournal of Pharmaceutical "cience, 35, ?CC1,/C6<//C$ ?3$ Pengfei, ) et al$ 9?CC1:, P*etermination of telmisartan inhuman plasma &y li4uid chromatographyItandem mass spectrometry, #ournal of Chromatography BQ, 6?6,/?3< /?7$ ?5$ Rane, GP et al$ 9?CC6:, P"imultaneous *etermination of %elmisartan and igh<Performance )i4uid Chromatographic ydrochlorothiaEide in Pharmaceutical PreparationQ, armoniEed %ripartite

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