Drug &

Polymer Profle
sTRAMADOL HCL
Structural Formula :

Name: (1RS,2RS)-2-[(Dimethylamino)methyl]-1-(3-methoxyphenyl)

Cyclohexanol hydrochloride.

Molecular formula: C
16
H
2
!"
2
Molecular wt : 263.#
Melting point : 1$%& to 1$1&.
Content : ''.% per cent to 1%1.% per cent (anhydro() )(*)tance).

CHARACTERS

Appearance : + ,hite, *itter, odo(rle)) cry)talline po-der.

Soluilit!: .reely )ol(*le in -ater, methanol and ethanol /ery )li0htly )ol(*le in acetone.

Categor!: centrally actin0 anal0e)ic
Dose : % m0 in )in0le do)e
Half"life: 1la)ma hal23li2e, tramadol a*o(t 6 h (increa)e) to 4 h -ith m(ltiple do)in0),
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#$armaco%!namics
5ramadol i) a centrally actin0 )ynthetic opioid anal0e)ic. +ltho(0h it) mode o2
action i) not completely (nder)tood, 2rom animal te)t), at lea)t t-o complementary
mechani)m) appear applica*le: *indin0 o2 parent and 61 meta*olite to 7-opioid receptor)
and -ea8 inhi*ition o2 re(pta8e o2 norepinephrine and )erotonin.
"pioid acti/ity i) d(e to *oth lo- a22inity *indin0 o2 the parent compo(nd and hi0her
a22inity *indin0 o2 the "-demethylated meta*olite 61 to 7-opioid receptor).
5ramadol ha) *een )ho-n to inhi*it re(pta8e o2 norepinephrine and )erotonin in /itro, a)
ha/e )ome other opioid anal0e)ic). 5he)e mechani)m) may contri*(te independently to the
o/erall anal0e)ic pro2ile o2 tramadol. +part 2rom anal0e)ia, tramadol admini)tration may
prod(ce a con)tellation o2 )ymptom) (incl(din0 di99ine)), )omnolence, na()ea, con)tipation,
)-eatin0 and pr(riti)) )imilar to that o2 other opioid).
Asorption
:acemic tramadol i) rapidly and almo)t completely a*)or*ed a2ter oral admini)tration.
5he mean a*)ol(te *ioa/aila*ility o2 a 1%% m0 oral do)e i) approximately 4;. 5he mean
pea8 pla)ma concentration o2 racemic tramadol and 61 occ(r) at t-o and three ho(r),
re)pecti/ely, a2ter admini)tration in healthy ad(lt).
<n 0eneral, *oth enantiomer) o2 tramadol and 61 2ollo- a parallel
time co(r)e in the *ody 2ollo-in0 )in0le and m(ltiple do)e) altho(0h )mall di22erence)
(=1%;) exi)t in the a*)ol(te amo(nt o2 each enantiomer pre)ent.
Distriution
5he /ol(me o2 di)tri*(tion o2 tramadol -a) 2.6 >?80 and 2.' >?80 in male and 2emale
)(*@ect), re)pecti/ely, 2ollo-in0 a 1%% m0 intra/eno() do)e. 5he *indin0 o2 tramadol to
h(man pla)ma protein) i) approximately 2%; and *indin0 al)o appear) to *e independent o2
concentration (p to 1% mc0?m>. Aat(ration o2 pla)ma protein *indin0 occ(r) only at
concentration) o(t)ide the clinically rele/ant ran0e.
Metaolism
5ramadol i) exten)i/ely meta*oli9ed a2ter oral admini)tration. +pproximately 3%;
o2 the do)e i) excreted in the (rine a) (nchan0ed dr(0, -herea) 6%; o2 the do)e i) excreted
a) meta*olite). 5he remainder i) excreted either a) (nidenti2ied or a) (nextracta*le
meta*olite). 5he ma@or meta*olic path-ay) appear to *e N and O-demethylation and
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0l(c(ronidation or )(l2ation in the li/er. "ne meta*olite (O-de)methyltramadol, denoted 61)
i) pharmacolo0ically acti/e in animal model). .ormation o2 61 i) dependent on CB12D6
and a) )(ch i) )(*@ect to inhi*ition, -hich may a22ect the therape(tic re)pon)e.
Elimination
5ramadol i) eliminated primarily thro(0h meta*oli)m *y the li/er and the
meta*olite) are eliminated primarily *y the 8idney). 5he mean terminal pla)ma elimination
hal2-li/e) o2 racemic tramadol and racemic 61 are 6.3 C 1.# and 4.# C 1.# ho(r), re)pecti/ely.
5he pla)ma elimination hal2-li2e o2 racemic tramadol increa)ed 2rom approximately )ix ho(r)
to )e/en ho(r) (pon m(ltiple do)in0.
Si%e Effects :
- !a()ea,
- /omitin0,
- Di99ine)), dry mo(th,
- Aedation, and headache.
- :e)piratory depre))ion appear) to *e le)) than -ith eD(ianal0e)ic do)e) o2 morphine,
+nd the de0ree o2 con)tipation i) le)) than that )een a2ter eD(i/alent do)e) o2 codeine
- 5ramadol can ca()e )ei9(re) and po))i*ly exacer*ate )ei9(re) in patient) -ith
1redi)po)in0 2actor).
- ,hile tramadol-ind(ced anal0e)ia i) not entirely re/er)i*le *y naloxone, tramadol-
ind(ced re)piratory depre))ion can *e re/er)ed *y naloxone.
Ho-e/er, the ()e o2 naloxone increa)e) the ri)8 o2 )ei9(re.
&n%ication :
<t i) ()e2(l 2or mild to modrate pain li8e in arthral0ia , m()c(lo)8eletal pain , colicE) and
po)t operati/e tra(matic ca)e).
+d@(/ant in )hort dia0no)tic and )(r0ical proced(re. +nd al)o ()ed in po)t operati/e and
la*o(r pain relie2 and )e/ere ac(te or chronic cancer pain.
Drug &nteractions
'se (it$ Carama)epine
1atient) ta8in0 carama)epine ma! ha/e a )i0ni2icantly red(ced anal0e)ic e22ect o2
tramadol. Feca()e car*ama9epine increa)e) tramadol meta*oli)m and *eca()e o2 the )ei9(re
ri)8 a))ociated -ith tramadol, concomitant admini)tration o2 tramadol and car*ama9epine i)
not recommended.
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Drug &
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'se (it$ *uini%ine
5ramadol i) meta*oli9ed to 61 *y CB12D6. *uini%ine i) a )electi/e inhi*itor o2 that
i)o-en9yme, )o that concomitant admini)tration o2 D(inidine and tramadol re)(lt) in increa)ed
concentration) o2 tramadol and red(ced concentration) o2 61. 5he clinical con)eD(ence) o2
the)e 2indin0) are (n8no-n. In vitro dr(0 interaction )t(die) in h(man li/er micro)ome)
indicate that tramadol ha) no e22ect on D(inidine meta*oli)m.
'se (it$ &n$iitors of C+#,D-
In vitro dr(0 interaction )t(die) in h(man li/er micro)ome) indicate that concomitant
admini)tration -ith inhi*itor) o2 CB12D6 )(ch a) 2l(oxetine, paroxetine, and amitriptyline
co(ld re)(lt in )ome inhi*ition o2 the meta*oli)m o2 tramadol.
'se (it$ Cimeti%ine
Concomitant admini)tration o2 tramadol -ith cimeti%ine doe) not re)(lt in clinically
)i0ni2icant chan0e) in tramadol pharmaco8inetic). 5here2ore, no alteration o2 the tramadol
do)a0e re0imen i) recommended.
'se (it$ MAO &n$iitors
<nteraction) -ith MAO &n$iitors, d(e to inter2erence -ith detoxi2ication mechani)m),
ha/e *een reported 2or )ome centrally actin0 dr(0).
'se (it$ Digo.in an% (arfarin
1o)t-mar8etin0 )(r/eillance ha) re/ealed rare report) o2 di0oxin toxicity and alteration o2
-ar2arin e22ect, incl(din0 ele/ation o2 prothrom*in time).
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Drug &
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#ol!mer #rofile
/0 &ND&ON ,12
<!D<"! 23# i) hi0h p(rity pharmace(tical 0rade -ea8 acidic cation exchan0e re)in.
C$aracteristics
/3 #$!sical
+ppearance : ,hite to o22 -hite 2ree 2lo-in0 po-der. .ree 2rom
.orei0n matter
6atrix : Cro)) lin8ed polyacrylic
Aol(*ility : <n)ol(*le in -ater and in common )ol/ent)
<onic 2orm : G
H
; 6oi)t(re : 3.$; (Apeci2ication- 1%.% 6ax)
Content
,3 #article si)e
:etain on 1%% FAA me)h : %.2 ; -?-
13 C$emical
.(nctional 0ro(p : -C""
-
23 Application
5a)te 6a)8in0 o2 *itter dr(0)
43 To.icit!
<ndion 23# i) a hi0h molec(lar -ei0ht cro)) lin8ed polymer. <t i) there2ore not
a*)or*ed *y *ody ti))(e) and i) totally )a2e 2or h(man con)(mption.
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Super%isintegrant #rofile
A0 Croscarmellose so%ium :
S!non!ms : +c-Di-AolI Cro)) lin8ed car*oxymethylcell(lo)e )odi(mI
explocelI modi2ied cell(lo)e 0(mI primello)eI )ol(ta*.
C$emical name : Cell(lo)e, car*oxymethyl ether,
Nonproprietar! name : F1: Cro)carmello)e )odi(m.
1hJ(r: Carmello)(m natric(m conex(m.
KA1!.: Cro)carmello)e )odi(m.
Functional categor! : 5a*let and cap)(le di)inte0rant.
Molecular weig$t : '%%%% - 4%%%%%
Melting point : 224
%
C
Description : Cro)carmello)e )odi(m occ(r) a) an odorle)), -hite or 0reyi)h
-hite 1o-der.
Soluilit! : <n)ol(*le in -ater, *(t rapidly )-ell) # to $ time) it) ori0inal
/ol(me on contact -ith -ater.
Application : Cro)carmello)e )odi(m i) ()ed in oral pharmace(tical
2orm(lation a) a di)inte0rant 2or cap)(le), ta*let), and 0ran(le).
50 So%ium starc$ gl!colate :
S!non!ms : Car*oxymethyl )tarch, )odi(m )alt, explota*, primo@el, /i/a)tar p.
C$emical name : Aodi(m car*oxymethyl )tarch.
Nonproprietar! names : F1: Aodi(m )tarch 0lycolate.
1hJ(r: Car*oxymethylamyl(m natric(m.
KA1!.: Aodi(m )tarch 0lycolate.
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Drug &
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Functional categor! : 5a*let and cap)(le di)inte0rant.
Molecular weig$t : %%%%% - 1%%%%%%
Melting point : Doe) not melt, *(t char) at approximately 2%%
o
C
Soluilit! :

Aparin0ly )ol(*le in ethanol (';), practically in)ol(*le in -ater. +t
a concentration o2 2; -?/ )odi(m )tarch 0lycolate di)per)e) in cold -ater and )ettle) in the
2orm o2 a hi0hly hydrated layer.
<t )-ell) (p to 3%% time) o2 it) /ol(me in -ater.
Applications : Aodi(m )tarch 0lycolate i) -idely ()ed in oral pharmace(tical) a) a
di)inte0rant in cap)(le and ta*let 2orm(lation).
C0 &n%ion 2/2 :
Description:
Characteri)tic)
+ppearence : ,hite to pale Cream po-der
6atrix : Cro))lin8ed acrylic co-polymer
.(nctional Lro(p : Car*oxylic +cid
<onic 2orm a) )(pplied: 1ota))i(m
Aol(*ility : in)ol(*le in -ater and in common )ol/ent)
.or e22ecti/e di)inte0ration o2 the ta*let, 634 to ,7 of <ndion #1# i)
recommended. 5he ad/anta0e) o2 <ndion #1# a) a ta*let di)inte0rant incl(de remar8a*le
)-ellin0 tendency on -ettin0, th() ca()in0 rapid di)inte0rationI there i) no l(mp 2ormation
on di)inte0rationI and it i) compati*le -ith commonly ()ed therape(tic a0ent) and excipient).
<ndion #1# doe) not )tic8 to p(nche) and die).
Application :
5he ad/anta0e) o2 ion exchan0e re)in) a) )(perdi)inte0rant) a) compared to con/entional
one) are that they )-ell on 0ettin0 hydrated *(t do not di))ol/e or ha/e an adhe)i/e tendency,
a 2eat(re commonly enco(ntered -ith 0(m). 5h() the ta*let di)inte0rate) e/enly. <on
exchan0e re)in) are e22icient at con)idera*le lo-er le/el) than recommended 2or con/entional
di)inte0rant). 5hey 2acilitate the compre))ion pha)e *y con2errin0 0reater hardne)) to the
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Drug &
Polymer Profle
ta*let) <on exchan0e re)in) -or8 eD(ally e22iciently -ith hydrophilic and hydropho*ic
2orm(lation), e)pecially -ith the latter -here the con/entional di)inte0rant) are ine22ecti/e.
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