4 Drug & Polymer Profile

8/11/2019 4 Drug & Polymer Profile

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Drug &Polymer Profle

sTRAMADOL HCL

Structural Formula :

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

Cyclohexanol hydrochloride.

Molecular formula: C16H2 !"2

Molecular wt : 263.#

Melting point : 1$%& to 1$1&.

Content : ''.% per cent to 1%1.% per cent (anhydro *tance).

CHARACTERS

Appearance : + hite, *itter, odorle crytalline poder.

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

Categor!: centrally actin0 anal0eic

Dose : % m0 in in0le doe

Half"life: lama hallie, tramadol a*ot 6 h (increae to 4 h ith mltiple doin0),

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#$armaco%!namics

5ramadol i a centrally actin0 ynthetic opioid anal0eic. +ltho0h it mode o

action i not completely ndertood, rom animal tet, at leat to complementary

mechanim appear applica*le: *indin0 o parent and 1 meta*olite to 7-opioid receptor

and ea8 inhi*ition o repta8e o norepinephrine and erotonin.

"pioid acti/ity i de to *oth lo ainity *indin0 o the parent compond and hi0her

ainity *indin0 o the "-demethylated meta*olite 1 to 7-opioid receptor.

5ramadol ha *een hon to inhi*it repta8e o norepinephrine and erotonin in /itro, a

ha/e ome other opioid anal0eic. 5hee mechanim may contri*te independently to the

o/erall anal0eic proile o tramadol. +part rom anal0eia, tramadol adminitration may prodce a contellation o ymptom (incldin0 di99ine, omnolence, naea, contipation,

eatin0 and prriti) imilar to that o other opioid.

Asorption

acemic tramadol i rapidly and almot completely a*or*ed ater oral adminitration.

5he mean a*olte *ioa/aila*ility o a 1%% m0 oral doe i approximately 4;. 5he mean

pea8 plama concentration o racemic tramadol and 1 occr at to and three hor,

repecti/ely, ater adminitration in healthy adlt.

<n 0eneral, *oth enantiomer o tramadol and 1 ollo a parallel

time core in the *ody olloin0 in0le and mltiple doe altho0h mall dierence

(=1%;) exit in the a*olte amont o each enantiomer preent.

Distriution

5he /olme o ditri*tion o tramadol a 2.6 >?80 and 2.' >?80 in male and emale

*@ect, repecti/ely, olloin0 a 1%% m0 intra/eno doe. 5he *indin0 o tramadol to

hman plama protein i approximately 2%; and *indin0 alo appear to *e independent o concentration p to 1% mc0?m>. Aatration o plama protein *indin0 occr only at

concentration otide the clinically rele/ant ran0e.

Metaolism

5ramadol i exteni/ely meta*oli9ed ater oral adminitration. +pproximately 3%;

o the doe i excreted in the rine a nchan0ed dr0, herea 6%; o the doe i excreted

a meta*olite. 5he remainder i excreted either a nidentiied or a nextracta*le

meta*olite. 5he ma@or meta*olic pathay appear to *e N– and O-demethylation and

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0lcronidation or lation in the li/er. "ne meta*olite (O-demethyltramadol, denoted 1)

i pharmacolo0ically acti/e in animal model. ormation o 1 i dependent on CB2D6

and a ch i *@ect to inhi*ition, hich may aect the therapetic repone.

Elimination

5ramadol i eliminated primarily thro0h meta*olim *y the li/er and the

meta*olite are eliminated primarily *y the 8idney. 5he mean terminal plama elimination

hal-li/e o racemic tramadol and racemic 1 are 6.3 1.# and 4.# 1.# hor, repecti/ely.

5he plama elimination hal-lie o racemic tramadol increaed rom approximately ix hor

to e/en hor pon mltiple doin0.

Si%e Effects :

- !aea,- /omitin0,

- Di99ine, dry moth,

- Aedation, and headache.

- epiratory depreion appear to *e le than ith eianal0eic doe o morphine,

+nd the de0ree o contipation i le than that een ater ei/alent doe o codeine

- 5ramadol can cae ei9re and poi*ly exacer*ate ei9re in patient ith

redipoin0 actor.

- hile tramadol-indced anal0eia i not entirely re/eri*le *y naloxone, tramadol-

indced repiratory depreion can *e re/ered *y naloxone.

Hoe/er, the e o naloxone increae the ri8 o ei9re.

&n%ication :

<t i el or mild to modrate pain li8e in arthral0ia , mclo8eletal pain , colicE and

pot operati/e tramatic cae.

+d@/ant in hort dia0notic and r0ical procedre. +nd alo ed in pot operati/e and

la*or pain relie and e/ere acte or chronic cancer pain.

Drug &nteractions

'se (it$ Carama)epine

atient ta8in0 carama)epine ma! ha/e a i0niicantly redced anal0eic eect o

tramadol. Fecae car*ama9epine increae tramadol meta*olim and *ecae o the ei9re

ri8 aociated ith tramadol, concomitant adminitration o tramadol and car*ama9epine inot recommended.

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'se (it$ *uini%ine

5ramadol i meta*oli9ed to 1 *y CB2D6. *uini%ine i a electi/e inhi*itor o that

io-en9yme, o that concomitant adminitration o inidine and tramadol relt in increaed

concentration o tramadol and redced concentration o 1. 5he clinical coneence o

thee indin0 are n8non. In vitro dr0 interaction tdie in hman li/er microome

indicate that tramadol ha no eect on inidine meta*olim.

'se (it$ &n$iitors of C+#,D-

In vitro dr0 interaction tdie in hman li/er microome indicate that concomitant

adminitration ith inhi*itor o CB2D6 ch a loxetine, paroxetine, and amitriptyline

cold relt in ome inhi*ition o the meta*olim o tramadol.

'se (it$ Cimeti%ine

Concomitant adminitration o tramadol ith cimeti%ine doe not relt in clinically

i0niicant chan0e in tramadol pharmaco8inetic. 5hereore, no alteration o the tramadol

doa0e re0imen i recommended.

'se (it$ MAO &n$iitors

<nteraction ith MAO &n$iitors, de to intererence ith detoxiication mechanim,

ha/e *een reported or ome centrally actin0 dr0.

'se (it$ Digo.in an% (arfarin

ot-mar8etin0 r/eillance ha re/ealed rare report o di0oxin toxicity and alteration o

ararin eect, incldin0 ele/ation o prothrom*in time.

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#ol!mer #rofile

/0 &ND&ON ,12

<!D<"! 23# i hi0h prity pharmacetical 0rade ea8 acidic cation exchan0e rein.

C$aracteristics

/3 #$!sical

+ppearance : hite to o hite ree loin0 poder. ree rom

orei0n matter

atrix : Cro lin8ed polyacrylic

Aol*ility : <nol*le in ater and in common ol/ent

<onic orm : G

; oitre : 3.$; (Apeciication- 1%.% ax)

Content

,3 #article si)e

etain on 1%% FAA meh : %.2 ; ?

13 C$emical

nctional 0rop : -C""-

23 Application

5ate a8in0 o *itter dr0

43 To.icit!

<ndion 23# i a hi0h moleclar ei0ht cro lin8ed polymer. <t i thereore not

a*or*ed *y *ody tie and i totally ae or hman conmption.

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Super%isintegrant #rofile

A0 Croscarmellose so%ium :

S!non!ms : +c-Di-AolI Cro lin8ed car*oxymethylcellloe odimI

explocelI modiied cellloe 0mI primelloeI olta*.

C$emical name : Cellloe, car*oxymethyl ether,

Nonproprietar! name : F: Crocarmelloe odim.

hJr: Carmellom natricm conexm.

KA!: Crocarmelloe odim.

Functional categor! : 5a*let and caple diinte0rant.

Molecular weig$t : '%%%% - 4%%%%%

Melting point : 224%C

Description : Crocarmelloe odim occr a an odorle, hite or 0reyih

hite oder.

Soluilit! : <nol*le in ater, *t rapidly ell # to $ time it ori0inal

/olme on contact ith ater.

Application : Crocarmelloe odim i ed in oral pharmacetical

ormlation a a diinte0rant or caple, ta*let, and 0ranle.

50 So%ium starc$ gl!colate :

S!non!ms : Car*oxymethyl tarch, odim alt, explota*, primo@el, /i/atar p.

C$emical name : Aodim car*oxymethyl tarch.

Nonproprietar! names : F: Aodim tarch 0lycolate.

hJr: Car*oxymethylamylm natricm.

KA!: Aodim tarch 0lycolate.

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Functional categor! : 5a*let and caple diinte0rant.

Molecular weig$t : %%%%% - 1%%%%%%

Melting point : Doe not melt, *t char at approximately 2%%oC

Soluilit! : Aparin0ly ol*le in ethanol (';), practically inol*le in ater. +t

a concentration o 2; ?/ odim tarch 0lycolate dipere in cold ater and ettle in the

orm o a hi0hly hydrated layer.

<t ell p to 3%% time o it /olme in ater.

Applications : Aodim tarch 0lycolate i idely ed in oral pharmacetical a a

diinte0rant in caple and ta*let ormlation.

C0 &n%ion 2/2 :

Description:

Characteritic

+ppearence : hite to pale Cream poder

atrix : Crolin8ed acrylic co-polymer

nctional Lrop : Car*oxylic +cid

<onic orm a pplied: otaim

Aol*ility : inol*le in ater and in common ol/ent

or eecti/e diinte0ration o the ta*let, 634 to ,7 of <ndion #1# i

recommended. 5he ad/anta0e o <ndion #1# a a ta*let diinte0rant inclde remar8a*le

ellin0 tendency on ettin0, th cain0 rapid diinte0rationI there i no lmp ormation

on diinte0rationI and it i compati*le ith commonly ed therapetic a0ent and excipient.

<ndion #1# doe not tic8 to pnche and die.

Application :

5he ad/anta0e o ion exchan0e rein a perdiinte0rant a compared to con/entional

one are that they ell on 0ettin0 hydrated *t do not diol/e or ha/e an adhei/e tendency,

a eatre commonly encontered ith 0m. 5h the ta*let diinte0rate e/enly. <on

exchan0e rein are eicient at conidera*le loer le/el than recommended or con/entional

diinte0rant. 5hey acilitate the compreion phae *y conerrin0 0reater hardne to the

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ta*let <on exchan0e rein or8 eally eiciently ith hydrophilic and hydropho*ic

ormlation, epecially ith the latter here the con/entional diinte0rant are ineecti/e.

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4 Drug & Polymer Profile