RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

BANGALORE, KARNATAKA.
M.PHARM SYNOPSIS
YEAR OF ADMISSION-JUNE 2008
TITLE OF THE SYNOPSIS
FORMULATION AND EVALUATION OF THEOPHYLLINE FLOATING
TABLETS.
BY
TOM DAMIEN
M PHARM, PART-I
DEPARTMENT OF PHARMACEUTICS
UNDER THE GUIDENCE OF
M. B.SOMES!ARA RAO, M.P"#$
A%%&'(#)* P&+*%%&
DEPARTMENT OF PHARMACEUTICS
INSTITUTION
SREE SIDDAGANGA COLLEGE OF PHARMACY
B. H. ROAD, TUMKUR-,-2.02
KARNATAKA.
1
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE
KARNATAKA
ANNE/URE - II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. Name of the Candidate
and Address
M. TOM DAMIEN
Kakkanattu (H),
Nellimattom (p.o.),
Kothamangalam,
Eranakulam(Dist),
Kerala,Pin !"#.
$. Name of the %nstitution S** S(00#1#21# C&33*1* &+ P"#$#'4
&.H. 'oad, (umkur)*+$1,$.
#. Course of -tud. and -u/0e1t 2 Pharm 3 Pharma1euti1s
4. Date of Admission 5une $,,!
*. (itle of the (opi16
FORMULATION AND EVALUATION OF THEOPHYLLINE
FLOATING TABLETS.
$
5.0

BRIEF REVIE! OF THE INTENDED !ORK 6

5.. NEED FOR THE STUDY6
'apid gastrointestinal transit 1ould result in in1omplete drug release from the
de7i1e a/o7e the a/sorption 8one leading to diminished effi1a1. of the administered
dose.
1
(herefore different approa1hes ha7e /een proposed to retain the dosage form in
the stoma1h. (hese in1lude /ioadhesi7e s.stems,
$
-9elling and e:panding s.stems,
#
and
floating s.stems.
4
%n some 1ases gastro retention is a1hie7ed /. 1on1omitant
administration of drugs or e:1ipients 9hi1h slo9s the motilit. of ;%(.
*
Perhaps the most
promising approa1h to a1hie7ing gastroretention is that of 1reating a s9elling or
e:panding s.stem in situ. <hen the drug is formulated 9ith a gel forming pol.mer su1h
as semi s.ntheti1 deri7ati7e of Cellulose, it s9ells in the gastri1 fluid 9ith a /ulk densit.
less than one. %t then remains /uo.ant and floats in the gastri1 fluid, affe1ting a prolonged
gastri1 residen1e time (;'(). (his floating dosage form is kno9n as a h.drod.nami1all.
/alan1ed s.stem (H&-).

H.drod.nami1all. /alan1ed s.stems 1an remain in the gastri1 region for se7eral hours
and hen1e signifi1antl. prolong the gastri1 residen1e time of drugs. Prolonged gastri1
retention impro7es /ioa7aila/ilit., redu1es drug 9aste, and impro7es solu/ilit. for drugs
that are less solu/le in a high pH en7ironment of small intestine. %t has appli1ations also
for lo1al drug deli7er. to the stoma1h and pro:imal small intestines.
+
%n spite of ha7ing a
lot of potential /enefits floating drug deli7er. is asso1iated 9ith 1ertain limitations. Drugs
that irritate the gastri1 mu1osa, those that ha7e multiple a/sorption sites in the
gastrointestinal tra1t, 9hi1h undergo signifi1ant first pass meta/olism and those that are
not solu/le and sta/le at gastri1 pH are not suita/le 1andidates to /e formulated as
floating dosage forms.
!
#
(heoph.lline, a potent =anthine /ron1hodilator and smooth mus1le rela:ant used in the
s.mptomati1 treatment of mild /ron1hial asthma and re7ersi/le /ron1hospasm,is found to
1ause high degree of to:i1ities in CN-,;% s.stem and 1ardio7as1ular s.stem 9hen used
in the dose range of 1,,)$*,mg in di7ided dose dail. due to in1reased (>$,?g@ml) serum
le7el. %n1rease need of patient 1omplian1e and demand for impro7ed therapeuti1 effi1a1.
ne1essitates sustain release drug deli7er. s.stem for these drugs. %n the present stud.
floating ta/lets of (heoph.lline are prepared /. effer7esant approa1h /. using
h.drophili1 1ellulose deri7ati7es using 2etho1el K1,,,K1* and pol.7in.l p.rrolidine K)
#, (PAP K)#,).Citri1 a1id and sodium /i1ar/onate are in1orporated as gas generating
agent
(he aim of present stud. is to e7aluate the effe1t of gel)forming pol.mer 2etho1el on
floating properties and release 1hara1teristi1s of theoph.lline.

4
5.2 REVIE! OF LITERATURE 6
1. 'a0endra et al.,($,,!) studied on 2onolithi1 floating ta/lets of Nimesulide /.
using HP2C , gaur gum, Car/apol 9ith sodium /i1ar/onate as gas generating
agents and 1on1luded that drug release 9as sustained signifi1antl. for 1$hr
maintaining ta/let integrit. and found that drug release o11ur /. means of
diffusion 1ontrol release .
"

$. 2ano0 N ;an/hire et al.,($,,+)studied on oral floating matri: ta/lets of Dilti8em
H.dro1hloride /. using 2etho1el K)1,,2 C' ,Compritol !!! A(B ,-odium
/i1ar/onate , su11ini1 a1id and 1on1luded that the effer7es1ent)/ased floating
drug deli7er. is a promising approa1h to a1hie7e in7itro /uo.an1. /. using gel)
forming pol.mer metho1el K 1,, C' and gas generating agent sodium
/i1ar/onate. A high le7el of /oth 2etho1el K)1,,2 C' and 1ompritol !!! A(B
fa7ors the preparation of the floating 1ontrolled release of D(C ta/lets. (a/let
hardness had little or no effe1t on the release kineti1s and 9as found to /e a
determining fa1tor 9ith regards to the /uo.an1. of the ta/lets.
1,
#. 2 5aimini et al.,($,,+)studied on formulation and e7aluation of Damotidine
floating ta/lets /. using 2etho1el (K 1,,, K 1*2), PAP K)#,, -odium
/i1ar/onate and 1itri1 a1id, la1tose and 1on1luded that the addition of gel)forming
pol.mer 2etho1el (K1,, and K 1*2) and gas generating agent -odium
/i1ar/onate and along 9ith 1itri1 a1id 9as essential to a1hie7e in7itro /uo.an1..
(he drug release from the ta/lets 9as suffi1ientl. sustained and Non)Di1kian
transport of the drug from ta/lets 9as 1onfirmed.
11
*
4. -hishu et al.,($,,+)studied on gastro)retenti7e floating deli7er. s.stem for
*)Dluoroura1il and 1on1luded that the formulation e:hi/ited ma:imum sustain
release of *)Dluoroura1il 9ith e:1ellent floating properties. %t appears that the use
of a floating t.pe gastro)retenti7e dosage form of *)Dluoroura1il ma. /e a /etter
therapeuti1 approa1h for the treatment of gastri1 tumors.
1$
*. ;rish - -onar et al.,($,,+) studied on preparation and in7itro e7aluation of
/ila.er and floating)/ioadhesi7e ta/lets of 'osiglita8one 2aleate /. using HP2C
K1,,2, -tar1h 1*,,, 2ai8e star1h, -odium /i1ar/onate and 1on1luded that
optimi8ed /ila.er and floating)/ioadhesi7e dosage forms 9hi1h e:hi/it a uniEue
1om/ination of floating and adhesion for prolonged residen1e in the stoma1h. (he
optimi8ed &
*
ta/lets formulation sho9ed a satisfa1tor. dissolution profile,
dete1hment stress and floating 1hara1teristi1s.(he ta/lets remained floating in the
stoma1h for up to !hr.
1#
. D2 Patel et al.,($,,+) studied on formulation and optimi8ation of Car/ama8epine
floating ta/lets /. using HP2C K 42, Eth.l 1ellulose, /ees9a:, sodium
/i1ar/onate and 1on1luded that the amount of HP2C K42 ,Eth.l
1ellulose,sodium /i1ar/onate had a signifi1ant effe1t on D
lag
,t
*,
and t
!,.
(hus /.
sele1ting a proper optimi8ation te1hniEue, proper /alan1e of formulation 7aria/les
1an /e a1hie7ed rapidl. 9ith minimum efforts to produ1e reEuired in7itro
/uo.an1. and drug dissolution profile.
14

+. AD Patel et al.,($,,*) studied on formulation and e7aluation of 'anitidine

Dloating ta/lets /. using HP2C K 42, HP2C K 1*2, HP2C K 1,,FA, sodium
/i1ar/onate and 1on1luded that 7is1osit. had a ma0or influen1e on drug release
from a h.drophili1 matri: as 9ell as floating properties. Dissolution profile of
kineti1 drug release eEuation found that drug release from a h.drophili1 matri:
o11urred 7ia diffusion me1hanism follo9ing sEuare root of time profile (Higu1hi
eEuation).Hardness of ta/lets had greater influen1e on floating Fag time 9hi1h
might /e due to de1rease porosit.. Bptimi8ed formulation 9as found to /e sta/le
at 4,G@+*H 'H for the period of three months.
1*

!. -an0a. - Patel et al.,($,,)studied on formulation and e7aluation of floating drug
deli7er. -.stem 1ontaining Clarithrom.1in for Heli1o/a1ter p.lori and 1on1luded
that h.drod.nami1all. /alan1ed ta/let of an anti/a1terial drug Clarithrom.1in 1an
/e formulated as an approa1h to in1rease gastri1 residen1e time and there/.
impro7e its /ioa7ila/lit..Among the pol.mer used to impro7e the gastri1
residen1e, 1ellulose pol.mer (HP2C K42, HP2C K1*2) sho9ed /etter 1ontrol
o7er drug release. Dormulated ta/lets ga7e satisfa1tor. results for 7arious
ph.si1o1hemi1al e7aluations for ta/lets like ta/lets dimensions, hardness ,9eight
7arition, ta/let densit., floating lag time, 1ontent uniformit. and in7itro drug
release.
1

+
-.

5.7 OBJECTIVES OF THE STUDY6
Dollo9ing are the o/0e1ti7e of present stud.6)
1) (o 1arr. out pre)formulation studies for possi/le drug @pol.mer intera1tion.
$) (o de7elop anal.ti1al method for the estimation of the drug in the formulation.
#) (o de7elop and formulate (heoph.lline floating ta/lets.
4) (o e7aluate the formulated dosage form /. offi1ial in 7itro /uo.an1. studies.
*) (o e7aluate the formulated dosage form /. offi1ial in7itro studies.
MATERIALS AND METHODS6
2aterial6
Drug6 (heoph.lline
Pol.mer6 2etho1el K1,,, 2etho1el K1*2, PAP K)#, et1.
2ethods6
De7elopment of Dloating ta/lets /. ;ranulation method @ -uita/le method

-.. S&8'* &+ 0#)#6
#9 5ournals su1h as,
1) %ndian 5ournal of Pharma1euti1al -1ien1es.
$) European 5ournal of Pharma1euti1al -1ien1es.
#) %nternational 5ournal of Pharma1euti1s.
4) Drug De7elopment I %ndustrial pharma1..
*) %ndian Drugs.
:9 9orld 9ide 9e/
'9 5)gateJHelinet
09 Fi/rar.6 -iddaganga College of Pharma1..
*9 E)li/rar.6 -iddaganga College of Pharma1..
!

-.2 M*)"&0 &+ '&33*')(&2 &+ 0#)#6
1) Pre)formulation studies for possi/le drug@pol.mer intera1tion /. %'@D-C
anal.sis.
$) Preparation of the Dloating ta/lets /. granulation method.
#) E7aluation of the 7arious properties of Dloating ta/lets.
#9 F3&; <&<*)(*% &+ 1#283*%
Angle of repose
&ulk densit.
(apped densit.
Hausner ratio
Carr inde:
:9 O)"* %)80(*%
Kniformit. of 9eight of ta/lets
Hardness I fria/ilit.
Drug 1ontent
%n7itro /uo.an1.
%n7itro dissolution studies

-.7 Does the stud. reEuire an. in7estigation or in7estigation to /e 1ondu1ted on patient
or other humans or animalsL
NO
-.= Has Ethi1al 1learan1e /een o/tained from .our institution in 1ase of +.#L

NO
"
8.
BIBLIOGRAPHY.
1. %annu11elli A, Coppi ;, &erna/ei 2( and Cameroni ', Air 1ompartment multiple
unit s.stem for prolonged gastri1 residen1e, Part %, Dormulation stud.. %ntl. 5. Pharm.
1""!M1+4, 4+)*4.
$. -antus ;, Fa88arini ; and &ottoni ;, An in 7itro)in7i7o in7estigation of oral
/ioadhesi7e 1ontrolled release furosemide formulations. Eur 5.Pharm. &iopharm.
1""+M 44, #")*$.
#. Deshpande AA, 'hodes C(, -hah NH and 2ali1k A<, Controlled)release drug
deli7er. s.stems for prolonged gastri1 residen1e6 an o7er7ie9. Drug De7. %nd.
Pharm. 1""M$$, *#1)*#".
4. 2enon A, 'its1hel <A and -akr A, De7elopment and e7aluation of a monolithi1
floating dosage form for furosemide. 5. Pharm. -1i. 1""4M !#, $#")$4*.
*. 2oes A5, ;astroretenti7e dosage forms. Crit. 'e7. (her. Drug Carrier. -.st. 1""#M
1,, 14#)1*".
. B8demir N, Brdu - and B8kan N, -tudies of floating dosage forms of furosemide6 in
7itro and in 7i7o e7aluation of /ila.er ta/let formulations. Drug De7. %nd. Pharm.
$,,,M $, !*+)!.
+. Pon1hel ; and %ra1he 52, -pe1ifi1 and non)spe1ifi1 /ioadhesi7e parti1ulate s.stem
for oral deli7er. to the gastrointestinal tra1t. Ad7. Drug Del. 'e7. 1""!M #4, 1"1)$1".
!. Fauritsen K,Clini1al pharma1okineti1s of drugs used in the treatment of
gastrointestinal Diseases. ClinPharma1okinet. 1"",M 1", "4)1$*.
". 'a0endra 5angde, Nilesh ;orde, -unil Hargude, -9arnlata -araf, -hailendra -araf,
2onolithi1 floating ta/lets of Nimesulide.(he Pharma1euti1al 2aga8ine %nstitute of
Pharma1., Pt. 'a7ishankar -hukla Kni7ersit., 'aipur (2ar1h $,,!)M 1)#.
1,
1,. 2ano0 N ;am/hire, Kshiti0 <Am/ade, -ushma D Kurmi, Ailasrao 5 Kadam
and Kisan ' 5adha7, De7elopment and %n Aitro E7aluation of an Bral Dloating
2atri: (a/le Dormulation of Diltia8em H.dro1hloride.
AAP- Pharm-1i(e1h. $,,+M ! (#),E
1)
E
".
11. 5aimini 2, 'ana AC and (an9ar N-, Dormulation and E7aluation of
Damotidine Dloating (a/lets. Current Drug Deli7er.. $,,+M 4, *1)**.
1$. -hishu, ;upta N, Aggar9al N, A gastro)retenti7e floating deli7er. s.stem
for *)Dluoroura1il . Asian 5ournal of Pharma1euti1al -1ien1es. $,,+M $ (4), 14#)14".
1#. ;irish - -onar, De7endra K 5ain, Dhanan0a. 2 2ore, Preparation and in 7itro
e7aluation of /ila.er and floating)/ioadhesi7e ta/lets of 'osiglita8one maleate.
Asian 5ournal of Pharma1euti1al -1ien1es. $,,+M $ (4), 11)1".
14. Patel D2, Patel N2, Pand.a NN, 5ogani PD,Dormulation and Bptimi8ation of
Car/ama8epine Dloating (a/lets.%ndian 5ournal of pharma1euti1al -1ien1e.
$,,+M"(),+#)++.
1*. Patel AD, Patel N2, Neole P;,-tudies on Dormulation and E7aluation of 'anitidine
(a/lets. %ndian 5ournal of pharma1euti1al -1ien1e. $,,*M+(),+,#)+,".
1. -an0a. - patel,'a. - and (hankur '-,Dormulation and E7aluation of Dloating drug
deli7er. s.stem 1ontaining Clarithrom.1in for Heli1o/a1ter p.lori.A1ta Poloniae
Pharma1euti1a)Drug 'esear1h.$,,M#(1),*#)1.
11
> -ignature of the 1andidate6
.0 'emarks of the ;uide6 'e1ommended
.. Name and Designation of6
11.1 ;uide6 M. B.SOMES!ARA RAO, M.P"#$
Asso1iate Professor,
Department of Pharma1euti1s.
11.$ -ignature6
11.# Co);uide6
11.4 -ignature6
11.* Head of the Department6 D. SURESH V KULKARNI,M.P"#$.,P".D.
Professor I Head,
Department of Pharma1euti1s.
11. -ignature
.2 1$.1 'emarks of the Chairman and
Prin1ipal
Dor9arded to the Kni7ersit. for appro7al
1$.$ -ignature
D.S.BADAMI
Prin1ipal,
S** S(00#1#21# C&33*1* &+ P"#$#'4,
&.H. 'oad, (umkur)*+$1,$.
.
1$