Formulation and Characterization of Atenolol-β-Cyclodextrin Orally Disintegrating Tablets - Ubaya Repository
I
B(mK OF PROGNAII
!SN
2017
lnternational Symposium
on Natural Medicines
a!
Sustainable Use of Natural Products for
Human's Health and Welfarea
IF
,:
-'-
--t-
IPB lnternational Coruention Center
24-25 August 2O17
8ogor, lndonesia
!
t ..]
lloclca by:
. Tlltlcel Orftrnra Borcexfi C..tlf lPA
. Icrrblakc Boccarct ClrrCr lPa
r fhe hdmdrn fuc.d.tho o{ NSrd lh{r
neroerdtofr
COMMITTEE
lome (nttp://isn m.lpb.oc.id)
>> Committee
IMPORTANT DATES
Steering Commitee
Dr. lr. Prostowo, MEng (Kepolo LPPN/ IPB)
Abstroct Submission
Prof. Dr. drh Agik Suproyogi (Wokil Kepolo Bidong Penelition
Deodline:
Prof. Dr. lr. lskondor zulkornoin Siregor (Direktur Riset
ff4q-2eF
July
31, 2017
Dr.
AccePtonce Notifi cotio n:
#y24.2017 August
SSl. MSi
Prof. Dr. Erni H Purwoningsih (eernipOo/ut)
Prof. Dr. Bombong eroyogo (eerhipoo/uNatn)
Deodline:
Prof. Dr. Ervizol A.[,4. Zuhud (PA)
lS, 2017
Prof. Dr. drh. Umi Cohyoningsih
lSNM20u Symposium:
August 24
-
Scientific Committee
25. 2017
Prof. Dr. Dyoh lswontini erodono, t',mgr
SEARCH
q
Prof. Dr. Ir. C. Honny Wijoyo, M.Agr (lPB
Prof. Dr. lr. Sondro Arifin Aziz. N/S (pB)
Apt
Prof. Dr. letie Wientorsih,
Dr.
SPONSORED BY:
M.Sc (tpB)
Momon Turjomon, DEA (Puslitbonghut-KLHK)
Dr. Noncy Oewi Yutiono (tea)
Dr.lr. Ninuk Purnoningsih, M.Si (pB)
Drh. Sulistyoni, Ph.D (tpB)
(pB)
Dr. Moto Nuritmoto. M.Si
Novriyondi Honif. D.Sc (tpB)
Orgonizing Commitee:
Choirmon:
Dr.
(https://mohkotodewoi
n
dones
io.co.id/)
Mohomod Rofi, M.Si (pB)
Vice-choirmon:
Rudi Heryonto,
;..l;..lli
(ea)
Prof. lr. Suminor S Achmodi, Ph.D (lPB)
Seorch
S.Si, M.Si
(pB)
Secretory:
e"r."Er g.qlefi
tep'
Susi lndorioni, STp., M.Si (pB)
(nttp://gen ecroft obs.co m/)
I
Treosuren
Solino Febriony,
S.Si. M.Si
Ninik Lestari Ningsih,
SE
(pB)
(pB)
don lnovosi
IPB)
IPB)
(Kepolo Pusot Studi Bioformoko Tropiko
LPPM IPB)
5, 2017
FulFPoper Submission
August
lrmonido Botuboro,
LPPN4
a
lD
a
Secretoriot
BrorenlNDo
Dewi Anggroini s, s.si. v.si (Pe)
o ooo a
FI. RIOFARMAKA INT'ONESIA
(http://biof orin do.in do network.
co.id/)
Titis Arifiono. s.si (PB).
zokio, AMd (PB)
Public Rclotions:
Anonto rusumo, uT (PB)
Dr. Eng. Wisnu
vektor Dewonto,
Dr.
ST,
M.Eng (PB)
otih Rostiono (Bolittro-Kementon)
Drh. zuroido, M.Si (Puslitbonghut-KLHK)
Hero Nurhoyoti, s.P, M.Sc (Bolittro-Kementon)
(nttps://www.buch i.co m/id- n)
i
Publicotions:
Novriyondi Honif, s.si.
Dr. Wulon Tri
HOSTED BY:
N4.sc,
wohyuni,
D.sc (PB)
S.Si., M.Si
(lPB)
Loelo Wulonsori, S.Si (lPB)
?iofua,aaRaaltl e,.u
(nttp:i/biof ormoko.i pb.oc.id/)
$
*n::*:,::';:;'1"".'
Progroms:
Siti So'dioh. s.si, Apt M.Si (PB)
Dr.
Muhommod Nursid, s.si, M.si (psosperP-rrp)
Dr.
Trivodito.
S.Si., rr,l.si
(Pa)
Drh. lnnes Moulidyo (PB)
(http:i/metobolo mics.i pb.oc.i d/
Sponsorships:
)
Rudi Heryonto, S.si. ri,l.si (Pa)
Dr. lr. Nevioty
zomoni, u.sc (ee)
Toopik Ridwon,
S.Si. t'rt.Sl
(Pe)
Drh. okto wismondonu. M.Epid (lPB)
Logistics:
s
Th€
l.rdoe66 As@llir
Antonio Koutsor,
ol NBtu..l Oruqs
Re$eclp.s
(http://www.perh pbo.com/)
i
S.Si (lPB)
sgo rirdous (tee)
Nunuk Kumiqti tt, s.rorm (Pe)
Forhonno Nurozizoh (PB)
M. Yusuf (tPB)
Ahmqd Yoni (PB)
Workshops:
Anggio Murni, s.si (PB)
O All right reserved lSNM20l7
Educotion Bose by Acme Themes (http://www.ocmethemes.com,
ORAL PRESENTATION SCHEDULE
Ilay 1, Thunsday,24 August
Time :14.3O-17.30
2O1 7
Room : Paralel 2 (Meefing Room B)
Prcscnhr & TitiE
Time
14.30-
Abstact_O19/
14.45
oP r0
14.45-
Abstract_034/
15.00
oP
15.0015.15
ABact_o70/
11
oP 12
Nabilah Amany
Gunawan
Pasaribu
Nikmatul Ikhrom
Eka
lalani.,
Abst-act_
11
5/
oP 13
M.FarmKlin., Apt.
Prof. Dr. Dyah
lswantini,
Antioxidant Biosensor on Superoxide
Dismutas€ from Indonesia Mioobes
M.Sc.Agr
Immobilized in lndonesia Natural Zeolite
15.3016.00
Break
Thin Layer
r6.00-
Atuad.-0zil
16.15
oP 14
16.r5-
Absb-dct_089/
16.30
oP 15
Wahyuni
r6.30-
Absract_099/
oP 16
Abstract_l20/
oP t7
Maximus
M
Taek, M.Si
Hendra Wrjafd,
Dr
Enih
Rosamah, M.Sc
Tatik Raisawati
16.45
15.4517.00
17.0017.15
6
Muntingia cabbura L.
S.Farm.,
15.1515.30
Induced Mutauofl By Gamma Ray fradiation
to Rauwlfia sswntina (L). Benth. ex. Kuz
Ethnomedkjne, Phitochemical, And Toxiticy
Actiw Of Several Medicinal Plants From
Sebangau Natbnal Part, Center Borneo
Etrect of Drying Methods and Age of Leaws
on Total Tannin
T€tona grandis L. and
Affiact_133/
oP 18
17.15-
/rbstract_og3/
17.30
oP 19
Siti Karimah
Dr
Dr.
Chromatographry Fingerprint
Analysis of lati *|c,rfia (Guaatna ulnibliS
Leaves
Wulan
Tri
Molecularly Imprinted FoVmer Modified
Carbon llaste Electrode for Voltamme8ic
Detection of Quercetin
Ethnornedicinal Plants Used for the
Treatrnent of Malaria in Malaka , West Tirnor
Rapid Detection of Squid Allergy Using
le Dipstick
Paddle-
Kno^ring Borneo Medicinal Plants For Skin
Diseases
Msphological of leaves and total flavonoid
gt chus
content
some accessions
of
anens!:s L.
d
11
ORAL PRESENTATION SCHEDULI
Day 1, Thursday, 24 Augnst 2Ot7
fime :14.3O-15.30
Room : Paralel 1 (Ballroom 3)
Talac
Ab.trl(t /
14.30-
Gode
Absfact_oo2/
14.45
@01
L4.45-
Ab6t?ct_004/
oP 02
15.00
15.0015.15
Abstract_046/
oP 03
Muhammad
Thorieq
Karina Citra Fdni,
S.Farm.,
M.Farm., Apt
Muhammad FarirJ
fuzal
BdutidirE: Eel mucus cintrnent as wourd
healinq bErapy
Formulation and Characterization of
AEndol-pqrclodextrin Orally DisintegratirE
TableG
Modified Electro-AcupunctJre Technology
And Standardized Extracts Of Dragon Fruits
As An
Parvovirus
10
15.15-
Ab6tract_090/
15.30
oP 04
Lilis Nurhadijah
Activitis
Immummodulator
of
Formulation
Wistar Rats
Ot
latropha Seed
on the
C-anirn
ard
Pare
Spermatogenesis of
1i
Formulation and Characterization of Atenolol-ftCyclodextrin
Orally Disintegrating Tablets
Karina Citra Ranir', Nani Parfatir, and Stephanier
rDepartment of Pharmaceutics, [Jbaya College of Pharmary, University of Surabay4
Surabaya" East Jav4 60293, Indonesia
PENGESAHAN
salinan/Foto k@i sesuar dsngan adinya
Avanti. M.Si., Apt.
*Corresponding author:
rDepartment
ofPharmaceutics, ubaya colege of pharmacy, University of Surabaya,
Surabay4 East Java, 60293, Indonesia
03 I -298 I I I 0/08 18030/.2202, 03 I _298 I 00
karinacitrarani@staf ubaya.
ac.
id
I
ABSTRACT
Atenolol is an antihypertensive drug and has been widely used in hypertension therapy.
The mechanism of atenolol is antagonist of competitive beta (llselective adregenergic
rec€ptor. Atenolol has a low solubility characteristic in water and gasric fluid. The rate
of
absorpion is often conrolled by the rate of dissolution for poorly soluble drugs. In this sudy,
the solubility of atenolol has been increased by inclusion complex using p-cyclodextrin made
by several methods (physical mixnrg kneading and solvent evaporation). Evaluation
characterization
of
atenolol-p-cyclodextrin inclusion complex mnsists
and
of drug content,
dissolution ,profih, Fourier Transformed Infrared analysis (FT-R), Differential Scanning
Calorimetry (DSC), X-ray Diffraction Q(RD), and Scanning Electron Microscope (SEM). The
results ofthe drug content analysis, dissolution test, and characterization showed that atenolol-
p-cyclodextrin inclusion complex, which has been made by solvent evaporation method was
the best composition. Therefore, a solvent evaporation metiod was chosen to prepare orally
disintegrating tablets of atenolol-p-cyclodextrin using direct compression technique. Orally
disintegrating tablets
of
atenolol-p-cyclodextrin were prepared using crospovidone
as
disintegrant. The results of pre-compression test and post-compression test revealed that orally
disintegrating tablets of atenolol-p-cyclodextrin inclusion complex had gmd physicochemical
characteristics and met quality requirements.
Keywords: atenolol, inclusion complex, p-cyclodextri4 orally disintegrating tablets.
INTRODUCTION
Atenolol is a competitive p(l) -selective adrenergic antagonists and has been widely used
in hypertension therapy. Atenolol is one ofthe most frequently used p-blockers in the treatment
of
cardiovascular disease, because
of its anti-hypertensic and anti-arrhythmic
properties
(Sweetmaq 20O9). Arenolol is slightly soluble in water. The solubility of atenolol in water
(25"C) is approximately 13.3 mg/ml (Sweetmarq 2009; Florey, 1984). Low solubility
characteristic of atenolol in water and gastric fluid caused the bioavailability of atenolol is
about 50plo following oral administration (Sweetman, 20O9). The rate ofabsorption ofthe drugs
which have low solubility characteristic is often controlled by the rate of dissolution (Shargel
and Pong,
2004) The rate of dissolution of low solubility drugs can be increased by several
methods such as decrease the particle size using micronization and nanoparticle techniques,
solid dispersion, salt formatioq co-crystal inclusion complex, etc. (Sinko, 2006; Kumare et
al., 2013). Host-guest complexes are used in the pharmaceutical industry to improve the
bioavailability, masking unpleasant taste, and improve the stability of drugs in aqueous
solutions (Pop et al., 2002; Borodi et al., 2008). As host molecules, commonly cyclodextrins
are used. Cyclodextrins (CDs) are toroidal-shaped cyclic oligomers
glucopyranose units which contribute
to
of
several guests-associated phenomena
o-(l,4fDin solution
@uha et al.,2Ol2). Cyclodextrins are cyclic oligosaccharides formed in 6 (cCD), 7 (pCD), or
8 crcD) (o-l,a)
-finked D-glucopyranose units. cylodextrins with more than eight
glucopyranose units do exist but are
of limited interest as drug solublizers and stabilizers
@ouroumis et d., 2013)
cylodextrins are organic compounds which have cyclic toroidal shaped. The arrangement
of monomers in the cyclodextrin molecules can be described as a ring a doughnut, a cylinder,
or more precisely a truncated cone. The struchre consist of a hy&ophilic extgior and the
hydrophobic exterior. The hydrophobic exterior structure caused by the hydrophobic carbon
backbones
of
of
glucopyranose monomers which construct the structure
p-cyclodextrin
@ouroumis et al 2013; Kurkoy et al.,2Ol2). Because of the cyclic structure of cyclodextrins
molecules, it was proposed that cyclodextrins should entrap a molecules in their cavity (Kurkoy
er al., 2012). Through complex formrition, the solubility
ofthe drugs
can be enhanced.
The results from the previous study stated that p-cyclodexrins has been widely used in the
pharmaceutical industry because ofthe ease of production and subsequent low price (Kurkoy
et al., 2012). The ability of p-cyclodextrins to produce inclusion complex compound is highly
affected by the size, shape, and the hydrophobic nature ofthe guest molecules (Prabhu et al.,
2012). Inclusion complex of drugs with cyclodextrin has been extensively studied due to irs
pharmaceutical interaction.
Tte inclusion complex of drug molecules with Scyclodextrins
cuased modificarion of pharmacokinetic properties of drug molecules such as
(i) increase the
dissolution of low solubility drugs, improves production effrciency, chemical stability, and
bioavailability of poorly water soluble drugs, (iii) caused the reduction of drug toxicity, (iv)
control the release profil ofthe drug. p-cyclodextrin has been widely used in pharmaceutical
technology because ofbig molecular cavities. Intemal cavity of ftcyclodextrin is 6 A. The big
molecular cavity ofp-cyclodextrin increase the possibilities ofthe drug which
in the cavity. In
genera.l, one molecule
of cyclodexrin will trap one
will
be entrapped
molecule
of drug in
cylcodextnn's cavity (Nikolic et d, 2007).
Inchrsio' corylo
B(mK OF PROGNAII
!SN
2017
lnternational Symposium
on Natural Medicines
a!
Sustainable Use of Natural Products for
Human's Health and Welfarea
IF
,:
-'-
--t-
IPB lnternational Coruention Center
24-25 August 2O17
8ogor, lndonesia
!
t ..]
lloclca by:
. Tlltlcel Orftrnra Borcexfi C..tlf lPA
. Icrrblakc Boccarct ClrrCr lPa
r fhe hdmdrn fuc.d.tho o{ NSrd lh{r
neroerdtofr
COMMITTEE
lome (nttp://isn m.lpb.oc.id)
>> Committee
IMPORTANT DATES
Steering Commitee
Dr. lr. Prostowo, MEng (Kepolo LPPN/ IPB)
Abstroct Submission
Prof. Dr. drh Agik Suproyogi (Wokil Kepolo Bidong Penelition
Deodline:
Prof. Dr. lr. lskondor zulkornoin Siregor (Direktur Riset
ff4q-2eF
July
31, 2017
Dr.
AccePtonce Notifi cotio n:
#y24.2017 August
SSl. MSi
Prof. Dr. Erni H Purwoningsih (eernipOo/ut)
Prof. Dr. Bombong eroyogo (eerhipoo/uNatn)
Deodline:
Prof. Dr. Ervizol A.[,4. Zuhud (PA)
lS, 2017
Prof. Dr. drh. Umi Cohyoningsih
lSNM20u Symposium:
August 24
-
Scientific Committee
25. 2017
Prof. Dr. Dyoh lswontini erodono, t',mgr
SEARCH
q
Prof. Dr. Ir. C. Honny Wijoyo, M.Agr (lPB
Prof. Dr. lr. Sondro Arifin Aziz. N/S (pB)
Apt
Prof. Dr. letie Wientorsih,
Dr.
SPONSORED BY:
M.Sc (tpB)
Momon Turjomon, DEA (Puslitbonghut-KLHK)
Dr. Noncy Oewi Yutiono (tea)
Dr.lr. Ninuk Purnoningsih, M.Si (pB)
Drh. Sulistyoni, Ph.D (tpB)
(pB)
Dr. Moto Nuritmoto. M.Si
Novriyondi Honif. D.Sc (tpB)
Orgonizing Commitee:
Choirmon:
Dr.
(https://mohkotodewoi
n
dones
io.co.id/)
Mohomod Rofi, M.Si (pB)
Vice-choirmon:
Rudi Heryonto,
;..l;..lli
(ea)
Prof. lr. Suminor S Achmodi, Ph.D (lPB)
Seorch
S.Si, M.Si
(pB)
Secretory:
e"r."Er g.qlefi
tep'
Susi lndorioni, STp., M.Si (pB)
(nttp://gen ecroft obs.co m/)
I
Treosuren
Solino Febriony,
S.Si. M.Si
Ninik Lestari Ningsih,
SE
(pB)
(pB)
don lnovosi
IPB)
IPB)
(Kepolo Pusot Studi Bioformoko Tropiko
LPPM IPB)
5, 2017
FulFPoper Submission
August
lrmonido Botuboro,
LPPN4
a
lD
a
Secretoriot
BrorenlNDo
Dewi Anggroini s, s.si. v.si (Pe)
o ooo a
FI. RIOFARMAKA INT'ONESIA
(http://biof orin do.in do network.
co.id/)
Titis Arifiono. s.si (PB).
zokio, AMd (PB)
Public Rclotions:
Anonto rusumo, uT (PB)
Dr. Eng. Wisnu
vektor Dewonto,
Dr.
ST,
M.Eng (PB)
otih Rostiono (Bolittro-Kementon)
Drh. zuroido, M.Si (Puslitbonghut-KLHK)
Hero Nurhoyoti, s.P, M.Sc (Bolittro-Kementon)
(nttps://www.buch i.co m/id- n)
i
Publicotions:
Novriyondi Honif, s.si.
Dr. Wulon Tri
HOSTED BY:
N4.sc,
wohyuni,
D.sc (PB)
S.Si., M.Si
(lPB)
Loelo Wulonsori, S.Si (lPB)
?iofua,aaRaaltl e,.u
(nttp:i/biof ormoko.i pb.oc.id/)
$
*n::*:,::';:;'1"".'
Progroms:
Siti So'dioh. s.si, Apt M.Si (PB)
Dr.
Muhommod Nursid, s.si, M.si (psosperP-rrp)
Dr.
Trivodito.
S.Si., rr,l.si
(Pa)
Drh. lnnes Moulidyo (PB)
(http:i/metobolo mics.i pb.oc.i d/
Sponsorships:
)
Rudi Heryonto, S.si. ri,l.si (Pa)
Dr. lr. Nevioty
zomoni, u.sc (ee)
Toopik Ridwon,
S.Si. t'rt.Sl
(Pe)
Drh. okto wismondonu. M.Epid (lPB)
Logistics:
s
Th€
l.rdoe66 As@llir
Antonio Koutsor,
ol NBtu..l Oruqs
Re$eclp.s
(http://www.perh pbo.com/)
i
S.Si (lPB)
sgo rirdous (tee)
Nunuk Kumiqti tt, s.rorm (Pe)
Forhonno Nurozizoh (PB)
M. Yusuf (tPB)
Ahmqd Yoni (PB)
Workshops:
Anggio Murni, s.si (PB)
O All right reserved lSNM20l7
Educotion Bose by Acme Themes (http://www.ocmethemes.com,
ORAL PRESENTATION SCHEDULE
Ilay 1, Thunsday,24 August
Time :14.3O-17.30
2O1 7
Room : Paralel 2 (Meefing Room B)
Prcscnhr & TitiE
Time
14.30-
Abstact_O19/
14.45
oP r0
14.45-
Abstract_034/
15.00
oP
15.0015.15
ABact_o70/
11
oP 12
Nabilah Amany
Gunawan
Pasaribu
Nikmatul Ikhrom
Eka
lalani.,
Abst-act_
11
5/
oP 13
M.FarmKlin., Apt.
Prof. Dr. Dyah
lswantini,
Antioxidant Biosensor on Superoxide
Dismutas€ from Indonesia Mioobes
M.Sc.Agr
Immobilized in lndonesia Natural Zeolite
15.3016.00
Break
Thin Layer
r6.00-
Atuad.-0zil
16.15
oP 14
16.r5-
Absb-dct_089/
16.30
oP 15
Wahyuni
r6.30-
Absract_099/
oP 16
Abstract_l20/
oP t7
Maximus
M
Taek, M.Si
Hendra Wrjafd,
Dr
Enih
Rosamah, M.Sc
Tatik Raisawati
16.45
15.4517.00
17.0017.15
6
Muntingia cabbura L.
S.Farm.,
15.1515.30
Induced Mutauofl By Gamma Ray fradiation
to Rauwlfia sswntina (L). Benth. ex. Kuz
Ethnomedkjne, Phitochemical, And Toxiticy
Actiw Of Several Medicinal Plants From
Sebangau Natbnal Part, Center Borneo
Etrect of Drying Methods and Age of Leaws
on Total Tannin
T€tona grandis L. and
Affiact_133/
oP 18
17.15-
/rbstract_og3/
17.30
oP 19
Siti Karimah
Dr
Dr.
Chromatographry Fingerprint
Analysis of lati *|c,rfia (Guaatna ulnibliS
Leaves
Wulan
Tri
Molecularly Imprinted FoVmer Modified
Carbon llaste Electrode for Voltamme8ic
Detection of Quercetin
Ethnornedicinal Plants Used for the
Treatrnent of Malaria in Malaka , West Tirnor
Rapid Detection of Squid Allergy Using
le Dipstick
Paddle-
Kno^ring Borneo Medicinal Plants For Skin
Diseases
Msphological of leaves and total flavonoid
gt chus
content
some accessions
of
anens!:s L.
d
11
ORAL PRESENTATION SCHEDULI
Day 1, Thursday, 24 Augnst 2Ot7
fime :14.3O-15.30
Room : Paralel 1 (Ballroom 3)
Talac
Ab.trl(t /
14.30-
Gode
Absfact_oo2/
14.45
@01
L4.45-
Ab6t?ct_004/
oP 02
15.00
15.0015.15
Abstract_046/
oP 03
Muhammad
Thorieq
Karina Citra Fdni,
S.Farm.,
M.Farm., Apt
Muhammad FarirJ
fuzal
BdutidirE: Eel mucus cintrnent as wourd
healinq bErapy
Formulation and Characterization of
AEndol-pqrclodextrin Orally DisintegratirE
TableG
Modified Electro-AcupunctJre Technology
And Standardized Extracts Of Dragon Fruits
As An
Parvovirus
10
15.15-
Ab6tract_090/
15.30
oP 04
Lilis Nurhadijah
Activitis
Immummodulator
of
Formulation
Wistar Rats
Ot
latropha Seed
on the
C-anirn
ard
Pare
Spermatogenesis of
1i
Formulation and Characterization of Atenolol-ftCyclodextrin
Orally Disintegrating Tablets
Karina Citra Ranir', Nani Parfatir, and Stephanier
rDepartment of Pharmaceutics, [Jbaya College of Pharmary, University of Surabay4
Surabaya" East Jav4 60293, Indonesia
PENGESAHAN
salinan/Foto k@i sesuar dsngan adinya
Avanti. M.Si., Apt.
*Corresponding author:
rDepartment
ofPharmaceutics, ubaya colege of pharmacy, University of Surabaya,
Surabay4 East Java, 60293, Indonesia
03 I -298 I I I 0/08 18030/.2202, 03 I _298 I 00
karinacitrarani@staf ubaya.
ac.
id
I
ABSTRACT
Atenolol is an antihypertensive drug and has been widely used in hypertension therapy.
The mechanism of atenolol is antagonist of competitive beta (llselective adregenergic
rec€ptor. Atenolol has a low solubility characteristic in water and gasric fluid. The rate
of
absorpion is often conrolled by the rate of dissolution for poorly soluble drugs. In this sudy,
the solubility of atenolol has been increased by inclusion complex using p-cyclodextrin made
by several methods (physical mixnrg kneading and solvent evaporation). Evaluation
characterization
of
atenolol-p-cyclodextrin inclusion complex mnsists
and
of drug content,
dissolution ,profih, Fourier Transformed Infrared analysis (FT-R), Differential Scanning
Calorimetry (DSC), X-ray Diffraction Q(RD), and Scanning Electron Microscope (SEM). The
results ofthe drug content analysis, dissolution test, and characterization showed that atenolol-
p-cyclodextrin inclusion complex, which has been made by solvent evaporation method was
the best composition. Therefore, a solvent evaporation metiod was chosen to prepare orally
disintegrating tablets of atenolol-p-cyclodextrin using direct compression technique. Orally
disintegrating tablets
of
atenolol-p-cyclodextrin were prepared using crospovidone
as
disintegrant. The results of pre-compression test and post-compression test revealed that orally
disintegrating tablets of atenolol-p-cyclodextrin inclusion complex had gmd physicochemical
characteristics and met quality requirements.
Keywords: atenolol, inclusion complex, p-cyclodextri4 orally disintegrating tablets.
INTRODUCTION
Atenolol is a competitive p(l) -selective adrenergic antagonists and has been widely used
in hypertension therapy. Atenolol is one ofthe most frequently used p-blockers in the treatment
of
cardiovascular disease, because
of its anti-hypertensic and anti-arrhythmic
properties
(Sweetmaq 20O9). Arenolol is slightly soluble in water. The solubility of atenolol in water
(25"C) is approximately 13.3 mg/ml (Sweetmarq 2009; Florey, 1984). Low solubility
characteristic of atenolol in water and gastric fluid caused the bioavailability of atenolol is
about 50plo following oral administration (Sweetman, 20O9). The rate ofabsorption ofthe drugs
which have low solubility characteristic is often controlled by the rate of dissolution (Shargel
and Pong,
2004) The rate of dissolution of low solubility drugs can be increased by several
methods such as decrease the particle size using micronization and nanoparticle techniques,
solid dispersion, salt formatioq co-crystal inclusion complex, etc. (Sinko, 2006; Kumare et
al., 2013). Host-guest complexes are used in the pharmaceutical industry to improve the
bioavailability, masking unpleasant taste, and improve the stability of drugs in aqueous
solutions (Pop et al., 2002; Borodi et al., 2008). As host molecules, commonly cyclodextrins
are used. Cyclodextrins (CDs) are toroidal-shaped cyclic oligomers
glucopyranose units which contribute
to
of
several guests-associated phenomena
o-(l,4fDin solution
@uha et al.,2Ol2). Cyclodextrins are cyclic oligosaccharides formed in 6 (cCD), 7 (pCD), or
8 crcD) (o-l,a)
-finked D-glucopyranose units. cylodextrins with more than eight
glucopyranose units do exist but are
of limited interest as drug solublizers and stabilizers
@ouroumis et d., 2013)
cylodextrins are organic compounds which have cyclic toroidal shaped. The arrangement
of monomers in the cyclodextrin molecules can be described as a ring a doughnut, a cylinder,
or more precisely a truncated cone. The struchre consist of a hy&ophilic extgior and the
hydrophobic exterior. The hydrophobic exterior structure caused by the hydrophobic carbon
backbones
of
of
glucopyranose monomers which construct the structure
p-cyclodextrin
@ouroumis et al 2013; Kurkoy et al.,2Ol2). Because of the cyclic structure of cyclodextrins
molecules, it was proposed that cyclodextrins should entrap a molecules in their cavity (Kurkoy
er al., 2012). Through complex formrition, the solubility
ofthe drugs
can be enhanced.
The results from the previous study stated that p-cyclodexrins has been widely used in the
pharmaceutical industry because ofthe ease of production and subsequent low price (Kurkoy
et al., 2012). The ability of p-cyclodextrins to produce inclusion complex compound is highly
affected by the size, shape, and the hydrophobic nature ofthe guest molecules (Prabhu et al.,
2012). Inclusion complex of drugs with cyclodextrin has been extensively studied due to irs
pharmaceutical interaction.
Tte inclusion complex of drug molecules with Scyclodextrins
cuased modificarion of pharmacokinetic properties of drug molecules such as
(i) increase the
dissolution of low solubility drugs, improves production effrciency, chemical stability, and
bioavailability of poorly water soluble drugs, (iii) caused the reduction of drug toxicity, (iv)
control the release profil ofthe drug. p-cyclodextrin has been widely used in pharmaceutical
technology because ofbig molecular cavities. Intemal cavity of ftcyclodextrin is 6 A. The big
molecular cavity ofp-cyclodextrin increase the possibilities ofthe drug which
in the cavity. In
genera.l, one molecule
of cyclodexrin will trap one
will
be entrapped
molecule
of drug in
cylcodextnn's cavity (Nikolic et d, 2007).
Inchrsio' corylo