ORIGINAL RESEARCH PAPER

TITLE:- A study on In Vitro Interaction of Cephradine ith !an"o #uice at $oer pH

%ony &a$$i'(
)epart!ent of Phar!acy* +GC Trust ,ni-ersity +an"$adesh* Chitta"on"
E!ai$: #ony!a$$i'.y!ai$/co!
&o0i$e No/ 12234253466676

A+STRACT
Cephradine is a first generation semi-synthetic cephalosporin antibiotic, is widely used in clinics for its activity
against both Gram-positive and Gram-negative bacteria. It is indicated for the treatment of urinary tract
infections, skin and skin structure infections, respiratory tract infections and otitis media. Interaction of
cephradine with mango juice were investigated by U-spectrophotometer in simulated gastric juice !p"
#.$%&.$'. In this research work, cephradine capsules were collected from drug shops. (he samples were
analy)ed according to *ritish +harmacopoeia !*+' method &. In this work in vitro dissolution studies were
carried out in ,--ml of acidic buffer !p" #.$%&.$' in a dissolution tester with a speed of .# rpm at &/0-..1C for
si2 hours. (he absorbance was measured by using U-spectrophotometer at a 3ma2 of $.4nm. Compare with
the absorbance of drug and the drug in presence of mango juice simulated gastric juice !p" #.$%&.$'. (he drug
release kinetics was also measured. It is observed from the drug release profile that, there is no significant
difference in the drug release curve of p" #.$%&.$.
Key Words:- Cephradine, U-spectrophotometer, 5issolution, 6ango juice.
INTRO),CTION
7oods and therapeutic products are both used for well defined purposes. In simple terms food provides energy for
sustenance, while therapeutic products are taken for managing ailments $.
"owever, over the years roles of foods have changed considerably. 8ow, food no longer is seen as simply the
provider of energy, but it is e2pected to provide physiological benefits for good health and productive lifestyles.
9ell managed combination of foods and therapeutic products plays important role in the prevention and
treatment of many diseases, including a number of chronic diseases such as cancer, diabetes, hypertension,
obesity. 6ost often food is combined with medicine to enhance the benefits of medicine - an additive and:or
synergistic effect; food-therapeutic product synergism. <t the most basic level, food is a comple2 mi2ture of
chemicals with many functional groups= hence, they not only confer positive effects, but may also make negative
contributions.
Cephradine is in a group of drugs called cephalosporin antibiotics. Cephradine fights bacteria in the body.
Cephradine is used to treat infections caused by bacteria, including upper respiratory infections, ear infections,
skin infections, and urinary tract infections >. Cephradine may also be used for other purposes not listed in this
medication guide. Cephradine is the most commonly used antibiotic for prophyla2is in orthopaedic patients as it
is safe and effective. 9e report a case of severe anaphylactic reaction to Cephradine in an elderly patient who had
no history of allergic reactions to any drugs until then.
?+@<8A is currently the most well known household name among the millions of people in *angladesh and
abroad also. Bince its inception in #,C-, +@<8 Group has grown up in stature and became the largest fruit and
vegetable processor in *angladesh. It also has the distinction of achieving prestigious certificate like IBD
,--#;$---, and being the largest e2porter of processed agro products . +@<8 is the pioneer in *angladesh to be
involved in contract farming and procures raw material directly from the farmers and processes through state of
the art machinery at our several factories into hygienically packed food and drinks products. (he brand ?+@<8A
has established itself in every category of food and beverage industry and can boost a product range from Euices,
Carbonated 5rinks, Confectionery, Bnacks, and Bpices. 4


8i"ure 4: Le0ac9 :Cephradine; Capsu$e 8i"ure 7: &an"o %uice :8rooto;
&ATERIALS < &ETHO)S
8eature of Cephradine standard

Cephradine !compacted powder'
+otency; ,,.#4F
GD5- 4 F! 86('
Drigin; China
Collected from; +harmik Gaboratories Gtd.
Rea"ents used in this or'
#. "ydrochloric acid,
$. Bodium hydro2ide,
&. Citric acid,
4. +ottasium chloride,
.. 5i-sodium hydrogen orthophosphate,
>. +otassium di-hydrogen orthophosphate.
(hey were all of analytical grade. Dne brands of cephradine capsule and the innovator brands with labeled
contents of .--mg each were obtained from retail pharmacies in Chittagong city. (he samples were checked
for their production and e2piry dates before purchasing.
Instru!ent ,sed in this &ethod
#. Hlectric balance
$. U- Bpectrophotometer
&. 5issolution <pparatus
4. (hermometer
.. p" 6eter
)ISSOL,TION RATE )ETER&INATION
(his was determined using the +harma (est 5issolution @ate (esting <pparatus !6odel 5->&.#$, "ainburg'.
(hese studies were conducted at &/0-..
-
C on an UB+ specification dissolution rate test type II apparatus !+addle
apparatus' with si2 section assembly according to the UB+ IIIII procedure with minor modification :,SP ==II
and N8 =>II* 4??@;/
7or in vitro dissolution studies simulated gastric medium !p" #.$ % &.$' and simulated intestinal medium !p"
>.C' were reJuired.
Preparation of si!u$ated "astric !ediu!:pH 4/7;
#---ml buffer solution with p" #.$ $.- ml of -.# 6 "Cl solution was taken in #---ml beaker and .--ml -.#6
"Cl solution were added into the #---ml beaker. <djust the p" #.$ with adding distilled % demineralised water
respectively. <fter adjusting the p" of the buffer solution the buffer solution were taken into#---ml volumetric
flask.
Preparation of si!u$ated "astric !ediu!:pH 5/7;
#---ml buffer solution with p" &.$ $.- ml of -.# 6 "Cl solution was taken in #---ml beaker and .--ml -.#6
"Cl solution were added into the #---ml beaker. <djust the p" &.$ with adding distilled % demineralised water
respectively. <fter adjusting the p" of the buffer solution the buffer solution were taken into#---ml volumetric
flask.
)isso$ution study state!ent
(he dissolution study of Cephradine!GebacK' were investigated firstly in the presence of tap water and then
same investigation were performed in the presence of buffer solution p" #.$ prepared by using both distilled and
demineralised water. (he dissolution study were investigated in the presence of buffer solution p" &.$ prepared
by using demineralised water.
(he dissolution study of Cephradine!Gebac' were investigated in the presence of $.-ml mango juice!+ran
7rooto' and >.-ml of buffer solution p" #.$. <gain dissolution study of Cephradine !GebacK' were investigated
in the presence of $.-ml mango juice >.-ml of buffer solution p" &.$.
)isso$ution study description
<ccording to the statement every time two capsules are places in the baskets, where one basket contain the the
drug !cephradine capsule form' and another basket contain the drug with mango juice. 7irst time drug was placed
in tap water and demineralised water. "ere one drug was placed in tap water and another was in demineralised
water. 8e2t time a drug was placed in buffer with p" #.$ and another was in combined solution of $.-ml mango
juice and >.-ml buffer p" #.$.again a drug was placed in buffer with p" &.$ and another was in combined
solution of $.-ml mango juice and >.-ml buffer p" &.$.again. (he operation in the acid stages were carried out
for > hours.(han the dissolution apparatus are switched on and the temperature was &/LC and the rpm was .#.<t
every time interval .ml solution were taken into test tube and the volume adjust by fresh media.(he time interval
were followings;-
-min, .min, #-min, $-min, &-min, 4.min, >-min, ,-min, #&.min, #,.min, $C.,min, &>-min !upto > hours'.
7rom the test tube of each,#ml were taken into #--ml volumetric flask and it is diluted to #--ml with buffer.
(han it was filtered, taken into cell and the released drug was assayed by using U spectrophotometer at $.4nm.
RES,LTS < )ISC,SSION
(he absorbances of standard Cephradine solution under a concentration range of # to #-Mg:ml !-.--# to
-.-# mg:ml' where the average of Concentration : <bsorbance were also calculated to determine the release
kinetics. 5ata are shown at Ta0$e 4 /
Ta0$e 4:
Conc :!"A!$; A0sor0ance Conc AA0sor0ance A-era"e
-.--# -.-/$ -.-#&CCCCC,
-.--$ -.#-$ -.-#,>-/C4&
-.--& -.#C$ -.-#>4C&.#>
-.--4 -.$>4 -.-#.#.#.#.
-.--. -.&#. -.-#.C/&-#>
-.--> -.&C/ -.-#..-&C/> -.-$##C$>->
-.--/ -.4$& -.-#>.4C4>&
-.--C -.4,C -.-#>->4$./
-.--, -..4& -.-#>./4.C>
-.-# -.>## -.-#>&>>>#$
8i"ure 5 : Btandard Curve of Cephradine !blue line' represents the measured absorbance were plotted
against the respective concentrations of the standard solutions which give a straight line in the
concentration range of # to #-Mg:ml !-.--#--.-# mg:ml'.
)isso$ution test of Cephradine in presence of #uice:7@3!$; in PH 4/7:B@3!$;
(he dissolution test of cephradine in presence of juice were conducted % collect the absorbance of the
dissolute solution after every . minutes. <ll the respected value are shown at Ta0$e 7
Ta0$e 7.
Ti!e:!inutes; A0sor0ance Ct C re$ease C Re!ain
$o" of C
re!ain
- -.-#$ -.---C#C. #.4/&&/C& ,C..$>>$#>4 #.,,&..&.,$
. -.-$# -.--#4&$4 $../C4#$# ,/.4$#.C/C/ #.,CC>..$-4
#- -.-& -.--$-4>& &.>C&44., ,>.&#>..4# #.,C&/--,&>
$- -.-4. -.--&->,. ...$.#>CC ,4.4/4C&##4 #.,/.&#>#$4
&- -.-># -.--4#>-,& /.4C,>/&&& ,$..#-&$>>> #.,>>#,-$#4
4. -.-C -.--.4.>,. ,.C$$.$$4 ,-.#//4//., #.,..-,C-C&
>- -.#.> -.-#->4#- #,.#.&,#C C-.C4>-C#& #.,-/>.C,/4
,- -.#.$ -.-#-&>C$# #C.>>$/,$ C#.&&/$-/4$ #.,#-$C,$.C
#&. -.##$ -.--/>&,/ #&./.#.&# C>.$4C4>C>$ #.,&./.#&,&
#,. -.-/> -.--.#C4# ,.&&#&,>$ ,-.>>C>-&/# #.,./4.>,$C
$C. -.-,C -.-->>C4/ #$.-&$.C, C/.,>/4#--. #.,44&$#C->
&>- -.#C, -.-#$C,$-># $&.$-./-,$ />./,4$,-C #.CC.&$C,&4
7orm the table it is found that percent release of the drug is increased upto ,- minutes and than decreased
again by time. <s well as the concentration of drug in e2perimental medium. "ence the percent remain and
log of percent remain decreased. (he graphical presentation of rate kinetics are shown at 8i"ure 6 * @ * B
respectively.

8i"ure 6 : 8i"ure @ :
Nero order plot of release kinetics of Cephradine 7irst order plot of release kinetics of Cephradine



8i"ure B: "iguchi plot of release kinetics
Re$ease para!eters of cephradine capsu$es in presence of #uice:7@3!$; in PH 4/7:B@3!$;
Para!eters Dero order 8irst order Hi"uchi

RE

3/@6@754B5F 3/6FF2FF4?7 3/2757BBFB
(he @-sJuared value is highest in case of "iguchi release kinetics
)isso$ution test of Cephradine in presence of #uice:7@3!$; in PH 5/7:B@3!$;
(he dissolution test of cephradine in presence of juice were conducted % collect the absorbance of the
dissolute solution after every . minutes. <ll the respected value are shown at Ta0$e 5
Ta0$e 5
Ti!e:!inutes; A0sor0ance Ct C re$ease C Re!ain
$o" of C
re!ain
- -.--4 -.---$/$C4 -.4,##$>#$# ,,..-CC/&CC #.,,/C>#C##
. -.-#C -.--#$$/C# $.$#-->/.4$ ,/./C,,&$4> #.,,-$,4#4>
#- -.-$/ -.--#C4#/ &.&#.#-#&#4 ,>.>C4C,C>, #.,C.&.C>4>
$- -.-&, -.--$>>-$> 4./CC4/,>/. ,..$##.$-&$ #.,/C>C,.
&- -.-.C -.--&,.>$, /.#$#&$C/4C ,$.C/C>/#$. #.,>/,#.,,4
4. -.->/ -.--4./-$- C.$$>&>$.#, ,#.//&>&/4C #.,>$/#/,4.
>- -.-C# -.--..$.#> ,.,4.&-&,4# ,-.-.4>,>-> #.,.4.->&>.
,- -.#-# -.-->CC,4- #$.4--,&4.4 C/..,,->.4> #.,4$4,,4/&
#&. -.#$4 -.--C4.C$C #..$$4,-,/4 C4.//.-,-$> #.,$C$>C$>#
#,. -.#4C -.-#--,.& #C.#/#>>>4> C#.C$C&&&.4 #.,#$,-&/-/
$C. -.#>$ -.-##-.-&& #,.C,->-/CC C-.#-,&,$#$ #.,-&>C&4&>
&>- -.#/$ -.-##/&$4. $#.##C4$&#C /C.CC#./>C$ #.C,>,/..C&
7orm the table it is found that percent release of the drug is increased by time. <s well as the concentration
of drug in e2perimental medium. "ence the percent remain and log of percent remain decreased.


8i"ure F : 8i"ure 2 :
Nero order plot of release kinetics of cephradine 7irst order plot of release kinetics of cephradine

8i"ure ?: "iguchi plot of release kinetics
Re$ease para!eters of cephradine capsu$es at in presence of #uice:7@3!$; in PH 5/7:B@3!$;
Para!eters Dero order 8irst order Hi"uchi

RE

3/2B3723F?5 3/5FBF2F@2 3/??342274
(he @-sJuared value is highest in case of higuchi release kinetics
)eter!ination of re$ease !echanis! fro! corre$ation coefficients :R
7
; :
7rom the drug release data of cephradine in presence of mango juice were treated in different kinetics orders
such as Nero Drder +lot, 7irst Drder +lot and "iguchi +lot and their correlation coefficients were determined
to identify their release mechanism.
Ta0$e 6 : Corre$ation coefficients deter!ination data for pH 4/7
Sa!p$e corre$ation coefficients :R
7
;
Nero order 7irst order "iguchi
Cephradine -.,>#,,#.>4 -.&>/&.-C&C -.,$.>.$,,$
Cephradine1&an"o #uice -..4.$&#>&/ -.4//C//#,$ -.C$&$>>/>
7rom ta0$e 6 it is seen that Cephradine in presence of 6ango juice at p" #.$.Indicates that the Correlation
Coefficients was close to # in case of "iguchi plot than Nero Drder and 7irst Drder Oinetics. Bo "iguchi
release kinetics predominates in simulated gastric medium of p" #.$.
Ta0$e @ : Corre$ation Coefficients deter!ination data for pH 5/7
Sa!p$e corre$ation coefficients :R
7
;
Nero order 7irst order "iguchi
Cephradine -.C.>&$#-C& -.#/.>&->-# -.,>>4,&.&&
Cephradine1&an"o
#uice
-.C>-$C-/,& -.&/>/C/.C -.,,-#CC$#
7rom ta0$e @ it is seen that Cephradine in presence of 6ango juice in simulated Gastric medium at p" &.$
indicates that the Correlation Coefficients is close to # in case of "iguchi plot that Nero Drder and 7irst
Drder kinetics. "iguchi release kinetics predominates in simulated gastric medium of p" &.$.
CONCL,SION
(he percent release data suggest that, in the simulated gastric medium !p"#.$ % &.$', the percent release of
Cephradine not increased significantly. It is also seen that in different p" the percent release neither
increased nor decreased when Cephradine is taken with the 6ango juice. 7rom the Correlation coefficients
determination data it is seen that, Correlation Coefficients !@
$
' is close to # in case of "iguchi plot. Bo
"iguchi release kinetics predominates in simulated gastric medium of p" #.$ % &.$.
It is also observed from the release kinetics profile !Nero order, 7irst order, "iguchi', both of the line are
close to each other and there is no significant distance between two line. *oth of the line appear in between
--$- percent of drug release. "ence, we can say that on the basis of our present study if the patient take
Cephradine and 6ango juice at a time, no harmful effect will occur.
ACGNOHLE)GE&ENT
I am greatful to the +harmik Gaboratories Gtd. for providing the Btandard sample of Cephradine for my research
work
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