469469469

Volume 13. Number 1. May 2012 (Spring)

The Pacific Journal of Science and Technology
http:/ / ww w . a k amaiun i er !i ty .u ! /" # S$.ht m
Studies on the Micromeritic Properties of Ibuprofen Microcapsules.
I.O. Adeleke, M.Sc.
1*
; I.S. Okafor, Ph.D.
1
; and . Alebio!u, Ph.D.
"
1
%a&ulty o' "harma&euti&al S&ien&e!( )nier!ity o' #o!( Nigeria.
"
%a&ulty o' "harma&y( *ba'emi +wolowo )nier!ity( ,le-,'e( Nigeria.
.-mail: ioa/elek e0 yahoo.&om
*
A#S$%A&$
,bupro'en mi&ro&ap!ule! were prepare/ by
&omple1 &oa&eration pha!e !eparation te&hni2ue
u!ing gelatin an/ grewia gum a! &oating
material!. 3elatin-a&a&ia gum wa! u!e/ to
mi&roen&ap!ulate ibupro'en a! !tan/ar/ 'or
&ompari!on. Mi&ro&ap!ule! were prepare/ with
the ratio o' 1:1 &ore: wall. Mi&romeriti& !tu/ie! o'
the two bat&he! o' ibupro'en mi&ro&ap!ule! were
&arrie/ out. $he 'low rate( angle o' repo!e( bulk
/en!ity( tappe/ /en!ity( true /en!ity( 4arr5! in/e1(
6au!ner ratio( an/ mean parti&le !i7e o' ea&h o'
the bat&he! o' mi&ro&ap!ule! were !tu/ie/. $he
!tu/ie! !howe/ that the mi&ro&ap!ule! prepare/
u!ing gelatin-grewia gum gae e1&ellent
'lowability( an/ !maller parti&le !i7e in &ompari!on
to that o' gelatin-a&a&ia gum mi&ro&ap!ule!.
(8eywor/!: 3rewia( gelatin( a&a&ia( &omple1
&oa&eration( mi&ro&ap!ule!( mi&romeriti&)
I'$%OD(&$IO'
,bupro'en i! a non-!teroi/al anti-in'lammatory
/rug whi&h al!o ha! analge!i& an/ antipyreti&
a&tiitie! (My&ek et al.( 2000). $he /rug i!
pra&ti&ally ery !lightly !oluble( but it i! rea/ily
ab!orbe/ 'rom the ga!trointe!tinal tra&t. $hi! /rug
&au!e! irritation o' ga!tri& mu&ou! membrane. ,t i!
al!o un!table to light. 6en&e( mi&roen&ap!ulation
o' the /rug in a polymeri& !hell woul/ be o'
a/antage to the!e /rawba&k!.
$he u!e o' new natural hy/rophili& polymer! a!
/rug &arrier! ha! re&eie/ &on!i/erable attention
in re&ent /e&a/e! (9emunan-:ope7 an/
;o/meier( 1<<=). 3rewia gum i! a poly!a&&hari/e
gum /erie/ 'rom the inner !tem bark o' e/ible
plant Grewia mollis #u!!. (%amily $ilia&eae). $he
plant i! a !hrub abun/ant in the !aannah region
o' >e!t +'ri&a. $he leae! an/ bark o' the plant
&ontain gum. ,n Nigeria( the /rie/ an/ puleri7e/
inner !tem bark o' the plant! i! u!e/ a! a
thi&kening agent in !ome lo&al /i!he! (*ka'or
an/ 4hukwu( 2003).
3rewia gum i! one o' the gum! that hae
potential appli&ation in pharma&euti&al
'ormulation!. $he gum i! reporte/ to be
&ompatible with many /rug! an/ e1&ipient!
(*ka'or et al.( 2001). $he i!olation( &hemi&al
&ontent!( phy!i&o&hemi&al an/ rheologi&al
propertie! o' the gum ha! been reporte/
el!ewhere (*ka'or et al.( 2001). +l!o the bin/ing
property( me&hani&al propertie!( water apor
permeability o' the gum 'ilm a! well a! the
in'luen&e o' granulating !olent! on /rug relea!e
'rom tablet! &ontaining grewia gum hae been
reporte/ (*ka'or et al.( 2003? *ka'or et al.( 200@).
;ut( no report ha/ been gien on the appli&ation
o' the gum in mi&roen&ap!ulation.
Seeral kin/! o' preparation! !u&h a! tablet!(
&ap!ule! an/ &oate/ pellet! hae been
!ugge!te/ 'or u!e a! oral e1ten/e/ relea!e
'ormulation!. ,n or/er to 'ormulate /rug pow/er
into the!e /o!age 'orm!( it i! ery important to
a!!e!! it! 'low propertie!. $he phy!i&al( &hemi&al
an/ pharma&ologi& propertie! o' a /rug are
a''e&te/ by the !i7e( !ur'a&e area an/ !ur'a&e to
olume ratio o' a /rug parti&le. "arti&le !i7e o'
material u!e/ in 'ormulation o' !u!pen!ion(
emul!ion! an/ tablet! i! o' great importan&e.
+l!o( the /i!!olution rate o' /rug pow/er! an/ it!
!tability i! greatly a''e&te/ by the parti&le !i7e
/i!tribution (*7ya7i&i( 1<<=).
$he aim o' thi! work i! to ine!tigate the e''e&t o'
mi&roen&ap!ulation pro&e!! on the
&ompre!!ibility an/ &ompa&tibility o' ibupro'en
pow/er u!ing gelatin-grewia gum in &ompari!on
to that o' gelatin-a&a&ia gum. 6en&e( the 'low
rate( angle o' repo!e( bulk /en!ity( tappe/
/en!ity( true /en!ity an/ mean parti&le !i7e o' the
mi&ro&ap!ule! were /etermine/. $he !u!taine/
relea!e /o!age 'orm! &an be obtaine/ by either
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Volume 13. Number 1. May 2012 (Spring)
The Pacific Journal of Science and Technology
http:/ / ww w . a k amaiun i er !i ty .u ! /" # S$.ht m
tableting the mi&ro&ap!ule! or 'illing the!e
mi&ro&ap!ule! into har/ gelatin &ap!ule!.
$here'ore( the 4arr5! (&on!oli/ation) in/e1 an/
6au!ner ratio o' mi&ro&ap!ule! were &al&ulate/ in
or/er to /etermine the 'low ability o' the
mi&ro&ap!ule!.
MA$)%IA*S
,n thi! e1periment we utili7e/ the 'ollowing:
3elatin bloom 2AB (granular) type + (%i!her
S&ienti'i& 4ompany( 4hemi&al Manu'a&turing
Cii!ion )S+)( grewia gum (pro&e!!e/ in our
laboratory) /i!tille/ water( 10D a&eti& a&i/(
!o/ium hy/ro1i/e( <BD ethanol (;C6 4hemi&al!(
.nglan/ )( 'ormal/ehy/e 3AD (Sigma +l/rei&h
:t/.( .nglan/)( a&a&ia gum (pro&e!!e/ in our
laboratory)( an/ ibupro'en (Mallin&kro/t
4hemi&al! ,n&. )S+).
M)$+ODS
Prepar a tion of Ibupr o fen M icroca p su les
$he metho/ o' "almieri et al. (1<<=) wa! a/apte/.
+ &ertain amount o' the ibupro'en pow/er wa!
in&orporate/ into a 2Dw/ 3rewia gum !olution at
@0
o
4. $hen an e2ual olume o' ED w/ gelatin
/e!ire/ temperature (-@A to 22

4)( the !pe&imen

&hamber re'rigeration wa! !wit&he/ o''( leaing
only the &on/en!er re'rigeration running. *n&e
the &on/en!er &hamber temperature wa! below -
30

4( the a&uum pump wa! !wit&he/ on. +!

apor went o'' 'rom the pro/u&t!( it 'orme/ a!
'ro!t on the !i/e! o' the &on/en!er &hamber.
6eat going into the pro/u&t &au!e/ the i&e to
!ublimate or apori7e. +ll the i&e in the pro/u&t!
eentually boile/ o''. $he /rie/ pro/u&t wa! then
&olle&te/ an/ analy7e/.
M icro m er itic Stud ies
$he bulk /en!ity a! well a! the tappe/ /en!ity o'
ea&h o' the bat&he! o' mi&ro&ap!ule! were
/etermine/ u!ing a mea!uring &ylin/er? while the
true /en!ity wa! /etermine/ u!ing a li2ui/
py&nometer with kero!ene a! the /i!pla&ement
'lui/. $he 'lowability o' the mi&ro&ap!ule! wa!
in/i&ate/ by the angle! o' repo!e( 4arr5!
(&on!oli/ation) in/e1 an/ 6au!ner ratio. $he 'low
rate o' the mi&ro&ap!ule! wa! /etermine/ u!ing
an .rweka 'low meter( while the angle o' repo!e
wa! ealuate/ u!ing the 'i1e/ height metho/.
%urthermore( 4arr5! in/e1 wa! &al&ulate/ u!ing
the e2uation:
Tapped density Bulk density
!olution at @0
o
4 wa! a//e/ to the !u!pen!ion an/
the !y!tem wa! &ontinually !tirre/. $he 'inal ratio
between the /rug an/ the two polymer! wa! 1:1.
$hi! new !u!pen!ion wa! then /ilute/ with pre-
Carr' s Index =
Tapped density
X 100
,1-
warme/ (@0
o
4) /i!tille/ water. +'terwar/( the p6
o' the !y!tem wa! a/Fu!te/ with 2D !o/ium
hy/ro1i/e to gie a p6 o' @.B with &ontinuou!
!tirring 'or 30 min!. at @0
o
4. @ ml 'ormal/ehy/e
>hile 6au!ner5! ratio wa! &al&ulate/ u!ing the
e2uation:
Tapped density
(3AD w/) wa! a//e/ with &ontinuou! !tirring 'or
30 min!. $he !y!tem wa! then &oole/ rapi/ly to @-
B

4 by !ubmerging the beaker &ontaining the

Hausner' s ratio = Bulk density
,"-
mi&ro&ap!ule! in an i&e bath. $he !upernatant
wa! /e&ante/ an/ the mi&ro&ap!ule! were 'iltere/
an/ 'ree7e- /rie/.
.re e / e 0d r 1 in 2
+n S;@ 'ree7e-/rying ma&hine (4rawley(
.nglan/) wa! u!e/ 'or thi! pro&e!!. $he
&oa&erate wa! 'iltere/ an/ !hare/ into "etri
/i!he!. $he!e "etri /i!he! were pla&e/ in the
!pe&imen &hamber o' the S;+ ma&hine. $o
'ree7e the pro/u&t!( the !pe&imen &hamber
re'rigeration button wa! pre!!e/ on the &ontrol
panel. >hen the pro/u&t! were 'ro7en to the
$he Stu/ent t-te!t wa! u!e/ to analy7e the
re!ult! obtaine/.
Part ic le S i/ e A na l 1 s is
"arti&le !i7e analy!i! wa! &arrie/ out to
/etermine the granulometri& /i!tribution an/
mean parti&le !i7e o' the mi&ro&ap!ule!. +
&ertain amount o' the mi&ro&ap!ule! wa!
weighe/ into .n/e&ott! !tainle!! !teel te!t !iee!
o' the 'ollowing aperture !i7e (e1pre!!e/ in
mi&rometer!) 1E00( 1000( A10( B00( 32B( 1E0(
1B0( 10=( an/ <0 mi&rometer aperture!.
471471471
Volume 13. Number 1. May 2012 (Spring)
The Pacific Journal of Science and Technology
http:/ / ww w . a k amaiun i er !i ty .u ! /" # S$.ht m
%)S(*$S A'D DIS&(SSIO'
$he mi&romeriti& propertie! o' the mi&ro&ap!ule!
are !hown in $able 1.
$able 13 Mi&romeriti& "ropertie! o' ,bupro'en
Mi&ro&ap!ule!.
Properties re!ia4elatin
Ibuprofen
Microcapsules
Acacia4 elatin
Ibuprofen
Microcapsules
%low rate (g/!e&) 2.E@=0 G 0.021 1.B1A0G 0.0<0
+ngle o' repo!e
(/egree!)
33.00 G 0.132 2E.33 G 0.=B3
;ulk /en!ity (g/&m
3
) 0.1AEA G 0.00A 0.1=A0 G 0.001
$appe/ /en!ity
(g/&m
3
)
0.1<E@ G 0.00B 0.1A0< G 0.002
$rue /en!ity (g/&m
3
) 1.0@23 G 0.013 1.03EE G 0.0@0
4arr5! in/e1 <.<3 2.2<
6au!ner ratio 1.11 1.02
Mean parti&le !i7e A<0 1200
$he mi&romeriti& propertie! o' mi&ro&ap!ule!
pre!ente/ aboe in/i&ate that the mi&ro&ap!ule!
pro/u&e/ u!ing 2D w/ grewia gum an/ ED w/
gelatin a! well a! 1D w/ a&a&ia( an/ 1D w/
gelatin a! &oating material yiel/e/ mi&ro&ap!ule!
with goo/ 'low propertie! /ue to the 'a&t that their
angle o' repo!e were 33
o
an/ 2E.33
o
( re!pe&tiely.
+! a general rule( pow/er with angle o' repo!e
greater than B0
o
ha! un!ati!'a&tory 'low propertie!
(+ulton( 1<<<). )!ually( the parti&le !i7e o'
mi&ro&ap!ule! i! larger than that o' raw material!?
hen&e the 'low property o' the /rug i! improe/ by
mi&roen&ap!ulating it. 6oweer( in or/er to
a!!e!! whether thi! improement woul/ be
enough 'or pro/u&ing gelatin &ap!ule! an/ tablet!
'rom the mi&ro&ap!ule! with the ne&e!!ary
amount!( the 4arr5! (&on!oli/ation) in/e1 an/
6au!ner ratio o' the mi&ro&ap!ule! !houl/ be
e1amine/.
Mi&ro&ap!ule! &ontaining grewia gum an/ gelatin
po!!e!!e/ !igni'i&antly (" H 0.0B) higher 'low rate
than tho!e ma/e with a&a&ia an/ gelatin.
$he alue! o' 6au!ner5! ratio an/ 4arr5!
&ompre!!ibility obtaine/ 'or the mi&ro&ap!ule! are
in &on'ormity with their 'low rate!. ;oth the 4arr5!
in/e1 an/ 6au!ner5! ratio in/i&ate e1&ellent an/
goo/ 'low re!pe&tiely (+ulton( 1<<<? *7ya7i&i(
1<<=). )!ually( the parti&le !i7e o' mi&ro&ap!ule!
i! larger than that o' raw material!? hen&e the 'low
property o' the /rug i! improe/ by
mi&roen&ap!ulation. $he bulk /en!ity o' ibupro'en
mi&ro&ap!ule! &ontaining grewia gum an/ gelatin
i! 0.1AEAg/&m
3
. $hi! i! !igni'i&antly (" H 0.0B)
higher than the bulk /en!ity o' 0.1=A0g/&m
3
obtaine/ 'or ibupro'en mi&ro&ap!ule! when
a&a&ia an/ gelatin were u!e/.
$he &oa&erating !y!tem &ontaining grewia gum
an/ gelatin (2 an/ ED w/) i! higher than the
!y!tem in whi&h a&a&ia an/ gelatin were u!e/
(1D w/ ea&h). $hi! may be re!pon!ible 'or the
high bulk /en!ity obtaine/ 'or the /rug in the
!y!tem &ontaining grewia gum an/ gelatin. So
al!o i! the tappe/ /en!ity. ;oth bulk an/ tappe/
/en!itie! a''e&t the pa&king &hara&teri!ti&! o'
pow/ere/ material (+ulton( 1<<<). ,n&rea!e in
tappe/ /en!ity i! a/antageou! in tabletting an/
en&ap!ulation be&au!e o' re/u&e/ 'ill olume.
$he parti&le !i7e o' material! i! another property
that a''e&t! the pa&king &hara&teri!ti& o' the
material!. $he mean parti&le !i7e obtaine/ 'or
ibupro'en mi&ro&ap!ule! &ontaining grewia gum
an/ gelatin i! A<0 Im. $he &orre!pon/ing mean
parti&le !i7e o' mi&ro&ap!ule! ma/e with a&a&ia
an/ gelatin i! 1200 Im. $he!e !i7e! are within
the range o' !i7e o' mi&ro&ap!ule! reporte/
el!ewhere (8umar( 2000). ,t &oul/ be !een that
the a&a&ia an/ gelatin &oa&erating !y!tem
pro/u&e/ a higher parti&le !i7e o' the /rug than
that &ontaining grewia gum an/ gelatin. "arti&le
!i7e a''e&t! 'low rate!( angle o' repo!e( bulk an/
tappe/ /en!itie! an/ the relea!e &hara&teri!ti&!
o' granule!( tablet! an/ &ap!ule! (+ulton( 1<<<).
$he re!ult! o' the parti&le !i7e analy!i! &arrie/
out to /etermine the granulometri& /i!tribution
an/ mean parti&le !i7e o' the mi&ro&ap!ule! i!
re'le&te/ in the graph! below.
120
100
E0
=0
@0
20
0
1E0 3E0 BE0 AE0 <E0 11E0 13E0
Particle diameter ,5m-
.i2ure 13 4umulatie "er&ent *er!i7e !.
"arti&le Si7e 'or ,bupro'en Mi&ro&ap!ule!
&ontaining 3rewia 3um an/ 3elatin.
&
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@A2
Volume 13. Number 1. May 2012 (Spring)
The Pacific Journal of Science and Technology
http:/ / ww w . a k amaiun i er !i ty .u ! /" # S$.ht m
10B
<B
EB
AB
=B
BB
@B
10=
.i2ure "3 4umulatie "er&ent *er!i7e !.
"arti&le Si7e 'or ,bupro'en Mi&ro&ap!ule!
&ontaining +&a&ia 3um an/ 3elatin.
&O'&*(SIO'
$he re!ult! obtaine/ 'rom thi! work in/i&ate that
3rewia gum whi&h i! more e&onomi&al an/ rea/ily
aailable &ompare/ to a&a&ia woul/ be aluable in
mi&ro en&ap!ulation o' /rug! pow/er! that are
inten/e/ 'or preparation o' gelatin &ap!ule 'ill an/
tablet pro/u&tion. $hi! i! /ue to the 'a&t that
!imilar re!ult! were obtaine/ 'or grewia/gelatin
mi&ro&ap!ule! a! well a! a&a&ia/gelatin
mi&ro&ap!ule!.
A&8'O9*)D)M)'$S
$he author! wi!h to thank the /epartment o'
"harma&euti&!( %a&ulty o' "harma&y( *ba'emi
+wolowo )nier!ity( ,le-,'e 'or it! a!!i!tan&e in
giing a&&e!! to the po!t-gra/uate "harma&euti&!
laboratory( a! well a! the 4entral S&ien&e
:aboratory o' the !ame in!titution 'or the u!e o'
!ome o' it! e2uipment.
%).)%)'&)S
1. +ulton( M... 1<<<. Pharmaceutics: The Science of
Dosage form Design. Ninth Edition. 4hur&hill
:iing!tone: :on/on. 2@A( =10.
2. 8umar( 9.V. 2000. JNano an/ Mi&roparti&le! a!
4ontrolle/ Crug Celiery Cei&e!K. J. Pharm. Sci.
3(2): 23@-2BE.
3. My&ek( M.#.( 9.+. 6aey( an/ ".4. 4hampe. 2000.
J+nti-,n'lammatory Crug! an/ +uta&oi/!K. ,n:
:ippin&ott an/ >illiam!. Lippincotts !llustrated
"e#iews Pharmacology. $Second Edition% @0E.
A. *7ya7i&i( M.( S. %erhan( an/ .. 3okhan. 1<<=.
JMi&romeriti& Stu/ie! o' Ni&ar/ipine 6y/ro&hlori/e
Mi&ro&ap!ule!K. !nternational Journal of
Pharmaceutics. 13E: 2B-3B.
E. "almieri( 3.%.( S.M. Cario( an/ ". >ehrle. 1<<=.
J3elatin-+&a&ia 4omple1 4oa&eration a! a
Metho/ 'or 8etopro'en Mi&roen&ap!ulationK. Drug
De#elopment and !ndustrial Pharmacy. 22(<L10):
<B1-<BA.
<. 9emunanM:ope7( 4. an/ 9. ;o/meier. 1<<=.
J.''e&t o' %ormulation an/ "ro&e!! Variable! on
the %ormation o' 4hito!an-3elatin 4oa&erate!K.
!nternational Journal of pharmaceutics. 13B: =3-
A2.
A#O($ $+) A($+O%S
Dr. I2natius S1l6ester Okafor, i! a "ro'e!!or o'
"harma&euti&! at the )nier!ity o' #o!( #o!(
Nigeria. 6e ha! oer 20 year! o' re!ear&h an/
tea&hing e1perien&e.
Dr. ben2a Alebio!u i! an +!!o&iate "ro'e!!or
o' "harma&euti&! at the *ba'emi +wolowo
)nier!ity( ,le-,'e( Nigeria. 6e ha! oer 20 year!
o' re!ear&h an/ tea&hing e1perien&e.
Mrs. Ibukun Olanre!a:u Adeleke, hol/! a
Ma!ter! /egree in "harma&euti&al $e&hnology.
She ha! oer 1B year! o' pro'e!!ional e1perien&e
in pharma&euti&al pra&ti&e.
S()S$)D &I$A$IO'
+/eleke( ,.*.( ,.S. *ka'or( an/ 3. +lebiowu.
2012. JStu/ie! on the Mi&romeriti& "ropertie! o'
,bupro'en Mi&ro&ap!ule!K. Pacific Journal of
Science and Technology. 13(1):@=<-@A2.
"a &i 'i& # ournal o' S & ien &e an/ $ e& hno l o g y
&
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7
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@. *ka'or( ,.S. an/ +. 4hukwu. 2003. J$he ;in/ing
"roperty o' 3rewia 3um ,,: Some "hy!i&al
"ropertie! o' So/ium Sali&ylate $ablet!K. &est
'frican Journal of (iological Sciences. 1@: <-21.
B. *ka'or( ,.S. an/ ,.M. Canat( ,.M. 200@. J$he
,n'luen&e o' 3ranulating Solent! on Crug
9elea!e 'rom $ablet! &ontaining 3rewia 3umK.
Journal of Pharmacy and (ioresourses. 1(1):A=-
E3.
=. *ka'or( ,.S.( +. 4hukwu( an/ *.8. )/eala. 2001.
30= B0= A0= <0= 110=
Particle diameter ,5m-
JSome "hy!i&al "ropertie! o' 3rewia 3umK.
Nigerian Journal of Polymer Science and
Technology. 2(1):A=-E3.