Majalah Ilmu Kefarmasian Majalah Ilmu Kefarmasian
Volume 9 Number 3 Article 4
12-30-2012
Preparasi, Karakterisasi dan Evaluasi Pelepasan Obat dari Beads Preparasi, Karakterisasi dan Evaluasi Pelepasan Obat dari Beads Kalsium Alginat Deksametason dengan Metode Gelasi Ionik Kalsium Alginat Deksametason dengan Metode Gelasi Ionik
Christye Aulia
Fakultas Farmasi Universitas Indonesia Kampus UI Depok Joshita Djajadisastra
Fakultas Farmasi Universitas Indonesia Kampus UI Depok, [email protected]
Follow this and additional works at: https://scholarhub.ui.ac.id/mik
Part of the Natural Products Chemistry and Pharmacognosy Commons, Other Pharmacy and Pharmaceutical Sciences Commons, and the Pharmaceutics and Drug Design Commons
Recommended Citation Recommended Citation
Aulia, Christye and Djajadisastra, Joshita (2012) "Preparasi, Karakterisasi dan Evaluasi Pelepasan Obat dari Beads Kalsium Alginat Deksametason dengan Metode Gelasi Ionik," Majalah Ilmu Kefarmasian: Vol. 9 : No. 3 , Article 4.
DOI: 10.7454/psr.v9i3.3351
!
"# # !$%
& $" & $"
& "
'()*+,-./012*34/56+(*,3/783839*+3+,)3 :3;12,3+/:3)<3+*/=>*?.)+*,3+/@>96>.+*3 A3<B1+/C3)1/=@4/7.B6;4/DEFGF
HIJKLHMK
NOPQRRQSTUVWXTYZ[W\]^ZQ^ZW_NX\`W]^WQWa]^ZQ^ZWTbW]OPQRRQS]TOW]OWScZWdT[TOeWfQUgZSZaW aZ[]hZUVW^V^SZR^WbTUWScZWSUZQSRZOSWTbWNX\W]^WaZ^]gOZaWSTW]OdUZQ^ZWScZWaUigWdTOdZOSUQS]TOW]OW ScZW[TdQ[WS]^^iZeW\ZjQRZScQ^TOZW]^WQWaUigWcQh]OgWQOS]k]OPQRRQSTUVWQOaWQOS]lmUT^]^WZnZdS^W Yc]dcW]^Wi^ZaWSTWUZoQ]UW^dQUWS]^^iZWQU]^]OgWbUTRWoT^SToZUQS]hZWNX\eWp]^WUZ^ZQUdcWoiUoT^ZWSTW dUZQSZWdQ[d]iRQ[g]OQSZWmZQa^WaZjQRZScQ^TOZWSTWmZWUZ[ZQ^ZaWTO[VW]OWScZWdT[TOeWXZQa^WYZUZW RQaZWmVWi^]OgW^Ta]iRkQ[g]OQSZWQOaWqQrsWQ^WdUT^^[]OtZUWmVW]TO]dWgZ[QS]TOWRZScTauWY]ScW UQS]TWmZSYZZOW^Ta]iRWQ[g]OQSZkaZjQRZScQ^TOZW_vwx`eWyWdTOdZOSUQS]TOWTbW^T[iS]TOW^Ta]iRW Q[g]OQSZWvWzWm{hWY]ScWhQU]QS]TOWdTOdZOSUQS]TOWTbWdUT^^[]OtZUW]^WrzW_bTURi[QWx`uWvzW_bTURi[QW r`uWQOaW|zW_bTURi[QWv`eWXZQa^WYZUZWdcQUQdSZU]}ZaWQOaWaUigWUZ[ZQ^ZWaZSZUR]OZaeWpZWUZ^i[S^W TmSQ]OZaWYZUZW^ocZU]dQ[WmZQa^WY]ScWQW^]}ZWUQOgZWmZSYZZOW~vWkWRWY]ScWScZWgUZQSZ^SW ZOdQo^i[QS]TOWZd]ZOdVWTmSQ]OZaWbUTRWScZWmZQa^WbTURi[QWxWY]ScWScZWQRTiOSWTbWex|zW QOaWQ ZUWdTQSZaWY]ScWiaUQg]SWxWi^]OgWQWPi]aWmZaWaUVZUWQooQUQSi^uWmZQa^WTbWbTURi[QW
|WYQ^WTmSQ]OZaWY]ScWQOWZOdQo^i[QS]TOWZd]ZOdVWTbW~uzeWXZQa^WbTURi[QWxWYZUZWTO[VWUZk [ZQ^ZaW]OW^STRQdcWoWQOaWOTSWQm[ZWSTWcT[aWioWScZWUZ[ZQ^ZWTbWScZWQdS]hZW^im^SQOdZW]OWdT[TO]dW ouWYcZUZQ^WmZQa^WTbWbTURi[QW|WUZ[ZQ^]OgWaZjQRZScQ^TOWgUQaiQ[[VWRTUZWScQOWWcTiU^W]OW dT[TO]dWouWQOaWcQ^WQWmZSSZUWUZ[ZQ^ZWoUTl[ZWbTUWScZWQdS]hZW^im^SQOdZeW
qQ[^]iRkQ[g]OQSZWmZQa^WdT[TOWaUigWaZ[]hZUVW^V^SZRWaZjQRZScQ^TOZWZiaUQg]SW
xW]TO]dWgZ[QS]TOe
ZOVQt]SW]OPQRQ^]Wi^i^WQSQiWNOPQRRQSTUVWXTYZ[W\]^ZQ^ZW_NX\`WRZUioQtQOWoZOVQt]SW oZUQaQOgQOWVQOgWSZUQa]WoQaQWtT[TOeW]^SZRWoZOgcQOSQUQOWVQOgWa]SQUgZStQOWiOSitWoZOgTk mQSQOWNX\Wa]UQOdQOgWiOSitWRZO]OgtQStQOWtTO^ZOSUQ^]WTmQSWoQaQWQU]OgQOW[TtQ[eW\Zt^QRk ZSQ^TOWRZUioQtQOWTmQSWVQOgWRZR][]t]WZbZtWQOS]W]OPQRQ^]WaQOWQOS]lmUT^]^WVQOgWaQoQSWa]k giOQtQOWiOSitWRZRoZUmQ]t]WQU]OgQOWoQUiSWVQOgWS]Rmi[WoQ^dQWToZUQ^]WNX\eWZOZ[]S]QOW]O]W mZUSiiQOWiOSitWRZRmiQSWmZQa^WtQ[^]iRkQ[g]OQSWaZt^QRZSQ^TOWVQOgWcQOVQWa][ZoQ^WoQaQW tT[TOeWXZQa^Wa]miQSWRZOggiOQtQOWOQSU]iRkQ[g]OQSWVQOgWa]^QRmiOgW^][QOgWaZOgQOWqQrsW qTUUZ^oTOa]OgWQiScTUwWT^c]SQeaQQa]^Q^SUQVQcTTedTR
 ¡0¢£¤¥£¦¦¤
§¨©¨ª¨«¡ª¬¡®¯°¨±¬¨²³¨´µ¡¶·ª¡¸¡ ·¡¤¡¹¯²¯¬º¯±¡»¼0»½¡0»0¡¥¡0¾1
!"#$##%
&'()*+,##%- $#'.$/00# % #112$$- 2.&3#)*!'.&3#2*!4.
&3#'*+5-6$ # #0""$7#
0#+8-"#6$ $-6"#$$# ##9':%;<::
=+>?"@#"#$#"#6#$3#)-$#A<!)4.
6#BC):: D$#-#"#% 6$3#4?"@#"$#9E!E<.+53#)6-
$#3#$"6""F 36"8 !%
$3#4"#?""-$6$ #""
F 3""87#$#6"$#6<@"8 + GHIHJKLMNOJP5 %Q Q#BC)::QQ"6%
#$## +
RS6"# TU5V#1#%W$
XYZ[\]^_^\Z
` abcdefgh`gciejekg`lklk`ehel`mciejn jehopd`qorbs`tgkbekb`umvwx`hbpjeklf`
ybcdefgh`zpo{c`tec`fosghgk`lskbpehg|` uzoprgc}`~x`gctefec`qbte{`lchlf`
ybcoqehec`mvw`teyeh`jbcdbqeqfec`hbpn qbchlfcde`epgcec`yeplh` sb{`fepbce`
ghl}`ybcdefgh`gcg`kbqegfcde`tgoqehg`tbcec`
kgkhbj`ybc{echepec`oqeh`hbphepbh`yete`
qegec`kybkgf`gkhbj`ybc{echepec`
dec`tghepbhfec`lchlf`ybcoqehec`gcg` tgpecec`lchlf`jbcgcfehfec`fockbcn hpekg`oqeh`kbepe`sofes`tbcec`tokgk`dec`
sbqg{`pbcte{`tgqectgcfec`tbcec`ybjn qbpgec`kgkhbjgf`upgbct}`~1x`bpeyg` ybcdefgh`zpo{c`tec`fosghgk`lskbpehg|`dec`
jbcdbpec`pbfhlj`ehel`pbfhokgjogt}` teyeh`tgoqehg`tbcec`fophgfokhbpogt`dec`
qbfbpe`sofes`uva }`~x`
` abcbsghgec`kbqbsljcde`jbcbceg`oqeh` echgqpohgf`lchlf`ybcoqehec`epgcec`
yeplh`yeke`oybpekg`ybcdefgh`mvw`defcg` tbcec`ybchofkgsgc`dec`tg`bcfeyklsekg` tesej`qbetk`fghokecnaa`uepgj}`~0~x` qbetk`feskgljnesgceh`uhejg}`~0~x` qbetk`gcf`ybfhgcehnfghokec`qbslj`teyeh`
jbce{ec`ybsbyekec`oqeh`es`gcg`tgfepbn cefec`ybchofkgssgc`jbplyefec`oqeh`dec`
seplh`tesej`egp`dec`jbjgsgfg`fbjlcfgn cec`qbkep`lchlf`qbptg|lkg`tepg`jehpgfk`kbn {gce`etecde`ybcbhpekg`egpec`fb`tesej`
jehpgfk`jbcdbqeqfec`jehpgfk`jbcbjn qec`tec`jbcesejg`bpokg}`efgqehcde`oqeh` teyeh`gflh`sbyek`tepg`jehpgfk`tec`seplh`bn segc`ghl}`|efhop`dec`teyeh`jbcdbqeqfec`
ybsbyekec`oqeh`dec`byeh`etese{`flpec`
kbjylpcecde`ypokbk`bcfeyklsekg`dec`
hbpqbchlf`ubqpgecgke}`~0~x` sb{`fepbce`
ghl`yete`ybcbsghgec`gcg`tgqleh`qbetk`tbfn kejbhekoc`tbcec`jbclcefec`esgceh` dec`tghelh`kgsec`tbcec`ze~`jbseslg` jbhotb`bsekg`gocgf`abjgsg{ec`tbfkejn bhekoc`kbqeeg`oqeh`yete`hbpeyg`yeke`
oybpekg`mvw`lchlf`jbc{ekgsfec`|opjlse`
qbetk`feskgljnesgceh`tbfkejbhekoc`dec`
teyeh`jbcochpos`ybsbyekec`tbfkejbhen koc`yete`fosoc`jbcgceh`fbseplhec`tbfn kejbhekoc`dec`hgtef`seplh`egp
` abclceec` yosgkefepgte` kbqeeg` jehpgfk`hbse{`qecdef`tglcefec`lchlf`
ybcepbhec`oqeh`tg`lklk}`{es`gcg`tgfepbcen fec`fbhbpkbtgeec`dec`slek}`kg|ehcde`dec`
!"#$%
&'%' #$$'!(%) '!%*%'+,'$ *%-!#
./#0012234' %'$5' '%#%%' #'# '#'#%'#$%%#) '%6%$&'789+:;(!8<<123
=%'%* $ '&&>%!+%)
# %% %23?!'%)
#'#%#%&%%%'@$) %%%&%%#'%&>$!% 5$'$&$$&&$%'#%' '&''@#%') % %$' %$'&$)
#%$$' $ $+/$( ' 8<0023>% # %!!$ @*
%%$#$ %'&
&>08AB1% %@ ##%&%%%
$*%( # &#(%$$%
&%%%*%%*'$ '@&&>C1+D@%%.E$
8<<023E$*% '$ '%%
'F?0<<##'$$%6) $&&$%'%*3
G @ %&%'%% %' # '
$ #$ )%' #$'$%
%%'$%#*%&' &$#%%# #%##') $$'!&$#$ )%'#)
$'$%$ %$$ !$ ' 'F?0<<3
HIJKLI MNOPQ
G%%%'#+:''G2
$*%%8C)R+G S&%2
&% #%'#+/T=S%2$(%)
%%('%($(&+SS?:)1U0<
VW/%$2'$ $'&$#'+X() '2*#%+D'$(!S%2$&#) '5''YW)W$+?!Z 01<<
S&%2'#+=Y?=2&>
'+X '(!10<?%& 2$%'5 $ +T 'S&%2[ *+=)
"/%$2%')'$3
\O]O^Q
4' %'+_ (!5E(!
E3W3E%2#$'$%+`G3T a2 'F?0<<+X6%#S%2
`XRC<<<#$ #+:(#S)
%2$#+:(#S%2#) !%5$5'+:(#S%2
%' !#$+:(#S%2 b $'%$'+&!
`G3E'(/%%$2$'%+?!%
E)'(!%7!%2/$&&#!
+:(#S%23
cdedfgheidf f f f jklmnOPO^Q\kOopQqONprnlsMNtr^OPQuk^s tO^on^tQvkwpOlkPOpx^
E$#$ )%'*%%%) %#$'$% '%%' $%#3?@ !#$'$%&)
%%%Uy0'!&%' )%' $&$#%& '%%' ) %'Uz{6# %!%#%3 V '%'$ '''$#%% %)
#%$*%%8CR# ) '%#$ #+8zUzBz{62
%%#(&'%&% #%8<<&
$*%'%' ##%$01
%'3?%@ '%*$&$!#%
'%%$%%% %#%
b %$'3E$*%'! '%' ##%#%&$ ! # +81|723
!"# $%&
!'
( )*+,-(.+/-012(+/304+5(,*.-+2*5+-64(
7+43(5*/+8(,0.*9043.+4(,0-+/15(,*43+4(
:6/02*9(*1,9+305;(<0==>(/+915+4(:*47+/15( ,0?1+5(,+90(@+2:19+4(*1,9+305;(<0==>( ABC(D===(-*?+3+0(:/+-50E0-*9>(5+/.(-*95+(
:*/+915(@+2:19+4(,+90(+-*564>(0-6:96:0/( +/.686/(,+4(+F1+,*-5G(<*/+4H1547+(:96-*-(
:*47+/15+4(?*+,-(.*9043(,0/+.1.+4(,*4I 3+4(2*43314+.+4(+/+5((J10,(?*,(,97*9G ( ( ( (
K%K LM NOPQRSTUVPTWXYZX[X\]TNOVU^
( )*451.(,+4(269_6/630(:*921.++4(
?*+,-(,+:+5(,0+2+50(,*43+4(2*4331I 4+.+4(+/+5(`aVPP]P\Tb[OaQYXPTW]aYX^aXcOT d<BefG
g]^QY]hR^]TiSRYVPTjVYQ]SO[TNOVU^TkiP]QOUT
`QVQO^TjlVYmVaXcXO]V[TnXPoOPQ]XPpTqrrst ( u0-590?1-0(1.19+4(?*+,-(,0*v+/1+-0(
,*43+4(+7+.+4(?*95043.+5(d-0*v*(-8+.*f(
?*91.19+4(=>2=w(=>Dxw(=>1=w(=>x01(22(
7+43(,0-1-14(-*@+9+(2*41914(,+90(1.1I 9+4(/1?+43(+7+.+4(:+/043(?*-+9G(
jOPOPQRVPTyVUVYTz]Y
( {+,+9(+09(,05*451.+4(2*43314+.+4(
+/+5(260-519*(@645*45G(
b|^]OP^]TjYX^O^
B}-0*4-0(:96-*-(,05*451.+4(,*43+4(2*2I
?+4,043.+4(?6?65(565+/(?*+,-(.*9043(7+43(
,0:*96/*8(5*98+,+:(565+/(?+8+4(7+43(,031I 4+.+4(:+,+(-++5(:*2?1+5+4(?*+,-G(u080I 5143(2*43314+.+4(:*9-+2++4(~
( i]TyVPURP\VPThVQpTb|^]OP^]TjOP
OYVcVPpTi]TWOP\OmhVP\TUVPTboV[RV^]T jO[OcV^VPThVQTUVY]TNOVU^T^OaVYVTPT]QYX
<*?*/1247+(,0/+.1.+4(:*2?1+5+4(-:*.I 5912(-*9+:+4(,+4(:*4*451+4(:+4H+43(
3*/62?+43(2+.-0212(,*.-+2*5+-64(
{6,*(6921/+( +59012(+/304+5 {+/-012(./690,+ +I/304+5~( u*.-+2*5+-64(
+.51(-+2?143(-0/+43
df df d2*405f
0 x  x(~(0 01
 x x x(~(0 01
x x  x(~(0 01
(6921/+-0(?*+,-(.+/-012I+/304+5(7+43(2*43+4,143(,*.-+2*5+-64
6921/+-0(/+915+4(:*47+/15
)+8+4 df
B1,9+305;(<0== G
ABC(D=== 1
+/. 0
-*564 =
F1+,*-5 0=
-6:96:0/(+/.686/ 1
!0"#"
$$%!&"'(!)"'*+( ,% -, %( % ,%(.((..((
% $%% /0102(..1
%( ((345,6*
789:;<=>?=@<=:A<B:CDB9E:><=:FGH9I=H9: JI=8IK<L<=
M%(%((.(N ( 0''"'.,1' %( $$%!)"'(..(((1 ..(%(.(N%(O''
2(..,(%,(P2(N * +3(%0"' %(% 1 ,%, 1'"N(
-(3(.( %( $$%
!)"'2(... ,%, * Q ((3 (.((..((
% $%% /0102%(.
R((P (*
SR((P (,%2%(.(.1 .(( (T
789:UI=@IVW<=@:
/P(.,(.($1 3(.R((P (
% ,*/P(((.(N 1 (1'.,-3(.
, 3(., ,3(!X
!0"#Y $$%!&"'Y(
$$%!)"',(31"1 ((% -Z%01"O'"[1"&'"2'"
0#'"01'"0\'(%%,(., %,
% ,%*]((.,(.,21
%(.(.((..(( T
^_`ab`cdefgagh`c`iejk`lecgm`n`eoiepdlnq S-(N (-% 1
%(%((.(%%3(.*
(..(( '"0 r!0"#Y $$%!&"'(!
)"'*03(..((1 ,(32''2O)Xs'"1X"
(.(N%((.(0'' * t (N , (P%( 3(#P!0"##P
!&"'(0P!)"'(
% 2!&"'((.1
%(2(..%(2,% 1 *
M%,(.0''"'.,(
(1
*u%(,%(.1 (.%Z%
% %(%3(01"O'"[1"&'"#&"2'(
0#'(%
'"0r!0"#"(P%((.%(# P(01"O'"[1"&'"#&"2' (0#'(% $$%!&"' (P%(30Pv01"O'"[1"&' (%w $$%!)"' (!&"'2(..% (*
t(.,(-,(30' ( ((3(.(
(..((%% $%% /01 0*
xyzo{e|y}ef^~yxyzy}
     
  
.(%3(., %1 (,%(.(((% %( .(%O,- (%1 ,%(,1.(%
3(.(2/%v#'0#w(%
2(%(3(.N% %%(3 (.(2( ,(%,,%3(.N%*t ,%(,.(( ( %(%(P(,2Z
!"#$%
"&$' '&"' '&"
" '&% (
)&'0 )&'* )&'+ ,-./-012(3"" 4&'
5678-9:;-71 <6-=>1 ?-9>@:.AB9C@7-;1 D6E>-.6;->F71=67C-71G:=0-C@;H1I2JJ 3"'&% "&
"K!
$4&'0L"' "
&'&'"MN022
$&' ' '$ % (O' &%
'P'"$""' '&%
#' $#
"#$"4&'Q(
?-0-E;60@>->@1<6-=>
RSTUVWXYZTX[\]^\_\`aXRSZYb
c!Nde$""'' '4%
&'0"4&'Q&'
#' "$"4&'0
&&K!% $(c!"'' '&#
$"$ ' &4"
$"$'&"'"#' ( fg'"Nde' '4%
&'0&&# $ '$"
h"'g"$
022i"&'" ( j'"&'$"
&"$k22i&'%
$ '"
$""l"#"
"'' %
&(O&'$"
" h!&"
$+222i"k222i&' %$" '"&
""$&'$"(
1,-./-01mn3"'& "&
#"' o4&'Qp
!"#$%&' ())&*&0++,'')&-"#
*"#*./&*"
"#*&"&))&'#.0 #&#)&%).')&%"
/&).".##*&
#1''##*-)."-2 .'")*)&'#*
#&#'')&%"2
#'*03'))&*&
4+++,5+++,"&-"*-6*
."-"&"70++''# )&'#.*--#&"#
*&)%&08)&"#."&9
#&)&%)."./)"#2
*"))&&&)")2
&))&%)."0
:;<=>;?@<;ABC@>DEAFD>=;CGHAIGDJ<
K#&*."&*"#"
)&-%-#&9&'.2
#1))"#
9&'*&#&41L.''#2 '"&*&+1(5''1'##&
""#*-*&&+1(5'' *&*-'9*-*&"
"&9%##&.%
#'.'#'"&#"&2
"0-'#"#%"&
%#'*'*
#'')&-#&*.
"&*"#1'#))&*#&
."&*"#"#"&M#0 N&*-#&*.*-*&
')#"-)&%).".#2 )$%&'(0#&#
*'')'*-*%*%"2 ')&%)."&"7 0++1-#&**&"'*-
*&0O&*#&)&"#* ."#'19)&-%- )&%)'*"1'-)"
)&%)&0
PQ
P/Q
P*Q
PQ
RSTUSVWXYW!#&%$%"%&$ !*#'2"#'"%$%&'00N&*&ZPQ0++,1P*Q 5++,1P/Q[+++,PQ5+++,0
!"#$%&%'%($&)*+!),-)#.-"/01.("2'),#-0,'-%2)"-./')+/$("'3)*044)&%$0/.)56)) 7,$,-$2)8))0449:));449:))24449)2));44496
<=>=>?@>ABCD
) E-".)F,0,$"#-2)#$)"$)$")&%$1 0/.)0)-,,-$)G:41)H4:42)I:)&%$0/.)2) -,,-$)G:1)H4:0;)I))2)&%$0/.)J)-,,1 -$)04:45)H)4:4;)I:)0,2/2K/##2)LM) F,2"2(#'2)2".")#$)"$)',$K")#$,2) F,0#"2)L2)F,0,2'/#),-)N2() ,$-"&')L"($%-#%F"-)N#2")F%."0,$).("2') 2)#.-"/0)#.%$")-,L"2((),-)N2() ',$,2'/#)0,0"."#")#,00F/2)/2'/#) 0,2N,$F)#,.,02)0,2K").,"L),1 -$6)OK")#$)"$)&%$0/.)5)0,2/2K/##2) 2".")N2().,"L)$,2L)-,,-$)P:02H4:02) I)#$,2)-,.0)F$%-,-)F,2N./'2)"(/1 2#2)."$2)/$)F2-)N2()0,0/2(1
#"2#2)#2/2(2)"$).0),-)L".2() 2)#,0/"2),-)',$.F"-")%.,L)F%."01 ,$)F,2N./')N2()-"&'2N)#/$2()L"$%Q.6
RSTUVWXYZX[WXU\W]U^_]T`UYWXUabcTdXcTU edXSdfWgWX
) E-".)/K")#2/2(2)h')#'"&)2) ,Q-",2-")F,2K,$F2)".#/#2)-,',.L) ',$.,"L)L/./)0,2,2'/#2)F,$-02) ($"-)h')-'2$)6)E-".)/K")#2/2(2)h')
#'"&))0,2/2K/##2))&%$0/.)0)0,0"."#") 2".")#2/2(2)h')#'"&)2),Q-",2-") F,2K,$F2)-,,-$)25:;5)I))2)GP:05) I:)&%$0/.)2)-,,-$)2J:02)I)2)G2:5G) I)2)&%$0/.)J)-,,-$)22:1i)I)2) G4:1i)I6)j"."),Q-",2-")F,2K,$F2)N2() /#/F),-$)"F,$%.,L)$")F,2((/22) F%."0,$1%'),2(2)F,$2"2(2)J80) -,L"2(()F%."0,$)F')0,2K")0'$"#-) N2()00F/)0,2K,$F)%'),2(2)"#6) k")-0F"2()"'/)#$,2)-"&'),#-0,'-%2) N2()'"#).$/').0)-"-',0)0'$"#-)0,1 2N,#2)%')',$"-F,$-")-,$)0,$1 ')2)',$."2/2(").0)0'$"#-)'2F)
!!"#!$%
$&&#'(
)' !!"'
*$+$'!+%
"%,-'' !.
!"#01/012'*$+.
$#13/342/$'$%
$5!#',!6'
#''5!+'!$!
#'5,,#$.
,#'! !!"
5!'$!$'$,#'. (
789:;<=><?@A=>
B+,,#"%,0'. $'!,',##'$CD0/EF 1/G'3/GH#,$C
&/'$!'!$'$C
#$#''$!,,#(C
I,+$,#
#'"%,0#,,#$' ,',#'$,#,. ,,!+'$'$C3/G(
),##',.!
#!'$!%, '%!,()'!$J%
!,',','$"%"!#!. '%,'!KLL.
$'$$%,%!!()'
!$+!5$,#!+' '"%,'$$%. %%!5,5##5
$!!!#%M'!+'
$!,',',#'(DN/
O'PO!/EG0GH(O'
$',',,!'!+'$,.
#5*CQ'
CK,,$%!%#%. !!'!+'$%.
!%!!(
RSATUAV9:W<T<XAVA=:Y@AZ:[A\9::]<A[V:^ATV9_ U?_`T>9=AZ:a<bVA?<ZAVc=
B+$$',!%',
#''&#+! ',!'%!$
#!/',,',,%'$C 0/E,E+,#,$C ,#,''+!' ,','$"%"!$C1/G,E+,
#,$''%','++. ,'$"%"!$C3/G,0+,
#,$','5!. '+!$',$C%% 5$',','$"%"!$C1/G #!'%(),. '$C,','J!+$$ !!"&I!%!#!'%'.
$!!"'$C.
&/',!!$$ !
!"''%%(d%,,', 5'#50GG,$' 23eG/1%K/'&$!0GG
$,(
C+$$ !!"&
I!%'#'"%,0Df,#3H ,,$!#J,$'$C ,#5,',,%'$C 0/E$$',!%5,.
&$02/-02/'##%' /$!,!%#!',!, ,!',',!%5!. '$'!'!',,!/ ',,$,!!,.
$$ !!"()',', ,%'$C0/E#'!',.
,$,#5*
'+,,#$' ,',CK$C0/E#!
#'!!$!'%#!5!+$ ',,!!!(g'.
$$$5!+'#' ,$,%"', !!"5
!""#!"!!$%&!"
#!'(!!
"!#!!&''!'"!
$%()#*
+)!$%"!,!
-#%(%.1/0
!#!!&-) ! 010!!"!)!$%
!23/214/#!
#%(%.3/0)!$%
!22/124*5! )#-
!"'!" #(!"
'!"!')#)"! (!-"#)!"!
"!!!"!.*6 !""
#.1/0$%)#
!"!# !'!")
!"'!"!!()#'-)!!
"!()*
5! )7)#(,) )!(!'%(
#)0 #' 8' )#)"!(!!"!
'!!"!()('9:;0<# )%!!#!')#
##! !)!(' ()(!*=)!-#!&)#!!
&)#!!""!'%(#) 29'&!")##">6000<! 7)#(,))!$% !7(*
+(,)#-)!$%! 7('%(#)29?'1<
) !' 8#
)(.0/@)! (!&!"-!")&!
!&@/AA4) @-/#!
"#))!!&!!"
#%(%.1/0! 03/214) @-))# #%(%.3/0!20/11
4) 0-!!' )1-)#%(%
.1/0 !""!21/004*+
#!'%(#)2&!")' )#!'!&'('!
!"!%(#)0!!&(
!&)#!&!"! )6B=
'(!'#&!""!,!
#!')!
!)!$%*+((&!"
) ##() )!!&)#/ !" '#!&# )' !""-(
!"'!"!!%#$%*C)
!!&%(#)2$%&!"
)#.0/@)''!
!"!%(#)0!#!
#!#!"'!"-"
#)#.1/0*6 #!&()!#)- "!,!.3/0!"!"
%()#">6000&!"!
!"#!#()#.3/0
!#!(,))!$%%(
#)2 #' 8)!-#"
-.1/09#(!#
!--#!#< )!-! (!&)#!&!"#!"
!""'"!!#
#!'&!"')#)#
#!!!-) '"
##)'&!"# !!&''!)!$%*6 )!-#!&##%(%
.3/0()!&)#'#) ()#!"#"#'()
#">6000!")(!!
#!$%!()#/
!#!-#) $%&!")# )''!&()(!9.1/0<*D %)#' !' ! )1-*
!"#
$%"&%&!%"'(0))*
#!"+"! ,-".
$%#"+#""#"%%. !*
&0/!+ #+"%%" "&!0"
11/)2/)3 456789:;<=>
#& # "&*%"
% %""
%+"#&#$%+*
"!#&%"!&&!! 1?)*@A))B3C,""0!!*
#!"! +!"#. !&0
$"&#!DA/0EF%+
"&"! +#. !&E*
%,""0!#!12/2AF3 G. !&0+$#!".!"
#&&+
-".+"%%"1 /%
#. !&E"""! ,
$%#"+#"!- ".""1 H!#!+ #!+A0"1 * 3
I<JK<L><M:<=
GNOPQ3R))D3STUVWXYZVW[\X]^_YZ]`Ya b[VTYc]STdVTeb[Y]fS^`Sg]hiij3kNCP*
NO/lm(%&%( 3n!3 l !o"Cn3R))D3p\q\]bYq\]rYZVsb[VcVt[]
ud[b[]vw!#"G&&k ! Cxl3n!3
y#!""z3R)0R3{WerYWYb[]dYT]qYWYqa ZeW[bYb[]_eYdb]|[Tq]reqZ[TYZaq[ZVbYT]
XeTtYTd\Tt]reTZVqb[scc[Tw}!* y!"*yOQ~Q3} 3 y!"}P3R))23zo !"!$$*
. !! .Q !$
# o"3dYTed]] W\t] ec[eW]
e[eb/22RRE2R123
Q"H&PQ/3R)003O !" "* %" H "#!&%
H!!"!. ! !""!" .H!*
# "!!" H+!H!"* -" 3w{wpw][w]p\ccw]eW[eb]p/2?3 k!"O3R)0R3{eX_\YZYT]dYT]qYWYqZeWa
[bYb[]_eYdb]q[ZVbYT]]ZW[rVc[UVbUYZ]f{{g] XeTtYTd\Tt]reTZVqb[scc[T]deTtYT]Xea ZVde]tecYb[][VT[qw}!y!"* yOQ~Q3} 3
k+O(/(!"+!Gk/(!"+~3R)0)3 } &" .1*
"H! #. !H !*
%"%3STd[YT]V\WTYc]VU]{YWXYe\Z[a
Yc][eTebw]2R00A*R?3
O!H+~3R))A3`Vec]ct[TYZ][WVa
Yrb\ceb]UVW]ecc]eWYrwzz*!$3 z !o%"3
P0!~/G&/(k3R))D3~*
%"*l+" !"H&($
. !(&"P .z" ""3
WVr[Yc]V\WTYc]VU]{YWXYe\Z[Yc]ea beYW/A2E??*EE)3
"(+!H "l *
" 3R))23e]T[Zed]ZYZeb]rYWXYa
VrVe[Yc]viZ]We[b[VT]YTd]Ze]TYZ[VTYc] UVWX\cYW]hZ]We[b[VT3"( +!H " l " / QH3 P H"3
"~3R)0R3{eX_\YZYT]dYT]qYWYqa ZeW[bYb[]_eYdb]qYcb[\XYct[TYZ]]reTZVqa b[scc[T]deTtYT]XeZVde]tecYb[][VT3}!* y!"*yOQ~Q3} 3