kk iv sem final new.pptx

8/9/2019 kk iv sem final new.pptx

1/67

PROCESS VALIDATION OF LOPINAVIR + RITONAVIR

(100 + 25 mg) ANTIRETROVIRAL COMBINATION

TABLET

1

INDUSTRIAL GUIDE

Mr. NAGESH PATIL

Sr.m!g"r #A $"%&.

Em'r" %rm'"&*',

H*!-"$*/ P!".

DEPARTMENT OF QUALITY ASSURANCE

TECHNIQUES

SINHGAD COLLEGE OF PHARMACY

VADGAON (BK), PUNE-041

PRESENTED B

,& V. !$r3r

M.Prm (IV&SEMESTER)

ACADEMIC GUIDE

Mr,. M.A.NAGRAS

A,,*,&!& Pr4",,4r

SCOP

VADGAON (B)/ PUNE6071


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10/6710

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11/67

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(100 6: /) A+* R!*"#%"&' *&'!*s5

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P! 4 4r39

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14/67

INSTRUMENTS AND E#UIPMENTS9E#UIPMENTS M3"

R& !" /"&+'&*#" (6:0 L) A+$.#" &"8

V"&*#"3 s*!" 6070 A+$.#" &"8

H#* !'* !*"!" T.!"# s.!" s$!+*$

C.''! @&$8!*! $& '' C& &$.

''&" *3! '!+!" C#+*& '!+!" A+$.#" &"8

C#"!ss#+ &$.+! L!/&$3 9100 P& .&"&$!*$&'s &''!&$.+!"!s

D!s*+/ !""+/ &$.+! 2*. !*&' !*!$*#" T!$.+# #"

A*# $#&*!" N!# $#*& :0D 70

B'8 &$8+/ &$.+! T.!"# s.!" s$!+*$

14

A!:&*' I!,&rm"!&, M3"

H5P5L5C &*!"s

Dss#'*#+ &&"&*s E'!$*"# '&


15/67

H4& M"& E?&r$"r 9

15


16/67

A$8!&g", 4 H4& M"& E?&r,*4! 9

Pr4"m, S48"$ : HME

P##" #&%&'&'*3 ! *# ##" APIs#''*3

Us! # HME !+.&+$!!+* #ss#'*#+

P##" s*&'*3 "+/ "#$!ss $&s! 3

.3"#'3ss

Us! # HME &s &'*!"+&*%! *# 2!*

&//'#!"&*!s

U+"!'&'! ss*&+! "!'!&s! &$*#+ Us! HME *# "!&"! ss*&+! "!'!&s!#s&/! #"

P##" s*&'*3 #" *#'!"&'*3 # API +*.! s*#&$. Us! # HME *# "!&"! !+*!"$ #s&/!#"

P##" *&s*! # *.! API Us! # HME *# "!&"! *&s*!-&s8!#s&/! #"s

16


17/67

Drug Pr4*":

Drg L4%*!8*r 9

S*"$*"!

C&*!/#"3 A+*"!*"#%"&'

C'&ss HIV P"#*!&s! I+.*#"s

M#'5 *5 96=5=00=

M!'*+/ #+* 164 *# 16;0

CH&' '! :-9 ."s

M!*'s H!&*$ $3*#$."#! P4:0 s3s*!

E$"!*#+ M#s*'3 !$&'

17


18/67

Drg R*&4!8*r 9

S*"$*"!

C&*!/#"3 A+*"!*"#%"&'IUPAC N&! HIV P"#*!&s! I+.*#"s

M#'5 *5 ;605>44

M!'*+/ P#+* 160 *# 166 0 C

H&' '! 7-: ."s

M!*'s H!&*$ $3*#$."#! P4:0 s3s*!

E$"!*#+ M#s*'3 !$&'

18


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DESCRIPTION OF MANUFACTURING PROCESS AND

PROCESS CONTROLS (F4r L4%*!8*r + R*&4!8*r T"& (100 + 25 mg) USP)

19

P $*


20/67

2020

R m&"r*, Pr4'",,

Ds!+s+/ # "&2 &*!"&'

L#+&%", "*#+&%" $##%#+!, $#''#&' s'$#+!#!

S*+/

S#"*#+ #+#'&"&*! G"&+'&*#+

M#+#*&+! 60 PHA H#* !'* !*"s#+

SJ! "!$*#+ ( M''+/)

C#''#&' s'$#+! #! IPS# s*!&"3' &"&*! USPNF s*+/

L"$&*#+

C#"!ss#+

O&"3 3!''#2 , "! 2&*!" IP $#&*+/

P&$8&/+/

Pr4'",, 4 $*grm


21/67

M!'&r*!gFormula :

Ingredients Use

A) Granulation

Drug Lopinavir (API) Antiretroviral

Drug itonavir (API) Antiretroviral

!opovi"one #in"er

!olloi"al $ili%on "io&i"e Lu'ri%ant

or'itan onolaurate ur*a%tant

o"iu+ $tear,l *u+arate Lu'ri%ant#) !oating o* -a'let

.pa"ar, ,ello/ !oating agent

Purie" /ater olvent *or %oating

21


22/67

Product Composition : lot !4. 1

22

Sr.!4. Nm" 4 m&"r* #!&*&: %"r &"&

*! mg.

#!&*&: %"r &'

*! 3g.

1 L#+&%" IP 10050 ;5;>0

6 R*#+AVIR IP 6:50 15=>>

; C#%#+! s + 447599: 775706

7 C#''#&' s'$#+! #! IP 95990 05:07

5 S#"*#+ #+#'&"&*! 765:00 654;:

@ C#''#&' s'$#+! #! 451;: 05701

S# s*!"3' &"&*! 95000 05476

Total core tablet 618.0 44.46


23/67

23

Pro"u%t %o+po$ition $a+e *or lot no 6,7

!r.no. "ame o#

material

$uantit% per

tablet in mg.

$uantit% per

batc& in 'g.

') !oating o*ta'let

8 .pa"r, ,ello/ 15450 0799 & 2 1558

9 Purie" /aterIp

A 440 & 2 880


24/67

Pr4'",,*!g 4 B&' L4& 9

S*! 15 Ds!+s+/ - As !" '' # "&2 &*!"&'5E!+*s +!!! LAF, !/.* B&'&+$!, $#+*&+!"s

S*! 15 S*+/ V"&*#"3 s*!" *."#/. 405 $.!$8 .3s$&' +*!/"*3 # s!%!

!#"! &*!" s!

S*! 75G"&+'&*#+ L#& s*! +/"!!+* + RMG #" 10 +5 2*.

!''!" &* &s* s!! &+ $.#!" # 5$.!$8 +/ *! s!! #!''!"

S*! 45 H#* M!'* E*"s#+ (HME) F!! "&*! 45: 8/ *#66 8/."5 s$"!2 "

100 9;: " *#"! 70 *# 90

S*! :5 SJ! "!$*#+ - F* 750 s$"!!+ *# $& '' '' *.! !*"&*!s &*

&s* s!! 8+! #"2&"5 s* *.! ''! /"&+'!s *."#/. 70 s!%! *#%"&*#"3 s*!"

24


25/67

25

S*! 95 L"$&*#+ S* $#''#&' s'$#+! #! IP s# s*!&"3'

&"&*! *."#/. 40 s!%!5 L#& /"&+'!s + 1:0 L $&/! +8!" &**&$.

* *# ''&" *3! $#+*& '!+!" #" : +5 '!+!" s!! &* 16 "+ &+&' #!

S*! ;5 C#"!ss#+ s+/'! "#*&"3 7; s*&*#+ L!/&$3 9100

!" +$.!s < 19 > #%&' s.&!

'#2!" +$.!s < 19 > 69

D!s< < 19 > #%&' s.&!

S*! >5 Ds!+s+/ # C#&*+/ M&*!"&'

S*! 105 P"!&"&*#+ # F' C#&*+/ "! 2&*!" #&"3 3!''#2 '&"/!

' #"&*#+ &%#!5 S*" #" 4: +5 '*!" *."#/. s'+ $'#*.5 Us!$#&*+/ s#'*#+ 2*.+ 64 .#"s5

S*! 115 C#&*+/ 3 N!# $#*&5 C#&*+/ # *&'!* *# ! #+! *# & 2!/.* /&+

# * 65:

S*! 165 P&$8&/+/ As !" &"8!* "!"!!+*5


26/67

A,,",,m"!& 4 'r*&*' %r4'",, %rm"&"r, 9

26

!r.no Process step Process parameter rationale C&ec's critcal steps


27/67

27

. setting

1 a/ +aterial A a/ +aterial u$e" arepro%ure" *ro+ approve"ven"or$

A o

2 Di$pen$ing o*ra/ +aterial

Di$pen$e ra/ +aterial a$per 'ill o* ra/ +aterial

Pro%e$$ "oe$ not avevaria'le ee%t on pro"u%tualit, /en "ene"operating pro%e"ure$ are*ollo/e"

#alan%e%ali'ration 'e*ore"i$pen$ingoperation to 'e"one

o

3 i*ting i*t lopinavir ritonavir%opovi"one %olloi"al$ili%one "io&i"e troug

40 $ieve

Pro%e$$ involve$ 'reaingo* agglo+erate$ i* an,

P,$i%al integrit,o* $ieve 'e*ore :a*ter u$e

o

4 Granulation Dr, +i&ing in rapi" +i&ergranulator 250 L /it tea""ition o* $or'iton+onolaurate

i&ing ti+e to en$ureproper +i&ing

i&ing ti+e $pee"o* i+peller :%opper

;e$

5 ee" rate

;e$

7 i*ting o* e&tragranular

ingre"ient$

$i*t te %olloi"al $ili%one"io&i"e : $o"iu+ laur,l

*u+arate troug 40$ieve

Pro%e$$ involve$ 'reaingo* $o*t agglo+erate$ i* an,

P,$i%al integrit,o* $ieve 'e*ore :

a*ter u$e :>ee" rate

o

!r.no. Process Process parameter setting (ationale C&ec's Critical steps


28/67

28

!r.no.step

8 Lu'ri%ation Lu'ri%ation o* granule$ /it $i*te"%olloi"al $ili%on "io&i"e : $o"iu+laur,l $ul*ate *or 5 +in ', eepingte %onta 'len"er $pee" at 12 rp+

i&ing ti+e toen$ure proper+i&ing properlu'ri%ationreuire" toa%ieve opti+u+

%o+pre$$ionpropertie$ *or nal'len"

te$ting a$ per$a+pling plan

;e$

9 !o+pre$$ion

!o+pre$$ te ta'let$ at opti+u+$pee" u$ing %o+pre$$ion +a%inelega%, 6100 $ingle rotar, 37 $tation

-o $et te%o+pre$$ionpara+eter$ : toa%ieve reuire"%o+pre$$e"

/eigt

-e$ting a$ per$a+pling plan

,e$

10 !oating !oating o* ta'let$ to 'e "one to a/eigt gain o* a'out 25 @

-o $et te %oatingpara+eter$ : toa%ieve reuire"%oating /eigtgain


,e$

12 Pa%aging A$ per 'at% pa%aging re%or"$ -o evaluatepa%agingpara+eter$


,e$


29/67

!ampling %!:

29

Pr4'",, ,&g" Sm%" *$ Sm%*!g $"&*, > !&*&: T",&,

L"$&*#+ 1 LG 01 *# 1 LG70

70 +* #s! s&'!s, 10 s&'!s+ *"'$&*! s.&'' ! $#''!$*! #*# 2.$. #+! s!* # 10 s&'!ss.&'' ! &+&'3J!C#''!$* & ##'! s&'! # 600/

B'!+ +#"*3T!s*+/ #+ ##'!

s&'!Ass&3, L#ss #+ "3+/

C#"!ss#+ I+*&', '! !+&* #* s!! .&"+!ss

100 *&'!*s &"! *# ! s&'! &*+*&', '! !+ # *&'!*$#"!ss! &* #* s!! .&"+!ss

P.3s$&' &"&!*!"sss#'*#+

$#"!ss#+&$.+! s!!

P##'! s&'! &*#* s!! .&"+!ss

100 *&'!*s &"! *# ! s&'! &s#''! s&'! &* #* s!! .&"+!ss

Ass&3, ss#'*#+


30/67

30

Pr4'",, ,&g" Sm%" *$ Sm%*!g $"&*, >!&*&:

T",&,

C#&*+/ P##'! s&'! C#''!$* 1 #''!s&'! &*!"+'#&+/ # $#&*!*&'!*s s&'+/&+**3 100 *&'!*s

D!s$"*#+ ,&ss&3 ,Dss#'*#+

P&$8&/+/ O+! ##'! s&'!$#''!$*! "+/ *.! !+*"!&*$. &$8+/ 5 S&'+/&+**3 &s !" +s.!

"#$* s!$$&*#+

S&'+/ &+**3 &s+s.! "#$*s!$$&*#+

P&$8&/+/&"&!*!"s "#B&*$.&+&$*"+/

"!$#"s

C4!&*.


31/67

)cceptance criteria :

31

S&g" T",& I! Pr4'",, C"'3,

L"$&*#+ D!s$"*#+ .*! *# # 2.*! /"&+'&" #2!"

B'!+ +#"*3 R!'&*%! s*&+&" !%&*#+ +#* #"! *.&+ :

Ass&3 N#* '!ss *.&+ >0 +#* #"! *.&+ 110 #'&!'! +* # "*#+&%" '#+&%"

C#"!ss#+ D!s$"*#+ .*! *# # 2.*! +$#&*! #%&' *&'!*s !#ss!2*. EM #+ #+! s! 6: #*.!" s!

Dss#'*#+ N#* '!ss *.&+ ;0 # '&!'! +* # "*#+&%" IP

s ss#'%! + 160 +5N#* '!ss *.&+ ;0 # '&!'! +* # '#+&%" IPs ss#'%! + 160 +5

C#&*! *&'!*s Ass&3 N#*'!ss *.&+ >0 +#* #"! *.&+ 110 # '&!'!

+* # "*#+&%" '#+&%" IP


32/67

32

!c&ematic sampling plan o# Conta"!$"r:

>ig B a+pling !%$!


33/67

Sm%*!g 4'&*4!,9

33

T4% 1 "& r4!& ; "& r4!& 5 r*g&r4!&

r*g&'3

1,11,61 7,17,67 :,1:,6: ;,1;,6;

B#**# 6 '!* "#+* 4 '!* &$8 9 "/.*"#+*

= "/.*&$8

6,16,66 4,14,64 9,19,69 =,1=,6=

C!+*"! - - - - > '! 10 #**#

>,1>,6> 10,60,70


34/67

Pr4'"$r":

1) .'tain 3 unit "o$e $a+ple$ *ro+ $#+*& 'len"er (%age'uner) *ro+ ea% po$ition a$ $o/n in a'ove gure an"a$ "e$%ri'e" in ta'le given 'elo/

2) C$e appropriate $a+ple tie*E /it te appropriate "ie to

o'tain $a+ple$ /it net /eigt o* 1 & to 3 & ti+e$ tetarget /eigt

3) C$e la'ele" : /eige" $a+ple %ontainer$ $u'+it te$a+ple to ualit, %ontrol "epart+ent *or te$ting along /itappropriate te%ni%al in*or+ation $eet

34


35/67

E?%"r*m"!&9

35


36/67

36

Pr4'",,*!g ,&g" Cr*&*' %r4'",, %rm"&"r, R"'4mm"!$"$ *m*&(,)r!g"(,)

C4&*!g O*'!* *!!"&*"! 69C *# 7=C

P!"s*&'*$ s!! 10 RPM *# 60 RPM

T#*&' A" P"!ss"! : 8/$6 *# 1: 8/$6

*"$ D"/ C#&*+/ >750 *# 10650

B&""!" C#&*+/ >750 *# 10650

E+*!"$ C#&*+/ >750 *# 10650

!ummar% o# Pr4'",,

Parameters:


37/67

R",&, > $*,',,*4!9

37

R",&, 4 "!$ !*4rm*&:9

Sm%" I$ B"!$*!g '4!&"!& 4

B"!$*!g '4!&"!& 4


38/67

38

'4!&"!& 4R*&4!8*r

'4!&"!& 4R*&4!8*r

B&' !4. 1 B&' !4. 2 B&' !4. ; B&' !4. 1 B&' !4. 2 B&' !4. ;

1 .5 .0 .7 102.1 100.2 100.0

2 .; .7 .7 102. 100.@ 100.1

; .; .; .0 100. 100.; .

7 .2 .@ .1 100. . 100.@

5 .2 . .0 100. 100. 100.@

@ .@ .5 .@ 10;.1 100. 100.1

.5 .0 .; 100.0 101.1 100.0

. .@ .; 100.; 100. .

.; .0 .7 102. 100.; 100.2

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kk iv sem final new.pptx

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