anneleen burggraeve - developme,nm,nt of process analytical and control methodologies for...

8/21/2019 Anneleen Burggraeve - Developme,nm,nt of Process Analytical and Control Methodologies for Pharmaceutical Wet

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Ghe Uiei

Fac f Phaaceica Sciece

DEELE F CE AALICAL AD CL EHDLGIE

F HAACEICAL E GALAI CEE

AELEE BGGAEE

Mae i Chei

Thei bied bai he degee f Dc i Phaaceica Sciece

2012

Pe: . D. . D B

Laba f Phaaceica Pce Aaica Techg (Ghe Uiei)

Ce: . D. C.

Laba f Phaaceica Techg (Ghe Uiei)


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The ah, he e ad he ce gie he ahiai c ad c a f

hi hei f ea e . A he e i iied b he La f Cigh, eecia

cceig he bigai efe he ce heee e ae cied f hi hei.

Ghe, Je 15, 2012

The ah The e The ce

Aeee Bggaee Pf. D. Tha De Bee Pf. D. Chi Veae


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ACKLEDGEE

A 4.5 , I . D ,

. I

.

I P. D. B, PD

. , P. D. D B ,

I

. I .

I , P. D. C ,

. P. D. J P R

.

S S , I

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, . L

M PA , I

, , . I , PA ,

L, A

. I C .

P .

I P. D. J

H .

H,

P. D. N S P. D. J H (

) .

S I (A I

), G FO (F O )

PD .


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F, I (A, J, S, N, J, K A)

, , .

S ,

PD. M & L L, ,

I , .

I G P .

A , . A 1000

PD, , ,

N . A M O

.

A


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TABLE OF CONTENTS

ABLE F CE

CAE 1 DC AD BECE 5

CAE 2 FDED BED GAA & EEA A E

GAA ECE 11

2.1. I 11

2.2. F 13

2.3. F 15

2.3.1. Geea decii f he ce 15

2.3.2. Pce eie 15

2.3.3. Tadiia ehd f ce c ad edi deeci 18

2.4. E 21

2.4.1. Geea decii f he ce 212.4.2. Pce eie 22

2.4.3. Tadiia ehd f ce c ad edi deeci 24

CAE 3 CE AACA ECG FDED BED GAA &

EEA 31

3.1. A 31

3.1.1. Idci 31

3.1.2. The PAT Faek 33

3.2. 36

3.2.1. Saia fie ecie 36

3.2.2. Pheic ee iagig 38

3.2.3. Fced bea efecace eaee 40

3.2.4. Nea ifaed ecc 41

3.2.5. Raa ecc 43

3.3. L 47

3.3.1. Nea ifaed ecc 49

F ABBEA 1


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TABLE OF CONTENTS

3.3.2. Iage aai 53

3.3.3. Fced bea efecace eaee 54

3.3.4. Saia fie ecie 55

3.3.5. Acic eii 56

3.3.6. Raa ecc 57

3.3.7. Cbiig ceea ce aae 58

3.4. L 60

CAE 4 EAA F E AA FE ECE A A G

F ACE G DG FD BED GAA 69

4.1. I 69

4.2. 72

4.2.1. Maeia 72

4.2.2. Fid bed gaai 72

4.2.3. Iie eaee ih aia fie ecie be 72

4.2.4. Deig f eeie 73

4.2.5. Chaaceiai f gae 74

4.2.6. Daa aai 74

4.3. 75

4.3.1. Cai beee iie SFV ad ffie LD e 75

4.3.2. DE aai 78

4.3.2.1. Cai beee iie SFV ad ffie LD DE e 78

4.3.2.2. Eaai f he (i)igificace f he DE fac baed iie SFV daa 80

4.3.2.3. Ifece f DE fac dei ad de f 83

4.3.2.4. Aee f gae dei ad fabii f iie SFV eaee 84

4.4. C 86

CAE 5 BAC ACA CE C (BC) F A FD BED GAA

CE G E AA FE ECE AD DC EEAE

EAEE 91

5.1. I 91

5.2. 93

5.2.1. Maeia 93

5.2.2. Fid bed gaai e 93



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TABLE OF CONTENTS

5.2.4. Deee f bach de 94

5.3. 97

5.3.1. Reaie bach ge eaai 97

5.3.2. Eaai f ceed bache 104

5.4. C 106

CAE 6 DEEE F A FD BED GAA CE C AEG

BAED EAE CE AD DC EAEE 111

6.1. I 111

6.2. 115

6.2.1. Maeia 115

6.2.2. Pce decii 115

6.2.3. Ceci f gae dc ifai dig ceig 116

6.2.3.1. Cae d A: iie SFV ad aie NIR ecc 116

6.2.3.2. Cae d B: iie SFV ad iie NIR ecc 116

6.2.3.3. Cae d C: iie FBRM ad iie Lighhe NIR ecc 117


6.2.4.1. Ka Fiche iai 117

6.2.4.2. Dei eaee 118

6.2.5. Deee f he gaai feedfad c aeg 118

6.2.6. Deee f a NIR ehd edic ed dc ie ce 122

6.2.6.1. Ue f ceia NIR be (cae d B) 122

6.2.6.2. Ue f Lighhe NIR be (cae d C) 122

6.3. 123

6.3.1. Cae d A: iie SFV ad aie NIR ecc 123

6.3.2. Cae d B: iie SFV ad iie NIR ecc 126

6.3.2.1. Qaiaie iig f he gaai ce 126

6.3.2.2. Deee f he gaai feedfad c aeg 128

6.3.2.3. Deee f a NIR ehd edic ed dc ie ce 132

6.3.3. Cae d C: iie FBRM ad iie Lighhe NIR ecc 133

6.3.3.1. Deee f he gaai feedfad c aeg 133

6.3.3.2. Deee f a NIR ehd edic ed dc ie ce 135

6.4. C 137


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TABLE OF CONTENTS

CAE 7 EAE AGEBAED EGA F EA AD DG

EEA G DFFEE EE FA 143

7.1. I 143

7.2. 146

7.2.1. Maeia 146

7.2.2. Mehd 146

7.2.2.1. Peeiai ad dig 146

7.2.2.2. Saig 147

7.2.2.3. Pheic ee iagig 147

7.2.2.4. Raa ecc 148

7.2.2.5. Mie aai 148

7.3. 149

7.3.1. Pheic ee iagig dig heiai 149

7.3.2. Pheic ee iagig dig ee fid bed dig 154

7.3.2.1. Paice ie diibi 154

7.3.2.2. Sface bighe ad iaiai 157

7.4. C 158

A & GEEA CC 161

FE EECE 167

AEAG & AGEEE BE 171

CC AE 179


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LIST OF ABBREVIATIONS

1

LI F ABBEIAI

AE acic eii

A aificia ea ek

AI acie haaceica igedie

BD bk dei

BC bach aiica ce c

CL c ii

DE deig f eeie

EC eecica caaciace gah

E eiheiai

FB fced bea efecace eaee

FDA Fd ad Dg Adiiai

F3D FahSie 3D

G gd afacig acice

HC hdehcee

ICH Ieaia Cfeece f Haiai

KF Ka Fiche

LD ae diffaci

LH Lighhe Pbe

C ie ce

CC iccaie cee

C iaiae ce ei

icae eace echg

I ea ifaed

L Na aia ea ae

A ce aaica echg

C icia ce

CA icia ce aai

ID Pia, Iega, Deiaie

L aia ea ae

LC aia ea ae ce


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LIST OF ABBREVIATIONS

2

D aice ie diibi

EE ea ae e f eiai

E ea ae e f edici

D adad deiai

F aia fie ecie

adad a aiai

D aed dei

hehie

AH hehie ahdae

H hehie hdae

D Xa de diffaci


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CHAPTER 1 INTRODUCTION AND OBJECTIVES

3

CHAE1

IDCI AD BJECIE


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4


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5

CHAE 1

IDCI AD BJECIE

Gaai i a geea e decibe ehd f ie eagee i he haaceica

id. Pde aice ae aggeaed i age, eae ce (gae) i hich

he igia aice ae ideifiabe [1]. Iee f e e de eie (e.g.,

fabii, bk dei, d fai, ik f ie egegai, ec.) iae he haaceica

id ad gaai a a ke ieediae ce e i id dage f

dci cee.

F eea decade afe he eaie k efed gaai, i eaied e f a a

ha a ciece ih high ecce ai [2]. Gaai ee efed baed a acice

ahe ha cieific aegie. The gaai behai f e fai a ediced

b he cieific deadig f he deig gaai heea, b eeie eig a

deake. Theefe, e eiica baed gaai kedge, a e heeica baed

kedge he aice eig echai a eied [3].

Udeadig he fdaea hica ad cheica heea ha cibe he gaai

behai ad gae eie, eabe de/edic h a aeia i gaae gie ha

fai eie, eie e ad eaig cdii ae adeae chaaceied.

Eiica de, echaiic de, a cbiai f bh ae cideed f deig a

gaai e [4].

Ne a bee f gae fai echai ad f he ce,

adeae gaai i ecea hif f a gaaia a gaai ciece [5].

The iceaig dci cae ad dci eed i cbiai ih he gd afacig

acice (GMP) ad aidai eiee eceiae he deee f ic ced

gaai cee. Tadiia, haaceica gaai i ced b iig ce

aaee [6, 7]. The ai f he afaced gae i aeed afead ia (ie

cig) aba aai f he ciica ai aibe f eeced ae. A e efficie

a c he gaai ce ci f he dc ai aee,

eeed ih eaie ce aaee adje cecig f deied chage i he

dc eie ad ce ge. Thi eai he deee f aaed gaai


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6

cee ha e iie ce aaica e diec eae he ciica dc

chaaceiic.

The ce aaica echg (PAT) cce iiiaed b he Fd ad Dg Adiiai (FDA)

i 2004 ffe a ega faek ecage hi ci iig ad c f

haaceica dci cee [8]. Ieeai f PAT hd ead he ideh

deadig ad c f he afacig ce ih iia ed dc eig

gaaee he ai. The iae ga i ceae a eaie baed eeae dci

eie. Ieeai f PAT aegie i eiced he cecia afacig

cae, b hd aead a dig ce deee die. The aied echie i he

iceae dc kedge ad ce deadig, hich i ca be eied dig

gaai cae. Mee, defiig a edi i e f iie eaed gae

eie (iead f ce aaee ae), ake ig f deee f

dci cae e ea. Adaai f he haaceica id ad ciecebaed

afacig ih e f ai ik aagee i a die b he iceaed c ied i

dg eeach ad he diiihig R&D dcii [9]. The eiai f ae ad f

ecii hae deceaed eee.

The ce e f ce aaee deeie he ae ad edi f gaai cee

i fe iadeae, ice i de acc f chage i feed aeia eie eea

dibace. Mee, dc ifai i ai baied afe ceig f a iied

be f ae, eeig ideh kedge ad efficie c f he ce. I hi

hei, he aicai f e ce aae f fidied bed gaai ad ei

heiai, caig diec gae dc ifai, a eaaed. Bh gaai

echie ae ce, a e ieeaed ce ad fai aaee ifece

gae eie. B diec iig f he ciica gae chaaceiic, a ideh

deadig f he gaai ce ca be achieed. I addii, cbiig he eaie

ceced gae dc ifai ih aiae daa ceig echie ad

cheeic eabe he deee f adeae ce c ad edi deeiai

cie dce gae ih he deied ai.

The fi a f hi hei ide a heeica backgd he aied gaai echie

ad PAT. I C 2, he fdaea f he echai cibig e gae gh ad

he chaaceiic f gaai ia fidied bed ad eiheiai ae diced.

C 3 ie he defiii f PAT accdig he FDA gideie ad he eaee

icie f he i hi hei aied PAT e. I addii, he ieae he fee


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died aaica ce e f fid bed gaai ad eiheiai i

diced, ih ehai he eaie caed gae dc ifai ad he chaege

eceed dig he e aicai.

Chae 4 7 ide he e f he efed eeiea die. The feaibii f aia

fie ecie a a eia PAT f he iie aice ie iig dig a fidied bed

gaai ce a ciica eaied i C 4. Heeih, a deig f eeie a

efed, eaiig he ifece f eea ce ad fai aiabe he gae ie.

Reaie baied ie ee caed ih he e f a ceia iig echie (ae

diffaci) ad a bee iigh i he gaai ce baed he ci ceced

gae ie ifai a baied.

Oce i a deaed ha aia fie ecie eabe he diec, fa ad decie

ie deeiai dig fid bed gaai, he echie a ed f he iaiae

aiica deig ad c f he ce (C 5). The eeed aach e iie

gae ie eaee cbied ih ci gae dc eeae egiai,

ad a ea fa deeci, hece edcig bah e (ad/ eceig) ad iig

gaai efficiec.

I C 6, a ea c aeg f a fid bed gaai ce a ed. Saia

fie ecie eaee ee aeded ih iie ea ifaed eca ceci,

eabig he ci gae ie ad ie iig. Gae ie ad ie

ajecie ee caed ih adiia ed dc ad eha ai eeae c

cha, hig he adaage f ieeig a adaced PAT e. I addii, a feed

fad ce c ehd a deeed, hee iie ceced gaai ifai

dig he ce aig hae a ed deeie he i dig eeae f he

cecie dig hae, gidig he ce ad he deied ed dc bk dei.

Ieeai f he aaed c aeg hd e i he dci f high ai

bache a e ea c.

I C 7, he aicai f a eaie iagig ehd dig he fia e f he ei

heiai ce, ae heiai ad dig, a eaaed. The aie ceced

iage dig he heiai ad dig f diffee ee fai caied ifai

eaed he ee ie diibi, hae ad face bighe. Thee aaee ided

aabe iigh i he fai heiai ad dig chaaceiic, hig he

eia f he echie a a fa ad decie eeach i he deee ad

iiai f a eiheiai ce.


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8

EFEECE

[1] B.J. Ei, J.D. Lie, i: R.H. Pe, D.W. Gee (Ed.), Pe' Cheica Egiee'

Hadbk, McGaHi, Ne Yk, 1997.

[2] J.D. Lie, Pde Techg, 130 (2003) 3540.

[3] S.M. Ie, J.D. Lie, K. Hagd, B.J. Ei, Pde Techg, 117 (2001) 339.

[4] I.T. Cae, F.Y. Wag, i: A.D. Saa, M.J. H, J.P.K. Seie (Ed.), Hadbk f

Pde Techg, Eeie, Aeda, 2007, . 499552.

[5] S. Kha, Phaa Tie, 42 (2010) 1415.

[6] D.M. Paikh, J.A. Bck, M. Mgae, i: D.M. Paikh (Ed.), Hadbk f Phaaceica

Gaai Techg, Mace Dekke Ic., Ne Yk, 1997, . 227302.

[7] D.I. Wi, S.L. Rgh, i: A.D. Saa, M.J. H, J.P.K. Seie (Ed.), Hadbk fPde Techg, Eeie, Aeda, 2007, . 189217.

[8] Fd ad Dg Adiiai, Gidace f Id; PAT A faek f iaie

haaceica deee, afacig ad ai aace, (2004)

[9] P. Kaegai, i: D.M. Paikh (Ed.), Hadbk f Phaaceica Gaai Techg

Thid edii, Ifa Heahcae, Ne Yk, 2010, . 597616.


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CHAPTER 2 FLUIDIZED BED GRANULATION & EXTRUSIONSPHERONIZATION AS WET GRANULATION TECHNIQUES

9

CHAE2

FLIDIED BED GALAI &

EIHEIAI A EGALAI ECHIE

Pa f hi chae ae acceed f bicai (ih i eii) i:

A. B, T. Mee, J.P. Re, C. Veae, T. De Bee, Pce aaica f

iig, deadig ad c f haaceica fidied bed gaai: a eie,

Eea Ja f Phaaceic ad Bihaaceic, acceed ih i eii.


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11

CHAE 2

FLIDIED BED GALAI &

EIHEIAI A E

GALAI ECHIE

2.1. IDCI

Gaai i defied a a aice ie eagee ce heeb a de aice ae

gaheed i age, eae ce i hich he igia aice ca be diigihed [1].

Hece, gaai ca be cideed a he haaceica ie f iig [2]. Iead f

edcig he aice ie, he ce ai a aice gh. T aj gaai ehd ae

ide aied, ae ad gaai [3]. A i ae gge, e gaai ie

he e f a bide iid, hich i idced agiaed de aice bidig hee gehehgh a cbiai f caia ad ic fce [4]. Dig bee dig, he e i

eed ia eaai ad e eae bd ae eabihed. The gae egh i he

ai eaed he id bidge, fed b hadeig f bide ad he caiai f

died aice. D gaai ehd ae baed he caci f he de a,

befe i i ched ad faciaed. Hece, aice ie eagee i achieed ih he e f

a bide iid, akig hi ce aica iabe f ie heaeiie dg.

Caed d gaai cee, e gaai ffe a bee c f dg ce

ifi, dc bk dei ad cacibii [5]. Hee, he ce i e cicaed

aidae ad c de he addiia eaai f bide iid ad eea dig

e. I i a e eeie ih egad ab, eie, eeg ad ace [6].

The e f gaai echie i he haaceica id i die b he iee f

e e de eie. Thee icde, iceaed bk dei, fabii ad bii,

edced ik f ie egegai ad d fai [7]. The afaced gae ae ai

abeed, fied i cae.


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12

I hi hei, he aicai f aaica ce e dig e gaai echie,

ae ad , a eaaed. Theefe, he

fdaea f he echai cibig e gae gh ad he chaaceiic f

gaai b fidied bed ad eiheiai ae diced i hi chae.


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13

2.2. FDAEAL F E GALE GH

Dig e gaai, a be f diffee echai ake ace. I hi k, he caificai

accdig Ie e a. [4] i cideed, ieig he e gaai ce a a cbiai f

hee diffee echai e f ae cee. Thee icde:

eig ad ceai f aice

cidai ad gh b cii f aeia i he gaa

aii ad beakage

Weig adace he ceai f fie de, hich i g ifeced b he diibi f

he bidig fid ad he de eie. The gh age ie cii beee

(aia) eed gae (i.e., caecece) gae ad feed de (i.e., aeig) eig iage gae ced f eea aice. Dig gae gh, he aggeae ae

bjeced caci fce (de bed agiai) caig he gae gada cidae.

Thi i accaied b a edci i ie ad i, ad fce eaed ai ad bide

iid he aice face. The ae f cidai deificai deed he eie f

he feed aeia, ch a aice ie diibi, aice hae ad face ghe. The fia

deificai ee deeie ed dc i ad heefe gae hade, egh ad

dii. High i gae ae eak ad fiabe (aed ceai f d dig dc

hadig), b dia fe a adaage fa dii ae hich ake gae i a

ia dc e c. The hid ae ce icde heea. L

bidig egh i he i aggeae ceae eak gae ha a i he

gaa, ifecig he fia gae ie diibi. Thi beakage i e ie i

gaai cee diaig high hea fce. Weak gae ae ceibe

face i he fid bed gaa dig bee hadig. The aciaed geeai f

d fie ceac he bjecie f gaai ad hd heefe be aided.

Dig a fid bed gaai ce, he bide iid addii ad eaai ake ace a he

ae ie, akig hi a ie gaai ce [8]. Hece, he hee ae echai cc

iae ad he cibi f each f he he deeed aggeae deed

gaai eie, ce eig ad feed aeia eie. The cbiai f he

dia ae cee deeie he fia gae ie diibi, ce ad i ad

heefe ed dc ai aibe.

Accdig he eaie a f iid hae, a be f diffee ae f he i

aggeae ae decibed, i.e., he , he ad he ae (Fige 2.1) [9].


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14

The heeih aciaed iceaig a f iid hae i eeed b he iid aai,

decibig he ai f e e ccied b he iid he a e e ihi he

aggeae. I each ae, a diffee e f bdig i hdig he aice gehe. I he

eda ae, iid bidge a aice cac i ae hdig he aice gehe, heea i

he caia ae a he id ae aaed ih iid ad he face iid i da i he

aice e de caia aci. The ieediae fica ae i chaaceied b id ha

ae cee fied ih iid. I addii hee hee age, a fh e, he ae

ha bee defied (Fige 2.1) [10]. Thi ae i chaaceied b he addii f e iid he

de ie ha he a eied cee fi a ie ad iaaicae id.

Hece, he iid cee d he id aice. If he de ae i achieed dig

ceia e gaai (i.e., fidied bed ad high hea gaai), geea ch

iid ha bee added ad gaai i be ccef [2]. Thi i ca he ce f

gaai b adig f a ei, hee he de ae i a ia age f he

ce.

F 2.1.Oeie f he f age f de eig (iid aai). The id aice ae

eeeed b ge cice ad he bidig iid i ced back.

( )


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15

2.3.FLIDIED BED GALAI

2.3.1. G

Dig fidiai, id ae bjeced a ga (a ai) hich ce he aeia f a aicae a daic fid ae. A ceai ga eciie he ga i he aice, aig a

ad dad ee, edig he aeia i he ga [11].

Phaaceica fidied bed gaai a fi decibed b We, he he eed he

e f he ai ei echie ca abe [12]. Thi a fed b a ae decibig he

ce f gaai ad dig ia he ai ei echie eae ceed abe

[13]. A fid bed gaai ce eai he ei f aice i a cica haed caie

b e f a (heaed) ai ea. The aied ai eci hd a e aice ee i

he caie, b kee he aeia f he fie bag (Fige 2.2). Gd fidiai ca be

ia ied b he fee dad f f he gae a he id f he caie. A

aice e ad d i he caie, a bide i i aed (i.e., aig hae).

Bide iid de ae deied he fidied aice i he a gaai e. Thi

eig cae he fai f gae accdig diffee echai (Seci 2.2). Afe

aig he eied a f bide iid, fhe fidiai eabe aid dig f he

gae i he ae eie (i.e., dig hae). Dig edce he eida ie f he

gae a ee ha ee he abii f dc acie(), ad ee he eiee f

dea ceig. A gd gaai i achieed he aice ae if ied ad

iid bidge beee he aice ae g ad ea d. The ie f he aggeae a

age f 0.1 2.0 .

Caed high hea gae, he ack f hea fce i a ceia fidied bed e i

he dci f e ad e dee gae ih bee dii ad cei

chaaceiic [14]. Geea, he fidied bed gae ehibi a ae ie diibi,

ih eied gae. The c be eceed dig fid bed gaai

icde he dci f eceie cae gae, eceie fie, fidiai, iciec

f fia ie ce, ied ad ifi f fiihed dc [15].

2.3.2.

A fidied bed gaa ci f eea ke ce (Fige 2.2, [16, 17]). A

(1)a eaig he ce ad iig ciica ce aiabe. A geea ide ai i

ed fidie he aice, a (2) i eeia f ai fieig, heaig, cig adea f hidi. Afe ecdiiig he ai, i i aed hgh he bed f id i he


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16

(3)ia he (4). The e f caie ad ai diib

be eeced accdig bai a e dc fidiai. The bide iid i idced

he fidiig aice ia a (5) e. The fid (bia) e i c

aied i fid bed gaai a i i abe fci a e iid ae ad ffe a

ced de ie, ideede f f ae. Wih hi e, he bide i (e fid) i

aied b ceed ai (he fid). The a ae ad age ca be dified b adjig

he ii f he ai ca dig he e eede ad b aig he ai ee eied f

aiai f bide iid.

F 2.2.Scheaic f a a fid bed gaa ih aige f i diffee ce: (1)

c ae, (2) ai hadig i, (3) dc caie, (4) ai diib ae, (5) a iaed e,

(6) , (7) ai eai chabe, (8) fie bag, (9) ai fie e, (10) eha be. A idicae

he dieci f he aif.

Deedig he cai f he a e, diffee e f fid bed gaa ae cideed

dcig gae ih aig chaaceiic [18]. Ta fid bed gaai, ih he e

caed a he f he chabe i he fee died ad ed echie [19]. The

bide iid i aed f he d he fidied bed, cece he fidiig

ai. Dig ba gaai, he e i iied a he bae f he chabe, i he

idde f he diib ae, ad iid i aed i he ae dieci f he fidiig ai. The

ba gaa ca be eied ih a aii c (i.e., We aii) ad a

ecia deiged diib ae egae he fidiai ae. The ae, ih efai

1

2

3

7

4

5

6

8

9

10


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ie deceaig f he cee he e a, eabe a highe ai eci iide he We

aii ha i he e egi ceaig a faiike ee. Idcig he a e a

he ide f he chabe, ebedded i he de bed dig gaai, ced

ageiaa gaai. Thi echie i a caed a fidied bed gaai de he

aig dik iaed a he b f he bed ( e f ai diib ae). Thi dificai f

he adad fid bed gaai e cbie he adaage f fidied bed ad high hea

gaai de he addiia echaica agiai. The a gaai ce i aked b

ceifga, high iei iig ad efficie fid bed dig, iedig a dc ha i e

heica, dee ad e caed aed gae [20]. The bide iid i

eiaiced (6) he e hgh a a ace ad big. T eaae aice f he

e ai, e i he fid bed eie ae ed. I he (7), he

age aice ae ihda a he e hei e. F (8) ca be eidica

hake eidce he ceced fie i he fidied bed. The ai eae he e hgh a

(9), eig he eida ae aice f he eha ai ad a (10)

fa, keeig he e a a e ee ha he dig ahee.

The ai aibe f he fia dc a be aiaed b chagig ce eaig

aiabe ( )ad dc fai aiabe ( ), hich affec

he deig gaai echai. Oeaig aiabe ae eaed he gaai

eie ad ca be diided i aaa aiabe ad ce aaee. Fai

aiabe ae defied b he chice f aig aeia ad bide i (Tabe 2.1).

A fac ifecig he eig f he de b he aed bide iid affec he fai f

iid bd ad heefe aggeae gh [21]. Eecia i fidied bed gaai, hee

eig fac ciica deeie he fia gae ie diibi de he eaie hea

fce ee dig ceig. The abece f hea fce age eic aice deificai

ad iid aai f he aggeae, heefe edcig gae gh b caecece.

Iceaig gae gh b iceaig he bed ie ee i diffic, a hi a e i bedcae de he fidiig caaci f he e a [22]. Deaied eie f he effec f

eaig ad fai aiabe he ai eie f gae dced b fid bed

gaai, ae aaiabe i ieae [6, 8, 16, 19, 2328]. A eie f he aaee i ied i

Tabe 2.1, ih he ai ha bide ad faca ae added i i ( a a d aeia

i he de i) ad he e i iaed a. I addii he idiida ifece f

eaig ad fai aiabe he ed dc ai, he aaee effec ae a

high cdeede. Hece, hee ieaci eed be ded ad ake i acc

dig iiai ad aica cae if e a achiee a deied dc ai. Fae


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ad cke [29] eieed he aaee ha eed cig dig e gaai, ad h

hi ifece ce c ad cae.

2.1. Oeie f a fid bed gaai eaig ad aeia aiabe ifecig gae

ai aibe ( ).

aaa aiabe ce aiabe aig aeia bide i

2.3.3.

Dig he fi aicai f fidied bed gaai, ecie c f he ce a abe.

A hiica ehd f deeiig he dig edi cied f feeig he eai chabe

f iceaig eeae [30]. Thi ehd k cideabe ie fie e ad a e

baed iii ad eiici. The ack f iig ad c e ade edcibe

gaai i a eiabe ae diffic [18].

C f he fai ce ad he ce i eeia ee he cie

dci f gae ih he deied ai chaaceiic (i.e., gae ie, ie diibi,

ie ce, dei, fabii ad fiabii). The ai aibe ae affeced b he

eie f aig aeia (Tabe 2.1), heefe aiai i feed aeia eie hd be

iiied. The e f a ai hadig i a fieig, heaig, cig ad hidi ea f

he ie ce ai [8, 16]. The ai dehidificai i eecia ia he he dci

i i caed i a ciae ih age ie aiai, a he bide iid eaai ae i

deeied b he cee f hea ad a afe. Hea i afeed he gae

eaae he bide e, hie a i afeed a a a f he gae i he


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dig ga. The caaci f he icig ai abb ie (i.e., dig caaci) deed

i eeae ad eaie hidi. Theefe, b cig hee aaee, a

edcibe dig caaci ca be achieed cibig a ced fid bed gaai

ce.

The ecdig ad c f ciica gaai ce aaee a iiia caied b a

eaic aag c deice, hich e ceed ai a a igaig edi ce

ifai f gaa eaig ie. The eaic igaig e ehibied a

deied iici ad afe, b i effeciee a high deede f he ea

ieeai ad aci ee dc ai ad accae daa ggig. Thgh he

deee f gaabe gic ce ad ce a e eiabe c, bach

dci ad daa aciii a achieed. A PID (Pia, Iega, Deiaie) ce i

c ed a a feedback c echai. I cacae a e ae f a ce aiabe

a he diffeece beee he eaed ce aiabe ad a deied e i. The ce

ae iiie he e b e f a cecie adje aci. The aif ae ad

eeae ae ica ce aiabe ha ca be adjed b a PID ce i fid bed

gaai. The ceced ce e iga ae ceed ad ca be ecaed ie a

bach ceificae. Dig he aig eid, ciica daa eaed he ie ai hidi ad

eeae, dc ad e ai eeae, aif, bide a ae, aiig ai ee

ad ee d ac he bed ae ceced. Dig dig, he ie ai eeae ad

hidi, dc ad eha ai eeae ad aif ae ci ied. I

aica, he dc ad eha ai eeae idicae he ge f dig ice fid bed

dig i ica chaaceied b age f ae [31]. The fi i hea afe iied ad

ced he eaai f ae f he aice i he bed. I h a iea deedec

ih ie ad he bed eeae eai ca dig hi hae ( ).

Whe face ad e aciaed ae ha eaaed, he eaiig ae diffe he

face f he gae befe i i , hich i gea affeced b he aice gee. Whe hea f ae ef eaae eache a ii ae dig hi ecd age, he eha ai

eeae i iceae, aachig he ie ai eeae. Hece, dig edi i ai

deeied b he eeae f he eha ai [8].

Reeach hed ha hi eeabihed ehd f deecig dig edi ia he eha ai

dc eeae, i eeaabe if he hidi ee f he ie ai i ced. B e

f he eeae diffeece beee he ie ai ad fid bed a (T), he effec f aiai

i ce ai hidi dig edi deeci i eiiaed [32]. Hee, e hd a

ake he ifece f fidiai he T echie i acc. Ie fidiai, ee f


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h eid, ca be a aj ce f deiai f he T echie, a he eeae f he

gaai a i eaie highe he fidiai i [33]. T hade hi iedeedec f

ce aaee, ia de hae bee ecgied be ef i he iig f bach

daa. Sccef bache ee eaaed f ccef e b a PARAFAC2 ehd baed

he iig f hee gaai ce aiabe (i.e., ie ai, e ai ad a eeae)

[34].


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21

2.4.EIHEIAI

2.4.1. G

Eiheiai i e f eea echie eae eeied dage f. Pee aeheica, feefig gae ih a a ie diibi, ica aig beee 500

ad 1500 i haaceica aicai. Theaeic adaage f ee a a dg deie

e icde e iiai f he gaieia ac ad a eed ik f ide effec de

de dig [35]. B e f ee, eea acie ce, icaibe dg dg ih

diffee eeae fie a be cbied i he ae dage i. Pee dced b ei

heiai ehibi a gd fabii, fiabii, high hade ad edcibe ackig [36].

Thee eie a cibe he eae ih hich he ee a be caed. Ei

heiai ehibi a high ce ied, ad high ee f he acie cd a be

icaed ih dcig a eceie age aice.

Cie ad Hade [37] ee he fi decibe he dci f ee ia ei

heiai i he haaceica id, ad Red [36] eabaed hi k hgh he

fhe decii f he eie ad ce echai. Eiheiai i a i

e ce ciig f he fig cecie age (Fige 2.3):

()

d f dg ad eciie() achiee a hgee de bed

() addii f bide iid he d a (i.e., e ) dce a (fficie)

aic e a

() haig f he e a i cide caed edae f if diaee (i.e.,

)

()

beakig f he edae i ae cidica d ad dig hee i heica

gae (i.e., )

F 2.3. Scheaic eie f he e ied i a eiheiai ce.

+


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The heica aice ae he died a eeae a a eeaed eeae (i a

e, a fidied bed icae e) i he deied eida ie ee i achieed. A he

diffee ce e ae ifeced b a be f ieeaed ce ad fai aiabe,

he eiheiai ce eie he ecea c bai he eied ee

ai. The ee ie diibi, hae, fiabii, dei, i, f eie ad

dii behai ae geea eaaed ae he ee ai [38, 39].

2.4.2.

D iig ad e gaai

A if bed ha be baied befe e gaai ca ake ace, a i affec he ee

ce ifi. A ee diibi a a e i ca eeig dig gaai,

f aeia ih age diffeece i ie ad bii eie [40]. D iig ad e

gaai ae a caied i he ae eie (e.g., aea ie, high hea ie,

iga bade ie), e a ci gaa i ed. The eied a f gaai

iid i geae ha ha f ceia e gaai echie ad i cbiai ih he

diei f he fid, i gea ifece he dea ce e f ei ad

heiai.

Ei

Dig ei, he aic e a i fced hgh a die ad haed i cidica aice

ih a if diaee. The ea edae diaee i deeied b he diaee f he

die, ad i egh deed he eie f he e a ad he ede e. A aie f

ede e ha bee deeed, ad ca be diided i hee cae baed hei feed

echai (i.e., he a b hich he e a i aed hgh he ei e): ce

feed ede, gai feed ede, ad i feed ede, h i Fige 2.4 [41].


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F 2.4.Scheaic eie f he ede e aied i eiheiai. Sce feed

ede ih aia (a), de (b) ad adia (c) e, gai feed ede ih cide (d), gea (e) ad adia

e (f) ad i feed a ede (g) [42].

Sheiai

A heie ci f a b ih fied idea ad a b ae dik ha ae a a high

eed (Fige 2.5). The heie i fied ih edae, ad de ficia fce geeaed

b aiceaice ad aiceeie ieaci, he edae ae iiia bke i

ae cide ad he ded i hee. T ehace he fce geeaed a aice e

ac i face, he b ae geea ehibi a ged face (chached ae

adia ae).

F 2.5.Scheaic f he aice ee i a heie [42].

G

a

c

b

d

e

f

g


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The afai f a cidica edae i a heica aice cc i ai age, ad

de hae bee ed decibe hi ce (Fige 2.6a ad b). Accdig Re [41]

(Fige 2.6a), he cide ae ded ff a he edge, fed b he fai f dbbe

haed aice, eiid ad fia hee. The de ed b Bae ad Re [43]

(Fige 2.6b) gge ha he cide ae ded ff a he edge, b ae addiia be

eig i he fai f a ehaed aice. Ne, a dbbe ih a ied idde i

fed, iiiaig aice beakage i heica aice ih a cai hei fa ide.

Fhe dig i he heie ceae cee heica aice. Rece, Kee ad

The [44] eed ha hee geea aded eeiai echai eed be eeded,

acc f he aeia afe beee ee aice (Fige 2.6c). I addii aic

defai, he ah a beed a aeia afe beee ee aice f diffee

fai. Heeih, egia diici i he a f a afe ad a ifece f he

ae ce ee beed.

F 2.6. Scheaic eeai f he diffee ee fai age dig heiai accdig

Re [41] (a), Bae ad Re [43] (b) ad Kee ad The [44] (c).

2.4.3.

Eiheiai ca be a efficie ehd aface ee dage f, b he

ce ehibi a ack f eiabe ad eadi eaed aaee eabih adeae c f

he ce [45]. Vai ce aaee affec ee ai, ad heefe a ic ced

afacig cede eed be fed.

C f he eeae dig ei i f igifica iace a he eeg diiaed

dig he ei cce ca iceae he ede eeae ad cae e f he iid


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eaae f he edae (aica f i face). Thi a ead a diffeece i he

ai f he edae dced a he begiig e he ed f he bach. The edced

(face) ae ce a affec he heiai age. I addii, ei eeae

c i eecia ia he ceig a heabie dg fai.

The a f he ede i ai deeied b he ei eed. Hece, f ecica

ea e d efe high ei eed. Hee, face defec bece e

ced ih iceaed ei eed, eadig e ai ee dig heiai

[46].

The heiai eed ad ie a be ced, a bh ifece he fia ee ai

b a be f ee eie [39].


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26

EFEECE

[1] B.J. Ei, J.D. Lie, i: R.H. Pe, D.W. Gee (Ed.), Pe' Cheica Egiee'

Hadbk, McGaHi, Ne Yk, 1997.

[2] J.B. Scha, Dg Deee ad Idia Phaac, 14 (1988) 20712090.

[3] L.L. Agbge, M.K. Vaa, i: D.M. Paikh (Ed.), Hadbk f Phaaceica


[4] S.M. Ie, J.D. Lie, K. Hagd, B.J. Ei, Pde Techg, 117 (2001) 339.

[5] C. Bache, P.M. Oe, P. Beee, J.M. Segaad, Ieaia Ja f

Phaaceic, 358 (2008) 6974.

[6] Z.H. Lh, D.Z.L. E, L.W. Cha, C.V. Lie, P.W.S. Heg, Ee Oii Dg Deie, 8

(2011) 16451661.[7] C. Aege, Dg Deee ad Idia Phaac, 11 (1985) 725741.

[8] D.M. Paikh, J.A. Bck, M. Mgae, i: D.M. Paikh (Ed.), Hadbk f Phaaceica


[9] D.M. Nei, J.M. CaJe, Ieaia Ja f Phaaceica Techg ad

Pdc Maface, 36 (1958) 422.

[10] C.G. Ba, The Cheica Egiee, 220 (1968) CE196CE201.

[11] R. Dii, S. Phi, Ja f Phaaceica Sciece, 98 (2009) 39333960.

[12] D.E. We, Ja f he Aeica Phaaceica Aciai, 48 (1959) 451454.

[13] D.E. We, Ja f he Aeica Phaaceica Aciai, 49 (1960) 8284.

[14] T. Like, W. Mb, Dg ade i Gea, 11 (1968) 182189.

[15] Ni Phaa Se (GEA), Phaaceica Techg Ee (Ma 1998).

[16] D.M. Paikh, i: M. Lei (Ed.), Phaaceica Pce ScaeU, Mace Dekke Ic., Ne

Yk, 2002, . 171220.

[17] M. Jacb, i: A.D. Saa, M.J. H, J.P.K. Seie (Ed.), Hadbk f Pde

Techg, Eeie, Aeda, 2007, . 417476.

[18] D.M. Je, Phaaceica Techg, 9 (1985) 5062.

[19] M. Bak, M.E. A, Dg Deee ad Idia Phaac, 17 (1991) 14371463.

[20] L. G, C.V. Lie, P.W.S. Heg, Dg Deee ad Idia Phaac, 30 (2004) 111

123.

[21] X.H. H, J. Cigha, D. Wiead, Ja f Phaaceica Sciece, 97 (2007) 1564

1577.

[22] S.H. Schaafa, N.W.F. Ke, M.T. M, L. Ba, A.C. Hffa, ALChE Ja, 45 (1999)

12021210.


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[23] J.A. Hee, Ieaia Ja f Phaaceica Techg ad Pdc Maface, 2

(1981).

[24] G.H. Kiee, T. Schaefe, Dg Deee ad Idia Phaac, 13 (1987) 803872.

[25] P.J. Sheig, R. Oie, i: A.S. Gdbeg (Ed.), Pde Sciece ad Techg, Hede,

Ld, 1981.

[26] W.J. Thie, Ieaia Ja f Phaaceica Techg ad Pdc Maface, 2

(1981).

[27] S. Siaaa, G. Miha, Ieaia Ja f Phaaceica Sciece ad Dg Reeach,

2 (2010) 236246.

[28] A. Heai, R. Cheif, K. Saeh, V. P, Pde Techg, 130 (2003) 1834.

[29] A. Fae, P. Yk, R.C. Re, Eea Ja f Phaaceic ad Bihaaceic, 52

(2001) 269277.

[30] K.A. Macia, M.T. Caaja, i: D.M. Paikh (Ed.), Hadbk f Phaaceica Gaai

Techg Thid edii, Ifa Heahcae, Ne Yk, 2010, . 567577.

[31] K.R. Mi, S.L. Nai, G.E. Peck, S.R. B, U.J. Giee, J.G. Se, S.J. Hag, K. Pak,

Phaaceica Sciece & Techg Tda, 1 (1998) 235245.

[32] M. Ade, P. Tkig, A.C.R. S, Pde Techg, 54 (1988) 1525.

[33] T. Liae, O. Aikaie, H. Raikke, S. Aiakie, J. Yii, Ieaia Ja f

Phaaceic, 357 (2008) 3743.

[34] S. Mae, S. Piaie, J. Lekie, S.P. Reiikaie, J. Keaie, K. Jaie, A. P,

Cheeic ad Ieige Laba Se, 96 (2009) 8893.

[35] H. Bechgaad, G. Hegea Niee, Dg Deee ad Idia Phaac, 4 (1978)

5367.

[36] A. Red, Mafacig Chei ad Ae Ne, 41 (1970) 4043.

[37] J. Cie, H. Hade, Dg & Ceic Id, 106 (1970) 3841.

[38] V.R. Siha, M.K. Agaa, A. Agaa, G. Sigh, D. Ghai, Ciica Reie i Theaeic Dg

Caie Se, 26 (2009) 275331.

[39] C. Veae, L. Bae, J.P. Re, Ieaia Ja f Phaaceic, 116 (1995) 131146.

[40] D.F. Ekbi, i: D.M. Paikh (Ed.), Hadbk f Phaaceica Gaai Techg,

Mace Dekke Ic., Ne Yk, 1997, . 333368.

[41] R.C. Re, Phaac Ieaia, 6 (1985) 119123.

[42] D.F. Ekbi, i: I. GhebeSeaie, C. Mai (Ed.), Phaaceica Ei Techg,

Mace Dekke Ic., Ne Yk, 2003, . 277322.

[43] L. Bae, J.P. Re, Ieaia Ja f Phaaceic, 95 (1993) 135141.

[44] M. Kee, M. The, Aa Phaciech, 11 (2010) 15491551.


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[45] D.I. Wi, S.L. Rgh, i: A.D. Saa, M.J. H, J.P.K. Seie (Ed.), Hadbk f

Pde Techg, Eeie, Aeda, 2007, . 189217.

[46] P.J. Hai, J.M. Ne, R.C. Re, Ja f Phaac ad Phaacg, 37 (1985) 81

83.


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CHAPTER 3 PROCESS ANALYTICAL TECHNOLOGY IN FLUIDIZED BED GRANULATION & EXTRUSIONSPHERONIZATION

29

CHAE3

CE AALICAL ECHLG I

FLIDIED BED GALAI &EIHEIAI

Pa f hi chae ae bihed/acceed f bicai i:

T. De Bee, A. B, M. Fee, L. Saee, J.P. Re, C. Veae, Nea ifaed ad Raa

ecc f he ice iig f haaceica dci cee, Ieaia

Ja f Phaaceic, 417 (2011) 3247.

A. B, T. Mee, J.P. Re, C. Veae, T. De Bee, Pce aaica f

iig, deadig ad c f haaceica fidied bed gaai: a eie,

Eea Ja f Phaaceic ad Bihaaceic, acceed ih i eii.


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CHAE 3

CE AALICAL ECHLG I

FLIDIED BED GALAI &

EIHEIAI

3.1. CE AALICAL ECHLG

3.1.1. I

F decade, haaceica afacig cied f bach ceig ih aba eig

cdced ad ceced ae ae he ieediae ed dc ai. I

addii he ffie eig, dc ai i eed b deeiig a aeia eie

ad haig a fied dg dc afacig ce [1]. Sie iaiae e ch a

ee, eeae ad H ae ed c he dci cee. The cee

heee ae fe f ded ad ae heefe cideed a iefficie backbe

(Fige 3.1, ). Liied eea dc ifai i ai baied afe afacig,

akig ce c diffic hich ca ead bach e.

F 3.1. Cai beee he adiia fied a f haaceica afacig () ad he PAT

baed aach eadig a b ad adjabe ce, gaaeeig he ed dc ai (b).

Thgh he deee f eaie aae, eea adiia ffie aba echie

hae bee eaced b eaie ai eaee i a idie (e.g., cheica, fd,

ADIIAL A

F AFACIG

I

Black -BoxFixed

I

M

Control Loop

ALEAIE


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32

agica, ec.) [2]. Thee eaie ce aaica ehd diffeeiae f he ffie

aba echie b he eaee ie, ih he fe he iecae f ecd (

ie) a ed h da f he ae. B eiiaig aa ae hadig, he

ae iegi i eaied ad he ik f e b he ea i edced. The gig iee i

he ieeai f e ce ce aaic ihi afacig idie i die b

he iceaed caabiiie f hee e ih egad bh cieific ad egieeig c [3].

The ce cheica ad hica aae efed i, iediae a he ce ea

eabe (aaic) ce c ih feedback ad/ feedfad, he edci f cce ie

ad afe iigai. I ha a, he dc ai ad ied a be iceaed ad ab c

edced. I he g , he iceaed ce ifai a he ci iee f

he ce. Ne hee fiacia die, he e f ce iig daa a he

chage i a afacig ce, b hig he eiaec f a ehaced ce he i

egieed ei. A ke aec eaie ce aai ad c i he high ee f

cei aciaed ih i deig, ieeai, daa ieeai ad aieace, hich

eie he ecea eeie [4].

De he ic egaed eie f he haaceica id, he ec ha bee

heia idce hee iaie e i hei afacig cee [5, 6]. Theefe,

eea gideie hae bee ie b he Uied Sae F D A [79] ad

he I C H (ICH) [1012] ie ce eface ad

dc ai i he haaceica id. The FDA iiiaie Pce Aaica Techg

ecage dee ad iee effecie ad efficie iaie aache i

haaceica deee, afacig ad ai aace. Cig he ai f he

dc dig iead f afe ceig, ad aifig (ad edcig) heeih he ce

aiabii i haaceica afacig i ed. The ci gaheig f ciica

ce ifai dig dci hd eabe he aii f a fied a b

afacig ce ih eaie ce adje, hece eig he ai f each eddc ad aidig bach e (Fige 3.1, b) [13]. Thgh hi eaie ai c

aach, he cce f i idced i he PAT gidace, i.e., eeae a a

he bach aface i cee. The aadig hif f bach ci ceig a

die he haaceica id ad PAT [14]. The beefi f ci ceig (e.g.,

edci i cae ie, e feibe ee chage i dead, e cce ie) d

be aed ih he e f ce aaic ad feedback ad feedfad c

kee he cee de c [15].


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3.1.2. A F

The FDA ha defied PAT a ,

(.., )

, [9]. Heeih,

he e aaica i PAT i ieed bad, icdig cheica, hica, icbigica,

aheaica, ad ik aai be cdced i a iegaed ae.

The ai f PAT i , hich i

cie ih he FDA ce dg ai e aig ha

, .

T cee dead he ce, a ciica ce f aiabii hd be ideified ad

eaied, ad he aiabii hd be aaged b he ce. I ha a, he accae ad

eiabe edici f he dc ai (e he deig ace) i eabihed gie ha he

aeia ed, ce aaee, ad afacig, eiea ad he cdii ae

ideified.

Thee ae eea PAT ad icie aaiabe eabig ad adacig he ieeai f a

PAT e i a haaceica dci ce. The PAT ide eea ifai

ab he cheica, hica ad bigica eie ehace ce deadig ad i

heefe eabe ce c ad iiai. Pce edi i ge be defied i

e f a fied ce ie, b ahe b he eaie eaed dc ai, iig

ce efficiec. A cbiai f iabe PAT i aa ecea achiee he deied

ee f deadig ad c, ad hee ca be caegied a fed [9]:

Miaiae f deig, daa aciii ad aai

Thgh he e f iaiae aheaica aache ch a aiica deig f eeie,

ee face ehdgie, ce iai ad ae ecgii i cjci

ih kedge aagee e, a cieific deadig f he eea ifacia

eaihi beee dc ad ce ca be achieed. Daa ceig ad cheeic

eabe eacig ef ifai f he ce iea ad he daa ea

ehace ce deadig ad eabe he deee f deeiiic de f ce

c [16, 17].

Pce aae

Pce aai b efig iaiae ce eaee (e.g., ee, eeae ad

H) ha eed ad he decie eaee f cheica, hica ad bigica


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aeia aibe b e ce aae. The eaee ii f hee aae eaie

he afacig ce ca be caegied a fed (Fige 3.2):

:he ae ieface i caed i he ce ea (iaie iaie), ad

dc ifai i deied ih eig ae f he ce

: he ae i dieed f he ce ia a aig , he eaee

eie ad a be eed he ce ea

: he ae i eed f he ce ad aaed i ce ii he

ce eie, ihi he iecae f afacig

F 3.2.Iaig he diffeece beee iie, ie ad aie dc eaee dig

afacig.

A aie aicai a ie e eaed he aig ad i e iecig ha

he iie ad ie echie. Ahgh iie eaee ae icke i idig dc

ifai, he ce iefacig i a c ifa he deeig a iie PAT aach

[18]. The cai f he iie be, i age f iei ad eeai deh eie

eeie ieigai ae a ei eaee eface ih iia iac he

ce. Vai echaica ieface deig hae be eaaed ad dificai he ce

eie hae be cideed.

Pce c

B e f ce iig ad c aegie, he ae f a ce ca be ied ad

acie aiaed aiai he deied ae. I ha a, he cie ai f he

aeia ad he fia dc ca be eed (Fige 3.1). Hece, he cce ( faie) f PAT

deed he ce figei baied b he eaie ce aae, b a

:

.


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he deee f a heeica eiica ce de ha adeae decibe he

cee ccig ihi he i eai [19].

Ci iee ad kedge aagee

The ci daa ceci ad aai e he ife cce f a dc cibe he

ci eaig ab he dc ad jif a f aa chage.

The e ad fci f PAT a a dig he ifea f a dc ce [20]. The

ehd aied dig he iiia deee hae a defiig ad deadig he ce

deig ace ad i eaihi he dc ai aibe. I addii, he efficie ad

b eaig cdii dce high ai dc ae ideified (ce iiai).

Dig cae, fhe ce kedge i ided b he ce aaic, ad he ce daa

baied dig iiia deee ae caed he i a fcae daa. The ce

aaic aied dig f cecia afacig a ce iig ad c

aiai ce be ad/ edce ce aiabii. The acica ieeai aec

ih egad afe, eiabii, aidai ad aieace a hae be cideed a hi age.


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3.2. EAEE ICILE F HE ALIED CE AALE

I hi hei, eea ce aae ee aied dig e gaai echie (i.e.,

fidied bed gaai ad eiheiai, Chae 2), caig he gae dc

ifai i eaie. I he fig eci, he eaee icie ad chaaceiic f

hee PAT e ae diced.

3.2.1.

The Pa IPP 70 be (Geechaf f Paike, Sg d Ueeechik, Chei,

Gea) e he eabihed icie f aia fie ecie (SFV) iae eae

he eci ad ie f idiida ig aice [2123]. Fige 3.3 cheaica dia he

Pa be deig.

F 3.3.Scheaic f he Pa be deig ad i ce. The be a idicae he dieci

f aice ee hgh he eaee e.

The Pa be i eied ih a eaee e iide he be cied f ahie

eaee id (Fige 3.3). Dig SFV eaee, a ae igh ae hgh he

be, ad aice aig hgh he eaee e bck he igh eceied b he deec

aa (Fige 3.4). I ha a, a b iga i geeaed, ad he feec f hi iga (

) i

eaed b h deec. I ae i ia he aice eci :

ih he aia fie ca, cedig he diace beee each deec (Fige 3.4).Kig he aia fie ca, he aice eci ca be cacaed.

....

...

.

. .

.

.

. .

L = 280

D=25

= (3.1)


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F 3.4.The eaee icie f aia fie ecie [24].

Deeiai f he aice ie i baed a ecda e (i.e., e iga), hich i

geeaed b a ige ica fibe he he aice ae hgh he ae bea (Fige 3.4). The

ie f he ig aice () i cacaed ig he ie f he e iga () ad he eci fhe aice ():

ih he diaee f he ica fibe.The ae i E. 3.2 deed he hae ad he ajec f he aice he cig heae bea (Fige 3.5). Theefe, he ie ae eaed b he SFV icie eee a aice

chd egh, hich i defied a he aigh ie beee a i he edge f a aice.The chd egh ca be eaed ahee he aice, f ee aec.

F 3.5. Deedig he ajec, ie ad hae f he aice, diffee chd egh ae cacaed.

The SFV daa caed f idiida aice ae accaed i a cica bffe, eig i he

cacai f chd egh (ad eci) diibi. The a be f eaed aice i

ke ca i hi cica bffe, idig a ci daed aice ie diibi

hgh eacee f he de eaed ie b he ee ae. A (be f aice

i he) aice bffe e i e aie ie e, hie a age ig bffe ceae a

hig f he eaed ie. Sie aaee deied f he chd egh diibi (e.g.,

D10, D50, D90) ca be ceaed agai he ie daa f he aice ie aae, keeig i

B :

= f0*g

E :

= * d

= (3.2)


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id ha he SFV echie de ae he aice be heica. The SFV echie

ide bh eic ad iea be ie diibi.

The Pa IPP70 be (Fige 3.6, ef) i cac, e b, cced f aie ee,

eie caibai ad ca be iaed diec i a ce ie ide ci aice

ie ad eci eaee. A age f acceie (Fige 3.6, igh) i aaiabe eed he

be aicai diffic ce eaee cdii (e.g., gea ad ick aeia).

The acceie ca be iaed i he eaee e (cii ce), ecig he ica

id ad adaig he be f diffee aice f. I addii, i he IPP 70S e, a

ceed ai ceci ee a ca ai big i f f he eaee id,

ad dii f ae f he aice adig i high. The e i iabe f ie

eaee i he aice ie age f 50 6000 ad he aice eci age f 0.01

/ 50 / ih a daa ae 20000 aice/.

F 3.6. Pice f he Pa be (ef) ad he cii ce (igh, ie).

3.2.2.

The FahSie 3D iagig i (FS3D, Ieige Phaaceic Ld., Fiad) ci f a

che CCD caea ceced a ea cee ih a ga id ad a ce [25,

26]. A aia f heic ee [27] ih hie igh ce, aced 180 f each he

i a hia ae ad a iiai age f 30, i ed ceae a 3D face f he eaed

ae (Fige 3.7).

F 3.7. Scheaic eeai f he heic ee iagig e.


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Dig eaee, he aice ae i eeed he iagig ie ga id,

ad he dieed ae i iiaed b he igh ce. The ieig dieci f he

caea i ke ca, b he dieci f he icide iiai i aied. I ha a,

digia iage ae caed dig each eaee (Fige 3.8, ef). The eig gadie fied

baied ih hi e cai diec ifai ab face a i ae ad idiec

ifai ab face a i ae. B ie iegai i he hia dieci, a 3D

face i baied (Fige 3.8, igh). Peak he 3D face ae aed be aice, ad b

e f he eak aea i hedieci, he e baed aice ie () i cacaed:

ih

he aice diaee,

he aea f he eak ad

he caibai ca.

F 3.8. Eae f he heic ee iage aciii (ef) ad 3D iaiai (igh).

I addii he aice ie diibi (eeed a iee diibi ad ie eceie), 2D

iage ad bighe ae ae deied f a ige FS3D eaee. The ge cae ae i

he digia iage f ae face ced he bighe f he face ad ae

chaaceied b a be i he age f 0 255, hee 0 i a back ad 255 i cee

hie. Cacai f he aice face bighe ide i baed diffeece i hee ge cae

ae.

Ice FS3D eaee ca be accihed hgh a iabe id, ad he

aice hae be aic f he dai f he eaee i de cae he FS3D iage.

The iaiee f he echie eiiae he be aciaed ih gig iide he

ce, b a iabe ce iefacig f he eaee eie ha be deiged. The

FS3D iagig e ed i hi hei ehibied a ie ei f 10 ad iage aea

diei f 1.2 1.6 c. The e a caibaed eae ie 5000 .

1 2

= (3.3) = (3.4)


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3.2.3. F

Siia he SFV echie, he fced bea efecace eaee echg (FBRM, Mee

Ted, USA) i a ae baed echie ha ide ice chaaceiai f aice [28]. A

bea f chaic ae igh i e hgh he FBRM be, ad b e f a e f ee he

ae igh i fced a a (Fige 3.9). Thi fca eed be caef caibaed

hae a ii a he ieface beee he be id ad he ig aice. Thgh

ai f he be ic a a high eed, he fced ae bea ca i a cica ah ac

he ig aice i f f he eaee id (caed a he be i). Whe he

fced bea hi a aice, he ae igh i backcaeed ad agaed hgh he be. The

dai f each e f backcaeed igh i iied b he (k) ca eed cacae he

aice chd egh. The ca eed f he FBRM echie ca be aied beee 2 / ad 8

/, eabig he eaee f had f chd egh each ecd. The eig FBRM

chd egh diibi ae baed he chd egh eaee f idiida aice,

ceced ihi a eeeced eaee ie.

F 3.9. Scheaic f he FBRM be deig ad i ke iea ce

(egh = 400 , diaee = 34.2 ).

Uike he f SFV eaee, he FBRM fae de af he eaed

chd egh i ek e be diibi, b ide he eaed a

chd egh diibi. Ceai beee FBRM chd egh diibi ad ie daa f

he, ffie ie aae ch a ae diffaci ad ieig hae bee eed f gaai

cee [29]. The gde f he ceai ica deed [30]:

he aice hae: ae diffaci ae he aice be heica, heea

FBRM de

fie i he eece f e cae aice: FBRM i eiie fie, heea

ae diffaci ad ieig ae

FBRM


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The FBRM echie eie caibai ad he be ca be iaed diec i a ce ie

ci ide aice ie eaee. The igia deiged be a eiie

id fig b he i dc a dig gaai [31, 32]. Rece, he FBRM C35

be ha bee ceciaied, hich i eied ih a echaica cae (ie) he

eaee id cea he ica id a a edefied ie iea. The e i

iabe f ie eaee i he aice ie age f 3 3000 .

3.2.4.

Nea ifaed (NIR) ecc die he abi f eecageic adiai i he NIR

egi, hich i accdig he Aeica Scie f Teig ad Maeia defied a he

aeegh age 780 2526 (cedig he aebe age 12820 3959 c 1) [33].

A he NIR abi bad e f ee cbiai bad f he fdaea id

ifaed ibai.

Dig NIR eaee, ae ae iadiaed b NIR igh. Se f hi NIR igh i abbed b

he ece, bigig he a highe ibaia ae (Fige 3.10).

F 3.10. Scheaic eie f he eeg ee aii aciaed ih IR ad NIR abi, he

Raa effec ad fecece.

O ibai aciaed ih chage i ece die e ca abb NIR adiai. A

die i he dc f chage (iie ad egaie) ad diace. Fige 3.11a h ha hee i

chage i die e dig he ech ibai f a X2 ece, hie f he ech

ibai f a XY ece (Fige 3.11b) hi i he cae. Hece, diaic ece eie a

eae die be NIR acie, hie aic ece eie a die idced b he


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ibai. Theefe, H2de abb NIR adiai hie OH, NH, CH ad SH bd ae g

NIR abbe. Mece ha abb NIR eeg ibae i de: echig ad bedig.

Sechig i defied a a ci chage i he ieaic diace ag he ai f he bd

beee a. Bedig ced a chage i bd age.

F 3.11. Scheaic f he ibe chage i die e dig he ech ibai f a X2(a) ad

XY (b) ece, eecie.

Fige 3.12a h hee ibe ibai ae f a diaic ece. The eia eeg f

hee ibai i deede he bd egh a ca be ee i Fige 3.12b, eeeig a

ahaic ibai de. A eiibi, he eia eeg i . Bigig he a ce

each he idce ei, eig i a iceae i eia eeg. Pig he a aa

f each he ead i fi iace aaci, eig i a iceaed eia eeg.

Fhe diacee f he a i e i diciai. Hee, deied f a

he, e ibaia eeg ee ae aed, eeeed b he hia ie i Fige

3.12b. Thee eeg ee ae eidia i a ahaic de.

A NIR ec cai ee ad cbiai f he fdaea idifaed bad. The

ee cc a ab ad hee ie he feec f he fdaea ibai, ih a

deceaig abi iei a ee iceae. Cbiai bad ae he f eea

fdaea f diffee ibai. Cbiai bad ae ica iaed a e eegie

ha ee.

F 3.12. Vibai ae f a diaic ece (a) ad he eeg ee accdig he ahaic

ibai de (b).

A B

A B

A B


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The NIR abi bad i a NIR ec ae ica bad, eaig ad eake ha he

cedig fdaea idifaed abi. Theefe, cheeic daa ceig i

aa aied eae he NIR eca ifai ae eie. De he da

deedece f he NIR iga he cheica a e a he hica ae eie (eig

f abi ad cae effec), a age ee f aae ifai ca be deied f e

ige NIR eaee. O he he had, if e i ieeed i he hica ae

eie, he cae effec i he NIR eca a iefee he deeci f he age cd.

Theefe, eca eeae befe cheeic aai i fe deied edce he effec

f iefeig aiace i hich e i ieeed, heeb iceaig he aiace de he

aaee f iee [34].

NIR ecc eabe a aid ae eaee (de f ecd), a a eaie c ad

i decie. A NIR ce aae, ieded f eaie iie ie ce

eaee, i eied ih fibe ic afe he NIR igh ad ef NIR eaee

aa f he ea. I addii, ecia deiged be eabe a aighfad ce

ieface.

3.2.5.

The Raa effec a heeica ediced b Seka [35] i 1923 ad beed f he fi ie

b Raa ad Kiha i 1928 [36]. The Raa effec i he ieaic caeig f eecageic

adiai a a e f he eeg echage beee he icide adiai ad eca ibai

[37].

Dig Raa eaee, ae ae iadiaed ih chaic ae igh. Tica,

ae dcig igh i he iibe (e.g. 532 ) ea ifaed (e.g. 785 ad 1064 ) egi

ae ed. The eeg f hi igh i high big ece a highe ibaia ae (Fige

3.10). M f he icide adiai i eaic caeed b he ae ece a he ae

feec (= eeg), hich e i he caed Raeigh adiai. O 108 i ieaic

caeed b he ae ece, eig f a eeg echage beee he icide igh

ad he ae. Thi ieaic caeig i caed he Raa effec. The ieaic caeed adiai

ca hae a e eeg (e feec) ha he icide adiai a highe eeg (highe

feec) ha he icide adiai. The fe e f ieaic caeig i caed Ske

adiai, he ae aiSke adiai (Fige 3.10). The hif i eeg ( aeegh) beee

he icide igh ad he Ske aiSke caeig ide ifai ab he ibaia

ae f he eaed ece. The iei f bh ieaic caeig cee i ia

he be f ece ha ca deg he cee. Hece, a eeae ai


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Ske adiai i cc, hie a high eeae (e.g., 500 C) a ae ece ae

aead i a highe ibaia ae a ca be deied f he Ba diibi, hece

faig aiSke adiai. Theefe, he Ske adiai i e c ed i Raa

ecc ice i iei i a highe ha he aiSke iei a eaig

cdii.

Mece ae Raa acie if a chage i ece aiabii cc eciai. The

aiabii f a ece i he eae ih hich he eec cd f a ece ca be died

afe bigig he ece i a eecageic fied (i.e., b igh iadiai) [38]. I he diffee

eeci e f Raa ad NIR acii (chage i aiabii ad chage i die e,

eecie) ie he ceeai f hee eca ibaia eccic echie.

Mece dcig gd iga i NIR eca igh dce eak iga i Raa eca ad

ice ea. Fige 3.11a hed ha he ech ibai f H2i NIR iacie de he abece f

a chage i die e. Hee, he age he bd diace, he fhe he eec ae

aa f he cei ad h he eaie he ca be ed. Thi chage i eae ih hich he

eec cd f a ece ca be died (i.e.; chage i aiabii) i eeded f Raa

acii ad heefe he ech ibai f H2i Raa acie.

A Raa ec dia he iei f he caeed adiai e he feec diffeece

beee he icide adiai ad he caeed adiai, eeed a aebe. Paek

deeed he fig eai ee he iei f Raa caeig, :

hee: i he eed f ighi Pack cai he iei f he icide ighi he be f igh caeig ecei he feec f he icide igh (H)i he ibai feec f he ece (H)i he edced a f he ibaig ai he Ba cai he eeae (K) i he ea ae iaia f he aiabii e

i he ai iaia f he aiabii e.

= 24 5 3

1 45 + 7 (3.5)


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E. 3.5 h ha he iei f he caeed igh i ia he be f ece (eabe aiaie aai), he iei f he icide ae igh ad . Theefe, ahighe ae iei ad a highe ae feec ehace he iei f he Raa caeig.

Beide hee aaee, he Raa iei i a deeied b iea (e.g., deec,

egh f ga fibe he ig be, ec.) ad ae (e.g., aig e, ae aice ie,

efacie ide f ae, ec.) aaee. Fhee, a caeig cc i a dieci,

a faci i deeced. Whe be ae ieeed i ce ea, he igh hich i

caeed i he ae dieci a hee he icide igh igiaed f i eaed.

A he Raa effec i ihee eak, he heea ch a igh abi ad fecece

ca iefee g. Mee, heaig, hdecii ad ae abai ca cc. The

icide ae igh ca be abbed he he aeegh f he ae igh ced a

abi bad i he ec f he ece, eig i he aii f he ece he

ecied ae. Deedig he ae aeegh, a aii he ecied ibaia eecic

ae ca cc. The abbed eeg i he afed ia adiaie aii i hea

eeg. Thi abi iefee ih he Raa effec a he iei f Raa caeig i

ia he iei f he ae igh (E. 3.5). Ligh abi ca be aided b e f

ahe aeegh ae. Fecece ca dce baia iefeece i Raa eca

he he ece i ecied a eecic ecied ae. The ece deca a e eeg

ee b a adiaie aii (he ibaia gd ae i he eecic ecied ae),

fed b he deca he eecic gd ae (Fige 3.10). Dig hi a deca, fece

adiai i eied, iefeig ih he Raa iga. Iefeece b fecece ca be aided

eig ae ih he (ge) aeegh ake e ha eciai he eecic

ecied ae cc.

A he iei f he Raa iga i ia he iei f he ae igh, i i faabe

e a high a ibe ae ieiie. Hee, decie effec ca cc b a high eeg

. Abi f he adiai ih ifficie eeg afe he dig, e iae heaig (ad ib deci). Lae abai i a hee hee aeia i

eed f he ae. Whe he eeg added he ae e ie i i age ha he

bd eeg ad he he eeg i diiaed, abai cc eig i a cae [37].

Raa ecc eabe ef aid ad decie eaee ih he eed

f ae eaai. Pbe ca be ced he ecee b fibe ic cabe ad

ieeed diec i he ce ea (ih he e iefacig). A Raa ec

cai bh aiaie ad aiaie cheica ad hica ifai. Uike NIR eca


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ha ai ehibi bad, eaig eak f OH, NH, CH ad SH ibai, Raa eca

ci f diicie eak ha ca be aiged fcia g ad ae eaie iee.


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3.3. LIEAE EIE F HE CE AALE ALIED I

FLIDIED BED GALAI

The deeci f gae gh dig fidied bed gaai ad he ce edi i

adiia baed he eaee f ce aaee (Chae 2). Hee, hee ae

cideed a idiec eaee a he aaee ae ae ceaed ih he gae

eie. A ie, hee ehd ae iadeae ice he d acc f chage i feed

aeia eie eea dibace. The cei f a gaai ce afe a fied

ie eid a he cae e dedig f he gae ad edce he bach ai.

Thgh he deee f iaie aai ha aid ide ifai eaed he

hica cheica aeia eie, gaai ce iig ad c ha

icaed he diec eaee f gae chaaceiic. Thee echie ehace he

ceced gaai ifai ad eabe deeie he gaai edi b he

achieee f deied gae aibe. The echie ae decie, ide a h

eaee ie ad a ai eaee e (Fige 3.2).

The ie ee f he fid bed i deeied b he ae f bide addii ad bide

eaai, hich eed be e baaced i de bai e fidiai ad highai

gae [39]. Hece, he fi gae dc eaee dig ceig cied f iie

ie deeiai ig a ifaed ie e, ic c he bed ie ee

dig gaai ad dig [4042]. Tabe 3.1 aie he fee died aaica

ce e i fid bed gaai, he eaie caed gae ifai ad he

chaege eceed dig hei aicai. Thi i be e eeie diced i he

fig eci.


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48

3.1.Oeie f he fee died aaica ce e i fid bed gaai, he

caed gae ifai ad he chaege eceed dig hei aicai.

TechieIie eaed gae e

dig fid bed gaaiChaege

NIR ecc

ie ce Fig f he eaee id dig iaieeaee.

idaeFig f he eaee id dig iaie

eaee.

ie

Fig f he eaee id dig iaie

eaee ad eaci f eea

ifai f he ceced eca.

bk dei

Fig f he eaee id dig iaie

eaee ad eaci f eea

ifai f he ceced eca.

iage aai

ieAdeae eeai f gae he

eaee eie ad daa hadig.ie diibi

hae

FBRM chd egh (diibi)

Fig f he eaee id.

The FBRM be hd be iaed a a heigh ha

i ifeced b ie egegai dig

fidiai.

The echie eae chd egh ad

heefe a cai f he FBRM ie daa ih

ie e f ceia iig echie ife deied.

SFV chd egh (diibi)

The SFV be hd be iaed a a heigh ha i

ifeced b ie egegai dig

fidiai.

The echie eae chd egh ad

heefe a cai f he SFV ie daa ih ie

e f ceia iig echie i fe

deied.

acic eii

ie ceEaci f eea ifai f hececed iga.

ie

(fidiai)

Raa ecc idaeFig f he eaee id dig iaie

eaee.

T a ee ee, ibeecic be [4345], icae eace echg [46, 47] ad

eecica caaciace gah [48] hae a bee ieigaed a eia eaie aae

i fidied bed. The effeciee f each f hee ehd accae deeie he ie

ce dig fid bed diga eaied ad he ai e ae aied i Tabe 3.2.


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3.2.Aicai f ibeecic be, icae eace echg ad eecica caaciace

gah dig fid bed dig.

Techie Mai e Refeece

ibeecic be

Reiabe gae ie eaee ih

ibeecic be dig fid bed dig (KaFiche a efeece).

[43, 44]

Ue f ibeecic be aiaie i

fid bed dig ad eaie he effec f ibai

dig.

[45]

icae eace echg

(MRT)

Gd ceai beee gae ae ce

deeied b MRT ad efeece ehd (i.e.,

dig ad Ka Fiche) dig fid bed dig. [46]

Tie aig i he dig ce hgh eaie

iig f ae ce b MRT.

Iceae f ce kedge b cbiig MRT

ih iaiae daa aai echie, aied

a idia cae gaa.

[47]

eecica caaciace gah

(ECT)

Ue f ECT eae gae ie dig fid

bed dig.

[48]Deee f a feedback c aeg baed

ECT eaee ie ce efficiec

ad dc ai.

3.3.1.

Fake e a. [49] iaed a NIR be i he dc bed f a a fid bed gaa,

ci cecig gae ifai. The be a iied i he dad f a a

i f high dc dei. The ecd deiaie abbace chage a 1932 ee

caibaed agai ie ce daa ad a acceabe adad e f caibai f he

eied ee f c a cacaed. Chage i e de abbace ac he eie

ec a gaai ceeded, eed f he aiai i gae ie. Pig he

abbace f a ige aeegh e ce ie hed he gada iceae i gae ie,

b i a ibe geeae iabe gae ie caibai de f aiaie

deeiai.

Raae e a. [50, 51] aied a e NIR efecace eccic ehd dig fid bed

gaai ad dig, deecig f aeegh iae ad ig hee f he f he

eaee f ie ce. The 1990 chaaceiic cbiai bad a ed f

ae deeci ad he 1740 ad 2145 iga f baeie ceci. Ciica he iie


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eaee a he igh ga, hich a ci b ih heaed ied ai. The

e hed ha he eie NIR ec a ecea f he eaee f ae. B

e f a fe NIR aeegh ad he NIR ae bad, eiabe ad aid deeci f

ie a ibe hgh he eie gaai ce. Cbiig NIR ifai ih

ed cha f he eeae diffeece beee ce ie ai ad gae, ad he ae

ce f ce ai eabed he ideificai f diffee ce hae, chaaceiic f

diffee fai [52]. Thi ided a e f he iig ad c f ae dig

fid bed gaai. The ehd a fhe ieigaed b dig he effec f bide chice

ad aice ie he accac f NIR ie eaee [53]. Picia ce aai

(PCA) ed a iig i he edci f he highdieiai f gaai ce daa

(e.g., gae ad ai eeae, hidi, NIR iga, ec.) [54]. B e f hi iaiae daa

aai echie, he gaai ce a decibed i a 2dieia ace hee he hee

ce hae (i.e., iig, aig ad dig) ee cea iibe. A he NIR ie

eaee i affeced b he aig hica eie f he gae (e.g., eeae,

aice ie, bk dei), he ceeaed aiabe decibig he ae f gaai ee

icded i NIR ie caibai de [55]. Thi aach ied he de edici

caabii. Miaiae caibai f iie ceced NIR eca ad ce aaee a

efed ig echie. The aificia ea ek (ANN) de ih backagai

agih hed he edicie e f he ideede e daa, caed he aia

ea ae (PLS) de. The NIR e a a ccef aied f aice ie eaee

f ai gade f iccaie cee dig fidiai, ig f he f

iae deeced aeegh [56]. Diffee ie aif ae did igifica ifece

he ecded abbace.

A Re e a. [57] ed hee NIR aeegh deeie he ie ce b i

ie NIR ecc. The ah ee abe d he dehdai behai f hehie

gae ig a e ichabe iccae fid bed de ih a ce ai c i ad

iie NIR ecc. The eie dehdai f aeia a ied b he ae ce

diffeece f ie ad e ai, he ee diffeece e he bed ad iie NIR ecc.

Mi e a. [58] idced a fadig ehd acceeae fid bed dig b e f NIR ad

eeae be. NIR eca ceci a accihed ih a MM55 gage, ci

iig he bed eea, hgh a e ieci id. The aeg ied he

ideificai f ciica NIR eadig cedig he ed f eaaie cig (Chae 2) ad

ig hi a a eeaeideede edi. The ah hed ha hica chage f

cd cced dig he eaaie cig age f dig a a ie ai eeae abe


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he eig i f a eig cd. Hece, ig eaie ad iaie NIR

eaee, he dig cce f a eig acie igedie a iied b edcig he

ea dig ie. Thi k a eeded b Widfg e a. [59], h eaied he effeciee

f he ehd ig diffee fai. A ie ce ga a deeed edic

he eeced dig ie edci ad heefe deeie a beefi aciaed ih he e f

acceeaed dig befe chagig he ce ce.

Fida e a. [60] ed NIR ecc iae i ie ce ad aice

ie i a fid bed gaa ad deeie i edi. Seca ee ceced ih a MM55+ NIR

gage hgh a ga id i he bed f he gaa. The id a fied ih a ecia

gake edce fig. I acice, he NIR eaee dig he ea age f gaai

ee a accae a eaee efed ae i he ce ice he ga id

becae aia fed b de dig he fi 10 i f gaai. The NIR deeied

ie ce ad aice ie ceaed e ih ffie efeece eaee (i.e.,

dig ad iage aai). Hee, i a ecea cec he aice ie eaee

(de ie) he he ie ce f he aeia a geae ha 3% /. Uig he

deeed e, fid bed gaai ca be ced b deeiig he bide addii

hd be ed (deied aice ie) ad he gae dig i ceed (deied ie

ce). Nieee e a. [61] a aied NIR ecc iae deeie gae

ae ce ad ie. High hea afaced gae ee died i a Aeaic fid bed

de (Ni), ih he NIR be aced i he a f he de, a he ae heigh f he aig

be. The PLS gae ie de ediced eida ae ce ci dig dig

ih e caabe he efeece ehd (i.e., Ka Fiche), heea he PLS gae ie

de a ifeced b he hidi f he gae (a beed b Fida e a.). Afe ea

f he iefeig ie hgh iiia dig, he NIR gae ie de ca be ed i

gae ie ad aii effec.

Hag e a. [62] ied he fid bed gaai f a Eaai fai b ea f i

ie NIR ecc ih he NIR be iaed i he dc caie. The ie ce

fie f eea gaai bache, deied f a NIR ie PLS de (Ka Fiche a

efeece), eabed eaie h gaai ifece abeig eie. Re hed

ha he abe chaaceiic deeded he eida ie ce f he gae,

b a he ie fie dig he eie fid bed gaai ce.

NIR ecc a aied iaie i fid bed gaai a idia cae

(Ga WSG300) [63]. Seca f ci ig ae ee acied b aachig he NIR


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ica be he ga id (ih iefeig he ce fai). PLS caibai

de ee deeed edic gae ie ce, ie diibi ad bk dei ig

he ie ecded NIR eca. B icia ce aai f he NIR eca, each e f

he gaai ce a ideified ad ied. A NIR ehd f iie deeiai f

he fidied bed dig edi baed ie ce edici a deeed ad

aaica aidaed cecia cae (300L) f a aed id dage dc [64]. A

ieface/ada ae a afaced ie he NIR be i he fid bed. T

deae he aicabii f he NIR de, aidai a efed fig he ICHQ2 (1)

gideie. Hee, he ice ehd a deeed ad aidaed ecie ih iie

ae hich eceiaed a cied ieeai f hee gideie.

A ideh ieigai he NIR ie edici accac ih egad aig effec

a eeed b Gee e a. [65]. Gaai ee efed a hee diffee dig cae

(65L, 300L ad 600L) ad NIR eca f bh daic, fig ad aia id ee ceced

hgh iei f he be diec i he ee. The ah deaed ha ce

heegeei aed a aj e i deeiai f aae edici accac. Mae ad c

ke [66] a ecded NIR eca f aic gae b e f a NIR be ha a eied

ih a ceci ad ge e he be i. Fig each NIR ec ceci

dig he fid bed gaai ce, fae e a daaceeiga ha iiiaed a ai

ge, ceaig he f a e ae.

Fig f he eaee id b he i a chaege he eiabe ceci f NIR

eca dig fid bed gaai. Si geea ie he e f a ai e ad

eciaied iefacig. Oce a iabe iefacig i fd, acceabe edici f gae

ie ce i achieed hgh he gaai ce ad eaie ed i deeci

f he dig hae (baed eida gae ie ce) i ibe. Seea die hed

ha cbiig he NIR ie ifai ih he adiia ceced ce aaee

iceaed gaai ifai, ied he edicabii f de ad cibed he

ce iiai. The e f NIR ecc ha bee eiced R&D cae. A fe

die aead eed he aicai f NIR ecc a ie deeiai echie

a age cecia cae hig ha he echie a eaie c f he ce,

eadig a edced eai ie ad a ied ciec f he gae dc. Deiig

accae aice ie ifai f iie ceced NIR eca f fidiig gae i e

chaegig ad eie fhe eeach.


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3.3.2. I

I addii NIR ecc, iageceig a e f he eaie echie aied dig

fid bed gaai diec eae gae chaaceiic. Ifai egadig he hica

gae eie (e.g., gae ie, ie diibi, hae) i eieed f he iage, hich

eie a age ee f caia ceig. Theefe, iagig deice ae a

eied ih ef ce hade he daa.

The ea k f Tai e a. [67] caig gae adheie ae caed he ide a f

he caie ad akig iage ih a CCD caea, a fed b a eie f ae b Waa

ad cke [6871]. Waa ad Miaai [68] deeed a ie iageceig e

ciig f a CCD caea, ica fibe, a eeh e ad a ai ge i. The iagig be

a aached he e idea f he caie eabig ie iig f gae gh i

a agiai fidied bed gaa. B e f heaed ge ai, de adhei he

eaee id a eeed. Eeie eceig ad iage ceig a ecea

befe deeiig gae ie diibi, edia diaee (Fee diaee) ad hae fac

(cicai ad aec ai). A he iagedeied gae ie diibi i bebaed,

afai i a abaed diibi a efed cae iage e ih

ceia iee aai. A ce ageee beee bh iig ehd a baied. Pig

he hae fac i fci f gaai ie hed ha gae becae e heica i he

ge f gaai. The edia gae diaee ae a ifeced b he ii f he

iagig be de aice egegai i he fid bed gaa he fidiig ai

eciie ee ed [70]. I a ccded ha he eaig a bad aice ie diibi,

he iagig e hd be aced i he e ii (ce he ai diib) he ai

eci hd be age. Se cai hd be cideed he eaig gae hae

fac. The ah a deeed a aaed fid bed c e b e f he iage

ceig i ad a c agih baed f gic [69]. The deeed e a abe

c gae gh ih high accac, de ai eaig cdii (i.e., agia

aia eed) ad de ae eie (a ai f ace i aig aeia).

Wheea adiia iagig die ce 2D backadhie ice, a e 3D iagig ehd

(SAY3D) a idced b Ne e a. [72] deeie he aice ie f gae bh ff

ie ad ie i a fid bed gaa. The iagig aaa (i.e., caea, cee ad Red

GeeBe ed) a aached 13 c abe he gaa diib ae f ie

eaee. Sae ee ceced i he cee, iage ee ake ad a ed ai


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ee eed he ae he ce beee iage. The decibed ehd eeed

iig, ad iiai ad fhe ehd deee ae diced.

Laiie e a. [73, 74] deeed a heic cce cacae he aice ie f

dieed de face de ced iiai cdii. The heic aach

aed aie iig f gae gh kieic i a fidied bed gaa [75]. Iage

ifai f edi ae a eaaed egadig he edici f gae abeig

behai. The echie a a eed f ie iig f fid bed gaai [25]. The

cee e decibed i he d f Ne e a. [72] a aied iae eae

he gae ie diibi b iage aai ad he gae ie ce ih NIR

ecc dig he eie bach gaai.

Gae iage ae a caed ia a iabe id ha a iaie daa ceci

ad aid he be aciaed ih ie fig ad ce dibace dig iaie

eaee. Hee, he ce iefacig ca be diffic f fid bed gaai cee

hee gae ae ca ig a high eciie. Oeaig aice, age ie diibi

ad heica aice chaege he eaci f hica ifai eaed he gae

ie (diibi) ad hae f he caed iage. Theefe, eeie iage ceig ad

eeie ae ecea. The iied k fd i ieae gge ha he e f iage aai

dig fid bed gaai i ea ad i fa f he aca aicai a cecia cae

dci.

3.3.3. F

The fced bea efecace eaee ie i deiged ack i eaie a chage

he aice ie ad i diibi. The echie ha aead bee ed i

caiai [76, 77] ad fccai [78, 79], ad i aicai gaai ha eceied

iee e he ece ea.

H e a. [29] ed he FBRM echie aie ieigae he gae gh kieic dig

fidied bed gaai. A he aice eed e i f f he eaee id

cacae he aice chd egh diibi, he FBRM (S400) be a ieed i a

ei f iic i ad aed gae. B aig a ageic i ba, he ei a

ge agiaed ad gae aig i f f he ahie be id ee eaed. The

ed f he chd egh (e.g., D10, D50, D90) aie eaed b FBRM ee ideica he

eaed b ffie ae diffaci ad iee aai. The diicie diffeece beee FBRM

ad ae diffaci/iee aai aice ie ae ee aibed he diffee eaee

echai.


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Iie FBRM (D600) eaee ee efed dig fid bed gaai ih he be

iaed iide he gaa a diffee ii [31]. The be id a caed i he

cee f he diib ae ad bh hia ad ed (45) ii f he be ee

eed. The ae a efeed a he fe a eiie id fig dig he

aig hae. Neehee, ig he ed ii, he FBRM be id eaied fed

ih ick aice dig gaai de ceai eeiea cdii. I addii, ie a

ee dig he fi 20 i f each gaai bach, caed b de aice ceig he

eaee id de hei high aic eecica chage dig iig.

The aie FBRM aicai hed ha he echie adeae decibe he gae gh

kieic, b he fig beed dig ice eaee iede he eiabii f he

FBRM echie a a iie ce aae. Adaai he be hae bee ade e

hee fig ie. The FBRM C35 be i eied ih a eied ai aciaed echaica

cae he ahie eaee id ee de ickig. The effeciee f he

cae ha aead bee e i he hah cdii f a high hea gaa [30]. Oce

aied i fid bed gaai, he echie a a a ie e i he eaie iig

ad c f fid bed gaai cee.

3.3.4.

I addii FBRM, aia fie ecie i a abe eaie eae he chd egh f a

ig aice. Bh echie ae deiged f ice aice chaaceiai ad eabe

he eaie ie eaee f agiaed aice ad gae dig fid bed gaai.

Neehee, he echie diffe baia i be deig ad eaee echai (ee

Seci 3.2).

SchidLeh e a. [80] eaied i iaai ad fae aaee f he SFV be

dig fid bed gaai i a Ga WSG 5 gaa. The gaai behai de ai

eeiea cdii a eaied ig he SFV be, ad SFV eaed D50 ae ee

caed ih ae diffaci ie. I addii, he edcibii f eaee e, he

afeabii f he echie a age ied gaa (WSG 15) ad he ifece f ce

aaie he SFV echie ee aeed.

Ne e a. [81] baied gae ie ifai dig fid bed gaai (i a Ga WSG 5)

ig a iie, aie ad ffie eeiea e f he SFV echie. Ahgh iie ad a

ie baied daa ee ceibe ie egegai, eaie iig f he gae gh


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a achieed. Siee aai f he fia gae a efed a a efeece ad i e

ceaed e ih ffie SFV daa.

Miaiae aiica c ehd baed SFV eaee ee deeed b Hag e a.

[82] f a Aeaic fid bed gaa caabe f afacig 35 kg bache.

The aicai f SFV dig fid bed gaai deae he echie abii

ci eae he gae ie diibi dig ceig, ih eeiecig fig

be. Hee, ih he iie aicai f a iig echie, e a ha cide he

heigh ih hich he e i iaed i he fid bed, a ie e a be ifeced b ie

egegai dig fidiai.

3.3.5. A

Paiceaice aicechabe cii ad fici dig fid bed gaai geeae

ibai ha cai ebedded hica ad cheica ifai. Thee ibai ca be

eaed b aig acic eii (AE) e he fid bed caie. Acic eii

ae a eaed i he high feec age (70 500 kH) a he ca eai agae hgh

id aeia b aeae aid i ai. Theefe, he iefeece f backgd ie

geeaed b echaica ibai (e.g., f he fa) i iiied. The ea acic eca

cai ifai ab eea ceeea eie ad cheeic echie ch a

PCA ad PLS ae aa ecea eac he deied ifai ad caibae he acic

iga [83]. Hece, fe he e acic cheeic i aied. The e hae a

diei ad ca be eai ed he (ide f he) gaa, eabig iaie

eaee f he gaai ge. I addii, acic eaee ffe eaie

ee, ae eaie ieeie ad ca be efed i haad ce eie

ih fhe eci.

Tji e a. [84] deeed ad aied a AE e i he fidiai cdii i aacae agiai fidied bed gaa. The effec f eea eaig aiabe he ea

AE aide ee eaied ad e hed ha he ea AE aide ceaed ih he

fidiai acii. Haee ad Ebee [85] deiged a e acic cheeic aach,

hich a ae aied i a eiidia fid bed gaa i he gaai ce

ae ad dc ai [86]. B e f ce baed acic daa, he ce ae ad

he ai f he dc iide he gaa ee ideified. I ha a, he acic

cheeic aach a e eiie he ea deeci f ciica gaai iai

(e.g., fai eadig ce hd) ha he adiia ce daa. The feaibii


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d hed ha acic cheeic ca be ed edic fidiai aif, ef f fie

he eac ad gae ie ce.

Mae e a. [87] decibed he e f aig AE dig fid bed gaai i diffee

cae die, deeig eaae de f gae ie ad ie. B e f iaiae

ehd, he gae ie ifai hidde i he AE eca a eaced, deie he

cibi f he gae eie he AE iga. Hee, accae gae ie edici

a achieed. The edici e ee aibed iee aai a a efeece echie,

hich ae ha gae ae heica ad f a a, a ie diibi i he iee

c. The gae ae ce a acked hgh he gaai ce, b he eaie

hidi f abie ai a ccia i deeiig gae ie. The eaie hidi idced

bachbach aiai ad ifeced he eiabii f he de. The ah a ed he AE

iga acied i he ea hae f gaai eiae ed dc ie diibi ia Na

PLS deig [88]. The aied ia ehd ided a deee deadig f fidied bed

gaai hig f he fi ie ha he AE iga caed dig he ceai hae ca

be ed edic ed dc gae ie diibi.

The iaiee ad ieeiee f AE eaee ha ecaged i aicai i

fid bed gaai. The AE iga cai bh cheica ad hica gae ifai, b he

eaci f he eea ifai i aighfad. Neehee, acic cheeic

ha aed i gaai ce ae ad dc ai, hich ided ea aig

f ciica ce iai.

3.3.6.

The aicai f Raa ecc i fid bed gaai ha cibed he eaie

iig ad deadig f idae afai. Haa e a. [89] aied Raa

ecc i he dg (i.e., iedae di) hdai ae dig fid bed dig.

The Raa be head a ieed i a abcae fid bed gaa hgh i i

addii . B e f he ceced Raa ifai, he eaihi beee dg hdai

ae ad abe hica abii a ded. Kgea e a. [90] ee

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