PREPARATION AND CHARACTERIZATION OF CHITOSAN-COATED CALCIUM ALGINATE FILM

M s. J e e r a d a M a h u t th o n

A T h e s is S u b m it te d in P a r t ia l F u l f i lm e n t o f th e R e q u i r e m e n ts fo r th e D e g r e e o f M a s te r o f S c ie n c e

T h e P e t r o le u m a n d P e tr o c h e m ic a l C o l le g e , C h u la lo n g k o m U n iv e r s i ty in A c a d e m ic P a r tn e r s h ip w i th

T h e U n iv e r s i ty o f M ic h ig a n , T h e U n iv e r s i ty o f O k la h o m a , a n d C a s e W e s te rn R e s e r v e U n iv e r s i ty

2 0 0 3I S B N 9 7 4 - 1 7 -2 3 2 0 -2

Thesis Title: P r e p a r a t io n a n d C h a r a c te r iz a t io n o f C h i to s a n - C o a te d C a lc iu m A lg in a te F i lm J e e r a d a M a h u t th o n P o ly m e r S c ie n c e

Thesis Advisors: A s s t . P ro f . R a ta n a R u j i r a v a n i tP ro f . A le x a n d e r M . J a m ie s o n

A c c e p te d b y th e P e tr o le u m a n d P e tr o c h e m ic a l C o l le g e , C h u la lo n g k o m U n iv e r s i ty , in p a r t ia l f u l f i lm e n t o f th e r e q u i r e m e n ts fo r th e D e g r e e o f M a s te r o f S c ie n c e .

/ k s . A^rC o l le g e D i r e c to r

(A s s o c . P ro f . K a n c h a n a B u n y a k ia t)

Thesis Committee:

(A s s t. P ro f . R a ta n a R u j i r a v a n i t )

(P ro f . A le x a n d e r M . J a m ie s o n )

(A s s o c . P ro f . N a n ta y a Y a n u m e t)

ไ^ร??«ฟobujx C j& tertauchrrl.,(A s s o c . P ro f . S u w a b u n C h ir a c h a n c h a i )

Ill

ABSTRACT

4 4 7 2 0 0 3 0 6 3 ะ P O L Y M E R S C IE N C E P R O G R A MJ e e r a d a M a h u t th o n : P r e p a r a t io n a n d C h a r a c te r iz a t io n o f C h i to s a n - C o a te d C a lc iu m A lg in a te F i lmT h e s is A d v is o rs : A s s t . P ro f . R a ta n a R u j i r a v a n i t a n d P ro f . A le x a n d e r M . J a m ie s o n , 9 5 p p . IS B N 9 7 4 - 1 7 -2 3 2 0 -2

K e y w o r d s : A lg in a te / C h i to s a n / C a lc iu m a lg in a te / C h i to s a n - c o a te d c a lc iu m a lg in a te f i lm

T h e e f f e c ts o f c r o s s - l in k in g w i th c a lc iu m io n a n d c h i to s a n c o a t in g o n m e c h a n ic a l p ro p e r t ie s , s w e l l in g b e h a v io r a n d d r u g r e le a s e c h a r a c te r is t ic s o f a lg in a te f i lm s w e r e s tu d ie d . F T I R s p e c t r a o f c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s s h o w e d th e c h a r a c te r is t ic p e a k s o f c h i to s a n in d ic a t in g th a t c h i to s a n w a s s u c c e s s f u l ly c o a te d o n c a lc iu m a lg in a te f i lm . T h e c h i to s a n c o a t in g o n c a lc iu m a lg in a te f i lm w a s a lso c o n f i r m e d b y n in h y d r in s ta in in g . C h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s s h o w e d b e t te r te n s i l e s t r e n g th a n d Y o u n g ’s m o d u lu s th a n a lg in a te a n d n o n c o a te d c a lc iu m a lg in a te f i lm s d u e to th e e le c t ro s ta t ic in te r a c t io n a t th e in te r f a c e b e tw e e n a lg in a te a n d c h i to s a n . B o th n o n c o a te d c a lc iu m a lg in a te a n d c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s p o s s e s s e d p H - s e n s i t iv e s w e l l in g c h a r a c te r is t ic s a n d c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s s h o w e d h ig h e r d e g re e s o f s w e l l in g th a n th e n o n c o a te d f i lm s . D ru g r e le a s e s tu d ie s o f th e f i lm s w e re c a r r ie d o u t a t 37 °c a t s im u la te d p h y s io lo g ic a l p H s ,i.e . p H 2 , p H 5 .5 , a n d p H 7 .2 , u s in g s a l ic y l ic a c id a n d th e o p h y l l in e a s m o d e l d ru g s . T h e a m o u n ts o f m o d e l d ru g s r e le a s e d f ro m c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s w e re lo w e r th a n th o s e f ro m th e n o n c o a te d f i lm s a n d d r u g r e le a s e a t p H 5 .5 g a v e h ig h e r e q u i l ib r iu m d ru g re le a s in g a m o u n ts th a n a t p H 2 .0 fo r b o th m o d e l d ru g s .

IV

บทคัดย่อ

จีรดา มหัตธน การเตรียมและการสืกษาคุณสมบัติของแผ่นฟิล์มแคลเซียมแอลจิเนตท่ี เคลือบผิวด้วยไคโตชาน (Preparation and Characterization of Chitosan-Coated CalciumAlginate Film) อ.ท่ีปรึกษา’. ผศ.ดร. รัตนา รุจิรวนิช และ ศ. อเลกซานเดอร์ เอ็ม เจมิสัน 95หน้า ISBN 974-17-2320-2

งานวิจัยนีศึกษาผลของการเช่ือมโยงให้เกิดโครงร่างตาข่ายด้วยอิออนของแคลเซียมและ การเคลือบผิวด้วยไคโตซานต่อคุณสมบัติเชิงกล พฤติกรรมการบวมตัวและลักษณะการปลดปล่อย ตัวยาของแผ่นฟิล์มแอลจิเนต ผลการวิเคราะห์สเปกตรัมของรังสีอินฟราเรด (FTIR)ilละการ ทดสอบด้วยสารละลายนินไฮดริน พบว่าไคโตซานได้ถูกเคลือบบนแผ่นฟิล์มแคลเซียมแอลจิเนต จากการศึกษาคุณสมบัติเชิงกลพบว่าแผ่นฟิล์มท่ีได้จากการเคลือบไคโตซานบนแผ่นฟิล์มแคลเซียม แอลจิเนตมีความทนทานต่อแรงดึงและค่ายังโมดฺลัสดีกว่าแผ่นฟิล์มท่ีไม'ได้เคลือบไคโตซาน เน่ืองI ' 1" 1 1 น้ี ,11 1 11จากมีแรงดึงดูดทางไฟฟ้าสถิตเกิดขนระหว่างพืนผิวของแอลจิเนตและไคโตซาน จากการศึกษา พฤติกรรมการบวมตัวพบว่า แผ่นฟิล์มแคลเซียมแอลจิเนตและฟิล์มท่ีได้จากการเคลือบไคโตซาน บนแคลเซียมแอลจิเนตมีลักษณะการบวมตัวต่อการเปล่ียนแปลงของความเป็นกรด-ต่างและแผ่น ฟิล์มท่ีได้จากการเคลือบไคโตซานบนแผ่นฟิล์มแคลเซียมแอลจิเนตมีค่าการบวมตัวสูงกว่าแผ่น ฟิล์มท่ีไม่ได้เคลือบไคโตซาน ในการศึกษาการปลดปล่อยตัวยาจากแผ่นฟิล์มทำท่ีอุณหภูมิ 37 องศาเซลเซียสในสารละลายบัฟเฟอร์ท่ีมีความเป็นกรด-ด่างเท่ากับ 2 5.5 และ 7.2 ในการศึกษาน้ี ใช้กรดซาลิไซลิกและทีโอฟิลีนเป็นยาด้นแบบ จากการศึกษาพบว่าการปลดปล่อยตัวยาจากแผ่น ฟิล์มท่ีได้จากการเคลือบไคโตซานบนแผ่นฟิล์มแคลเซียมแอลจิเนตมีค่าการปลดปล่อยตัวยาน้อย กว่าแผ่นฟิล์มท่ีไม่ได้เคลือบ นอกจากนีเม่ือเปรียบเทียบค่าการปลดปล่อยตัวยาท่ีทำในสารละลาย บัฟเฟอร์ท่ีมีความเป็นกรด-ต่างเท่ากับ 5.5 มีค่าการปลดปล่อยตัวยาสูงกว่าในสารละลายบัฟเฟอร์ท่ี มีความเป็นกรด-ต่างเท่ากับ 2

V

ACKNOWLEDGEMENTS

T h e a u th o r w o u ld l ik e to th a n k th e P e tr o le u m a n d P e t r o c h e m ic a l C o l le g e , C h u la lo n g k o m U n iv e r s i ty , w h e re th e a u th o r h a s g a in e d h e r k n o w le d g e a n d e n r ic h e d h e r s k i l l in p o ly m e r s c ie n c e . T h e a u th o r w o u ld a ls o l ik e to a c k n o w le d g e S u ra p o n F o o d C o m p a n y fo r t h e i r s u p p o r t in s u p p ly in g s h r im p s h e lls , th e r a w m a te r ia l u s e d th r o u g h o u t th is w o rk . A ls o , th e a u th o r w o u ld l ik e to th a n k K P T C o o p e ra t io n (T h a i la n d ) fo r k in d ly s u p p l ie d N a O H s o lu t io n u t i l i z e d fo r th e p r e p a r a t io n o f c h i to s a n .

T h e a u th o r w o u ld l ik e to e x p r e s s g ra te fu l a p p r e c ia t io n to h e r a d v is o r s , A s s t . P ro f . R a ta n a R u j i r a v a n i t a n d P ro f . A le x a n d e r M . J a m ie s o n f o r t h e i r in v a lu a b le s u g g e s t io n a n d c r i t ic i s m .

T h e a u th o r w o u ld a ls o l ik e to a c k n o w le d g e P ro f . S e ic h i T o k u r a fo r h is h e lp f u l s u g g e s t io n .

T h is th e s i s w o rk is p a r t ia l ly fu n d e d b y P o s tg r a d u a te E d u c a t io n a n d R e s e a r c h P r o g r a m s in P e tr o le u m a n d P e tr o c h e m ic a l T e c h n o lo g y ( P P T C o n s o r t iu m ) .

T h e a u th o r is a ls o in d e b te d to h e r f a m ily a n d f r ie n d s fo r th e ir e n c o u r a g e m e n t a n d u n d e r s ta n d in g d u r in g h e r s tu d ie s a n d th e s i s w o rk .

TABLE OF CONTENTS

PAGET it le P a g e iA b s tr a c t ( in E n g l is h ) iiiA b s tr a c t ( in T h a i) ivA c k n o w le d g e m e n ts VT a b le o f C o n te n ts v iL is t o f T a b le s ixL is t o f F ig u r e s x ii

CHAPTERI INTRODUCTION 1

II LITERATURE REVIEW 32 .1 A lg in a te B a s e d M a te r ia l fo r D r u g D e l iv e r y S tu d ie s 32 .2 C h i to s a n B a s e d M a te r ia l fo r D r u g D e l iv e r y S tu d ie s 6

2 .3 C o n t r o l le d D ru g D e l iv e r y S y s te m s 102 .4 C h i to s a n - C o a te d C a lc iu m A lg in a te B a s e d

M a te r ia l fo r D ru g D e l iv e r y S tu d ie s 15

III EXPERIMENTAL 173 .1 M a te r ia ls 173 .2 E q u ip m e n t 173 .3 M e th o d o lo g y 18

3 .3 .1 P r e p a r a t io n o f C h i t in a n d C h i to s a n 183 .3 .1 .1 P r e p a r a t io n o f C h i t in 183 .3 .1 .2 P r e p a r a t io n o f C h i to s a n 19

3 .3 .2 C h a r a c te r iz a t io n o f C h i to s a n 193 .3 .2 .1 D e g r e e o f D e a c e ty la t io n 193 .3 .2 .2 V is c o s i ty - A v e r a g e M o le c u la r

W e ig h t 2 0

vii

CHAPTER PAGE

3 .3 .3 C h a r a c te r iz a t io n o f S o d iu m A lg in a te3 .3 .4 P r e p a r a t io n o f C h i to s a n - C o a te d C a lc iu m

2 1

a lg in a te F i lm s 2 1

3 .3 .4 .1 P r e p a r a t io n o f A lg in a te S o lu t io n 2 1

3 .3 .4 .2 P r e p a r a t io n o f C h i to s a n S o lu t io n 2 1

3 .3 .4 .3 P r e p a r a t io n o f A lg in a te F i lm s3 .3 .4 .4 P r e p a r a t io n o f M o d e l D ru g -

2 2

L o a d e d A lg in a te F i lm s 3 .3 .4 .5 P r e p a r a t io n o f C a lc iu m A lg in a te

2 2

F ilm s3 .3 .4 . 6 P r e p a r a t io n o f C h i to s a n - C o a te d

2 2

C a lc iu m A lg in a te F i lm s 2 2

3 .3 .5 C h a r a c te r iz a t io n a n d T e s t in g o f F i lm s 3 .3 .5 .1 F o u r ie r T ra n s f o r m In f r a r e d

23

S p e c tr a 233 .3 .5 .2 N in h y d r in S ta in in g 233 .3 .5 .3 M e c h a n ic a l T e s t in g3 .3 .5 .4 S w e l l in g B e h a v io r

23

D e te r m in a t io n 233 .3 .5 .5 D r u g L o a d in g D e te r m in a t io n 2 43 .3 .5 . 6 D r u g R e le a s e S tu d ie s 2 4

IV RESULTS AND DISCUSSION 254.1 P r e p a r a t io n o f C h i to s a n 254 .2 C h a r a c te r iz a t io n o f C h i to s a n 2 6

4 .2 .1 S tru c tu ra l C h a r a c te r iz a t io n 2 64 .2 .2 D e g r e e o f D e a c e ty la t io n 2 74 .2 .3 V is c o s i ty - A v e r a g e M o le c u la r W e ig h t 2 7

vin

4 .3 C h a r a c te r iz a t io n o f A lg in a te 2 94 .3 .1 S tru c tu ra l C h a r a c te r iz a t io n 2 94 .3 .2 V is c o s i ty - A v e r a g e M o le c u la r W e ig h t 3 0

4 .4 C h a r a c te r iz a t io n a n d T e s t in g o f F i lm s 314 .4 .1 F T E R S p e c tr a C h a r a c te r iz a t io n 314 .4 .2 N in h y d r in S ta in in g 3 24 .4 .3 M e c h a n ic a l P r o p e r t i e s 33

4 .4 .3 .1 T e n s i le S tr e n g th 334 .4 .3 .2 Y o u n g ’s M o d u lu s 354 .4 .3 .3 E lo n g a t io n a t B r e a k 3 6

4 .4 .4 S w e l l in g ร ณ d y 384 .4 .4 .1 E q u i l ib r iu m W a te r C o n te n t 384 .4 .4 .2 E f fe c t o f p H 3 9

4 .4 .5 D r u g R e le a s e S tu d ie s 4 2

V CONCLUSIONS 51

REFERENCES 52

APPENDICES 55Appendix A D e te r m in a t io n o f m o le c u la r w e ig h t

o f c h i to s a n a n d a lg in a te 55Appendix B M e c h a n ic a l p r o p e r t ie s o f th e f i lm s 65Appendix c u v s p e c t r u m o f m o d e l d ru g s 71Appendix D C a lib r a t io n c u rv e o f m o d e l d ru g s 73Appendix E D a ta o f d r u g r e le a s e 75

CURRICULUM VITAE 95

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IX

LIST OF TABLES

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2.1 E n v i r o n m e n ta l ly s e n s i t iv e p o ly m e r s fo r d r u g d e l iv e r y 144 .1 Y ie ld s o f c h i t in p r o d u c e d f ro m s h r im p s h e ll 254 .2 C o n v e r s io n o f c h i to s a n f ro m c h i t in 254 .3 F T I R c h a r a c te r is t ic a b s o r p t io n b a n d s o f c h i to s a n 2 64 .4 D e g re e s o f d e a c e ty la t io n o f c h i to s a n 2 74 .5 T h e v is c o s i ty - a v e r a g e m o le c u la r w e ig h t o f c h i to s a n 284 .6 F T I R c h a r a c te r is t ic a b s o r p t io n b a n d s o f a lg in a te 2 94 .7 D e g r e e o f s w e l l in g a n d p e r c e n t w e ig h t lo s s o f d ru g -

lo a d e d f i lm s 4 8A 1 R u n n in g t im e o f s o lv e n t a n d c h i to s a n s o lu t io n T r e a t 1 55A 2 T h e d a ta o f r e la t iv e v is c o s i ty (r|rei), s p e c i f ic v is c o s i ty

(pSp), r e d u c e d v is c o s i ty ( rๆed) 55A 3 R u n n in g t im e o f s o lv e n t a n d c h i to s a n s o lu t io n T r e a t 2 57A 4 T h e d a ta o f r e la t iv e v is c o s i ty (r|rei), s p e c i f ic v is c o s i ty

59(r|sp), r e d u c e d v is c o s i ty (ๆred) 57A5 R u n n in g t im e o f s o lv e n t a n d c h i to s a n s o lu t io n T r e a t 3 59A 6 T h e d a ta o f r e la t iv e v is c o s i ty (ๆ rei), s p e c i f ic v is c o s i ty

(r|sp), r e d u c e d v is c o s i ty (ๆ red) 59A 7 R u n n in g t im e o f s o lv e n t a n d c h i to s a n s o lu t io n T r e a t 4 61A 8 T h e d a ta o f r e la t iv e v is c o s i ty (r|rei), s p e c i f ic v is c o s i ty

(ทุรp), r e d u c e d v is c o s i ty (ท ุred) 61A 9 R u n n in g t im e o f s o lv e n t a n d a lg in a te s o lu t io n 63A lO T h e d a ta o f r e la t iv e v is c o s i ty (ๆ rei), s p e c i f ic v is c o s i ty

(ๆ sp), r e d u c e d v is c o s i ty (ๆ red) 63B 1 T e n s i le s t r e n g th o f th e f i lm s in d r y s ta te 65B 2 Y o u n g ’ ร m o d u lu s o f th e f i lm s in d ry s ta te 6 6B 3 E lo n g a t io n a t b r e a k o f th e f i lm s in d ry s ta te 6 7

X

B 4 T e n s i le s t r e n g th o f th e f i lm s in w e t s ta te 6 8

B 5 Y o u n g ’s m o d u lu s o f th e f i lm s in w e t s ta te 6 9B 6 E lo n g a t io n a t b r e a k o f th e f i lm s in w e t s ta te 7 0C l S u m m a r y o f m a x im u m w a v e le n g th (Xm ax)of e a c h ty p e

o f m o d e l d r u g 72D 1 T h e d a ta o f c a l ib r a t io n c u r v e o f s a l ic y l ic a c id s o lu t io n 73D 2 T h e d a ta o f c a l ib r a t io n c u r v e o f th e o p h y l l in e s o lu t io n 7 4E l T h e r e le a s e o f s a l ic y l ic a c id f ro m c a lc iu m a lg in a te f i lm

a t p H 2 .0 75E 2 T h e r e le a s e o f s a l ic y l ic a c id f ro m c a lc iu m a lg in a te f i lm

a t p H 5 .5 7 7E 3 T h e r e le a s e o f s a l ic y l ic a c id f ro m c a lc iu m a lg in a te f i lm

a t p H 7 .2 7 9E 4 T h e r e le a s e o f s a l ic y l ic a c id f ro m c h i to s a n c o a te d

c a lc iu m a lg in a te f i lm a t p H 2 8 0E 5 T h e r e le a s e o f s a l ic y l ic a c id f ro m c h i to s a n c o a te d

c a lc iu m a lg in a te f i lm a t p H 5 .5 83E 6 T h e r e le a s e o f s a l ic y l ic a c id f ro m c h i to s a n c o a te d

c a lc iu m a lg in a te f i lm a t p H 7 .2 84E 7 T h e r e l e a s e o f th e o p h y l l in e f ro m c a lc iu m a lg in a te f i lm

a t p H 2 85E 8 T h e r e le a s e o f th e o p h y l l in e f ro m c a lc iu m a lg in a te f i lm

a t p H 5 .5 8 7E 9 T h e r e le a s e o f th e o p h y l l in e f ro m c a lc iu m a lg in a te f i lm

a t p H 7 .2 89E 10 T h e r e le a s e o f th e o p h y l l in e c h i to s a n c o a te d c a lc iu m

a lg in a te f i lm a t p H 2 9 0E l 1 T h e r e le a s e o f th e o p h y l l in e c h i to s a n c o a te d c a lc iu m

a lg in a te f i lm a t p H 5 .5 9 2

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XI

TABLE

E 1 2 T h e r e le a s e o f th e o p h y l l in e f ro m c h i to s a n c o a te d c a lc iu m a lg in a te f i lm a t p H 7 .2

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94

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LIST OF FIGURES

FIGURE PAGE2.1 C h e m ic a l s t r u c tu re o f a lg in a te 42 .2 T h e e g g - b o x m o d e l fo r b in d in g o f d iv a le n t c a t io n to a lg in a te s 52 .3 C h e m ic a l s t r u c tu r e o f c h i t in 72 .4 C h e m ic a l s t r u c tu r e o f c h i to s a n 72 .5 D r u g le v e l in th e b lo o d f ro m (a ) t r a d i t io n a l d ru g

a d m in is t r a t io n a n d (b ) c o n t r o l le d d e l iv e r y d o s in g 1 1

2 .6 D r u g d e l iv e r y f ro m a ty p ic a l m a tr ix d ru g d e l iv e r ys y s te m 1 2

2 .7 D r u g d e l iv e r y f ro m e n v ir o n m e n ta l ly s e n s i t iv e r e le a s es y s te m s 13

2 .8 D ru g d e l iv e r y f ro m (a ) b u lk e ro s io n a n d (b ) s u r f a c ee r o s io n s y s te m s 15

4 .1 F T I R s p e c t r u m o f c h i to s a n 2 64 .2 T h e p lo t o f r e d u c e d v is c o s i ty a n d in h e r e n t v is c o s i ty

v e r s u s c o n c e n t r a t io n o f c h i to s a n s o lu t io n 2 84 .3 F T I R s p e c t r u m o f a lg in a te 2 94 .4 T h e p lo t o f r e d u c e d v is c o s i ty a n d in h e r e n t v is c o s i ty

v e r s u s c o n c e n t r a t io n o f a lg in a te s o lu t io n 3 04 .5 F T I R s p e c t r a o f (a ) p u r e a lg in a te f i lm (b ) c a lc iu m

a lg in a te f i lm (c ) c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm 314 .6 N in h y d r in t e s t fo r (a ) p u r e a lg in a te f i lm , (b ) c a lc iu m

a lg in a te f i lm , (c ) c h i to s a n - c o a te d c a lc iu m a lg in a te f i lma n d (d ) c h i to s a n f i lm 3 2

4 .7 T e n s i le s t r e n g th in th e d r y s ta te o f f i lm s 3 44 .8 T h e te n s i l e s t r e n g th in th e w e t s ta te o f f i lm s 3 44 .9 Y o u n g ’s M o d u lu s in th e d r y s ta te o f f i lm s 354 .1 0 Y o u n g ’s M o d u lu s in th e w e t s ta te o f f i lm s 3 64 .1 1 E lo n g a t io n a t b r e a k o f th e f i lm s in d r y s ta te 3 7

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4 .1 2 E lo n g a t io n a t b r e a k o f th e f i lm s in w e t s ta te 3 74 .1 3 E q u i l ib r iu m w a te r c o n te n t o f c a lc iu m a lg in a te a n d

c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s 384 .1 4 S w e l l in g b e h a v io r o f c a lc iu m a lg in a te a n d c h i to s a n -

c o a te d c a lc iu m a lg in a te f i lm s a s a fu n c t io n o f p H 3 94 .1 5 S w e l l in g b e h a v io r o f c a lc iu m a lg in a te a n d c h i to s a n -

c o a te d c a lc iu m a lg in a te f i lm s a t p H 2 a s a f u n c t io n o fim m e r s io n t im e 4 0

4 .1 6 S w e l l in g b e h a v io r o f c a lc iu m a lg in a te a n d c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 5 .5 a s a f u n c t io n o fim m e r s io n t im e 41

4 .1 7 S w e l l in g b e h a v io r o f c a lc iu m a lg in a te a n d c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 7 .2 a s a f u n c t io n o fim m e r s io n t im e 41

4 .1 8 S a l ic y l ic a c id r e le a s e p r o f i le fo r c a lc iu m a lg in a te a n dc h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 2 .0 43

4 .1 9 S a l ic y l ic a c id r e le a s e p r o f i le fo r c a lc iu m a lg in a te a n dc h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 5 .5 43

4 .2 0 S a l ic y l ic a c id r e le a s e p r o f i le fo r c a lc iu m a lg in a te a n dc h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 7 .2 4 4

4 .2 1 T h e o p h y l l in e r e le a s e p r o f i le fo r c a lc iu m a lg in a te a n dc h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 2 .0 4 4

4 .2 2 T h e o p h y l l in e r e le a s e p r o f i le fo r c a lc iu m a lg in a te a n dc h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 5 .5 45

4 .2 3 T h e o p h y l l in e r e le a s e p r o f i le fo r c a lc iu m a lg in a te a n dc h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s a t p H 7 .2 45

4 .2 4 E f f e c t o f p H o n s a l ic y l ic a c id r e le a s e d f ro m c a lc iu ma lg in a te a n d c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s 4 7

4 .2 5 E f f e c t o f p H o n th e o p h y l l in e r e le a s e d f ro m c a lc iu ma lg in a te a n d c h i to s a n - c o a te d c a lc iu m a lg in a te f i lm s 4 7

FIGURE PAGE

XIV

4 .2 6 C o m p a r i s o n o f th e a m o u n ts o f m o d e l d ru g s re le a s e d f ro m c a lc iu m a lg in a te a n d c h i to s a n - c o a te d c a lc iu ma lg in a te f i lm s a t p H 2 .0 4 9

4 .2 7 C o m p a r i s o n o f th e a m o u n ts o f m o d e l d ru g s re le a s e d f ro m c a lc iu m a lg in a te a n d c h i to s a n - c o a te d c a lc iu ma lg in a te f i lm s a t p H 5 .5 5 0

4 .2 8 C h e m ic a l s t r u c tu re o f s a l ic y l ic a c id 5 04 .2 9 C h e m ic a l s t r u c tu r e o f a n h y d r o u s th e o p h y l l in e 5 0A 1 T h e p lo t o f r e d u c e d v is c o s i ty ( p Sp/c) a n d In ((P rei) /c )

v e r s u s c o n c e n t r a t io n o f c h i to s a n s o lu t io n : • = ( p Sp/c) a n d

= In ((Prei) /c) 5 6A 2 T h e p lo t o f r e d u c e d v is c o s i ty (Psp/c) a n d In ((Prei) /c )

v e r s u s c o n c e n t r a t io n o f c h i to s a n s o lu t io n : • = (Psp/c) a n d

= l n ( ( p rei ) / c ) 58

A 3 T h e p lo t o f r e d u c e d v is c o s i ty (Psp/c) a n d In ((Prei) /c ) v e r s u s c o n c e n t r a t io n o f c h i to s a n s o lu t io n : • = (Psp/c) a n d

= ln((Prei)/c) 6 0

A 4 T h e p lo t o f r e d u c e d v is c o s i ty (Psp/c) a n d In ((Prei) /c )

v e r s u s c o n c e n t r a t io n o f c h i to s a n s o lu t io n : • = (Psp/c) a n d

= ๒ ((P rei)/c) 6 2A 5 T h e p lo t o f r e d u c e d v is c o s i ty (Psp/c) a n d In ((Prei) /c)

v e r s u s c o n c e n t r a t io n o f c h i to s a n s o lu t io n : • = (Psp/c) a n d

= ๒ ((Prei) / c ) 6 4C l U Y s p e c t r u m o f th e o p h y l l in e 71C 2 u v s p e c t r u m o f s a l ic y l ic a c id 71D 1 C a l ib r a t io n c u rv e o f s a l ic y l ic a c id s o lu t io n 73D 2 C a l ib r a t io n c u r v e o f th e o p h y l l in e s o lu t io n 7 4

FIGURE PAGE