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University of Nigeria
Research Publications
OKOLI, Ngozi Dorathy
Aut
hor
PG/M.PHARM/95/21614
Title
An Evaluation of Bioadhesive Properties of Prosopis and Mucuna Gums
/Fac
ulty
Pharmaceutical Sciences
Dep
artm
ent
Pharmaceutics
Dat
e
November, 1997
Sign
atur
e
AH EVAWATION OF BIOADHBSIVE PROPERTIES OF PIZOSOPIS AND tlU(=UNA GUtS
DEPARTtlEN.II OF PHARHAWVTICS, FACULTY OF J?HARWWVTICAL SCIENCES
UNIVERSITY OF NIGERIA NSUP[KA
AN EVALUATION OF BIOAIlHESIVE PROPERTIES OF PROSOPIS ALSD MN=UNA GUMS
OKOLI NWZI DORATHY
W/MPHARM/95/21614
A DISSERTATION SUBMITTED IN PARTIAL E7JLFILLMENT OF THE REQUIRJ3MENT FOR THE
AWARD OF THE MASTER OF PHARMACY (M. PHARM) DEGREE IN THE DEPARTMENT OF
PHAIIMACEIJTICS, FACULTY OF PHARMACEUTICAL SCIENCES, UNIVERSITY OF NIGERIA,
NSUKKA.
ACTING HEAD
DR. M-U. ADIKWU
DEPARTMENT OF PHAKMACEUTICS
UNIVERSITY OF NIGERIA, NSUKKA
Okoli Ngozi Dor~thy, a post graduate student in the Department of
Pharmaceutics Reg. No EG/M.Phamn/95/21614, has satisfactorily completed the
degree of Master of Pharmacy in Physical Pkarmacautics.
The work embodied in this thesis is original and has not been submitted in
part or full for any other diploma or degree of this or any other University.
Supervisor Head of Department
iii
DEDICATION
To my Atmty, Joy Adigwe anrf my 1Jncle Anayo Adigwe.
I am grateful to my supervisor, Dr, M.IJ. Adikwu whose motivation,
encouragement and advice has brought me this far. I equally thank Mr. V.C. Okure
for his contribution to this work.
I am also thankful to Dr. E.C. Ibezim, Dr. A. Chukwu, Dr. S. Udem, S. I.
Ofoefule, K. I - Chukwu, who made their contributions in diverse ways. I wish to
thank Messrs A. iJka, S.M. Obialo, Kalu Ogboso, who provided the equipment for the
work.
I remember my colleagues, Okey Esimone, Kenneth Ofokmsi , and Kenneth Muko
for their encouragement and wonderful company.
To everlasting God, I give all the glory. It is by His grace and strength
that I was able to complete this work. Thank you father for all the care I
received from members of my family.
ABSTRACT
Many tropical gums exis t whose properties are similar t o those of
the cellulose derivative imported From western countries. In t h i s study,
two tropical gums were extracted from Prosopis afr icana and Mncma
flagillepes seeds and were studied for bioadhevive properties. Adhesion to
porcine in tes t ina l mucin and t o glavs beads were studied. The strength of
the films formulated from the gums were determined by w l i c a t i o n of
torque m d recording the force a t brea kpc~int. The surface properties of
the films were studied by microscopy.
Three methods were used t o evaluate the bioadhesive properties of
the gum. Fi lm coated glass beads were analyzed for the bioadhesion
properties using normal saline as detaching f luid. The film coated glass
rod was also used for the evaluation by determing the maximum force for
separating the film coated glass rod from mucin gel using spring balance.
Lastly l iquid gum bioadhesive force was determined too by use of Haake
rota visco as speed factor of 27 and shew r a t e of 156. Factors that
influence bioadhesive force were studied too and these were concentration,
glass bead s ize , pt?, contact time and coat size.
The resul-ts indicated tha t prosoyis gum had bioiirfiesive properties
comp;irable with those of eod1.1~1 car-boxy methly cellulose. The gum from
M~crma flwillense has less bioadhesive properties. Based on the resul t s
obtained from the adhesive studies on glass beach and hog in tes t ina l
mucin, adhesive values of 1,2 and 4 were assigned t o prosopis g m , sodium
carboxy methyl cellulose and mucin gum respectively. When studied for
elongation and break point, the most e l a s t i c of the gums was prosopis ,gum,
followed by sodium carboxy methyl cellulose, while mucuna gums was the
least e las t ic . On microscopy, prosopis gum and sodium carboxy methyl
cellulose formed formed films of equal consistency, tha t is with gores.
When bioadhesive properties of gum evaluated through three methods
where compared, three different values where obtained, The bioadhesive
force of the l iquid is the greatest l . The bioadhesive force of l iquid
prosopis is as high as 2805 dynes- The bioadhesive properties of the gums
was affected by coat s ize , contact t i m e , concentration and glass bead
size. The pH affected only the bioadhesive force of scmc and its optimum
pH for maximum bioadhesive force is 5.5. A large coat s ize of the films
resulted i n increased bioadhesive force for a l l the films. The optirmun
time for high bioadhesive force of prosopis and mucuna film is 20 mins.
while tha t of scmc is 30 mins. The bioadhesive concentration of prosopis,
mucuna and scmc were 2.5%, 10% and 5% respectively. Smdl s izes of coated
glass beads adhered bet ter than the bigger sizes. From the above
resul t s , it can be s tated tha t prosopis and mucuna gums can be used as
bioadhesive material-
TABLE OF CONTIWE
TITLE PAGE
CERTIFICATION
DEDICATION
ACKNOWLEDGEMENT
ABSTRACT
TABLE OF CONTENTS
LIST OF TABLES
LIST OF FIGURES
CHAPTER 1
1.0 Introduction 1.1 Bioadhesion 1.2 Mucus 1.3 Mechanism for formation of broaclhesion 1.4 Theories of bioacihesion 1.4.1 Electronic theory 1.4.2 Adsorption theory 1.4.3 Wetting theory 1.4.4 Diffusion theory 1.4.5 Fracture theory 1.5 Evaluation of bioadhesion 1.5.1 In v i t r o method 1.5.2 In s i t u or ex vivo method. 1.5.3 In vivo method 1.6 Factors affecting evaluation of
bioadhesion 1.7 Materials with bioacihesive properties 1.8 Gums 1.9 Structure and constituents of gums 1.10 Precipitation and purif icat ion of gums 1-11 Properties of gums 1.12 Uses of gums
i
i i
iii
iv
v
v i i
x i
x i i
1.13 Types of controlled release bioadhesive dosage form anrf sites of application
1 4 Theories of membrme trmsfer of drugs
Materials and methods Materials Source of prosopis gum Source of rnucuna gum Preparation of gum Preparation of prosopis gum Preparation of mucutla gun Particle analysis Determination of particle diameter Determination of true density Determination of volume of each particle Determination of area of particles Determination of number of particles in test powder Determination of area of powder bulk Bulk density Water content of material Degree of deduction Preparation of films Preparation of tnplasticized films Preparation of plasticized films Evaluation of films casts Macroscopic and microscopic examination Water vapour permeability evaluation Evaluation of mechanical properties Evaluation of bioadhesive strenght of films Evaluation of factors affecting bioadhesion Preparation of mucus gel Determination of bioadhesive force of films Determination of bioadhesive force of gums in liquid form
3.0 ~esults and discussion 3.1 Particle analysis 3.2 Screening of the dry ,gum for adhesiveness 3.3 Film evaluation 3.3.1 Macroscopic and microscopic examination of the films
3.3.2 Water vapour permeability studies 3.3.3 Evaluation of mechanical properties 3.4 Determination of bioadhesive concentration of
different gums 3.5 Evaluation of factors affecting bioadhesion of
adhered glass beads 3.5.1 Effects of size of glass beads on bioadhesion 3.5.2 Effect of solvent on bioadhesion 3.5.3 Effect of flow rate on the resistance to washing 3.5.4 Effect of absence of mucin on bioadhesive bond 3.6 Bioadhesive strenght of polymer films and factors
affecting it 3.7 Evaluation of bioadhesive force of the gums in
liquid forms
CHAPTER4 Conclusion REFERENCES APPENDIX
Tables Page
1. Various bioadhesive materials with their bioadhesive values
2. Particle analysis for muctma, prosopis gums obtained in the laboratory by coacervation method
3. Water vapour permeability constants for the films
4. Mechanical properties values for the films
5. Effect of gum concentration on bioadhesion
6. Determination of bioadhesive component of liquid forms of the gums studied
7. Effect of bead diameters on bioadhesion
8. The effect of type of washing fluid on bioadhesion
9. Effect of absence of mucin on bioadhesion
10. Fracture analysis of gum coated glass rod at different contact time
11. Variation in maximum bioadhesive force (MBAF) with contact time
12. Effect of pH different mucin gel on the bioadhesion
13. Variation in BAF with coat size
14. Variation of MBAF of suns with coat size
15. Effect of gum dispersion concentration on bioadhesive viscosities and force of adhesion
List of figures Figure
Schematic representation of the set up for evaluation of mechanical properties
Schematic representation of the set up for evaluation of bioadhesive concetration of the gum
Schematic representation of the set up for evaluation of bioadhesive force of the film
The effect of flow rate on percentage of glass beads undetached
Plot of bioadhesive force against elongation of prosopis at different contact time
Plot of bioadhesive force against elongation of SCMC at different contact time
Plot of bioadhesive force against elongation of SCMC at different contact time
Plot of maximum bioadhesive force against coat size
Page
glycopmteina (0.5 - l.OX(,Z ( 3 ) . Nasal mucuv tias s greater ~ ~ i t o i ~ n ~ . of
e lec t ro ly t~ . s { i 2 ; ' :f;ilrl. glyca-p.=.r~r,eins (up tc: 3::;) ) me
I;omgositir~n of ;O'CX.CUS m,3y change with ctisexse s i t u ~ t i f i r i s . Tt is
I r ~ p ~ p t x , t o ii.n&rst,nd these p h y ~ i o l o g i m l ch~ . r ig~e t o cleslgn 1c:u.ilg
prg&icts . ; i ~ i n g bi.snrjh~si,.~r mxterials H3 the carrier. Snme b i ~ l o g i c . ~ l
3ijrf.~(:fi~ s~.I .c~ 3s skin cree.te problerne i n t.?rms cf s.dh-.si~,-e ?.i--i~g
del ivery 1 4 ': .
One [jf the majar problem i n the del ivery of drupe
transdermally is t h e i r ~ e l a t i v e impermeability through the skin.
Nevertheless t h i s method o f delivery is very attracr,isre, and 0ffei.s
m.mv advantages over a1 te rna t ivc routes of druq a&inistrat , ion i 5 \ .
There has been much interest . i n developing transdermal devices which
allow itr~ugs to permeate through the skin a t a rate high enough for
therapeiutic eff ic iency. fine wav of increasing drug del ivery through
bioadhes ive materiais is t,o iuclude absorption enhancers during the
formulation of t,he drug product,. Many bioenllancers p r inc ipa l ly ac t
on the ~ t r a t u n i cornem and revers ibly reduce the t ranspor t
res is tance. The ef f ieiency of many enhancers and t h e i r f~u&nientai
mechanism of s c t i o n have been emluatec! over the veam ( 6 , 7 ! .
Based on the Isnowledge of the various b io lase rs on adhesive
bond material can be developed i f the nature of t,he surface of
bioadhesive poly-rner, the f i r s t . Izver ai the naturai t i s sue and
Table 1
- 7 . 11 ,~rious bioa.dhesive mat.eriai.3 x i ~ h their hioadhesive values
Material Bioridheuive values
2uiver;izrd anci soa~reci I n t.raTer ~mci the S r r n peeelpi r,atei w i t i i et h . m c 11.
.:,r. 3,C.":.OnF. 1 5.3 ;' .
IF_. to ol:cl.lrerici2 .?f mr:)s+, gun p3il,ryaccharid..s i n n ~ n - f r r e
mstmer b:n w i t . - I other, plailr strbsxances e~.lch (3s I,?';, p.n-4?ic3.~, i ,:I-L ?-!f
.?rr- ds:rnt? hy f i ltt-r ing . prec i p t a . t ir:? .?:-tr? !-.-, ,-.rnr rl r..ic:fi:s - - .
E l e c t : r : ~ ; p ~ ~ ~ + r ~ ~ i ~ 1 3 glcis: f i j 3 p > - . ,. ;..: :I-.-:,,:, .? p?. ,:-~!-!:- ,~ i,f
. " 0 . T-,{,,y ;. c\.* f i f -.-:.~,3.v-.+. p:,j.T.?y!p-:: . ~ I I ~ ~ 1 +-.r -, + p,1pz, - 3 y y 7 l = - . l ~ ~ ~ , . ? ) :17~ y< : , np
> , V , C C . 9 .> .,-,. . . ,
, .. .,, 11 1 :aL=~,;5 %,j-,= ,:r?ll::t .~.J;--T: ,: f ~ : ~ . c ~ . ~ : : ~ ~ ~ ? , i-:n , s ing le peai?, 13 an
- . - 3713 !V?.-i (:a! I.! I<: y:: .-.?fl? y i f!,1:29. - ? z i i j ~ i ~ , : ~ , p ] ~ ~ l i > p ~ ~ ~ ~ -
1.T1 Properties of gums
The h s i c ~:~ri:~peptr.ies Frtli~h a r e i_' i IERIOn tr:. . d i p . 1 ~ ~ ?:~IAT. :I:?
- . t . h i c : ~ e n i n p ail<? v i s c o s i ~ , r / imyart.in5 .>n ~~1~prsr-1 . :=:7::r;.~ l;!<e 3 i ~ 1 . 3 : I:.,:, ,
wir i,;:jl i~ + - , . - , , 7 - t_l,+.-.r.:~,:.<!. p I : : , of ,3 L -.
\;3,7,:j .?,? 7 1 -. i.:j,c .
. > ,
1 t : 5 , 3 f t j tI-jpp~ni-!o~lr up:.:: vi,y,;n:z j t , ~ 3nrj t,!:?:' ;i.l.: kr.i:!i:
- . - qm,! 1 .- i f ~ ~ i n ~ ?.!iij y ~ ~ g ~ I ? i - ] ~ y l q ; ,i.*.:-;?:;~.pl 4 +:. :! * . ' t - , , ~ , - , - ! <+mi :-.,:,.:- ,v>.5.=.,1. - A .~ . . _. .-._ .. . . ,. . L . -. .. . ... ... r--zrr i~~
- . p - : ~ ~ . j ; ~ ; : t;,i.,::: Y,~-! ~ ' ! . , ~ T I J ~ , .:.::.:..~IJ..:I~:I~.~,:T.~,:: 1 . r ~ ( 4 5 1 . & y ~ 1 y ~ ~ i ~ ~ : h , ~ y i C . : ~ ~
. , i t i . ..., . r ; . - r s ~ <:ti~'i 4i.i-. gt7i7~1p2 a t t a c h d t r ? (?lxe,ing are highly viscous end
st.>!-# le ir, solt,:tion. i i ' i u c i 3 s i t . y of >miysaccharides ape i r i f luenced ?Y?
pi-l . t,emperature. salt m l u t i l ~ n 5r.c . i !55 ) . A_rlo~,her nro::!errVr cornon t,o
sun is ge l l in2 . Gel l ing is exhibited by few gums ( 5 6 1 .
7 ~lurt ,hermore. i n t h e Ficirv ea1.1at i on r 1 , the :Iru!-r concen t r a t ion
in the piasma i:! extrenlelv mail compared TO the dm!: cor~cer:t.ration
i n the ga . s t , ro in t e s t in s l tract , . the d i f Eerence between C g i and Cp i::
:lor, require energy input. Xinwtmsis is t h e process of eng.~lfement
MATERIALS AND ~ I O E
Methods
where r is the rarti1.1~ 3f wr. t , ic le
2.3.4 Determination of area of partic1.e~
J-1 , - 5 Evaluation uf f i l m casts
2.5 .1 Macroscopic and microscopic cxaninatian
Y2i..ro..jcl:~pir_. exmiinat i m of f i l m s w3.s d.c)r,e by vima. l a d
t.act il=. r_:bsiirva+,ians while : : ~ C ' ~ O S C O F ) ~ C e>:mina.r,ion was carried ~ ig t
-i with a magnifying I m z . For rrrarroscopic emmin:ition. the f l ? m w v t .
ohserved fay cracking t,~nrl.ency. opar ir.?r. .md t;.xr.:~rc hii in rcs i TV
,percent , 111.1mber :if pu re r i.n a ::)riat,.?::+, :I.F:~) and hr:or:rrgpn~.it.y s y w
~-tl-~at=.r~.:cd - . mi.r.raa~-.~i:.-~].3.:;.
a-: ;, r , ,. . , . ._ Water viipmr permeability evaluation
. . Fiater. v:l.pmr per..rws.i>i l i ty ::,t,?.!.::;es (on e3.r.b f i l r ! ~ f~ 3.e +:un&~t P :j
- - . 1z::ing r: t..~r:qt ~ i . 6 01 rl11 r11.l r.;tpa::it.y wi th 3 circiljar perfnrr:..+,ion i :;.?
err? , at. the center of t . 1 ~ 1 id c?nt..?.ining 3C! g ~ 3 f ::a.lcinm ::hlr;ride ac
. . ... ct;.:: ic-an.; . H .-:i!-c-?:l,x- fi In? ( E?:! cm: r wse cut pandnmls~ from t h e
cilsr. pre dried films and ueed t o waJ. the t o p or' the bo t t l e s u ~ l n g
3. layer i7f iabi~mtary f i l m s . The l i i : ! wa;: sl:rec7<:i< m i +he i-,y8r,r lb:
> - wt...igh~,:i i ~ i + ! . i a - ~ . ~ : ~ usin? ,?,.:: a:-,~1;~+ i ::,?.l 7 - y . 1 >tli:f , 3li7i:)1~ 1 7'47!:1 -
S a u t , ~ r Ebifigen. 'rje,t. !?>i-:~tan:\? ) ai:d I.:er:si, ,.~!~::list,~.;rred 7.' :!ll;bi.~:~:- -:(,ar
t.,pylp? y- -j ?. 1.1 r!: f (11 Gt:. . ; 5. ,>': !:,::+ 1- 112. b7.33 re-^? j ~ h e r j 3t ir..fiervals of ';
. . G:-, ,,. ,-I . s' 2 . c . ' h? :.?at.er wj:cur pernleabi lit-? r 'ans~,ant was ~ralcui.3.wili
fl- ., , e w h film ~ x i n g +,he c q i . ~ a ~ i o r l :
F i g - 1: The schematic representation of the set up for evaluation of mechanical p r o p e r t i e s of the films
Retor t '$?and --
Separating F lask
Inclined Base
Polyethyelme Tubs
Adhered Coated Gla
Fig. 2: The schematic r e p r e s e n t a t i o n of the set u p for evaluation of bioadhesive concentration of the gums.
. . . &'
, - Evaluation of factors affecting bioa&.esion
. . - , '+.:f,rl:r.s ( f lot< r -? tp sni:: , l z y i l f .21,3;.,:: ! j c ~ ~ ~ i : ! : y ~ ; ) ? ~ l [l l L i , i :.. ij,: 7 , : +( .
2.7 Preparation of rnuclls PC?
7 L:: ri.!-,t;<l I * -; -- _ . , . . # - . , I - - : . t . _ d l . . - ci-.- - _ _ . . _ Y . , ! - I G , ... ::j,:mL?;- j ;, :- . , . - . : , Y . , - rn ' z , 1 - t n,, I .,- - .
' I . , . . , - -
' : I , T ..,L!.:> , 1 : , , .,..:* . .-. ; . r - 2 , * . , 9- ,-,*<.-,-.- ,, . - . .. . . . - .. 1 . . . , I . . .. .. , . . . .- . . ., 8.. i -:i ' l '
. . ; , , , . . , .. . ~ . ._., : - . - - . . . .
-,>[ 7. ,:.:L:.L'.l:;'-' ::-; '-,A; i:rll<,?,b= ,-.<I, !.- 7.
. 1 . . I 8 - * - 1 !lf, 8-.i--,ui;:],L -
. - . . - , % - , +;-,., llt;:L,y-4 ;;; --!-i , : , , l8~;3l T - r x , ~ j , 7 >- - * - - - > i j q ( -1.: - - . c . . - i l . , . - , " r:y -
a .,.l L,,; ,. , -: =,. ,.,, -!<2 L!>..,. ,.li-I.,.. , >.!.ii!iT@ ! 4. - 1 : ; : .
.. ; . .- 51, ,-I p4- p-c 1 ?, ; - -
, .. _ ' 2, - f : j I 3 . : f 1 : 1 ,2 fzer ;.?%iCr]-L ,? i t,,ki!3
. - :~~r;:,?n-r,s (.7pr~_' : - * ~ ~ t , y i f l ? ~ . p < ] i - ~ ~ i n q 1: (bc :~~2t~p? T _ * ? ~ T " ~:-l,lg:.:~ . i:TL- . > . _ . '?I -
i !z , 7 r, ,F " l_lenk=imy!, engl.lnl-! : .3t ,..:!?!! r y v . m i l l , : fc:- 1 I? . PI- s???nr.n:ir .3nt . ;7.95
- - .-4 i Z L ., i. - - . .:.L. : -. :...* c.i.c: - I 2 ?,.I -? ;-!+ 1 1 - w ~ r .- zp i .L:Q:PT-- ~,+~i:e:; . Thy .ge 1 T J , : ~ 5; c i i ~ . ~ y s y < ! . wi$,j :
-1: -> I 77,zm, < * . .ng merilbr.sfie <?r. ~ L J h .:i-r, 4 %p diaiyo3t.e was ~ f . < , j : ~ d , :i.~i r-,YI
(-",' " . - . - .. u . . ~ e ' : ~ g17.5: ~,.-i,:tl;?. ir: 3 f:.ryzpr I I L ~ T . ~ ~ i ~ spc i .
'. ., . :;I ._. De-tennlination of bioadheuive force of f i l w s
. . - . . . p i g ? b i ~ ~ ; ~ ~ ~ ~ ~ ~ : r f. ._ir.~p );i?:r,we:; yl l : f l T.~_~:IT?<:. q::'?~ L - ~ q d at-:,-?. ?yjf:.lr:
7 - ~~3.5 i'etp:.~linc-':! r . ? ~ i z i g , y zr:i.ir;g ::;i.lxnr.- rui i i , : :el ::<111I'.j, !:41-3?1p, rL . : )y~: rp~
. -. - - . I , . . 7 3 . !.l,.,p-~- Fil:n ,:qt;:ing o r gi383 T.;_I+-~ F:%C ?for:?
,:Jj~q,jnr:. T ~ F J inar: ~ ~ I J F . ~ I J . S <j.I!j.~_:~'~rg<,?n3 ~ : f t.Tlr_'. g;L:nIc :.t: [he~r
l>j-~j,?~(fi-lt::,.iv~% ,:~:~r~~:f.~r~l;~.:~l:,j;:~~~~. ~ ? ~ y c l ,:j.:myirl~;' L ~ ~ T pc>rj :( :..:;:)L.~:?:.:L,.I.J.;~~:~ s:i
. - - - , -. . . -. I r ,rp'i "-. -2 ,-, , ! 8 . 6 .-..:.,;,.~.4'; - ,,,8,T. :,+ . 5 > *>i., ~ , : j ~ h ;J ;~i;tgi.;::.: ~-~.-1~3r 1 Ti',! 4it,4. ,rL.. :... ,%.. .,, ' - .
- . I -1,- .r3f.p-l?--.,T , , , , ,., \ nj=. ';,.- .[-.! --,,-,.2 1 ,; 112,;- c, ' ! j +!- -. - , *T; , ,i-: 2 - -, ~- .,,:, .- . , , . ,,'! . ;;;,;:. ,: -A,,- _ ! < I .
,- ,- - , - , , , , . ; , r r . . , - ! , .,-I , ; , ; ; - ; : , r ,F,- ! g~.,,;:.~ A r .<-, ;,$ ;:,;; :, :. , ~ ! r!!: ,,;,---* 5 ;=:-p.rj -fl>z. k;q 12,;-,<-.f!
- - - . . - 7 ?:..::.; . l r j <: !..I . . . . , , - , . - cl -~;.i,:f W33 ~j~3~.11?: ~ P T ~ L I T J ~ ~ 3~ 3 p ~ t ~
f 1 ~PJ:WC t 'vnm :.he 1 . ~ ~ I ! : ) z E ? . T ~ c ~ :\lol.lfsi~jp Y J ~ T , ~ fgr.:? ,?if
.:.&e31:\1: kr . r t2 I - I : - , + ~ - ; - T;f~p y,:h~m>.r.j.c ~ ~ ~ ~ p P s ~ n ~ . s t i c r : , t ~ ~ , g 2f ~ p p E:??: ~ J F ip
- , - . shfi-pn in ?I%. .3. The fr,yc!:;crr- arlal!:eie ;I7 nj.r_rgrjhpgi(~n ~ 3 9 aisrl
"-;7 . . .. ~vaiusr-e,3.. I r:c : l i f f erer;~. f 9 ~ 7 . ~ 1 ~ 3 that a f ' f ~ ~ ~ 01~xt,:-psi~~;. w ~ y p
- . , ~~::cirt 1 er! t c \ r i and :kse t;er.p cr_lnt,a.ct :imp ! 11:? - 41:) mins : . =.oat 1.7eighr
! - - 1 4 - 1 - g \ .911~! pIl ( 3 7-21 . 2 1 ~ ~ 5 3 t W P ~ & T ~ 3 . 3 v.rlried by
ia:r!r-.ae ing he rmmber of coa.t.ing pm.~~.&we? 911 gisss rod.
2.2 ktemimtion of bic~.3c?hesive force of gum3 in liquid fom
The frjrce of b i c d k s i o n of iiqiltids ~ a . 9 ev.qhzt.~. , j by using,
viscometry method. Vario~ls aqueous c i i spers i~ns of prosoyiz, SCrii!
3-id r1~~1::un.z g?m.s s a :wi 1 : ~ s mircin gel L 2.5% w/w from st.ornacr:
Retort Stand
Glass M uci
Spring R alance
Glass Rod
V iel Containing - n
Fig, 3: The schematic representation of the set up for evaluation of bioadhesive force of the films,
-. c;r' p i g ) were greparer:i. \/ ls!;cmetrLlr r+pa;iing r<r mur i n p i ,? lone ;.T,
:.TmpoY.,?r:~ I r,<f. s:( i 11 W ~ F t.a:er. usi.ng H H & ~ tovis,:~:! c mnfi~.? 72 22 .
. - .b;ap j Ectri'b5. &-rlin, kips? Germa:ly I 3 7 3 syqp;! T.5r.T.ctr r? f 2'7. !'he
result, V.IS & ~ ~ i ~ , l i f ~ - . T j ri:; ( 2 . F l i t % *h+ . F ; ~ P eq~~j.pmer:f. and ~ k r yam? speed
- : 3y71y. ,. . ~.*iwc;.n.-tric reatjing of mixsnre 3f mucin gel 3n:i gmn an a
-7- m t i c l 3 were a l so t&.sn . Ltze mrn viscosit.!: ~ , p , was
determined. usln.g i3sw31d viscometer . I3ioacjr~eslve v i scos i ty b was
caicuiated from eclila~ion 7 ) and bioadiesive fame was aiso
caicu.is.tecl from eclua-cion t it3 1
'b = T. - PI-p .... ! 1 L i
- come of adhesion = L x sigma .... 1121
where si~nio. = r ~ t e of shear..i! 5-1 i . . . . l i . 3 1
-, tkL2 S i r ! -,i4hr iorl 1.4 ~ ~ p r - , zm J ~ t . -.r ... dU , ,,.- , - . ,Lty and K, ice, ?;he v:sr,.osir,y of mixtu.rc! c c ~ f
21.m 3sld niucin g e l . E: i.3 %he s*iscosity of tkie gui only.
3-.?..3 Evaluationof mcchanicalpm]~~trt-ies
, . - - . ,., - - <-,nlc,3; p fy>p:2p~,~ ,>2 !:lf f:!::,:., '!;,-.:..-.. : . * ~ . v = * ~ , :.;:!?a;: : , - , ,7- . .< 1 j . I,?. Y - "1' . -
. . -7.. . .
. , 7 qr ., \: !..i r y ,,: ,-; ;j.-; . r y-1,:~' -1 : ,y:,r+:j:?,y.-:i ;jyi,j p r y 1:' :+I-;-. :,,*y;,; -i T j -,:-., - 2 L ' .!. -
, ' < ' L .-.- . . .:i , -,, .-[, , , .- .-,-, -, + -, : ';':,I-. -> A - ,,. ,, -,,-!.: -:., j-r,c f;-:r ,::::.L i;:,i - ~, .7-y- . , i-; . : W i ~ . h t l ? ~
~
- . I , , = , - , J - . .= - f . . T v , l i , , . ,. ;. . - , fP5w -.,:, p u i n t . pisszf? icst icrii Iliec.resse5
-
t . + -:, .,.. <, -. .:1.? ztryng--r.h and e l a z t TS I I I I T ~ . ~ ~ ~ . F4prr.erl: E ' L S T ; ~ . ~ T ~ D S I TLT;. b ~ e a . ~
T)- i -7.k - - ,-, P, c,; .-, C :*
,\_ ,.. f:-\-p pp2snpi,? ~~L:z.F'.ss~(.: fr~ir~i L~,? . +,:I fipr; pl3.st ir. izpmj Tc;hF;-
r~i~cnn.:i g m in 3.n i .?r~plas t , i ,~ izec? f r m a ! r,;hich TJ;AS uny l i a . 3 1 ~ i i?.s
*v : l !~~e a?, W?., . S i r n i 1 . w ~f f e,:t af; ylwt,icim.ti<,n on i_.eilulosp ethers
e th::l ,:rllula;e f ree fil.ma w e r E obta.ined i 73 ! . Flast,icizat.ion
saft,ens all the films and rn..~.dc~ it p l k b l ; i t.2 t.;ork with. !:;ly:?riilr:
- . m:~y Ti3ve a~3ievi .d +hese moi!;f i.-..ar.ions of mechan<.r.,s.l ;\;-. ; 8 i - t - ~ : iv; i:;:,:
- - . - . $ ~ l ~ , P ~ p 7 ~ i l - i ~ j,T:Pj.: t;yTkypr; :jp 2-i1.J; - y-L:!.Lri:, 7,;: p+j! . l . ;y pcki~,qf~e:----,~<:\i?,~f,<*!-.
- . - ,;-;- i-j 6, .? 1 ~ , z A ; : / 5)
Table 6
&termination of bioac1.hcsive component of liquid f oms of the fl.rms studied
n - viscosity o f component of bioadhesion. M = apparent: viscosi ty of mucin P = apparent viscosity of gum alone, T = apparent viscosity of mucin and gum alone Fce = force of adhesion. SHR rate = shear rate
Table 7
Effect of bead diameters on bioadhesion
aq~~?.eous gwl I w m '? (X)
Prosopis I 2.5 I il I-.
A d
il <2 3
1' I I 11
3'lr~u ra.-t,e was m n s t , a r ~ t , 21:) rrrls/:ilin. rktaching f li~.id was W . s.r.llne
I I I ;sy .3 1 4.0 11 ~7 ,,orensen's
I , ~,Il,.!sp'rl3 ?:I-: I
11 a I/
bixf f e r -
17. , ;, , . .j;j,,j '~ f;,: : i -I.=: k-4i ,-!
I$ :r,-, 1 ci.3
- 1 r ' i (3 . IN HCl
Sorensen' s pho sphatr buffer
30
0
i N o m d s a l i n e i 0
. - n e a r n e u t r s l pH 3 i::.ez fop , e::3mgj? qy, nlouth :jni? srr,alj.. 5:;: iw . . - - . . . I p y t ; - ~ ~ ~ ~ r ; g c:t T,?;. &slpe; : i ~ ] r . . ~ , t i o ~ ,:I? ~r.;,t.j;~~~ .::I: -3" ;-. -. I . , ~ ! J . J - . . - I ,..3XlCi? 3.T
- - rhy s i r e .:,f 3pl.l im:a~~ jgrl, p~.?z~:;.i: ij$i:la:]yLe&~ &'11~.,4 zc regime-,--
$+? :,argil.-ref. ::I at,onra.c.yl :,in~:c ort iy 213:; ~l,5;;~ i y 4 a .;~'11t - !jcr.t,ar-herj. g f i ~ f i
!j. 1:': 3;:l w:!..: 1.13prj 3 5 ;iL;' ~ r _ l i ~ ~ ~ , y i t .
: ? . E l . ::. R f f w t of flow rate an the resjst.ance t,o washing
-- - 7 - . \/ ar;:i.ng r lr;w C - C ~ T ( 2 3 - ~ f 117 - tjl:J rrlls,:~iLia ~-:=.pc etllpl,?q*e~ -!-o.~il-~c;
~?:p>r.i:flri~:. T'.i+ ~.:;.p?rin,:?rl'-.j, r.?rJs CQ~~&J.,~:~,F.,:?. t . ~ .-j=cprtain $ffe<:; 35
- a - . , . t i t e:ffcct ,:)f f l r j w on wrpcqri$
. . , . giax !,?adz ~~i~:ir-t,acr~s~A. zrrira tissue is shc~wn in Fig. 4. The ~ l m k r of
eac'il gmi ?a3r.r.d ~ 1 3 3 9 I : e . y k ~ m d e t , . . from tkl=. t.iz;su/z;-, at. each flaw
rate varied. At +,he f1i.w rat,e nf 10 zn 25 mls,/'slin, the pprcenr
glass heada detached was LOO?; for. a l l the g~ms st.udieci, x h i k s.: t h ~
- . f l ~ w ra-r.ee of 40 to ij(! mls ,*niin, *,he rerrl.eT;r_ ;_rf g l ~ . ~ ~ '!..~a.& ,.:'? !,:I.: !,.:;i
. e . . gr.ea.t.ly <:ffpr.er!. rr.rJm :me p-uj~ ;13 : ; ,~ l r : . ! . , ; - l ,~ . ,~ . . T';, ;,,.;&;~?, kk-!.:
10 2 0 30 40 5 0 60 7 0 Flow rate imls/min)
E f f e c t s of f l o w r a t e of washing s o l v e n t on p e r c e n t a g e g l a s s b e a d s unde tached from mucus l a v e r w i t h g l a s s b e a d s s i z e of 5 mm and normal s a l i n e a s washing s o l v e n t : -8- p r o s o p i s , + SCMC.* mucuna, d a t a r e p r e s e n t s t h e mean o f a d e t e r m i n a t i o n s ,
Table 9
ac #t u f at~sence of rn~wia on biusdhesiur l Eff .. .
Present
. - C Note : 1 t 7 I . . 2 r , : rJeL,a.chi.rg , I ~ i c !
3 .
5. 'GT-IS f , ~ t ~ i L , I L , - ~ F ' [ I I ~ ~ ~ :,::I 1; i~,.! e,L3..5,!, i.:!?!~.<l < . ! . L ~ Y ~ . * ? Y , 5 LULL-
I , -- 4 i!?.. Present 0 ii7 - LL wia ' 1,) i Absent i is8 .. I I/ I
I (i
I
- !I
i Prese-ittr.
7 - 7 9 i o a f i c n i w s t r e n g t h of pnlymer film3 and f x t o r o lzffecting
it
- . where F: Fs .work, of a&esirjn i . , ~ iz -t,he or tile f i l m 1 x 1
canTact with the rum5-I .
The cu.rvez obtained (figs.5-7 are ?,ypLrslly .:>f the s h x p ~
observed by Martini et: 2,; 1 40.r 2nd E)onr.hel e-c 31' ! 41 1 . The ;_.upve I::
4 , ' < :, char.acteri ;~d hy thz.ee rc?c:ign..;: irl tl-p (:yij.,i;:,:~.z z.r2,yp i,:,.-% , . ~ : L
. - fr)rrf? ir~r-r[?<~s?s :ipp:,e::<.d?)ly yi1~,1; ,-ml;<lLk:-,: - fL;, . ; f i4 - , r :+- - .> , I , . ,i. ', .
. . -y ) ,~~ ,K;>kf ( i t;.;,; ;,,,,-. 0 .-. 1 ,:, - ; ;,, 8 * , . - 2- : -. -, . -
- , , , ,- ;.: ,,..,,, 2. . ,,:L#-, 7 -., 1 m ... - , , . 4 L , - , - 1 6 > L - . .,LA.-, ... L C ! '. : :,t13., :.,; :I r,,-.,:1:,:
,"" ' , " -.-:..-.. - ' . - -
7 . . . - . . - ,-,;. ;p,-,t I-.- -- T-r.;,r(j T C j 7 r . . - , z . r - - 8 , - , :!l',7:A..:. .. N[/ . : ' :.r , + , - . 2 , . . a % " ' - .>,-I 1
=,,-j-* - '; . . - .
. .-.;: i I : . . - I ' .. $:q - . - ,np 3 ?,:,:-,(? ,+. i5rLif icarLt .a-:er ..he . ~ y g < , ~ r ~ i l I -
-,.,-.!i;-:? , . , . - -. t.:: ~:-~?m~;'":e df=:?.:{;.kfl(p;fi of ?kiiF matri:;. 3.z , 4 1 1 . Tj l ip
, , - ? , 1 3 - - 7 .
. - , .a .. -. - f.~:.l.i - ~r,.-rx~n-l;.j~[~ !-~i.:::~:)~it:~r~:,:-l fr,r,I.II' sm,-,ng thFl ~ T J I I ~ 3, , ; , ~ l i - i ~ ~ ~ : ~ i ~ ~ ~ l , ~ ~
. . - . if -l . iff~.y~.a,-.c ~ 1 - i i;~.er.-p - 6: g ~ ; f i ,:ha-iaz 1.7i~,i1 rf,>j.i:ljz,
t i r Pr.:,sog;i.~~ th.3.t 1:;rlc: pc,3.?i.F in?r?~.ai_.r,i:ln wi th he m-lr_'.3sai
;KTWX.I-; j-iae ...reat el- mu:<im~m rji oa&-ps ive for-? 3 f 4 - (1: :%me
+l~-bngatir:it 11rf 16 mn 9firj. c:'~_rlt,x~:t t$xlq -.f 5:' :rliri~ .
Wk t El:: b W Ad:: of ( kp.:~ :i ( \,:;,:I \
I I
f ~ e Ads Aa
7 Cdy (m3)
Prosopis 2.5 I(! 17 3.0 0.36 1 - 5x10-3 1.. 15 0- 71
'7 i') 4-11) i).",;? ,A<. 19 - 1 . & ~ . O - ~ i~ - :I?:? i) -!l? I , ,, 11-42 1 t.':.:l.n-3 -- ------ - I
40 - 2.5 i3-37 1 - !.);<lg - 2. 1.19
Scrn~: 5 1(:i 11 I ;j-R7 1. 3s?0--" 0 - 28 0-1:
20 .-,.> i. - 3-9 0.71 3 .4~10-3 , 0 -22 O.!l3 - I 30 18 3.5 0.55 / 5.3~10-3 0 . 17
40 7 3.5~10-~ 0 - 2 1
10 7 l-!ja --.-.
1.03 10.03 - $ -i
1.40 0.05 /! ? -7 c I - , ; . !I A. . *:I ..I .. . .: I ' 1
1 11 1 ;' , 1 I; y f l , 7 4 -
D i s t a n c e moved b y s p r i n g b a l a n c e ( m m )
l!Fig. 5 : P l o t o f b i o a d h e s i v e f o r c e a g a i n s t e l o n g a t i o n f o r mucuna gum- 10 mins.-& 20 m i n s . a 30 mins . 4 40 m i n s .
E l o n g a t i o n ( m m )
F ig . 6 : P l o t of b i o a d h e s i v e f o r c e a g a i n s t e l o n g a t i o n o f p r o s o p i s gum a t d i f f e r e n t c o n t a c t t ime.,a,10 m i n s . 4 20 mins.
Fig . 7: P l o t o f b i o a d h e s i v e f o r c e a g a i n s t e l o n g a t i o n o f SCMC gum a t d i f f e r e n t c o n t a c t time-m- 10 rnins.- 20 m i n s . -srr 30 mins. 40 mins.
Table 12
pEi Max. adhe v ive force IMBF)
L ~ ~ , ~ ? < , + . - : I -- ---- + - - - - . ~ ------+ , I
Fig. 8: P l o t of bioadhesive f o r c e aga ins t coa t weight o f , d i f f e r e n t gum coat& prosopis.-m-- m u c u n a . . ~ S C M C .
Va.riat,ion in BAF with coat s i z ~
c.~:~~::,;lril+, cr,r:!r,.a.red - +.a r-r.;ls,spia 3.'; I.:Iw r -.Q.,- -.*-.ra ,at.r..jt.io:~. it ~ C W Z . th.=~t
i r ~ ~ , e ~ p e r ~ e t r:~. t, &>n ~f 3 . u ~ :flt,~t 2.s; 77-35 l . ? J r e p i:~: 3 , j I:.;- n-:~->~ai.;; ,F.:L x:.+,t1
1 (-,q " ',-. - - - zz.._421fi&rr.y ;:h~cnir:sl bs:>rldin?:. F-r-c~:.cjpiz h3;3~ g'r.ra.+,ep ~:~crorr,l2le:-:.ilar-
': - ;i.:.: . -; r :j-l:.l.t i n t ?~,:~.:t ~ ~ ~ - ~ 3 3 b 1 y nLug+ls : h,rui 3 i - + '- \ L "/T,f;' a- .*. . a;'_; 3?;<t\.rn I->-- - .'
i t s g p : l t , e ~ 1;; >,:L<]>lfy 5 >,.y *.:is !:':>z iQ- -
EF!:;~-lh;:~~io~i i;~: c1.n ifi:.prf,~i':ial $p:-b:~m~n.,n 2~ty-j it r.euult,z. \.r]ieri
ei-ir-r,gy bar pier F r i t ~ w e n rii.i.cLfi a . ~ d ~3.~71 is , : ! ~ ~ t z q y r J ('76 i . ni5rr.f ,:my-.
,: 2iigh bloadhesive ' ~ F s c o z i t y fur pr;isopis cou.16 b ~ . ~JI-E t , ~ 1 o ~ ~ ~ e r
in+i-rf 2c is.1 enprw betweerr the g?m .rind mur_.'1-7: . tkns~.,y~ent; l!,r. zu r f
energy of the ~ 1 m s i n f hr.nr_.ps t.heir )-1ioa;3hesive visr.cjsj.ty f 77 :.
Ae r-a? Se seen i n Tehle i5 increasing ~cmcent ra t ion f m m 0.57;
t o 2 . W for prosoyis d i ~ p n t l y raiepd t.he bioadhwive viscosity
component f rlxn 24.12 to 4i? -entipoise. Sirni1s.r effects were
~bt.aiiied for rrmw-l.r_r. xu! SC!K .
Effect of flow rate of washing .solvents on ';: glass beads tuldetached with o ther facts-s f norma? saline as wsshing solvent, glass bead size of 5 mi ) c m n s t a n t .
1 .
. ; IT! qt r. t 'LO", , i % j ( mls/min ) undetached ( '%I
I
Effect uf contact time on bioadhs ive ii3rce of gum coated glass rod.
Appendix :2
