I ndian Journal of Pure & Applied Physics Vol. 30. March 200 I . pp. 1 52- 1 54

Ultrasonic velocity and absorption studies on drug release pattern .

fr�m different ethylcellulose b'itses __ 9R _ gGeetha, �ji>arthasm'athy* & 5Manavai�� l Department of Physics. '" III,nilt,tc of PhltP",!!eet:lttc!!l-ffi-�. Annamalai University. Annamalai Nagar 60R ()�

-- . Received 1 6 August 2000: revised 28 September 2000

f Ul t rasonic veloci ty and ahsorpt ion studies h:we been carried out in the drug spartloxaci n added to d ifferent,

hases viz . . et� l lu lose : pol y ethylene gl ycol ( EC : PEG) . ethylcel iu lose : hydroxy propyl methyl cel lu lose ( EC : HPMC) ancl ethy l cel lu lose : cudrajit ( EC : EUD) . The clastic properties o f the different hases with and without drug are esti mated and < I ll overall view about the drug release pallern is give::J

I J, 'I/'C. { .

1 Introduction

Periodont i t i s is a dental d isease which occurs commonly now-a-days. It is an i nflammatory response to bacter io logical i nfection ' and can be arrested through systemat ic admi n i strat ion of ant ibiot ics . It has been found that the d iscont inuat ion of therapy results in the re­coloni sat ion of potent ia l pathogen i n the periodontal pocketc. Hence long term antibacterial therapy is req u ired for complete eradication of the d isease.

The l oca l de l i very of an ant ibiotic at periodontal pocket is considered to h ave an excel lent potent ial and i s an alternati ve to trad i t ional therapy, s i nce low dosage i s requ i red with lesser s ide effects14. In recent years considerable attent ion has been focused to deve lop sustai ned release dosage form of drugs for periodontal d i seases . The present study has been carried out with a view to deve lop a sustai ned re l ease clo.�age form of sparfloxaci n as a dental i mplant . The l i terature shows that sparfloxac i n is a superior anti bacteria l agent among the qui nolone ( C , ,)H22F2N"Ol) group, with lot of side effects when consu med ora II y" ' .

U l trason ic ve loc i ty and absorption studies i n pol ymers have proved t o be useful i n understanding t he physico-chemical behaviour of the part icular system. The review of l i terature on acoustical stud ies of polymer sol u t i ons reveals t hat these measurements ,Ire u sed 1 0 est i mate the d ifferenl e lasl ic propert ies of the molecules7 s, from which the type of mo lecular i n1eract i ons C i l \ l he very wel l understood .

2 Experimental Details

The pure samples of sparfloxac in and polymers were obtained from Torrent Pharma Ltd, Ind ia and used as such. The solvents - i sopropy l alcohol and d ich loromethane were obtai ned from BDH company . The solut ions were prepared by add ing a

known weight of polymer to a fi xed volume of so lvents C I : I ) and then sti rr ing under reflu x lI s inl! it magnetic stirrer unt i l a c lear solut ion was obtai ncd and then, known weight of drug ( sp,lrflnxac i n j i ,� added with a l l the three bases. The u l trason ic velocity (c) and absorption C alf) were measured us ing a p luse echo i n terferometer ( 1 0 MHz) by t he standard procedure') with accuracies 0.0 I cfr and I (Ir; respect ive ly . Dens i t ies (p ) were determi ned us in� a spec i fi c grav i ty bott le and v iscosity ( 11 ) was esti mated us ing a Ostwald viscometer . A I I the measurements were carried out at room temperature

303 K.

3 Physical Parameters

The various phys ical parameters were calcu lalecl from the measured val ues us in� the standard formul ae :

Adiabatic compress ib i l i ty �, = I /eer ;

I nternal pressure PiY = TI'/�, where Y i s t h e ra t io of speci fic heat capac it ies ane! I ' i s the thernl,t I expanston;

I I � I n ter-molecu lar free l ength I�I = Kr3 . ThL' � ,

valucs of K for d iffercnt temperatu res were I , I " CI I from the work of J acobson :

R AKKAPPAN ef al. :UV & ABSORPTION STUDIES ON DRUG RELEASE 1 5 3

T,]h le I - U l t rasonic veloci ty and related parameters in ethyl cel lu lose hases with and without drug spartloxaci l l ci issol ved i l l the

mi xture or d ich loromethane and i sopropyl alcohol ( I : I )

Samples C P llsx 1 0'"

Ills· 1 kglll· .1 Ns·2 III

EC+PEG (Y: I ) 1 066 1 027 1 . 5750

EC+PEG + drug 1 070 I OJ O 2.665Y

EC+H PMC « ) : I l 1 063 1 025 2,46 1 0

EC+ H P M C + drug I O()6 I 02X 2. 579R

EC+EUJ) «) I l l OW 1 0 1 3 2 . 3 1 1 2 EC+E U D + d rl lg I O()2 1 0 1 7 2 ,44 1 X

C l a ssical absorpt ion : ( all)c1:t"= 8 1lhls l3pCl ;

Excess a bsorpt i o n : ( a./f)cxlCSs = ( ali)ohs-( a(f)c:1:tss .

4 Results and DisclIssion

From Table I it is obviolls t hat the velocity i nc reases in a l l the three systems after add i n g the drug to the bases. The i ncrease in velocity is h i gher in the case or EC : PEG base than in the other two bases viz. EC : HPMC and EC : EUD. Ad i abatic compress i b i l i ty decreases on add i t ion of d rug to the bases and t he decrease is more dominan t in EC :

PEG base . I ntern a l pressure ?iY i nc reases and i ntermo l ec u l a r free length L, decreases when the drug is added . There is n o s ign i fi cant d i fference i n

c l assical absorpti o n . The observed absorpt i on ( alf ) i ncreases i n a l l the three systems o n addi n g drug to the base . But the i ncrease i s very sma l l i n EC : PEG base system compared to the other two systems. The

i n c rease in ( a.ll)nl" i s h i gher i n EC : EUD than EC : HPMC systcm.

I t can be secn from the Table that compress ib i l i ty i s smal l er in the EC : PEG based

. formu l at ion when compared wi th other two drug added bases . The fact t h at L, decreases i nd i cates that the mo lec u l es are very c l ose i n EC : PEG based system . It is a l so reflected i n i n ternal pressure, From the structure of t he bases and the drug, the i nteract ion i s mai n l y between t he O-H group of the base and carbo x y l and a m i n o group of d rug. Among the three bases, t he O-H group is not ava i l able i n eudra j it , hence the i nteract ion i s very s ma l l i n the BC : EUD formu lat i o n . I n the other two c ases, t he PECI has more hydro x y l groups compared with HPMC. A l though hydroxyl group i s avai l ab le i n HPMC. but its confi gu rat ion and conformat ion d oes not favour the i nteract ion of OH with carbo x y l and

P x ) {r l l l L, I', Y x 1 0"

N· I Ill" A p,]sc;t i

8.5687 O.5X41 :l4M�

X ,47Y9 O.5X 1 2 lXm R.6330 O.5XM l44X

8 .5603 0 . 5X39 3520

R .7R50 O.5Y 1 6 :l27n

X.7 1 X2 O.5X93 l5h5

amino group of d ru g . Hence the EC : PEG has m01T hydrogen bonds which n ot o n l y strengthen t he i ntermo l ec u l ar forces res u l t i ng i n a decrease ( I f compres s i b i l i ty but a l so i nc reas i ng the ve l oc i ty i ll that formu l at ion/ II I , It i s wel l known that i ntern;i I pressure i s i nc reased i n hydrogen bonded .�ystem " ' : . The i nfrared and u l tra v i o l et spectroscopic studies i n t hese systems, confirm that b i nd i n g o f drug t o EC : PEG i s more than i n EC : HPMC and EC : EUD

bases.

Tahle 2 - U ltrasonic ahsorption a n d re l aled par,]Illt"l c rs i n

ethyl cel l u l ose hases w i t h a n d without d ru� sp,] r l lox ; lc i l l

d issol ved i n the mi xture o r d ich lor<llllet hane ,l ilt! i sopropyl

alcohol ( I I ) Samr lcs ( aJ/\,h, ( aJl lcla." (aJ/cL"."

x 1 0 . 1 ) x I ( r " x I ( r I )

N PIll I S� Nplll· I S' I " N p l11' s-

EC+PEG (<J: I ) I X 1 .07 54,420 1 1( J . (,�

EC+PEG + drug I XC,. 7() 55 .540 1 .\ I . 1 (, EC+ H P M C (Y: t ) 1 4 1 .50 5 1 .555 XX ' ») EC+HPMC + drug 1 5l).4() 54 .46X I O'-l ' JJ

EC+ E U D (Y: I ) 1 57 .6Y 50.366 1 07 . . � l

EC+ E U D + drug I X3 ,4() 52 .543 I :1 ( l .Xh

The i nc rease i s observed in absorpt ion aher add i ng d ru g to the EC : PEG and i s l ess when compared to the other two formu l at ions . I n genera l . t h e absorpt ion i s al ways l ess i n a n ordered s truct u re . The c l oser pac k i ng due t o h yd rogen bond g; lVl' 1ll0 1'l' ordered structure i n EC : PEG bast' syste m . B t l l i l l the case of the eudraj i t . where the bOll c i ing I � i mposs ib le t h e d rug mo lecu les a rc rand0l1 1 l y oriented w h i c h cause more i nc rease i n ahsorpt ion i l l

1 ."4 INDIAN .I PURE & APPL PHYS, VOL 39, M ARCH 200 1

that system. In the case of EC : PEG the i ncrease i n

(uJfLhs I S moderate because the strength of hydrogen bond i ng between the mo lec u l es i n the system I ies between EC : PEG and EC : EUD systems .

5 Conclusion

I t may be concl uded that the sparfl oxac i n d ru g h a s morc b ind ing with EC : PEG t h a n with the other two bases. Thus, the drug b i n d i n g order i s g i ven by

EC : PEG > EC : HPMC > EC : EUD. The above res u l ts are in good agreement with spectroscopi c ana lys is o f these three systems .

References

Loesche W .I . S yed S A. Morrison E C c'l al . . ./ Clill Period.

); ( 1 9); 1 ) 29.

2 .Ioyslon- l3cchal S. 1111 /)('11 1 .1. 1,7 ( 1 9X7) 52 .

•

3 Addy M . Langeroudi M &. Hassan H . 1111 /),'1 1 1 .1. 1,5 ( 1 ()X5 )

1 24.

4 Addy M & Langeroudi M . ./ Clill PC'I"iod. I I ( 1 9X4) :n(). 5 M artindale. £r1m pl/(/mIllCOI}()C'ill ( Thc Pharlll�lceli l ical

Press. London). 1 996. 2n. 6 Carl)(1/1 (llld Rlihillsleill:Spcll/Zoxacill II/(J/logmlill. R i lont"­

pOlilenc Rorer Ed. 1 994.

7 Rakkappan C. S r i n i v:Jsa Rao A &. Krishnan I \ , 1'''''1 " Illc/ie/ll

A cad Sci. ( ClrC'1II Sci) . 1 0 1 ( I l)Xl) 429.

X H asslin S K. EliI' PO/yll/ ./. 24 ( I l) X X ) 795 .

9 Sri n i vasan K R. Krishnan S &. Sri varaillan A. !'/"()(" Smill.

Tran.wlucer Teclllw/ogl' (Cochin : NPOL). 1 975. 2X1, .

1 0 N;]lllbi narayan<ln T K &. Srin i vasa Ran A. On"/" Sd. 4X

( 1 979) 203 .

I I Vel illuroug<llle S &. Krishnan B . Illt/ioll .I Plrr.\· II. () I ( I ()X 7 ) l OS .

1 2 Scnl h i l K &. Rakkappan C. Asiall ./ Plr rs. 1, 1 1 9(>? ) 4(,7 .