A Study of the Suspending Properties of Anacardium...
Transcript of A Study of the Suspending Properties of Anacardium...
Journal of Scientifi c & Industri al Research Vol. 59, December 2000, pp 1038- 1043
A Study of the Suspending Properties of Anacardium occidentale Gum
E C Ibezim *, M Khanna and S Singh Divi sion Of Pharmaceuti cs,
Ccntral Drug Research Institute (CSIR), Lucknow 226 00 1, India
Revised received: 10 April 2000. accepted: 12 July 2000
The suspending propert ies of the gum obta ined frolll AlloC((rdillll/ occidelltale (cashew), a tropi cal food plant , have been eva luated . Chalk suspensions ha ve been prepared with di ITerent concentrations (2.5 - 20.0 per cen t w/v) o f the gum, stored for 56 days and various stability indices such as sed imentation ratio, rate of redi spersibility, rheological changes and pH variati ons have been studied. The crfec ts of preserva ti ves, electrolytes and pH on the stabil i ty of the suspensions have also been studied.
Vecgulll has been used for comparati ve purposes.
Introduction Anacardium occidentale Linn ., commonly known
as cas hew nut , is a food plant of the family Anacardi aceae, It is native of West Indies, but introduced into Africa and India by the Portuguese. In Indi a it is found in coastal fores ts specia ll y in South . The fru its are ri ch in vitamin C and sugars , and are eaten world wide for nutritive va lue. The gum obtained from the bark / slem of AII([cardiu fII
occidentale is recommended in leprosy, ringworm , corns, hair problems and obstinate ul cers. Sufficient information regarding the pharmacognosy and phytoche mistry of this plant is avail ab le in the literature l. 7.
We report he re the suspe ndin g prope rti es or cashew gUill , a white powder, hav ing a low ash content. The gum has a very low content of pentosan X
,
and on complete hydrolysis , breaks dow n to L-arabinose, o-galactose, rh amnose and o-galacturonic acid moieties,Autohydro lys is of gum gives ri se to a degraded gum and sugar mi xture consist ing of Larab inose and L-rhamnose. Mild hydro lys is with sulphuric ac id yields o-ga lac tose and aldobiuronic acid'). The molecular weight of the gum has been reported to be of the order of 64000 daltons .
'" Author for correspondence
Suspens ions are biphasic systems in which fine so lid particles are suspended or di spersed in a fluid phase. Pharmaceutical suspensions are mainly used for oral admini strat ion of drugs, but also find use as extern al app lications and parenteral products. The principles of preparation of stable and pharmaceutically acceptab le suspensions are general in nature, and are appl icable to a wide variety of chemical compounds. In thi s study, chal k has been used as a model disperse phase.
Since suspensions are thermodynamica ll y unstable systems, tending to coagulate on storage, the critical aspect of fo rmul at ing pharmaceutically acceptable suspensions is the choice of suspending agents that can give ri se to either flocculated or defloccul ated systems. Suspending agents include protective co ll oids, viscos ity induc ing agents, surfactants and dispersing agentslO. Naturally-occurring protective co ll oids used as suspending agents are mostly amorphous , transluscent sol ids insoluble in alcohols and other inorgan ic solvents, but so luble in water to yield viscous adhes ive so lu tions, or are swo ll en by imbibiti on of water into a j e ll y li ke mass". These are essenti all y gums obtained frol11 a variety of trees and shrubs belongi ng to a nu mber of fa milies , espec iall y from Legulllinoseae, Ro-
IBEZIM et al. : SUSPENDING PROPERTIES OF ANA CA RDIUM OCCIDENTALE GUM 1039
saceae, Anacardiaceae, Combretaceae and Stercul iaceae ' 2.
Apart from the natural polysaccharides, sem i-syntheti c polysaccharides such as carboxymethyl ce llulose, methyl cellulose and meth ylethyl cellulose, hydroxypropyl methyl cellulose as well as syntheti c polymers like polyvinyl pyrrolidone and carboxy vi nyl polymers have been used as suspendin g agents. Inorganic agents like clays, bentonite and hectorite have also been used ').
Suspensions are ideal delivery sys tems for insoluble and bitter tasting drugs '4 and for patients unable to swallow tablets and capsules. Suspensions offer the advantage of greater chemical stab ili ty since the drug is not in so lution, can be put in the form of powder along with the vehicle which can be added at the time of use. Suspensions sometimes result in en hanced bioavai libility' 5.'6. Gums can also be used in a plethora of other formulations like tablets and even foods ' 7. ' 8 .
Materials and Methods Al l chemicals used in this study were of Reagent
Grade.
Preparation ofAnacardiUln Gum The exudate from the stem bark of AnacardiUl 12
occidentale was soaked in 0.1 per cent (w /v) sodium metabisulphite so lution for 24 h, and the resu lting gelatinous dispersion was passed through a muslin c loth to remove incomplete ly hyd rated masses. The gu m was prec ipitated with acetone and dried at 60°C in an oven fo r 12 h. It was then pulverized, sieved through a 125 !lm sieve and used.
Preparation of Chalk Suspensions Chalk suspensions were prepared with 2.5 , 5, 10,
12.5 and 20.0 per cent of Anacardiul1l gum (w/v ) and with 2.5 per cent Veegum@. The suspensions were prepared by dispersing 109 of cha lk in 100 mLof aq ueous dispersions of the gums in de-ionised water, blending with a Silverson mi xer (Model LR2) for 10 min at 500 rpm , and pass ing through a hand-
held homogeniser (Model URT-I, Ormerod). The suspensions were stored at 28°C, in stoppered measuring cy linders in undisturbed compartments for 8 weeks.
Stability Studies The sed imentat ion rat ios were determined by
plac ing 100 mL of the suspension in stoppered measuring cylinders ; measuring the height of the sedi ment (H ) at regular time interva ls, and expressing
" it in rel at ion to the ori ginal height (H ) of the I)
suspension Ino. Thus, sedimentat ion ratio comcs as H IH .
" 0
The red ispersibility numbers were determined by placing 10 mLof the suspensions in test tubes and determining the number of times the tube needed to be rotated through 360° at 30 rpm to cause the sed imented particles to just leave the bottom of the test tube21
. An electric motor (model LT 200, DARB , England) was used.
The viscos ity of vari ous suspensions was measured using a Haake-Rotovisco viscometer (model RV 110).
The pH of the suspensions was determined using a pH meter (model 7065, Electronic Machines , England).
The effect of preservatives was determined by s tudyin g th e sedim entati o n rati os a nd redispersibility numbers of suspensions containing 0.1 per cent (w/v) each of benzoic acid cetrimi de , chlorocresol and chloroform-water (di s). The effects of electro lytes on suspension stability were determi ned by add ition of different concentrat ions of KCI , MgC I
2, FeCI) and NaCi and study ing the effcct on
the sedimentation ratio and ease of red ispersibility. The effect of pH on stabil ity was studied by adjusting the pH of the suspensions to 5.2, 7.3 and 12.5 and noting the effects on sedimentat ion profile and ease of redi spersion.
The degrees of floccul at ion were determined by express ing the height of flocculation in relation to the height of the deflocculated sys tem, determined by centri fugin g the suspension ror 15 minutes.
1040 J SCI IND RES VOL. 59 DECEMBER 2000
1·0
0 ·9
o·a
o ~ 0 ·5 :J r o ~ 0 ·4 o ~
c o :g 0 ·3
c <11
~ 0 ·2 <11
If)
0 ·1
-..- 2.5 .,.
--6-- 5·0 .,.
--0-- 10.0 .,.
--<:r- 12·5 .,.
___ 20.0·'.
2 3 4 5 56 Time(Days)
Figure I- Sed imentati on pro fil es of suspensions prepared with di ITerent concentrati ons of A I1ClW rdilll 1/ gum
Results and Discussion Anacardium gum was found to be non-soluble
but imbibed water and increased its vi scosity. The
sedimentation profile of chalk suspensio ns prepared with different quantities of Anacardiul11 gum is depicted in Figure I. Stability was documented as the ratio of the sedimentation height and the ori g inal height of the suspension . Higher sed imentation ratios impl y hi gher stab ility22 . Since loose sediments are easier to re-d isperse in comparison to caked sediments, a pharmaceutica l suspension is often formulated as a flocculated suspension. It was observed that the sedimentation ratio of the suspensions increased unti I a c ritical concentration of 10 per cent (w/v ) was reached; whereafte r it began to decrease.
Felmester et a l. 23 observed simil ar concentrat iondependent behaviour in sulphaguanidine suspensions that were flocculated with an io nic polysaccharide. At a concentration higher than the critica l polymer concentration, polymer bridging causes the suspe nded particles to become comp lete ly surrounded by the polymer and thus lead to floc formation.
Table 1- Red ispersibility numbers of chalk suspensions prepared wllh A l1 l1cardilllll gum and Veegum®
Suspension content
2.5 per cent Veegum®
2.5 per cent
AI/acardilll/l
gum
Red ispcrsib ility number
Week I Week 2 Week 3 Week 4 Week 5
07 15 17 25 30
02 02 01 02 02
The sedimentation profiles of 2 .5 per cent (w/v) Anacardium occidentale gum suspension and 2.5
~er ~ent (w/v ) Veegum® suspensions are depicted III Figure 2. The suspension prepared with Veegum{K) was seen to maintain a higher sedimentation ratio throughout the period of storage.
The resl~lts of the study on ease of redispersibility are shown III Table I. The suspensions prepared with 2.5 per cent Anacardium gum ma intained a uni form redispersibility number of 2 throughout the duration (8 weeks) of the study, as opposed to the
c~ntinu a l increment in the number for the suspens ions prepared w ith a s imil a r concentration of Veegum® to as much as 30. Thi s implied that the
suspensions prepared with Allacardium gum were more easily re-dispersed and the suspensions did not cake on storage. It is a des irable property that
suspensions : hould not cake and should be easily re-dl spersed I-or accu racy in dos in g22.
The effect of preservatives on the stability of the suspensions conta ining Anacardium gum is pre~ented in Figure 3 . Ch loroform-wate r (dIs) greatly Improved the sed imentation behav iour of the suspensions . Benzoic acid, cetrimide and chlorocresol did not improve it appreciably. Preservatives are sometimes essentia l in pharmaceutical suspensions to prevent breakdown of the system arising from the poss ible growth of microbes on the polyme rs often ll sed as suspendin g agents.The results of the influence of preservatives on the re-dispers ibility number, presented in Table 2, indicated a s imilar
pattern as in the sedimenta tion exerc ise except th at
IBEZIM ef a/.: SUSPENDING PROPERTIES OF ANA CARDIUM OCCIDENTALE GUM 104 1
0 I -::> I
.2 E c .Q
0 C '" §
" ~
10
o 9
0 ·6
0·5
0 ·4
0'3
0 · 2
0 ·1
2 5
Time(Ooys)
--0-- 2·5 '/, Anocardium gum
-----<r--- 2·5'/, Veegum
56
Fi gure 2- Sedimentati on profil e of chalk suspensions prepared with 2.5 per cent AnC/cardilllll gum and 2.5 per cent Veegum®.
the chloroform-water containing suspensions had a higher re-di spersibility number initi ally.
The addition of electrol ytes to the suspension prepared with Anacardiul1l gum did not quite affect the sedimentation profile. Ferric chloride increased the height significantl y after the second week of storage, probably due to some aggregations associated with changes in the zeta potential induced by lhe tri valent cation21
. The effects of added electrol ytes on the re-di spersion number of the suspensions prepared with AnacardiUln gum are presented in Tabl e 3, showing that FeCI , had the most adverse effect on the sedimentation behaviour. Thi s effect also increased with increase in the molarity. The other electrolytes had little or no effec t and even increas ing their molarities showed no significant difference .
The effect of pH on the stab ility of the suspensions prepared with Anacardiul11 gum is depicted in Figure 4. It was found that increas ing the pH increased the stability of the chalk suspensions and the suspension was very stable at alkaline pH of 12.5. This is to be expected as chalk itse lf is basic in nature and will bc more stable at alkaline pH . All the suspensions prepared at various pH conditi ons however maintained a uniform re-dispersibility nUIll ber of 2 throughout the period of storage.
Table 2- Red ispersibility numbers of chalk suspensions prepared with 10 per cent AnC/cwdilllll gum and different preservati ves
Preservat i ve (0 .1 per cen t, w/v )
Chl oroform-water (dis) Cetrimide
Chl orocresol
Benzoic acid
No preservative
Redispersibi lit y number after Week I Week 6
09 05
02
12
02
03 08
06
06
02
Table 3-EITect of added electrol ytes on the redipersi bility numbers of chalk suspensions prepared with 10 per cent
AnC/cCinlillll l gum
Elect rol yte Redi spersion number at different molarities
O.IM 0.2M O.4M O.6M 0.8M
KCI 3 3 3 3 3
MgCl ; 8 10 5 5 5
FeCI , 4 2 3 6 6
aCI 4 4 2 2 3
Tab le 4 - pH variations of chalk suspens ions prepared wi th 2.5 per cent Allacardilllll gum and Veegum'"
Suspension conten t pH values after storage
Fres h I Week 8 Weeks
2.5 per cent AII(/("(/ rdillll/ gum 7.96 11.18 I:U4
2.5 per cent Veegulll'" 9.82 10.03 10.5 1
The results of the pH vari ations upon storage of the suspensions prepared with 2.5 per cent (w/v) Anaca rdium occidentale gum and 2 .5 per cent (w/v) Veegum® are presented in Table 4.The pH of the fresh suspension containing the Anacardiul7l gUIll was hi gher than the pH of the gum dispersion and
1042 ] SCI (ND RES VOL 59 DECEMBER 2000
'0 :r -..
1-0
0'91\ 0 -8
i 05 -_2
"§ 04 c .2 o C 0 -3 ., E U j; 02
0 ·1
• -
3 4
Time(Weeks)
5
_ Chloroform water
-0- Benzoic acid
--+--- Citrimide ~ Clorocresol
-0- Without preservative
6
Figure 3-Sedimentati on profi le or chalk suspensions prepared with 10 per cen t Allacardilllli gu m and contain ing benzoic acid; ch lorocresol; cetrimide; Chlorororm water and wi thou t preservati ve.
o I
1· 0
of 0 ·3
5 0 ·2 a c <l> E U j; 0 ·1
---6-- 5 ·2 -0-- 7· 3 --0--12·5
2 3 4 56
TimE-(Oays)
Figure 4-- Sedimentation pro fil e or chalk suspensions prepared with 10 per cent Alla('ardilllll gum at the roll owing pH
this pH increased steadily upon storage. A simil ar pattern was observed in the suspension prepared with Veegum® except that the pH of the fresh suspension was lower than the gum di spersion. The observed changes in pH upon storage may be attributed to processes like hydrolysis or microbial decomposition 2~ . The viscosity of the chalk suspension containing 2.5 per cent (w/v ) Anacardiul7l. gum was 4.698 cp as against 18 .792 cp for the suspension
contallllllg a similar concentrati on of Veegum®. Hi gher viscos ities often imply greater stability. These viscosities however did not change much upon storage of suspensions. The suspension prepared with 2. per cent (w/v) Anacardiu111. gum had a flocculation number of 3.2 while suspensions prepared with a similar concentration of VeegumC,i) had a number of21.2. Flocculation is a highly desirable property insuspensions2:i .
Anacardiuln occidentale gum has been found to possess good suspending properti es though the suspending profile of Veegum®, a currently marketed agent, seemed to be superior. In view of the ri sing costs of pharmaceutical gums like Acacia and Veegum ® and th eir fluctuatin g ava ilabili ty2627 .
Anacardiu111 occidentale gum can be exploited for use in pharmaceutical suspensions and other formulations.
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