review article pharmaceutical properties and applications...

Hindawi Publishing CorporationJournal of PolymersVolume 2013 Article ID 938726 8 pageshttpdxdoiorg1011552013938726

Review ArticlePharmaceutical Properties and Applications of a NaturalPolymer from Grewia mollis

Elijah I Nep Patricia O Odumosu Ndidi C NgwulukaPatrick O Olorunfemi and Nelson A Ochekpe

Biomaterials and Drug Delivery Research Group Faculty of Pharmaceutical Sciences University of Jos PMB 2084 Jos 930001 Nigeria

Correspondence should be addressed to Elijah I Nep elijahnepbiodrudelcom

Received 22 March 2013 Accepted 16 June 2013

Academic Editor Alain Durand

Copyright copy 2013 Elijah I Nep et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

The use of naturally occurring biocompatible materials has been the focus of recent research activity in the design of dosage formsfor immediate and controlled release formulations Grewia gum is an intracellular gum obtained by extraction from the innerstem bark of the shrub Grewia mollis (Malvaceae) It grows abundantly (wild or cultivated) in the middle belt region of Nigeriaand the mucilage has been used by indigenes of this belt as thickener in soups Grewia gum has been investigated for potentialapplications in pharmaceutical dosage formsThe industrial extrapolation of the applications of the gum has however been slowedby the limited structural toxicological and stability data available on the gum This paper highlights ethnobotanical uses of Gmollis shrub and discusses the structural features functional properties and applications of grewia gum with emphases on itspharmaceutical potentials

1 Introduction

Plant materials are playing increasing role as alternatives tochemical food additives and synthetic pharmaceutical excip-ients Natural polysaccharide gums swell to form highly visc-ous solutions or dispersions in aqueous media They havethe advantage of biocompatibility low cost and relativeabundance [1] compared to their synthetic counterpartsTheyare widely used in the pharmaceutical industry as polymersin various drug delivery systems [2ndash7]

Grewia polysaccharide gum is a natural resource thatcould be used as an excipient in the pharmaceutical industryin Nigeria to reduce the costs of pharmaceutical products Itmay provide a suitable alternative to the synthetic counter-parts which are expensive andmostly imported It is obtainedby extraction (maceration in cold or hot water) of the innerstem bark of the edible plant G mollis Juss (Malvaceae) InNigeria G mollis from which the gum is extracted growsabundantly (wild or cultivated) in the middle belt region ofthe country where it is used as thickener in local delicacies

This review delineates the ethnobotanical uses physico-chemical properties structural properties and the potentialapplications of the gum in drug delivery systems

2 Grewia mollis Plant

G mollis belongs to the flowering plant genus Grewia It wasformerly placed in the family Tiliaceae or SparrmanniaceaeToday most authors place the genus in the mallow familyMalvaceae

21 Botany The plant has been described [8 9] as a shrub orsmall tree growing to attain a height of 105m with youngbranches densely stellate-pubescent The young branchesturn dark grey to black or reddish brown when older

The leaves of the plant are elliptic to elliptic-oblongusually between 20 and 145 cm long and 07 and 55 cmwideThey are acute to slightly acuminate at the apex broadlyrounded or obliquely truncate at the base The leaf marginsare coarsely and sharply serrate more or less glabrous tosparsely minutely stellate-pubescent above but densely andfinely greyish to brownish white-pubescent beneath [9]

The flowers are yellow and bisexual sepals 6ndash10mm longpetals obviate to oblong 4ndash6mm long plusmn2mm wide andsometimes notched at the apex The ovary is 15ndash2mm longand densely hairy [9]

2 Journal of Polymers

Table 1 Ethnomedicinal uses of G mollis plant

Use Plant part Preparation ReferencesWound healing Bark leaves Mucilages are applied to ulcers cuts sores and snake bites [9 13]Cough Bark roots Decoction [9 13]Fever Bark Leaves and fruit Extract of bark andor leaves Fruits are also eaten for this purpose [9 13]Diarrhoea Stem bark Decoction [9 24]Child birth Pain Stem bark leaves Maceration decoction [9 13]Colic Bark leaves Infusion [9]Constipation Bark Mucilage [9]Rickets Leaves Decoction [9]Palpitation Roots leaves Decoction [9]Sore eyes Root shavings Sap squeezed out and applied under the eyelid [9]Rheumatism Roots Paste [9 13]Anal prolapse Bark Pounded and dissolved in water [9 24]

Figure 1 G mollis plant The figure is adapted from httpwwwprota4uorg [10]

The fruit has been described as unlobed and globosedrupe of about 4ndash7mm long and 5ndash7mm wide coveredwith a fine whitish tomentellum The fruits are green whenyounger and turning yellowwhen older [8 9] A digital imageof the aerial part of the plant is shown in Figure 1

22 Propagation G mollis grows in the wild and can bepropagated by seed or seedlingsThe seeds are collected fromthe dried fruits that may have fallen on the ground [9]

3 Uses of the Aerial Parts of G mollis

The different parts of G mollis have been used for differentpurposes across the regions and places where the plant growsor is cultivated

31 Mucilage from Leaves and Stem Bark In the DemocraticRepublic of Congo the bark is kneaded with water into aviscous substance that is added to sauces while in Gabon theinner bark is sometimes eaten as food In Nigeria the innerstem bark is used as thickener in soups and in local cakesmade from beans or corn flour commonly called ldquoKosairdquo andldquoPunkasaurdquo in Hausa (Nigeria) respectively [11 12]

The infusion of the bark obtained by cold or hot macera-tion in water is applied to give a smooth surface to mud wallsand floors [13] while the wood ash is used as salt substituteincluding the ash of the leaves stems and roots [9]

32 Vegetables and Fruits The flowers buds and youngshoots are added to soups and sauces as garnishing while inSudan the young leaves are cooked and eaten as vegetablesThe fruit is eaten raw or boiled [9]

33 Ethnomedicinal Uses Several ethnomedicinal uses of theinfusion decoction maceration or mucilage from the leavesroots or stem bark ofG mollis have been documentedTheseethnomedicinal uses are described in Table 1

4 Biological Evaluation and ChemicalConstituents of G mollis

Several scientists have investigated the histopathological andtoxicological effects of extracts of G mollis on laboratoryanimals

Onwuliri et al [14] conducted toxicological and histo-pathological studies in rats using the ethanolic extract ofthe stem bark of G mollis Tannins saponins flavonoidsglycosides balsam phenols terpenes and steroids wereisolated from the stem bark but alkaloids were absent Theextract exhibited toxic properties at the lethal dose (LD

50)

of 1500mgkg body weight The convoluted tubules of thekidney but no structural effects on the liver and heart wereobserved suggesting that the extract may be safe in humansbut should be usedwith caution on patients with renal failure

Studies by Obidah et al [12] on the toxic effects ofthe stem bark of G mollis showed that the addition of thepulverized stem bark to the normal diet of male Wister ratsat concentrations of 0 1 5 and 10 given to them as feedfor 4 weeks resulted in no deaths and remarkable changesin appearance were not observed in the treated animalsHowever rats fed with 10 dietary level showed significant(119875 lt 005) increases in serum transaminases activities whichwas accompanied by decreased food intake There was noobserved effect on serum alkaline phosphatase activity ureacreatinine triglycerides cholesterol glucose concentrationsand body and organ weights in their study These workersconcluded that dietary exposure of rats toG mollis stem barkpowder at high concentrations (10)may cause some adverseeffects especially liver injury

Journal of Polymers 3

O

HO

HO

O

OH

OH

(a)

OO

OH O

OHO O OH

HO OHOHOH

OHHO

OHOOC

(b)

HO

OH

COOHOH

(c)

HO

OH

OHCOOH

(d)

HO

H

H H

H

(e)

O

H

H H

H

O

OH

OH

HOHO

(f)

NNH

O

(g)

Figure 2Molecular structure of isolates fromaerial parts ofGmollis (a) Luteolin (b) 7-(1-O-120573-D-galacturonide) 41015840-(1-O-120573-glucopyranosyl)-310158404101584057-tetrahydroxyflavone (c) 7120573-hydroxy-23-enedeoxojessic acid (d) 7120573-hydroxy-23-deoxojessic acid (e) 120573-sitosterol (f) 120573-sitosterol-3-O-glucoside and (g) 6-Methoxyharmane

It may be argued however that gum extracted from thestem bark ofG mollis when used as excipient is incorporatedinto formulations in smaller proportions usually lower thanthe 10 proportion added to the feed of the animals in theforegoing study Consequently it may be expected that thelow use level of G mollis gum as excipient in formulationsshould not cause any adverse effects in humans

Asuku et al [15] evaluated the methanolic extract of Gmollis leaves for its antioxidant and hepatoprotective pro-perties by an in vivo procedure They reported significant(119875 lt 005) hepatoprotective potential evidenced by the lowe-ring of serum levels of bilirubin aspartate aminotransferaseand alanine aminotransferase and decreasing of malondi-aldehyde levels in rats pretreated or posttreated with carbontetrachloride (CCl

4) They concluded that G mollis leaves

contain potent antioxidant compounds that could offer pro-tection against hepatotoxicity and ameliorate preexisting liverdamage and oxidative stress conditions

Saleem et al [16] assessed the nutritive value of the leavesand fruits of three grewia species under semiarid environ-ment and the results of the study indicated that the threespecies could be introduced as a source of fodder in animalproduction farms and silvopastoral systems

41 Compounds Isolated from G mollis Al-Youssef et al[17] evaluated the methanolic extract of the aerial part of Gmollis and reported isolation of a number of phytochem-ical constituents such as flavonoids (luteolin and 7-(1-O-120573-D-galacturonide)-41015840-(1-O-120573-glucopyranosyl)-310158404101584057-tetrahyd-roxyflavone) triterpenoids (7120573-hydroxy-23-enedeoxojessicacid and 7120573-hydroxy-23-deoxojessic acid) and steroids

(120573-sitosterol and 120573-sitosterol-3-O-glucoside) The molecularstructures of these isolates are shown in Figure 2

Rosler et al [18] earlier reported the isolation of 6-meth-oxyharmane (Figure 2(g)) a Harman alkaloid fromG mollisHarman alkaloids belong to the class of 120573-carbolines Theybind strongly to benzodiazepine receptors in the brain toinduce inverse agonist effects to benzodiazepines such asconvulsive anxiogenic and memory enhancing effects [19ndash21]

Efiom and Oku [22] working on the n-hexane fractionof G mollis root extract collected in Niger State Nigeriaisolated two triterpene compounds lup-20-en-3-ol and 13-hexyloxacyclotridec-10-en-2-one

42 Phytochemical Screening Antibacterial and Anti-Infla-mmatory Properties Shagal et al [23] reported the presenceof saponins and phenolic compounds in the ethanol fractionof G mollis leaves while glycosides were additionally presentin the ethanolic stem bark extracts Tannins volatile oils andflavonoids were also observed in the ethanolic root extracts

Antibacterial studies on the ethanolic leaf and rootextracts were reported to exhibit inhibitory activity againstStaphylococcus aureus andEscherichia coliwhile the stembarkextract exhibited activity against S aureus and SalmonellatyphiTheaqueous root extracts showed no inhibition againstthe same organisms except for the aqueous leaf extractwhich showed some inhibitory activity against Streptococcusspp and E coli The aqueous extract of the stem bark alsoexhibited inhibition against S typhi which possibly justifiesthe use of the plant in the treatment against diarrhoea anddysentery


Al-Youssef et al [17] investigated the in vitro antibacterialactivity of the aerial part of G mollis collected in Akba-Al-Abar Saudi Arabia against various strains of bacteria suchas Staphylococcus epidermidis (ATCC 9615) Bacillus subtilis(ATCC 1174) S aureus (ATCC 25175) Klebsiella pneumonia(ATCC 33495) Pseudomonas aeruginosa (ATCC 12453) andE coli (ATCC 10536) Moderate inhibitory activity was exhi-bited by the methanolic extract against S epidermidis Bsubtilis and S aureus when compared with the standardantibiotics cloxacillin (5mcgdisc) amoxicillin (10mcgdisc)and ciprofloxacin (5mcgdisc) The extract also showedinhibitory activity against oral cavity pathogen S aureus atMIC value of 64mcgml and 128mcgml against methicillinresistant S aureus (MRSA ATCC 15187) respectively Theauthors reported a time and concentration dependent killingby themethanolic extract ofGmollis against S aureus (ATCC25175)

The development of a new class of polyurethane nano-fibers containing aqueous extract of aerial parts ofGmollis byone step electrospinning was reported by Musarat et al [25]for its potential biomedical application as an antimicrobialfiberThey incorporated the aqueous extract into the polymermedia in order to influence the morphology and size of thepolyurethane nanofibers Further testing of the extract loadednanofibers was also observed to inhibit the growth of E coli(ATCC 52922) and S aureus (ATCC 29231)

Al-Youssef et al [17] also investigated the anti-infla-mmatory activity of the same extract at 500mgkg whichshowed pronounced anti-inflammatory effect after twohours Their findings provide preliminary evidence suggest-ing that fractions of G mollis exhibit inhibitory effects ininflammatory process and support the use of this plant forthe treatment of arthritis dermatitis and wounds in Africanand Saudi Arabian traditional medicine

5 Grewia Polysaccharide Gum

Interest in grewia polysaccharide gum as a pharmaceuticalexcipient has been on for over a decade [26] This growinginterest is informed by the viscous property of the gumextracted from the inner stem bark of the G mollis plantConsequently the gum has been extracted and some of itsphysicochemical properties evaluated

51 Extraction and Purification Several approaches to theextraction of the gum from the inner stem bark of the shrubhave been reported [27ndash30] Briefly the dried and pulverizedinner stem bark of the G mollis shrub is dispersed indemineralized water using an impeller The fibrous materialfrom the dispersed mucilage is removed by straining througha muslin cloth Thereafter the mucilage is centrifuged beforeextraction of the gumwith 96 ethanolThe extracted gum isredispersed in water and reextracted to get a beige-colouredgum which is then dried in an oven at 50∘C for 8 h

The gum can be further purified by treatment with 01Msodium hydroxide or hydrochloric acid or with sodiumchloride followed by extraction with 96 ethanol It mustbe noted that treatment of the natural material with dilutealkali dilute acid or electrolytes could result in modification

of the parent material with consequent variations in thephysicochemical properties of the resultant material

52 Some Physicochemical Properties of Grewia Gum Thegum contains traces of metals (Ca K Na Mg Zn and Fe)and a viscosity-average-molecular weight of 316000 [28]Metals constitute about 61 of the gum while proteinsand lipids account for 124 and 0021 respectively It has ahigh intrinsic viscosity with a swelling capacity greater thantragacanth and methylcellulose

Grewia polysaccharide gum slowly hydrates and swells inwater The gum has aqueous solubility of about 02mgmL[29]The low solubility of the gumwas attributed to insolublecell-wall materials making up a larger proportion of the gumHowever the presence of acetyl groups has been reportedto account for the insolubility of certain gums in water [31]Grewia polysaccharide gum has been shown from Fourier-transformed infrared (FTIR) spectroscopic studies to containacetyl groups which may account for the low solubility of thegum in water [29] Generally water poorly soluble gums dueto presence of acetyl groups are improved by deacetylationwith dilute ammonia [31ndash33]

The rheological properties of the gum dispersion andthe water vapour permeability of aqueous-based grewiagum films have been reported [27 34] The aqueous dis-persions of the gum at different concentrations exhibitedpseudoplastic flow behaviour The viscosities of the gumdispersions decrease with increase in temperature The effectof incorporation of electrolytes to dispersions of the gumwasalso investigatedThe result showed a decrease in the viscosityof the gumbrought about by electrolyte which is proportionalto the concentration as well as the valence of the cation andthese findings have been confirmed by other workers [29]

53 Chemistry of GrewiaGum Okafor [27] using paper chro-matography reported that the primary structure of grewiapolysaccharide gummay comprise of d-glucose d-rhamnoseand galacturonic acid Nep and Conway [29 35] determinedthe monosaccharide composition of the gum using gaschromatography These workers reported that the primarystructure of grewia gummay comprise five neutral sugars d-rhamnose d-arabinose d-xylose d-galactose and d-glucose(Figure 3) The mean relative concentrations of these sugarsin the polysaccharide were determined as glucose (6714)rhamnose (62) xylose (272) galactose (961) andarabinose (1271)

The FTIR spectral analysis of the gum exhibited thetypical bands and peak characteristics of polysaccharides [29]as shown in Figure 4These authors attributed the broad bandoccurring at about 3425 cmminus1 to the presence of hydroxyl(ndashOH) groups while the peak obtained at about 2927 cmminus1was attributed to stretching modes of the CndashH bonds ofmethyl groups (ndashCH

3) of the rhamnose Absorption bands

around 1618 and 1420 cmminus1 were attributed to carboxylategroups of uronic residues of galacturonic acid while theregion between 1500 and 1800 cmminus1 and absorption peaksat 1735 cmminus1 and 1256 cmminus1 were linked to the presence ofcarboxylic and acetyl groups respectively The absorption


0000 3000 6000 9000 12000

12

3 4

5

minus1Eminus02

Figure 3 GC chromatograms of alditol acetates from grewiapolysaccharide gum after hydrolysis with 2NH

2SO4(Adapted from

Nep and Conway [29])

Grewia (air-dried)

60

70

80

500 1000 1500 2000 2500 3000 3500 4000 Wavenumbers (cmminus1)

T(

)

Figure 4 FT-IR spectra of grewia gum (adapted from Nep andConway [29])

band between 500 and 900 cmminus1 may represent the fingerprint region for grewia polysaccharide gum

The gum has also been characterized using other tech-niques such as scanning electron microscopy (SEM) gelpermeation chromatography (GPC) differential scanningcalorimetry (DSC) and thermogravimetric analysis of theextracted sample Also spectroscopic techniques such as X-ray photoelectron spectroscopy (XPS) solid-state nuclearmagnetic resonance (NMR) and 1H and 13C NMR tech-niques [29] have been employed in the characterization ofgrewia gum Based on findings from the various techniquesthe gum has been described as a typically amorphouspolysaccharide gum of high thermal stability with an averagemolecular weight of 5925 kDa expressed as the pullulanequivalent

The effect of drying methods (air-drying freeze-dryingand spray-drying) on the physicochemical properties of thegum has been investigated using the techniques outlinedabove [35] Solid-state NMR results indicated that dryingtechnique had little effect on the structure of the polysac-charide gum but X-ray photoelectron spectroscopy (XPS)showed that surface chemistry of the gum varied with dryingmethodsThermogravimetric analyses showed that oxidationonset varied according to the drying method The workersconcluded that for industrial extrapolation air-drying of thegum may be preferable to spray-drying and freeze-dryingwhen relative cost product stability and powder flow are thepriority in tablet formulation for instance

445540353025201510

50

minus5minus7689

575 80 100

Hea

t flow

endo

up

(mW

)

120 140 160 180 2012Temperature (∘C)

Cimetidine

Grewia-cimetidine (1 1)

Grewia

Peak = 14216∘C

Peak = 14213∘C

Onset = 14011∘C

Area = 207264 mJDelta119867 = 69088 Jg

Onset = 14011∘C

Area = 363097 mJ

Delta119867 = 139653 Jg

Figure 5 DSC traces for cimetidine grewia gum and cimetidinegrewia gum physical mixture (1 1) under nitrogen atmosphere anda scan rate of 10∘Cmin up to 200∘C (adapted fromNep and Conway[39])

6 Pharmaceutical Values of GrewiaPolysaccharide Gum

61 Preformulation Studies The assessment of possible inter-actions between a drug and different excipients used informulation usually precedes large scale development tri-als of solid dosage forms [36 37] Physical and chemicalinteractions between excipients and active pharmaceuticalingredients (API) are common place [38] and necessitate thescreening of novel excipients for possible incompatibilitiesIn view of the suitability of grewia polysaccharide gum asformulation excipient in solid or liquid dosage forms studieson the potential interaction or incompatibility of the gumwith pharmaceutical actives andor excipients used in soliddosage formulation are imperative

Nep and Conway [39] investigated potential interac-tions between grewia gum and cimetidine ibuprofen andsome standard excipients used in the formulation of tablets(Figure 5) The thermal and molecular behaviours of mix-tures of grewia gumwith cimetidine ibuprofen and the stan-dard excipients (lactose monohydrate magnesium stearatecolloidal silicone dioxide and microcrystalline cellulose)were analyzed using differential scanning calorimetry andFT-IR spectroscopy to assess potential interactions Theresults obtained indicated that grewia gum is an inert naturalpolymer which can be used alone or in combination withother excipients in the formulation of pharmaceutical dosageforms

62 Pharmaceutical Applications Investigations into thepharmaceutical application of gum from G mollis were firstreported in the early 2000s [27 28 34 40 41] The gumwas reported to possess excellent binding property in sodiumsalicylate tablets (Okafor and Chukwu [40]) It was foundto be as effective as gelatin when employed as a binder inconcentrations of 2ndash6 ww At the same concentration thegum was more effective as a binder than maize starch oracacia gum

Audu-Peter and Gokum [42] found that the method ofincorporating the gum into tablet formulation had effect


0102030405060708090

100

0 500 1000 1500 2000

Ibup

rofe

n re

leas

e (

)

Time (min)

Grewia 16Guar 16Ethyl cellulose 16

Figure 6 Release profiles of ibuprofen from thematrices containing16 ww of grewia guar or ethyl cellulose in phosphate buffersolution at 37 plusmn 1∘C (119899 = 3 mean plusmn sd) (adapted from Nep andConway [44])

on tablet properties They discovered that tablets with bettertablet properties such as hardness and friability were pro-duced when the gum was incorporated by activation withwater than by wet granulation or direct compression Acidand thermal treatment of the gum resulted in improved drugrelease from tablets attributable to reduced viscosity of thegum (Audu-Peter and Isah [43])

Emeje et al [28] in 2008 investigated the binding propertyof the gum These workers compared the binding propertyof the gum with polyvinyl pyrolidone in paracetamol tabletformulations and analysed the compression properties of theformulations using density measurements and application ofHeckel and Kawakita equation They found that grewia gumcompares favourably with the standard binder PVP and maybe a useful substitute binder in paracetamol formulations

Grewia gum has been investigated as a sustained releasepolymer matrix in ibuprofen [44] It was used at a concen-tration of 16 32 or 48 to formulate tablets of ibuprofenThis was compared with similar formulations prepared usinghydroxypropyl methylcellulose (HPMC) guar gum or ethylcellulose as the polymer matrix The results indicated thatgrewia gum at these concentrations was capable of sustainingthe release of ibuprofen tablets up to 24 hours (Figure 6) Sim-ilarly these scientists demonstrated the potential of grewiagum to sustain the release of a water-soluble drug in tabletformulations [45] Tablets of cimetidine containing 40 ofgrewia gum were prepared by direct compression

Similar formulations containing HPMC gum Arabiccarboxy methylcellulose or ethyl cellulose were prepared forcomparisonThe results indicated that grewia gumwas supe-rior to hydrophilic matrices of HPMC carboxy methylcellu-lose and gum Arabic in sustaining the release of cimetidinefrom tablets In both instances the workers concluded thatgrewia gum may be a useful excipient when used alone orin combination with other polymers to modify the releaseof soluble drugs or poorly soluble drugs from polymericmatrices

Grewia gum fractions obtained by centrifugation at4500 rpm for 30 minutes with average molecular weightsbetween 230 and 235 kDa have been shown to demonstrateimproved aqueous solubility that was useful in deliveringmore solids to the substrate when used as a film coating agent[26 30]

Grewia gum has also been evaluated as a mucoadhe-sive in tablets [46ndash48] Nep and Okafor [47] showed thatthe gum compared favourably with tragacanth when usedas bioadhesive in tablet formulation Nep and Conway[48] compared the mucoadhesive performance of com-pacts or gels of grewia polysaccharide gum with those ofguar gum carboxymethylcellulose hydroxypropyl methyl-cellulose and carbopol 971P A software-controlled pen-etrometre TAXTPlus texture analyzer (StableMicrosystemsUK) was used to measure the detachment force of thecompacts while the polymer gels were evaluated for hardnessstickiness work of cohesion and work of adhesion Theresults showed that grewia gels had a significantly greaterwork of adhesion than carboxymethylcellulose gels (119875 lt005) and HPMC gels (119875 lt 0001) The mucoadhesive per-formance of grewia compacts was comparable to those ofHPMC and carbopol 971P compacts (119875 gt 005) It was conc-luded that grewia polysaccharide gum should be suitable forthe formulation of retentive drug delivery devices

The application of the gum as a suspending agent inpaediatric formulations has been reported [49ndash51] Thesuspending ability of air-dried or freeze-dried grewia gumin ibuprofen suspension was compared with similar sus-pension formulations containing xanthan gum sodium car-boxymethylcellulose or acacia gum as suspending agents[49] The stability of the ibuprofen suspension formula-tions was assessed using parameters such as appearancepourability viscosity rheology sedimentation volume andredispersibility Other evaluation parameters used includedegree of flocculation zeta potential andmicrobial loadTheresult from the study indicated that air-dried or freeze-driedgrewia gum may provide a suitable alternative as suspendingagent in paediatric suspension formulations

7 Conclusion

Grewia gum is a natural resource whose potential pharma-ceutical values have been established Our literature surveyrevealed that pharmaceutically grewia gum has been wellinvestigated for its application as binder disintegrant ormucoadhesive in solid dosage forms and as stabilizer or sus-pending agent in liquid formulations However the scientificresearch on grewia gum is yet to be translated into industrialapplications due to the absence of detailed physical andchemical characterization stability data and scientificallyvalidated bioactive properties Although the use of grewiagum as thickener in local delicacies spans generations it maybe necessary to reconcile the ethnomedicinal use of extract ofthe aerial parts of the plant with the absolute requirement thatexcipients are pharmacologically inert Detailed scientificinvestigations that will fill in these details will not only helpin furthering the scientific understanding of grewia gumbut importantly it will assist in realizing its commercial


potential as pharmaceutical excipient Furthermore grewiagum should be explored in design and development of otherdrug carriers such as micro- and nanomaterials membranescapsules and hot-melt extruded carriers and in wound heal-ing applications Grewia gum holds promise as an excipientto be explored for the unmet needs in drug delivery

Conflict of Interests

The authors certify that there is no conflict of interests withany financial organization regarding thematerial discussed inthe paper

References

[1] C W Vendruscolo C Ferrero E A G Pineda et al ldquoPhysic-ochemical and mechanical characterization of galactomannanfromMimosa scabrella effect of drying methodrdquo CarbohydratePolymers vol 76 no 1 pp 86ndash93 2009

[2] H E Huber and G I Christenson ldquoUtilization of hydrophilicgums for control of drug release from tablet formulation 1disintegration and dissolution behaviourrdquo Journal of Pharma-ceutical Sciences vol 1 pp 59ndash66 1996

[3] T R BhardwajM Kanwar R Lal and A Gupta ldquoNatural gumsand modified natural gums as sustained-release carriersrdquo DrugDevelopment and Industrial Pharmacy vol 26 no 10 pp 1025ndash1038 2000

[4] J Varshosaz N Tavakoli and S A Eram ldquoUse of natural gumsand cellulose derivatives in production of sustained releasemetoprolol tabletsrdquo Drug Delivery vol 13 no 2 pp 113ndash1192006

[5] O K Udeala andA Chukwu ldquoThe binding property ofmucunagum in sulphadimidine and chloroquine phosphate tabletsrdquoNigerian Journal of Pharmaceutical Sciences vol 1 pp 59ndash661985

[6] M R Bilany ldquoSuspensions and emulsionsrdquo in PharmaceuticsThe Design and Manufacture of Medicines M E Aulton Edpp 383ndash405 Churchill Livingstone Philadelphia Pa USA 3rdedition 2007

[7] D L Middleton S H S Leung and J R Robinson ldquoOcularbioadhesive delivery systemsrdquo in Bioadhesive Drug DeliverySystems V Leenaerts and R Gurny Eds pp 179ndash202 CRCPress Boca Raton Fla USA 1990

[8] C Whitehouse M Cheek S Andrews and B Verdcourt ldquoTili-aceae and Muntingiaceaerdquo in Flora of Tropical East Africa HJ Beentje Ed p 120 AA Balkema Rotterdam Netherlands2001

[9] D Louppe A A Oteng-Amoako andM Brink Plant Resourcesof Tropical Africa 7(1) Timber 1 PROVA FoundationWagenin-gen Netherlands Backhuys Publishers Lenden NetherlandsCTA Wageningen Netherlands pp 298ndash300 2008

[10] ldquoDigital image of Grewia mollis plantrdquo httpwwwprota4uorgprotav8asph=M11M15M17M18M25M26M27M34M36M4M6M7M8M9ampt=Grewiamollisampp=Grewia+mollisDescription

[11] L S Gill Ethno-Medical Uses of Plants in Nigeria University ofBenin Press Benin Nigeria 1992

[12] W Obidah J L Godwin J Z Fate and M A MadusolumuoldquoToxic effects of Grewia mollis stem bark in experimental ratsrdquoJournal of American Science vol 6 no 12 pp 1544ndash1548 2010

[13] J M Dalziel The Useful Plants of West Africa Crown AgentsLondon UK 1937

[14] F C Onwuliri J D Mawak D L Wonang and E A OnwulirildquoPhytochemical toxicological and histo-pathological studies ofsome medicinal plants in Nigeriardquo International Journal ofNatural and Applied Sciences vol 2 pp 225ndash229 2006

[15] O Asuku S E Atawodi and E Onyike ldquoAntioxidant hep-atoprotective and ameliorative effects of methanolic extract ofleaves of Grewia mollis Juss on carbon tetrachloride-treatedalbino ratsrdquo Journal of Medicinal Food vol 15 no 1 pp 83ndash882012

[16] N A Saleem M El-Nour and A A M Khalid ldquoThe nutritivevalue of leaves and fruits of three grewia species under semi-aridenvironmentrdquo Journal of Agricultural Science and Technologyvol B2 pp 956ndash964 2012

[17] H M A Al-Youssef M Amina and A M El-Shafae ldquoBiolog-ical evaluation of constituents from Grewia mollisrdquo Journal ofChemical and Pharmaceutical Research vol 4 no 1 p 508 2012

[18] H Rosler H Framm and R N Blomster ldquoThe isolation of6-hydroxyharmane from Grewia mollisrdquo Journal of NaturalProducts vol 41 no 4 pp 383ndash384 1978

[19] W Pfau andK Skog ldquoExposure to120573-carbolines norharman andharmanrdquo Journal of Chromatography B vol 802 no 1 pp 115ndash126 2004

[20] P K Goyal ldquoPhytochemical and pharmacological properties ofthe genus Grewia a reviewrdquo International Journal of Pharmacyand Pharmaceutical Sciences vol 4 no 4 pp 72ndash78 2012

[21] P Venault and G Chapouthier ldquoFrom the behavioral pharma-cology of beta-carbolines to seizures anxiety andmemoryrdquoTheScientific World Journal vol 7 pp 204ndash223 2007

[22] O O Efiom and E Oku ldquoIsolation and characterisation oftriterpene lup-20-en-3-ol and 1 3-hexyloxacyclotridec-10-en-2-one from the root of Grewia mollisrdquo New York Science Journalvol 5 no 11 pp 138ndash141 2012

[23] M H Shagal D kubmarawa and Z Idi ldquoPhytochemicalscreening and antimicrobial activity of roots stembark and leafextracts of Grewia mollisrdquo African Journal of Biotechnology vol11 no 51 pp 11350ndash11353 2012

[24] N Idika and M Niemogha ldquoThe diversity of uses of medicinalplants in Nigeriardquo in A Textbook of Medicinal Plants of NigeriaT Odugbemi Ed p 63 University of Lagos Press LagosNigeria 2008

[25] A Musarat H M Al-Youssef T Amna et al ldquoPolyurethaneGmollis composite nanofibers for biomedical applicationsrdquoJournal of Nanoengineering and Nanomanufacturing vol 2 pp85ndash90 2012

[26] I J Ogaji E I Nep and J D Audu-Peter ldquoAdvances innatural polymers as pharmaceutical excipientsrdquo PharmaceuticaAnalytica Acta vol 3 article 146 2012

[27] I S Okafor ldquoThe rheological properties of grewia gumrdquoNigeriaJournal of Polymer Science and Technology vol 2 pp 169ndash1752001

[28] M Emeje C Isimi and O Kunle ldquoEffect of Grewia gum onthe mechanical properties of Paracetamol tablet formulationsrdquoAfrican Journal of Pharmacy and Pharmacology vol 2 pp 1ndash62008

[29] E I Nep and B R Conway ldquoCharacterization of Grewia Guma potential pharmaceutical excipientrdquo Journal of Excipients andFood Chemicals vol 1 no 1 pp 30ndash40 2010

[30] I Ogaji ldquoCharacterization and application of grewia gum asa film coating agent in theophylline hydrochloride tabletsrdquoPharmaceutics and Pharmaceutical Technology vol 308 2011


[31] A Setia S Goyal and N Goyal ldquoApplications of gum karayain drug delivery systems a review on recent researchrdquo DerPharmacia Lettre vol 2 no 5 pp 39ndash48 2010

[32] D Le Cerf F Irinei and G Muller ldquoSolution properties of gumexudates from Sterculia urens (Karaya gum)rdquo CarbohydratePolymers vol 13 no 4 pp 375ndash386 1990

[33] A Imeson ldquoExudate gumsrdquo in Thickening and Gelling AgentsFor Food A Imeson Ed pp 66ndash97 Chapman and HallLondon UK 1992

[34] I S Okafor and A Chukwu ldquoWater vapour permeability ofaqueous-based grewia gum filmrdquo Nigeria Journal of PolymerScience and Technology vol 2 pp 176ndash182 2003

[35] E I Nep and B R Conway ldquoPhysicochemical characterizationof grewia polysaccharide gum effect of drying methodrdquo Carbo-hydrate Polymers vol 84 no 1 pp 446ndash453 2011

[36] G Bruni V Berbenni C Milanese A Girella and A MarinildquoDrug-excipient compatibility studies in binary and ternarymixtures by physico-chemical techniquesrdquo Journal of ThermalAnalysis and Calorimetry vol 102 no 1 pp 193ndash201 2010

[37] M J Peres-FilhoM PNGaeti S RDeOliveira RNMarretoand E M Lima ldquoThermoanalytical investigation of olanzapinecompatibility with excipients used in solid oral dosage formsrdquoJournal of Thermal Analysis and Calorimetry vol 104 no 1 pp255ndash260 2011

[38] M E Brown E M Antunes B D Glass M Lebete andR B Walker ldquoDSC screening of potential prochlorperazine-excipient interactions in preformulation studiesrdquo Journal ofThermal Analysis and Calorimetry vol 56 no 3 pp 1317ndash13221999

[39] E I Nep and B R Conway ldquoPreformulation studies on grewiagum as a formulation excipientrdquo Journal of Thermal Analysisand Calorimetry vol 108 no 1 pp 197ndash205 2012

[40] I S Okafor and A Chukwu ldquoThe binding property of Grewiagum in sodium salicylate tabletsrdquo West African Journal ofBiological Sciences vol 14 pp 9ndash21 2003

[41] I S Okafor and I M Danat ldquoThe influence of granulatingsolvents on drug release from tablets containing grewia gumrdquoJournal of Pharmacy and Bioresources vol 1 pp 76ndash83 2004

[42] J D Audu-Peter and B G Gokum ldquoEffect of methods of incor-porating grewia gum as binder on tablet propertiesrdquo NigerianJournal of Pharmaceutical Research vol 4 pp 68ndash73 2005

[43] J D Audu-Peter and S Isah ldquoEvaluation of grewia gum asbinder in paracetamol tabletrdquo Journal of Pharmacy and Biore-sources vol 4 pp 68ndash73 2007

[44] E I Nep and B R Conway ldquoGrewia polysaccharide as a phar-maceutical excipient inmatrix tabletsrdquo Journal of Excipients andFood Chemicals vol 2 no 1 pp 3ndash15 2011

[45] E I Nep and B R Conway ldquoPolysaccharide gum matrixtablets for oral controlled delivery of cimetidinerdquo Journal ofPharmaceutical Sciences and Research vol 2 no 11 pp 708ndash7162010

[46] E I Nep and I S Okafor ldquoEvaluation of the bioadhesiveproperty of Grewia Gum in mebendazole tablet formulation1 in pig gastric mucusrdquo Nigerian Journal of PharmaceuticalResearch vol 4 no 2 pp 52ndash58 2005

[47] E I Nep and I S Okafor ldquoEvaluation of the bioadhesiveproperty of Grewia gum in indomethacin tablet formulation inpig gastric mucusrdquo Journal of Pharmacy and Bioresources vol 3no 2 pp 62ndash69 2006

[48] E I Nep and B R Conway ldquoGrewia gum 2 mucoadhesiveproperties of compacts and gelsrdquo Tropical Journal of Pharma-ceutical Research vol 10 no 4 pp 393ndash401 2011

[49] E I Nep and B R Conway ldquoEvaluation of Grewia polysac-charide gum as a suspending agentrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 3 no 2 pp 168ndash173 2011

[50] J O Kadiri and I S Okafor ldquoEvaluation of the suspendingproperty ofGrewia gum inmetronidazole suspensionrdquoNigerianJournal of Pharmaceutical Research vol 8 no 1 pp 247ndash2542010

[51] I J Ogaji and SWHoag ldquoEffect ofGrewia gumas a suspendingagent on ibuprofen pediatric formulationrdquoAAPS PharmsciTechvol 12 no 2 pp 507ndash513 2011

Submit your manuscripts athttpwwwhindawicom

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

CorrosionInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Polymer ScienceInternational Journal of



CeramicsJournal of


CompositesJournal of

NanoparticlesJournal of



International Journal of

Biomaterials


NanoscienceJournal of

TextilesHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Journal of

NanotechnologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

CrystallographyJournal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014


CoatingsJournal of

Advances in

Materials Science and EngineeringHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Smart Materials Research



MetallurgyJournal of


BioMed Research International

MaterialsJournal of


Nano

materials


Journal ofNanomaterials


Table 1 Ethnomedicinal uses of G mollis plant

Use Plant part Preparation ReferencesWound healing Bark leaves Mucilages are applied to ulcers cuts sores and snake bites [9 13]Cough Bark roots Decoction [9 13]Fever Bark Leaves and fruit Extract of bark andor leaves Fruits are also eaten for this purpose [9 13]Diarrhoea Stem bark Decoction [9 24]Child birth Pain Stem bark leaves Maceration decoction [9 13]Colic Bark leaves Infusion [9]Constipation Bark Mucilage [9]Rickets Leaves Decoction [9]Palpitation Roots leaves Decoction [9]Sore eyes Root shavings Sap squeezed out and applied under the eyelid [9]Rheumatism Roots Paste [9 13]Anal prolapse Bark Pounded and dissolved in water [9 24]

Figure 1 G mollis plant The figure is adapted from httpwwwprota4uorg [10]

The fruit has been described as unlobed and globosedrupe of about 4ndash7mm long and 5ndash7mm wide coveredwith a fine whitish tomentellum The fruits are green whenyounger and turning yellowwhen older [8 9] A digital imageof the aerial part of the plant is shown in Figure 1

22 Propagation G mollis grows in the wild and can bepropagated by seed or seedlingsThe seeds are collected fromthe dried fruits that may have fallen on the ground [9]

3 Uses of the Aerial Parts of G mollis

The different parts of G mollis have been used for differentpurposes across the regions and places where the plant growsor is cultivated

31 Mucilage from Leaves and Stem Bark In the DemocraticRepublic of Congo the bark is kneaded with water into aviscous substance that is added to sauces while in Gabon theinner bark is sometimes eaten as food In Nigeria the innerstem bark is used as thickener in soups and in local cakesmade from beans or corn flour commonly called ldquoKosairdquo andldquoPunkasaurdquo in Hausa (Nigeria) respectively [11 12]

The infusion of the bark obtained by cold or hot macera-tion in water is applied to give a smooth surface to mud wallsand floors [13] while the wood ash is used as salt substituteincluding the ash of the leaves stems and roots [9]

32 Vegetables and Fruits The flowers buds and youngshoots are added to soups and sauces as garnishing while inSudan the young leaves are cooked and eaten as vegetablesThe fruit is eaten raw or boiled [9]

33 Ethnomedicinal Uses Several ethnomedicinal uses of theinfusion decoction maceration or mucilage from the leavesroots or stem bark ofG mollis have been documentedTheseethnomedicinal uses are described in Table 1

4 Biological Evaluation and ChemicalConstituents of G mollis

Several scientists have investigated the histopathological andtoxicological effects of extracts of G mollis on laboratoryanimals

Onwuliri et al [14] conducted toxicological and histo-pathological studies in rats using the ethanolic extract ofthe stem bark of G mollis Tannins saponins flavonoidsglycosides balsam phenols terpenes and steroids wereisolated from the stem bark but alkaloids were absent Theextract exhibited toxic properties at the lethal dose (LD

50)

of 1500mgkg body weight The convoluted tubules of thekidney but no structural effects on the liver and heart wereobserved suggesting that the extract may be safe in humansbut should be usedwith caution on patients with renal failure

Studies by Obidah et al [12] on the toxic effects ofthe stem bark of G mollis showed that the addition of thepulverized stem bark to the normal diet of male Wister ratsat concentrations of 0 1 5 and 10 given to them as feedfor 4 weeks resulted in no deaths and remarkable changesin appearance were not observed in the treated animalsHowever rats fed with 10 dietary level showed significant(119875 lt 005) increases in serum transaminases activities whichwas accompanied by decreased food intake There was noobserved effect on serum alkaline phosphatase activity ureacreatinine triglycerides cholesterol glucose concentrationsand body and organ weights in their study These workersconcluded that dietary exposure of rats toG mollis stem barkpowder at high concentrations (10)may cause some adverseeffects especially liver injury


O

HO

HO

O

OH

OH

(a)

OO

OH O

OHO O OH

HO OHOHOH

OHHO

OHOOC

(b)

HO

OH

COOHOH

(c)

HO

OH

OHCOOH

(d)

HO

H

H H

H

(e)

O

H

H H

H

O

OH

OH

HOHO

(f)

NNH

O

(g)






























0000 3000 6000 9000 12000

12

3 4

5

minus1Eminus02


2SO4(Adapted from


Grewia (air-dried)

60

70

80


T(

)





445540353025201510

50

minus5minus7689

575 80 100

Hea

t flow

endo

up

(mW

)

120 140 160 180 2012Temperature (∘C)

Cimetidine


Grewia

Peak = 14216∘C

Peak = 14213∘C

Onset = 14011∘C

Area = 207264 mJDelta119867 = 69088 Jg

Onset = 14011∘C

Area = 363097 mJ

Delta119867 = 139653 Jg








0102030405060708090

100

0 500 1000 1500 2000

Ibup

rofe

n re

leas

e (

)

Time (min)










7 Conclusion






References




























































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




O

HO

HO

O

OH

OH

(a)

OO

OH O

OHO O OH

HO OHOHOH

OHHO

OHOOC

(b)

HO

OH

COOHOH

(c)

HO

OH

OHCOOH

(d)

HO

H

H H

H

(e)

O

H

H H

H

O

OH

OH

HOHO

(f)

NNH

O

(g)






























0000 3000 6000 9000 12000

12

3 4

5

minus1Eminus02


2SO4(Adapted from


Grewia (air-dried)

60

70

80


T(

)





445540353025201510

50

minus5minus7689

575 80 100

Hea

t flow

endo

up

(mW

)

120 140 160 180 2012Temperature (∘C)

Cimetidine


Grewia

Peak = 14216∘C

Peak = 14213∘C

Onset = 14011∘C

Area = 207264 mJDelta119867 = 69088 Jg

Onset = 14011∘C

Area = 363097 mJ

Delta119867 = 139653 Jg








0102030405060708090

100

0 500 1000 1500 2000

Ibup

rofe

n re

leas

e (

)

Time (min)










7 Conclusion






References




























































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




















0000 3000 6000 9000 12000

12

3 4

5

minus1Eminus02


2SO4(Adapted from


Grewia (air-dried)

60

70

80


T(

)





445540353025201510

50

minus5minus7689

575 80 100

Hea

t flow

endo

up

(mW

)

120 140 160 180 2012Temperature (∘C)

Cimetidine


Grewia

Peak = 14216∘C

Peak = 14213∘C

Onset = 14011∘C

Area = 207264 mJDelta119867 = 69088 Jg

Onset = 14011∘C

Area = 363097 mJ

Delta119867 = 139653 Jg








0102030405060708090

100

0 500 1000 1500 2000

Ibup

rofe

n re

leas

e (

)

Time (min)










7 Conclusion






References




























































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials




0102030405060708090

100

0 500 1000 1500 2000

Ibup

rofe

n re

leas

e (

)

Time (min)










7 Conclusion






References




























































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials







References




























































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials
































CeramicsJournal of







Biomaterials




Journal of


Journal of





CoatingsJournal of

Advances in








MaterialsJournal of


Nano

materials



review article pharmaceutical properties and applications...

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