Modified Terminalia randii gum as a binder in metronidazole tablet formulation

IOSR Journal Of Pharmacy 

(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219 

www.iosrphr.org Volume 4, Issue 10 (October 2014), PP. 28-32 

Modified Terminalia randii gum as a binder in metronidazole 

tablet formulation 

1, 

OluyemisiAdebowaleBamiro*, 2, OlusegunDeru, 3, Lateef Gbenga Bakre, 

4, 

Onyinye Jennifer Uwaezuoke 

1, 2, 3, 4, 

Dept. of Pharmaceutics & Pharm. Tech., Faculty of Pharmacy OlabisiOnabanjo University, Nigeria 

ABSTRACT: The aim of this work is to acetylate Terminalia randii gum and evaluate its effectiveness as a 

binder in metronidazole tablet formulations. The gum was extracted using standard methods. The extracted gum 

was acetylatedand used at varying concentrations (1%-5%w/w) as a binder in metronidazole tablets and 

compared with a standard binder, polyvinylpyrollidone (PVP) using wet granulation. The granule properties 

were assessed using bulk and tapped densities, Carr's index, Hausner's ratio, angle of repose and flow rate. The 

mechanical properties of tablets were assessed using friability, crushing strength and crushing strength 

friability ratio while the release properties were evaluated using disintegration time, and dissolution time for 

50% and 80% of the drug (t 50 and t 80 respectively). Statistical analysis using ANOVA was carried out with 

computer software graph pad prism (Graph pad software INC. San Diego, USA). At 95% confidence intervals, p 

value less than or equal to 0.05 were considered significant. 

There was no significant difference (P>0.05) in the granule properties.Formulations prepared with 

acetylated gum (ATR) had significantly lower (P0.05) in the release properties of the 

formulations. 

ATR could be substituted for PVP as a binder in pharmaceutical formulations. 

KEYWORDS-Acetylation, Metronidazole, Release properties, Tablet, Terminalia randii gum 

I. INTRODUCTION 

Gums are natural polysaccharides consisting of multiple sugar units linked together to form large 

molecule. Gums may be classified as natural, semi synthetic or modified and synthetic gums [1]. These natural 

gums have found great use in the pharmaceutical industries due to their non-toxicity, ready availability and they 

are biodegradable. They have been explored as emulsifier, suspending agent, adhesives and binding agents [2], 

[3]. Most natural gums are safe for oral use in the food and pharmaceutical industries [4]. However, the use of 

these gums could be associated with certain problems such as pH dependent solubility, uncontrollable swelling, 

change in viscosity on storage and possibly microbial contamination [4]. Chemical modifications of these gums 

can becarried out to minimize these problems. 

Carboxymethylation of gums has been shown to increase the hydrophilicity thus, making them more 

soluble in aqueous systems [5]. Grafting of acrylic acid on gums has been shown to modify the swelling 

characteristics and drug release properties of gums [6], [7]. 

In this present study, Terminalia randii gum has been modified by acetylation and its binding 

properties in metronidazole tablet was compared with a standard binder polyvinyl pyrrolidone. 

II. MATERIALS AND METHODS 

Materials 

The materials used were metronidazole (gift from Bond chemicals, Awe, Nigeria), Lactose BP (Ind- 

Swift Labs Ltd, Parwanoo, India), Corn starch powder BP (BDH, England). Magnesium Stearate (LobaChemie 

PVT Ltd, Mumbia India), PolyvinylpyrrolidoneUSP K29/32 (molecular weight: 58,000) (ISP Technologies, 

IncWayne, USA). Terminalia randii gum obtained from OlabisiOnabanjo University, Nigeria. All other 

materials were analytical grade. 

2.1 Gum Extraction 

Terminalia randii gum was extracted using the method described by Bamiroet al, [8].The gum was 

hydrated in chloroform water double strength for 5days with intermittent stirring, and extraneous materials were 

removed by straining through a calico cloth. The gum was then precipitated from solution using absolute 

28

Modified terminalia randii gum as a binder in metronidazole tablet formulation 

ethanol. The precipitated gum was filtered washed with diethyl ether and then dried in a hot air oven at 40 o C for 

24 hours. The purified gum was then pulverized and packed in an airtight container. 

2.2 Acetylation of Terminalia randii gum 

Extracted gum (10g) was dispersed in 100ml of distilled water with constant stirringfor 30mins.The 

slurry was adjusted to pH 8.0 with NaOH. 1.2g of acetic anhydride was added to the slurry and the reaction was 

allowed to proceed for another 5 minutes. The pH of the slurry was adjusted to 4.5 with 0.5M HCL and then 

filtered through Wathman filter 1 paper. The residue was thoroughly washed with distilled water to completely 

remove some acid that may be present in the product and finally air dried at room temperature. The acetylated 

gum was characterised using Fourier Transform Infrared Spectroscopy (FTIR). 

2.3 FTIR of acetylated and natural Terminalia gum 

The FTIR spectrum of the gum was recorded with a Perkin Elmer RXI spectrophotometer 

(Connecticut, USA). The dry gum powder was mixed with potassium bromide (KBr) and pressed into pellets. 

The spectrum was obtained by scanning between 4000 and 500cm -1 

2.4 Tablet Preparation 

100g batch sizes were prepared containing 60 % w/w metronidazole (drug), 30 % w/w lactose (diluent) 

and 10% w/w corn starch (disintegrant). Metronidazole granules were prepared using wet granulation method. 

Acetylated Terminalia gum (ATR) was used as a binder at different concentrations (1-5 % w/w), while PVP was 

used as a standard. The granule properties of the granules were evaluated using USP 2007 methods. The 

granules were compressed on a Carvierhydraulic machine (Model C, Carver Inc., Menomonee Falls, WI) with 

predetermined load for 30 seconds. The tablets were stored in air tight containers for 24 hours to allow for 

elastic recovery. 

2.5 Tablet properties 

Friability was determined with a DBK friabilator test apparatus (Mumbai, India) set to rotate at 25 rpm 

for 4 minutes. Determinations were done in triplicate. 

Crushing strength was determined with a DBK Instrument Tablet Hardness Tester MODEL EH 01. 

Five tablets were taken from each batch and the results were given as mean ±SD. 

Disintegration test was carried out in distilled water at a temperature of 37±0.5 0 C in a DBK Tablet 

Disintegration test apparatus (Mumbai, India). Determinations were done in quadruplicates. 

The in vitro dissolution test was carried out in 900ml 0f 0.1M HCL at a constant temperature of 37 

±0.05 0 C using a rotating basket apparatus method rotated at 100 rpm. 5 mL samples were withdrawn at different 

time intervals and replaced with fresh samples. The amount of metronidazole released in each sample was 

determined using a UV spectrophotometer (Cecil CT 2041200 series) at a wavelength of 277nm. Determinations 

were done in triplicates. 

Statistical analysis was carried out using ANOVA (analysis of variance) with computer software graph pad 

prism 4 (Graph pad software Inc. San Diego, USA). At 95% confidence interval, p ≤ 0.05 were considered 

significant. 

III. RESULTS AND DISCUSSION 

The FTIR ofTerminalia randii gum and acetylated Terminalia randii gum are presented in Figs. 1 and 

2. The peak at 1749cm -1 is a C=O stretching which indicates esterification which is brought about by the 

presence of an acetyl group. 

The granule properties are presented in Table 1. The mean granule size was observed to increase with 

increase in binder concentration. This could be attributed to strengthening of bonds between particles as there 

would be more binder per bond as the concentration is increased [9], [10]. The bulk densities generally 

decreased with increase in binder concentration. The flowability of a material is an important parameter in the 

production of tablets. The flow properties were determined by evaluating the angle of repose, Hausner’s ratio, 

Carr’s index and the flow rate. Angle of repose less than 25 o indicates very good flow, 25 o to less than 50 o 

indicates good flow while greater than 50 o is poor flow. Granules produced by the two binders exhibited good 

flow property. The Carr’s index is a measure of the flow-ability and compressibility of a material. All the 

granule formulations had Carr’s index of less than 15 o which indicates good flow properties. Hausner’s ratio less 

than 1.2 indicates good flow. All the formulations had less than 1.2, indicating good flow [11]. 

29


The tablet properties are presented in Table 2. The mechanical properties of a pharmaceutical tablet are 

quantified by crushing strength and friability. These are ability of the tablets to withstand the rigors of 

transportation, dispensing and handling [12]. The friability was observed to decrease as concentration of binder 

increased, while crushing strength increased with increase in concentration of binder. This could be due to the 

heat produced during the compression of the tablets which caused melting of binding agent, which on cooling 

solidify to form strong solid bonds between the particles. All the formulations passed the friability test by 

showing friability values of less than 1% w/w [13]. The mechanical properties of formulations containing ATR 

were significantly lower (p

Binder 

Conc 

of 

binde 

r 

Bulk density 

(g/ml) 


Table 1: Micromeritic Properties of Granules 

Tapped 

density 

(g/ml) 

Flow rate 

(g/sec) 

Angle 

repose 

( O ) 

of 

Carr’s 

index 

( O / O ) 

Hausner 

ratio 

Contro 0.00 0.483±0.00 0.523±0.01 3.95±0.44 35.24±0.21 7.62±1.77 1.07±0.01 445 

Mean 

granule size 

µm 

PVP 1.00 0.416±0.20 0.450±0.00 4.74±0.52 36.74±0.56 7.41±1.28 1.08±0.01 485 

2.00 0.396±0.18 0.430±0.00 5.90±0.56 37.35±0.21 7.53±1.33 1.08±0.01 515 

3.00 0.416±0.19 0.430±0.00 6.63±0.57 36.62±0.21 3.10±1.33 1.03±0.01 585 

5.00 0.410±0.18 0.453±0.00 7.88±0.60 36.00±0.21 9.54±1.13 1.10±0.01 710 

ATR 1.00 0.427±0.00 0.433±0.00 5.20±0.41 48.86±0.56 1.55±1.34 1.01±0.01 755 

2.00 0.410±0.00 0.430±0.00 5.73±0.31 48.57±0.52 4.65±0.00 1.05±0.00 765 

3.00 0.400±0.01 0.440±0.01 7.22±0.29 49.63±0.14 9.09±0.20 1.09±0.00 770 

5.00 0.407±0.00 0.417±0.01 9.78±0.47 49.22±0.42 2.32±4.02 1.02±0.04 860 

The release properties of the tablets were assessed using disintegration and dissolution times (t 50 and t 80 

i.e. time required for 50% and 80% of the drug to be released respectively). The disintegration time of tablets is 

the rate limiting step in dissolution and consequently absorption of the active ingredient. The British 

Pharmacopoeia [13], states that uncoated tablets must disintegrate within 15 minutes. All the formulations 

disintegrated in less than 15 minutes. The result of the release properties are presented in Table 2. The 

disintegration time was observed to increase with increase in concentration of binder.Formulations containing 

ATR at 5 % w/w had significantly lower (p0.05) in the dissolution time. 

Table 2: Tablet Properties 

Binder 

PVP 

ATR 

Concentration 

(% w/w) 

Friability 

(%) 

Crushing 

strength 

(N) 

CSFR 

Disintegration 

time 

(Min) 

T 50 

(min) 

T 80 

(min) 

0.00 0.36±0.01 18.58±2.97 51.61 0.03±0.00 2.35 4.45 

1.00 0.53±0.03 27.46±3.80 51.81 0.07±0.01 2.35 4.50 

2.00 0.48±0.01 59.54±3.45 124.04 0.14±0.01 2.52 4.75 

3.00 0.44±0.01 96.68±3.88 219.72 0.38±0.06 2.75 5.25 

5.00 0.45±0.04 104.88±3.57 233.07 0.79±0.02 2.80 5.75 

1.00 0.69±0.02 22.56±2.86 32.70 0.07±0.02 2.25 5.25 

2.00 0.40±0.01 26.58±2.78 66.45 0.22±0.01 1.85 3.75 

3.00 0.30±0.02 39.56±3.00 131.87 0.31±0.00 2.35 5.35 

5.00 0.36±0.02 31.72±3.45 88.11 0.38±0.05 2.55 5.75 

31


Figure 3: Plots of percentage metronidazole released against time in formulations containing 5% w/w ATR and 

PVP 

IV. CONCLUSION 

The data obtained from this study indicates that acetylated Terminalia randii gum could be substituted 

for polyvinyl pyrrolidoneas a binder in tablet formulations, especially where a tablet that is not “too strong” but 

with similar release property is required. 

REFERENCES 

[1] K. OforiKwakye, Y. Asantewaa and S. Lugrie kipo.Physicochemical and Binding Properties of cashew tree gum in metronidazo 

letablet formulations.Int.J Pharm Pharm Sci, 2( 4), 2010, 105109 

[2] H. Rahim, M. A Khan, A. Badshah, K.A Chishti, S. Khan and M. Junaid. Evaluation of Prunusdomestica gum as a novel tablet 

binder. BJPS, 50(1), 2014, 195-202. 

[3] R. Kumar, S.R. Patil, M. B. Patil, M. S. Paschapur, R. Mahalaxmi Isolation and evaluation of the emulsifying properties of 

tamarind seed polysaccharide on castor oil emulsion. Der Pharmacia Lettre, 2 (1), 2010, 518-527 

[4] V. Rana, P. Rai, A.K. Tiwary, R.S. Singh, J.F. Kennedy and C.J.Knill. Modified gums: Approaches and applications in drug 

delivery. Carbohydrate Polymers, 83, 2011, 1031-1047. 

[5] G. Dodi, D. Hritcu and M. I. Popa. Carboxymethylation of guar gum: Synthesis and characterization. Cellulose Chem. Technol., 

45 (3-4), 2011, 171-176 

[6] B.R. Sharma, V. Kumar and P.L. Soni. Ceric ammonium nitrate-initiated graft copolymerization of acrylamide onto Cassia tora 

gum. J Appl. Polymer Sci. 90, 2002.3250-3255. 

[7] P. Goyal, V.Kumar and P. Sharma. Graft copolymerisation of acrylamide onto tamarind kernel powder in the presence of ceric 

ion. J Appl. Polymer Sci.108, 2008a, 3696-3701. 

[8] O.A Bamiro, V.R Sinha, R. Kumar, O.A Odeku. Characterization and evaluation of Terminalia randii gum as a binder in 

carvedilol tablet formulation. Acta Pharm Sci. 52, 2010, 254-262. 

[9] S. Esezobo and V. Ambujan. An evaluation of starch obtained from Plantain-Musa Paradisiaca-As a binder and disintegrant for 

compressed tablets. J Pharm Pharmacol, 34,1982, 761-765. 

[10] M. Luangtanan-Anan and J.T. Fell. Bonding mechanisms in tableting. Int J Pharm. 60, 1990, 197-202 

[11] J.I Wells, Tablet testing, in J. Swarbick, J.C Boylan (14 Ed), Encyclopedia of Pharmaceutical Technology(Marcel Dekker, New 

York 1997) 401-418. 

[12] G.S Banker and N.R Anderson, Tablets, in L. Lachman, H.A Liberman special Indian (Ed), The Theory and practice of 

Industrial Pharmacy (CBS Publishers and Distributor, New Dehli, 2009) 293-345 

[13] British Pharmacopoaeia (BP). The Commission Office London. 2009; 111: 6578 – 6585 

[14] O.A.Odeku and O.AItiola. Evaluation of the effects of Khaya gum on the mechanical and release properties of paracetamol tablet 

formulation. Drug Dev Ind Pharm 29,2003, 311-320. 

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Modified Terminalia randii gum as a binder in metronidazole tablet formulation

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