Design and Evaluation of Controlled Release Bhara Gum Microcapsules of Famotidine for Oral Use


Nayak Bhabani Shankar*1, Nayak Udaya Kumar2, Patro K Balakrishna2 and Rout Prasant Kumar1

1Jeypore College of Pharmacy, Rondapalli, Jeypore-764002, Koraput, Orissa, India

2Glenmark R and D Unit, Navi Mumbai, India

*Corresponding Author E-mail:



A new sustained release microencapsulated drug delivery system employing bhara gum derived from Terminalia bellerica (roxb) has been proposed in this present study. The microcapsules were formulated by ionic gelation technique using famotidine as the model drug  and were evaluated for particle size, sphericity measurement, yield percentage, drug entrapment efficiency, wall thickness, swelling property, in vitro drug release profile and drug release kinetic study. The effect of different drug: bhara gum ratio on in vitro drug release profile was examined and compared with guar gum remaining all the parameters constant. The gum microcapsules with good structure and satisfactory yield were produced. Microcapsules employing bhara gum exhibited slow release of famotidine over 10 hr. Fickian release was observed from most of the formulation with bhara gum. It was concluded that the gum possess substantial release controlling properties that could be used for sustained drug delivery.


KEY WORDS:   Swelling properties, kinetics, matrices, mucilage.




Sustained release (SR) drug delivery system significantly improve therapeutic efficacy of a drug. Drug release retarding polymers are the key performer in such systems. Much of the development in SR drug delivery systems is focusing in the preparation and use of polymers with specificity designed macroscopic and microscopic structural and chemical features. Number of natural, semi synthetic and synthetic polymer materials are used in the controlled delivery of drugs. Recent trend towards the use of vegetable and nontoxic products demands the replacement of synthetic additives with natural one1. In view of the easy availability of the plant and high demand of gum through the world, the gum obtained from Terminalia bellerica was investigated for its application as a release rate retarding polymer2, 3. The natural materials have been extensively used in the field of drug delivery for their easy availability, cost effectiveness, ecofriendliness, capable of multitude of chemical modifications, potentially degradable and compatible due to natural origin. Past research therefore studied and acknowledged various natural gum like agar, konjac , guar gum ,chitosan , xanthan , sodium alginate and lotus bean gum etc.


For potential pharmaceutical and biomedical application4. These particular explicates the rationale why proposed article concerns the evaluation of natural gums for sustained drug delivery. Gum Bhara is a yellowish natural gum of plant Terminalia bellerica roxb. (Bhara) belongs to family Combretaceae3.


Terminalia bellerica is a handsome tree with characteristic bark attaining a height up to 40 m and a girth of 1.8-3 m, found in deciduous forests throughout the greater part of India3. It has been mainly used as a demulcent and purgative. It is also used as an emulsion in cosmetic industries2, 3. In the hilly region of Orissa, West Bengal, Sikkim, Madhya Pradesh, this gum has been utilized as an indigenous system of medicine. These wide applications of bhara gum propose their hydrophilic nature, and compatibility with the physiologic environment. Famotidine, a potent H2-receoter antagonist was widely used in the treatment of peptic ulcer in a dose of 20 mg b.i.d associated with adverse effects like diarrhoea, dizziness, headache and anorexia etc. The plasma half life of drug was 2.5-3 hr as reported in literature, which may exhibits toxic effect in prolong use5. Hence an attempt was made in this current study to investigate the ability of bhara gum in form of microcapsule for sustained delivery of famotidine.



Table 1. Evaluation parameters of various microcapsules.








Particle size (µm) (X±SEM)







Circularity factor (X±SEM)







Yield (%) (X±SEM)







Drug entrapment efficiency (%) (X±SEM)







Loose surface crystal study (% of total drug) (X±SEM)







Swelling index (%)







Wall thickness (µm)







All values are expressed in mean ± standard error mean. Significant at 95% confidential interval (p<0.001). F1: Famotidine: bhara (1:2); F2: Famotidine: bhara (1:4);  F3: Famotidine: bhara (1:6);  F4: Famotidine: guar gum (1:2);  F5: Famotidine: guar gum (1:4); F6: Famotidine: guar gum (1:6)




Bhara gum was collected from Ganjam (Orissa) in the month of October. The plant was authenticated by Regional Research Laboratory (RRL), Bhubaneswar, Orissa. Famotidine was received as a gift sample from Nicholas Piramol India limited, Mumbai. All other chemical and reagents used in this study were of analytical grade and procured from authorized dealer. One way analysis of variance (ANOVA)  was adopted to find out the significance of in vitro drug release data at 5 % level of significance (p<0.05). 


Figure 1. Particle size analysis of various formulations


Purification of natural gum 6 :

The gum collected from the plant was soaked with distilled water and shaken for 4-5 hr. The viscous solution obtained was passed through muslin. The mucilage was precipitated out by addition of 95% ethanol in the ratio 1:1 with continuous stirring. The coagulated mucilage which formed as a white mass floating on ethanol was transferred to an evaporating disc and treated successively with ethanol. The coagulated mass was dried in oven at 40-50 °C powdered by passing through sieve and stored in air tight containers    (yield =23.87 % w/w).


Preparation of microcapsules 7 :

Famotidine loaded microcapsule were prepared by ionic gelation method. Briefly 200 mg of sodium alginate, 200mg of gum Bhara and 100 mg of drug were dispersed


in 10ml water with a constant stirring at 300 rpm for 30 min. The resultant dispersion was added drop wise through a syringe (17 gages) into the Cacl2 solution (10 % w/ v). The so formed microcapsules (1:2 w/ w ratio) were kept for 30 min for complete reaction and afterwards, microcapsule were recovered by filtration through a sintered glass filter, under vacuum, dried in hot air oven at 60° for 1 hr. The other drug: polymer ratios (1:4 and 1:6 w/w) were prepared and the same method was adopted for preparation of guar gum microcapsules in ratios (1:2. 1:4 and 1:6 w/ w) keeping all the parameters constant


Table 2. In vitro drug release profile of famotidine microcapsule formulations

Time (hr)







































































F                       3.990

df                       5, 48

p                      < 0.05

Datas are expressed in percent cumulative drug release Significant at 5 % level of significance (p<0.05)

F1: Famotidine: bhara (1:2); F2: Famotidine: bhara (1:4);  F3: Famotidine: bhara (1:6);  F4: Famotidine: guar gum (1:2);  F5: Famotidine: guar gum (1:4); F6: Famotidine: guar gum (1:6)


Percentage Yield and Drug entrapment efficiency (DEE) 8 :

The microcapsules were evaluated for percentage yield and percent drug entrapment. The yield was calculated as per the equation 1,


Percentage yield = [Weight of microcapsule recovered] x 100/ [Weight (drug + polymer)]   ………….(1)


Drug loaded microcapsules (100 mg) were powdered and suspended in 100 ml water solvent system. The resultant dispersion was kept for 30 min for complete mixing with continuous agitation and filtered through a 0.45 µm membrane filter. The drug content was determined

Table 3. Correlation coefficients values in various kinetic models tested to describe drug release from the microcapsules.

 Kinetic Models

Correlation coefficient ( r)

F1 (X±SD)

F2 (X±SD)

F3 ±SD)

F4 ±SD)

F5 ±SD)


Zero order

0.6125 ±0.024

0.6892 ±0.034

0.7215 ±0.031

0.9677 ±0.025

0.9888 ±0.019

0.9708 ±0.011

First order

0.5001 ±0.051

0.4176 ±0.028

0.4129 ±0.034

0.4337 ±0.037

0.5160 ±0.029

0.5571 ±0.033

Higuchi square root

0.8983 ±0.017

0.9662 ±0.018

0.9523 ±0.017

0.9532 ±0.025

0.9464 ±0.019

0.9843 ±0.018

Korsmeyer-Peppas equation

0.9885 ±0.016

0.9356 ±0.045

0.9914 ±0.011

0.5956 ±0.027

0.8872 ±0.021

0.9142 ±0.024

Diffusion release exponent(n)









spectrophotometrically (UV-Visible-1700, Shimadzu, Japan spectrophotometer) at 265 nm using a regression equation derived from the standard graph (r2 = 0.9978).

The drug entrapment efficiency (DEE) was calculated by the equation 2,

DEE = (Pc / Tc) X 100          ….. (2)


Where, Pc is practical content, Tc is the theoretical content. All the formulations were analyzed in triplicate (n=3).


Particle size measurement 8 :

The size of the prepared microcapsules was measured by the optical microscopy method using a calibrated stage micrometer. Particle size was calculated by using equation 3,

Xg = 10 x [(ni x log Xi) / N]   …….. (3)


Where, Xg is geometric mean diameter, ni is number of particle in range, Xi is the mid point of range and N is the total number of particles. All the experimental units were analyzed in triplicate (n=3).


Determination of sphericity 9 :

The particle shape was measure by computing circulatory factor (S). The tracing obtained from optical microscopy were used to calculate Area (A) and perimeter (P).

This will indicate the approximate shape of the prepared microcapsule calculated by the equation 4,

S = P2/ 12.56 × A               ………… (4)


Loose surface crystals study 10 :

The Famotidine encapsulated Bhara gum microcapsules prepared were evaluated by loose surface crystal study to observe the excess drug present on the surface of microcapsules. From each batch, 100 mg of microcapsule was shaken in 20 ml of 0.1N Hcl for 5 minute and then filtered through whatman filter paper 41. The amount of drug present in filtrate was determined spectroscopically and calculated as a percentage of total drug content. 


Determination of wall thickness 12 :

Wall thickness of microcapsules was determined by method of Luu et al using equation 6,

h = [r (1-P) d1/3{Pd2+ (1-P) d1}] × 100          .. (6)


Where, h= wall thickness, r = arithmetic mean radius of microcapsules, d1 and d2 are densities of core and coat material respectively, P is the proportion of medicament in microcapsules



In vitro drug release 13 :

In vitro drug release study was carried out in USP type-II dissolution test apparatus. Microcapsules were placed in basket of dissolution vessel containing 900 ml of 0.1N Hcl maintained at 37±1° and stirred at 50 rpm.  Aliquots of samples (5 ml) at an interval of 1 hr were withdrawn and filtered through a whatman filter paper. The samples were analyzed for famotidine content by UV-Visible spectrophotometer at 265 nm .All the experimental units were analyzed in triplicate (n=3).


In vitro drug release kinetic studies:

Kinetic model had described drug dissolution from solid dosage form where the dissolved amount of drug is a function of test time. In order to study the exact mechanism of drug release from the microsphere, drug release data was analyzed according to zero order14, first order15, Higuchi square root16, Korsmeyer- Peppas model17.The criteria for selecting the most appropriate model was chosen on the basis of goodness of fit test.


Statistical Analysis 18 :

Statistical data analyses were performed using the one way ANOVA at 5 % level of significance (p < 0.05 )  and standard error mean (SEM) at 95 % confidence interval.



The famotidine loaded Bhara gum and guar gum microcapsules were prepared by ionic gelation technique described in text. The results, shown in Table 1, demonstrated that the microcapsules obtained under these conditions were found to be spherical and without aggregation and mean geometric particle size was found in a range of 71.57 to 94.75 µm. The particle size distribution of all the formulation was presented in Figure 1. The percentage yield of all the formulations was found to be satisfactory and each formulation demonstrated high drug entrapment efficiency (DEE), as summarized in Table 1. The formulation F4 showed higher DEE among all the formulations. The microcapsules were seems to be spherical as the circularity factor calculated very close to 1.00 and the loose surface crystal study showed a satisfactory amount of drug present on the surface of microcapsule shown in Table 1. The swelling percent of all the formulation was found in a range of  80.23 to 91.53 % and  wall thickness of all the formulations was found in range of 13.01 to 38.69 µm represented in Table 1. The in vitro drug release profiles for all the batches were shown in Table 2. All the identify formulations showed constant release profile. The in vitro drug release profile was graphically presented in Figure 2. To recognize the kinetics of drug release from microcapsules, release data was analyzed according to different kinetic models. Table3 designates that drug release from F4 and F5 formulations obey zero order kinetics, while the release data of F2, F5 seems to fit best in Higuchi square roots model and F1, F2 release drug following Korsmeyer- Peppas model. The release mechanism was predominately diffusion controlled for all formulations. Statistical verification with one way ANOVA method certified the fact that the drug release data were found to be significant for F value (3.990) at 5 % level of significance  (P< 0.05).


Figure 2. Drug release profile of various prepared microcapsules

F1: Famotidine: Bhara (1:2)   F4: Famotidine: Guar gum (1:2)

F2: Famotidine: Bhara (1:4)    F5: Famotidine: Guar gum (1:4)

F3: Famotidine: Bhara (1:6)    F6: Famotidine: Guar gum (1:6)



Gum obtained from Terminalia bellerica after purification was found as amorphous free flowing powder with a yellowish brown color. It exhibited good solubility in water and gave viscous solution on standing. Significant differences in particle size were found for the prepared microcapsules. The Variations in particle size increases with respect to gum concentration for both the gum formulations. As regards the effect of gum concentration, drug entrapment efficiency was decreased at higher gum concentration. The efficiency of release of famotidine from prepared microcapsules was the key factor in the successful optimization of a formulation. The present study demonstrated that F1, among all other formulations, have a significantly slower release pattern in terms of their total drug load. Several kinetic models describe drug release from the microcapsules represented in Table 3. The formulation F2 and F5 was followed Higuchi square root kinetic model indicating the diffusion controlled drug release. The drug release of bhara gum microcapsules (F1,F2 and F3) were by Fickian mechanism as the diffusion coefficient (n) was found equal or less than 0.5 and guar gum microcapsules (F4, F5, and F6) showed  non fickian diffusion mechanism (0.5<n<1). With a comparison between the corresponding ratios (1:2, 1:4 and 1:6 w/w) of two gums, Gum Bhara was found more effective than guar gum at low concentration (1:2 w/w) in sustaining the drug release rate. In context to the intense world wide research for natural polymer, it can be envisaged that future workers would indulge in optimization of the various formulations of the investigating polymer to promote its commercial scale up, for effective management of peptic ulcer.



Authors wish to thank Nicholas Piramol India limited, for providing gift sample of Famotidine. We are also thankful to the staff of regional research laboratory (RRL), Bhubaneswar, orissa for their relentless cooperation.



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Received on 22.08.2008       Modified on 10.09.2008

Accepted on 12.10.2008      © RJPT All right reserved

Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008;Page 433-436