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Prasanta Kumar Choudhury, et al. / International Journal of Advances in Pharmaceutical Research 

IJAPR 

Available Online through 

www.ijapronline.org 

Research Paper 

ISSN: 2230 – 7583 

DEVELOPMENT OF ACRYCOAT-L100 COATED CALCIUM-ALGINATE 

MICROSPHERES FOR COLON SPECIFIC DELIVERY OF ORNIDAZOLE 

Prasanta Kumar Choudhury* 1 , Padala Narasimha Murthy 1 , Niraj Kanti Tripathy 2 

1 Department of Pharmaceutics, Royal College of Pharmacy and Health Sciences, Berhampur-760002, Odisha, India 

2 Department of Zoology, Brahmapur University, Bhanja Bihar, Berhampur-760007, Odisha, India 

Received on 25 – 01 - 2012 Revised on 23 – 03- 2012 Accepted on 27– 04 – 2012 

ABSTRACT 

In the present investigation, pH-dependent and controlled drug release microspheres of Ornidazole were developed 

to deliver the active molecule to the colonic region. Microspheres were prepared by Emulsification-Ionic gelation 

technique with some modifications, using different proportions of Ornidazole and sodium alginate. Calciumalginate 

microspheres so formed were further coated with Acrycoat L100 to achieve pH sensitive properties and 

specific biodegradability for colon targeted delivery of Ornidazole. Microspheres were evaluated for size, 

morphology, sphericity study, % yield, loose surface crystal study, drug content and entrapment efficiency. In vitro 

drug release study was conducted by buffer change method to mimic GIT environment using buffer solutions of 

varying pH. The investigations revealed that microspheres prepared with Ornidazole: Sodium alginate ratio (1:1) 

found to be optimized with in vitro drug release of 46.243 ±3.30 %, hence further coated with Acrycoat L100, 

which shows only 18.361±1.59% drug was released in first 5 hours and 62.400±3.28% in 12 hours, which proves 

the potentiality of Acrycoat L100 for colonic delivery of drugs. 

Key Words: colon specific drug delivery, Emulsification-Ionic gelation technique, Ornidazole, sodium alginate, 

Acrycoat L100, pH-dependent in vitro drug release 

INTRODUCTION 

The Colonic Drug Delivery Systems have recently 

gained importance for delivering a variety of drugs. 

Colonic drug delivery may be achieved by either oral 

or rectal administration. 

For correspondence 

*Prasanta Kumar Choudhury 

Lecturer, Department of Pharmaceutics 

Royal College of Pharmacy and Health Sciences 

Andhapasara Road, Brahmapur, Ganjam 

Odisha, India, Pin-760002 

Email: prasant_pharma@yahoo.com 

Mobile: +919437261737 

Phone: 06802260024 

Fax: 06802260025 

Rectal administrations of drugs for colon targeting 

always face high variability in the distribution of 

drug, when they are administered in form of dosage 

forms like enemas and suppositories, which are not 

always effective. Therefore, the oral route is the 

most preferred. Conventional oral formulations 

dissolve in the stomach or intestine and are absorbed 

from these regions. The major obstacle with the 

delivery of drugs by oral route to the colon is the 

absorption and degradation of the drug in the upper 

part of the gastrointestinal tract (GIT) which must be 

overcome for successful colonic drug delivery 1 . 

In conditions were localized delivery of the drugs is 

required in the colon or drugs which are prone to 

degradation in the environment of the upper GIT, 

colonic drug delivery may be valuable. Drug release 

at this site will ensure maximum therapeutic 

benefits. Oral delivery of drugs to the colon is 

valuable in the treatment of diseases of colon 

(ulcerative colitis, Crohn's disease, carcinomas and 

infections) whereby high local concentration can be 

IJAPR / May. 2012/ Vol. 3 / Issue. 5 / 914 – 921 914


achieved while minimizing side effects that occur 

because of release of drugs in the upper GIT or help 

to avoid unnecessary systemic absorption of the 

drug. Ulcerative colitis is the inflammatory disease 

of the colonic mucosa which is usually treated with 

salicylates or glucocorticoids. However, during the 

periods of remission, Ornidazole is the drug of 

choice. In this case it is desirable to localize the 

release of Ornidazole to the afflicted site in the 

colon. Thus, Ornidazole was used as a model drug in 

the present study 2 . 

Ornidazole, a 5-nitroimidazole derivative 

with anti-protozoal and anti bacterial properties 

against anaerobic bacteria was selected as a drug of 

choice to develop enteric coated microsphere 

formulation to minimize the influence of the stomach 

emptying time on drug release and to guarantee that 

the microspheres could enter the small intestine 

intact for treatment of some colonic diseases like 

ulcerative colitis, irritable bowel syndrome 2 . 

MATERIALS AND METHODS 

Materials 

Ornidazole was obtained as a gift sample from Micro 

Lab. Limited, Chennai, India, Sodium Alginate and 

light liquid paraffin procured from Loba Chemie 

Ltd, Mumbai, India. Acrycoat- L100 procured from 

Corel Pharma-Chem, Gujarat, India. Span 80 was 

procured from s.d. fine-chem Ltd., Mumbai, India. 

All other solvents and reagents were of analytical 

grade. All the other chemicals and solvents used 

were of laboratory reagent grade. 

EXPERIMENTAL METHOD 

Characterization of drug and analytical studies 

The drug was characterized for Physical appearance, 

Solubility, UV spectral analysis, IR Spectral 

analysis. 

Drug Polymer Interaction Study by FTIR 

Analysis 3 

To eliminate the possibility of polymer interfering 

with the analysis of drug, Infra-red spectrum was 

taken by using the Shimadzu, FTIR model no. 

affinity-1 by scanning the sample in potassium 

bromide (KBr) discs. Before taking the spectrum of 

the sample, a blank spectrum of air background was 

taken. The sample of pure drug, pure polymer and 

the formulations/physical mixtures containing both 

the drug and polymer were scanned. 

Preparation of Sodium- alginate microspheres 4 

The sodium alginate microspheres were prepared by 

Emulsification-Ionic gelation method. The Sodium 

alginate dissolved in distilled water to form a 

homogenous polymer aqueous solution. Then 

Ornidazole was added to the aqueous solution 

containing Sodium alginate with thorough stirring to 

form a smooth viscous dispersion. The resulting 

dispersion was then added in a thin stream to liquid 

paraffin (light) containing span 80 (1 % w/v) in a 

beaker while stirring at 1000 rpm by using a 

mechanical stirrer. The stirring was continued for 5 

minutes to emulsify the added dispersion as fine 

droplets. Calcium chloride (10% w/v) solution was 

then added slowly while stirring for ionic gelation 

(or curing) reaction. Stirring was continued for 15 

minutes to complete the curing reaction and to 

produce spherical microspheres. The mixture was 

then centrifuged and the product thus separated was 

washed repeatedly with water and dried at 60°c for 6 

hours. By using this method, microspheres of 

different drug: polymer ratio (2:1, 1:1, 1:2), were 

prepared. The microspheres prepared were coded as 

SAM. The composition of different formulations is 

mentioned in Table 1. 

Coating of Sodium-alginate microspheres 5 : 

Coating of sodium alginate microspheres containing 

ornidazole was performed using emulsion solvent 

evaporation technique. Sodium alginate 

microspheres were suspended in 15 ml of an organic 

solvent (1:1, acetone: methanol) in which Acrycoat 

L-100 was previously dissolved to give 1:5 core/coat 

ratio. This organic phase was emulsified into 100ml 

of liquid paraffin containing span 80 (1% w/v). The 

system was stirred at 1000 rpm with mechanical 

stirred for 4 hr at room temperature. The Acrycoat L 

100 coated microspheres were collected and rinsed 

with n-hexane and dried in vacuum desiccator for 48 

hr. 

Evaluation of Formulations 

Particle Size Analysis 6 

Particle size distribution of the 

microspheres was determined by optical microscopy 

using calibrated ocular eyepiece. Fifty microspheres 

were evaluated and the experiment was performed. 

Geometric mean diameter was then calculated using 

the equation: 

X g = 10 X [(n i X log X i ) / N] ----------------------------- 

- (Equation 1) 

Where Xg is geometric mean diameter, n i is no of 

particles in the range, X i is the mid point of range, N 

is total no of particles analyzed. 

6.5.2. Determination of Shape and Sphericity 7 

Morphological appearance and surface 

characteristics of the microspheres were studied by 

dispersing the microspheres in liquid paraffin and 

observed under 250X magnification using an optical 

microscope. 



The particle shape was measured by computing 

circularity factor (S) 8 . The tracing obtained from 

optical microscopy were used to calculate area (A) 

and perimeter (P), which are used to calculate the 

circularity factor (S) by using the equation: 

S = P 2 / (12.56 X A) -------------------------------- 

(Equation 2) 

6.5.3. Measurement of the Yield of the Microencapsulation 

Process 9 : 

The weight of the obtained microspheres after drying 

was divided by to the total of polymers and drug 

used. Calculation was done as per the equation 

mentioned below 

Yield of micro encapsulation (%) = 

Produced microspheres (mg)/ Drug (mg) + 

Polymer (mg) X 100--------------- (Equation 3) 

6.5.4. Determination of drug content 10 

The drug content in Sodium alginate microspheres 

was determined by taking accurately weighed 100mg 

of microspheres in a glass mortar and powdered by a 

glass pastel and treated with 100ml of Phosphate 

buffer of pH 7.4 in a closed volumetric flask and left 

over night. Then it was transferred into a 250ml 

beaker and stirred by magnetic stirrer using Teflon 

coated magnetic bead, the temperature was 

maintained at 37ºC. At the end of 1 hour, it was 

centrifuged and supernatant was filtered, the filtrate 

was analyzed spectrophotometrically at 319nm (UV 

1700, Shimadzu, Japan). Dilution was done 

whenever required using Phosphate buffer pH 7.4. 

6.5.5. Drug Entrapment efficiency (DEE %) 9 

Entrapment efficiency of the microspheres was 

calculated using the formula 

DEE % = Practical Drug Loading/ Theoretical 

Drug Loading X 100 

6.5.6. Loose surface crystal study 11 

Loose surface crystal study was done to observe the 

excess drug present on the surface of microspheres. 

From each batch 11mg of microspheres were shaken 

in 100 ml of phosphate buffer pH 7.4 for 5 minutes 

and then filtered through whattman filter paper 41. 

The amount of drug in the filtrate was determined 

spectrophotometrically at 319 nm and calculated as a 

percent of total drug content. This estimates the 

surface entrapment of the drug by the microspheres. 

6.5.7. In Vitro Drug Release from Microspheres 12 

In vitro drug release studies were carried out using 

USP dissolution rate test apparatus (basket 

apparatus, 100 rpm, 37 ± 0.1°C) by buffer change 

technique 6 . Microspheres bearing Ornidazole were 

suspended in simulated gastric fluid (SGF), pH 1.2 

(500 ml), for 1 hr. The dissolution media was then 

replaced with mixture of simulated gastric fluid and 

simulated intestinal fluid (SIF), pH 4.5 (500 ml) for 

next two hours, then for next two hours simulated 

intestinal fluid (SIF) pH 6.8 (500 ml) and the release 

study was carried out for a further in simulated 

intestinal fluid (500 ml) pH 7.4. 

Samples were withdrawn periodically and 

compensated with an equal amount of fresh 

dissolution media. The samples were analyzed for 

drug content by measuring absorbance at 

corresponding max of the dissolution medium, 

using UV spectrophotometer (UV 1700, shimadzu, 

Japan). 

6.5.8. Drug release mechanism and kinetics 13, 14 : 

In order to establish the mechanism and kinetics of 

drug release from the microspheres, the experimental 

data obtained from the in vitro dissolution study was 

fitted with different kinetic models like zero order 

(% release vs. t), first order (log % release vs. t), 

Higuchi’s model (% release vs. √t), Korsmeyer and 

peppas model (ln Q vs. ln t)etc. 

Korsmeyer’s model is widely used; when the release 

mechanism is not well known or when more than 

one type of release phenomena could be involved. 

Korsmeyer and Peppas equation: Q = Kt n , 

Where Q is the fractional drug release in time‘t’. 

K= constant incorporating of structural and 

geometric characteristics of controlled release 

device. 

n = diffusional release exponent indicative of release 

mechanism. 

The ‘n’ value could be used to characterize different 

release mechanisms as per the description given 

below: 

n = 0.5 [Fickian Diffusion (Higuchi Matrix)] 

0.5 < n < 1 [Anomalous transport] 

n = 1 [Case II transport (Zero order release)] 

n >1 [Super case II transport] 

The best-fit model was determined statistically 

employing comparison of correlation coefficients. 

The preparation of graphs and statistical calculations 

were carried out with the help of Microsoft Excel ® 

software. 

RESULTS AND DISCUSSION 

Characterization of Drug and Analytical Study 

The model drug selected (ornidazole) was 

characterized and analyzed for its physical 

appearance and solubility, which was complies with 

the monograph as specified in Indian pharmacopoeia 

and British pharmacopoeia. UV and IR spectral 

analysis was done and the drug shows similar data as 

mentioned in different official publications. By FTIR 

analysis principle shoulders were obtained at wave 

numbers 3174 cm -1 , 1536.37 cm -1 , 1361.80 cm -1 , 

1268.25 cm -1 , 1150.59 cm -1 , 828.46 cm -1 these are 



almost same as reported in the monograph for 

ornidazole. 

Drug Polymer Interaction Study 

Drug-polymer interaction study by FTIR for pure 

drug, pure polymer and the formulations containing 

the respective polymers showed that there is no 

shifting of the principle shoulders the drug with the 

use of the polymers incorporated into the 

formulations. Hence this confirms that there is no 

such chemical interaction between the drug and the 

polymers (Figures 1 and 2). 

Formulation design and preparation of 

Microspheres 

Microspheres of sodium alginate loaded with 

Ornidazole (ONZ) were successfully prepared by the 

emulsification-ionic gelation techniques using light 

liquid paraffin in the external phase. The effect of 

drug polymer ratios was analyzed in order to 

optimize the formulation. It was observed that by 

changing drug: polymer ratio the shape, size as well 

as the entrapment efficiency of formulations 

considerably influenced. The microspheres were 

discrete and fairly spherical in shape while the 

surface roughness was slightly increased with the 

incorporation of the drug. 

Particle Size Analysis 

The mean diameter of dried microspheres was 

determined by optical microscopy. The optical 

microscope was fitted with a stage micrometer by 

which the size of microspheres could be determined. 

The mean diameter of all the microsphere 

formulations containing different ratios of drug: 

polymer amounts are shown in Table 2. Particle size 

of microspheres was found to be in the range of 

31.56±3.92 µm to 39.02±3.90 µm. It suggests that 

the size of the microspheres increased as the amount 

of polymer incorporated into the formulations was 

increased. 

The size of the microspheres is controlled by the size 

of the dispersed polymeric droplets in oil phase. 

When the concentration of the polymer in the 

formulation was increased, there was increment in 

the size of dispersed droplets that resulted in the 

formation of microspheres having bigger particle 

size. The increase in the particle size was remarkable 

after coating the sodium alginate microspheres with 

Acrycoat L100 (Table 3). 

Determination of Shape and Sphericity 

All the microsphere formulations have the circularity 

factor nearest to “1” which proves that they are 

almost spherical in shape (Table 2). But the surface 

roughness was observed with incorporation of drug 

and due to entanglement of the microspheres with 

each other. 

Yield (%) of the Microspheres production 

The yield (%) of the microsphere formulations was 

found to be increased with increase in the polymer 

amount in the formulations, which signifies the less 

product loss during preparation of the microspheres. 

Percentage drug loading and encapsulation 

efficiency 

In Sodium alginate microsphere formulations with 

increase in drug : polymer ratio from 2:1 to 1:1 

entrapment efficiency was increased (i.e. 

74.307±3.27 (SAM1) to 80.75±5.58 (SAM2) but it 

was decreased when the polymer amount was 

increased to 1: 2 ratio (Table 2). 

Loose surface crystal study 

The loose surface crystal study was done to estimate 

the amount of drug present in the surface of the 

microsphere formulations. As the drug : polymer 

ratio was increased the surface entrapment of the 

drug on the microsphere surfaces was decreased 

which is suitable for the colonic delivery of the drugs 

and the surface entrapment of drug shows a less 

amount of drug lose due to the process variables. 

Highest surface entrapment was observed SAM1 

(21.385 ± 1.02 %) (Table 2) 

In vitro drug release study 

The microsphere formulations were subjected to in 

vitro drug release rate studies in SGF (pH 1.2) for 1 

hr and in mixture of SGF and SIF (pH 4.5) for next 2 

hrs in order to investigate the capability of the 

formulation to withstand the physiological 

environment of the stomach and small intestine. The 

amount of drug released from the microspheres after 

12 h studies is shows that the amount of Ornidazole 

released during first 5 h studies was found to be 

55.597 ± 3.13 %, 46.243 ± 3.30 %, and 44.205 ± 

4.73 % for SAM1, SAM2, and SAM3 respectively 

(Figure 4) which is not suitable for the drugs which 

are intended for the colonic delivery. Hence needs to 

be protected by an extra coating formulation which 

was done by applying Acrycoat L 100 coat around 

the sodium alginate microsphere formulations. After 

coating with Arycoat L 100 (core coat: ratio-1: 5) the 

percent drug release was decreased remarkably in the 

initial 5 hours of the dissolution study which proves 

that Acrycoat L 100 can withstand the upper GI 

environment and can release the drug at the targeted 

site, the colon. 

The release of the drug was much faster during the 

6-12 hour study period. It is due to the fact that 

during the initial period (0-5 h) the strength of the 

barrier was too high to be broken and during 6-12 

hour period the network was somewhat loosened 

which facilitated the release of drug. 



Drug release mechanism 

The experimental data was fitted to different kinetic 

models like zero-order, first-order etc in order to 

establish the release pattern of the drug from the 

microspheres. The experimental data was also fitted 

to Higuchi’s model and Korsmeyer’s model to 

ascertain the mechanism of drug release from the 

microsphere formulations. 

The correlation coefficient of the slopes of these 

matrices showed an adequate fit to the zero-order 

kinetics (Table 4). All the formulations followed 

Higuchi’s equation proving that the release is by 

diffusion mechanism. The ‘n’ values obtained for 

uncoated sodium alginate microsphere formulations 

after fitting into Korsmeyer and Peppas equation are 

closely approximate with n =0.5, indicating Fickian 

diffusion (Table 4). 

CONCLUSION 

The sodium alginate microspheres prepared by 

emulsification-ionic gelation method showed higher 

in vitro drug release in the SGF (pH 1.2) and in 

mixture of SGF and SIF (pH 4.5); hence these were 

coated with Acrycoat L100 for colonic delivery. The 

in vitro drug release data of coated microspheres 

attests the potentiality of Acrycoat L100 coated 

alginate microspheres for colon-specific delivery of 

the drugs. Hence this formulation approach can be 

further exploited for colon specific delivery of other 

model drugs. 

Figure 1: FTIR Spectra of (A) Formulation containing sodium alginate and ornidazole, (B) Pure Sodium 

alginate, (C) Pure Ornidazole 

Figure 2: FTIR Spectra of (A) Pure Acrycoat L100, (B) Acrycoat L100 and ornidazole, (C) Acrycoat L100 

and Sodium alginate 



Batch 

code 

Batch code 

Table 1: Formulation Composition of Sodium Alginate Microspheres 

Quantity of 

Amount of Amount of Drug: 

distilled water 

drug (mg) polymer(mg) polymer ratio 

(ml) 


Cacl 2 

solution(ml) 


liquid 

paraffin(ml) 

SAM1 1000 500 2:1 30 40 150 

SAM2 1000 1000 1:1 30 40 150 

SAM3 1000 2000 1:2 30 40 150 

Drug : 

polymer 

ratio 

Table 2: Evaluation Parameters of uncoated Sodium Alginate Microspheres. 

Yield of 

production % 

Particle 

size(µm) 

Circularity 

Factor (S) 

Values are expressed as Mean average ± SD (n=3) 

Drug loading 

(mg)/100mg or 

Entrapment 

Efficiency % 

Loose surface 

crystal study 

(Surface 

Entrapment %) 

SAM1 2:1 98.52 ± 3.35 31.56±3.92 1.07 ± 0.015 74.307±3.27 21.385 ± 1.02 

SAM2 1:1 91.81 ± 2.17 37.42± 3.37 1.06 ± 0.012 80.759±5.58 19.343 ± 1.06 

SAM3 1:2 95.46 ± 3.36 39.02±3.90 1.02 ± 0.020 78.481±2.25 20.518 ± 1.22 

Table 3: Average particle size, Entrapment efficiency, and circularity factor of Acrylcoat L100 coated 

Sodium Alginate Microspheres. 

Batch code Drug : polymer ratio Particle size(µm) Circularity Factor (S) 

CSAM1 2:1 64.98±3.46 1.02 ± 0.045 

CSAM2 1:1 79.24±3.84 1.11 ± 0.025 

CSAM3 1:2 81.86±2.81 1.06 ± 0.047 

Values are expressed as Mean average ± SD (n=3) 

(A) 

Figure 3: Photomicrograph of Sodium alginate microspheres (at 100X), (A) Dried Sodium alginate 

microspheres, (B) Sodium alginate microspheres suspended in liquid paraffin 

(B) 


%Cumulative drug release 

% Cumulative drug 

release 


100 

80 

60 

40 

20 

0 

0 1 2 3 4 5 6 7 8 9 10 11 12 

Time (hrs) 

SAM1 SAM2 SAM3 

Figure 4: Percentage Cumulative drug release of uncoated Sodium Alginate microspheres. 

80 

70 

60 

50 

40 

30 

20 

10 

0 

-10 

0 1 2 3 4 5 6 7 8 9 10 11 12 

Time (hrs) 

CSAM1 CSAM2 CSAM3 

Figure 5: Percentage Cumulative drug release of Acrycoat L100 Coated Sodium Alginate microspheres. 

Table 4: In vitro Dissolution kinetics for microsphere formulations 

Zero – Order First – Order 

Formulation code 

(R 2 ) 

(R 2 Higuchi (R 2 Korsmeyer’s Korsmeyer’s 

) 

) 

Plot (R 2 ) exponent “n” 

SAM1 0.9055 0.9210 0.9915 0.9777 0.3709 

SAM2 0.9578 0.9405 0.9586 0.9586 0.4238 

SAM3 0.9506 0.9021 0.9878 0.9849 0.4696 

CSAM1 0.9694 0.8054 0.9205 0.9892 1.7698 

CSAM2 0.9826 0.7327 0.9198 0.9666 2.3437 

CSAM3 0.9783 0.7216 0.9002 0.7735 2.0252 

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