Formulation and Development of Extended Release Floating Tablet ...

International Journal of Recent Advances in Pharmaceutical Research July 2011; 3: 25-30 

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Abstract 

Formulation and Development of Extended Release Floating 

Tablet of Atenolol 

* RANGASAMY MANIVANNAN, VIVEK CHAKOLE 

Department of Pharmaceutics, JKKMMRF’s – Annai JKK Sampooraniammal College of Pharmacy, 

B.Komarapalayam, Namakkal, Tamilnadu, India. 

The purpose of this research was to prepare gastro retentive drug delivery system of Atenolol by wet granulation method. 

Ten formulations (F1-F10) of Atenolol tablets were prepared by using various grades of Hydroxylpropylmethyl cellulose 

i.e., HPMC K4M, HPMC K15M, HPMC K100M. Sodium bicarbonate and citric acid was incorporated as a gas generating 

agents. Atenolol floating matrix tablets were evaluated in terms of their physico-chemical parameter like weight 

variation, friability, hardness, drug content, floating lag time, total floating time and specific gravity. The results of in vitro 

drug release studies showed that the optimized formulation (F8) could extend drug release (99.5%) for 24 hours. The 

release pattern of atenolol was fitted to different models based on coefficient of correlation (r). Formulations F2, F4, F6 

and F8 and showed zero order model as the best fit model. The swelling studies showed formulation (F8) containing 

HPMC K4M has higher swelling indices than HPMC K100M and HPMC K15M. The present study concluded that floating 

tablets of Atenolol can be good way swelling and good improve the bioavailability of Atenolol. 

Keywords: Atenolol, HPMC K4M, Gastro retentive systems. 

1.0. INTRODUCTION 

Floating drug delivery systems were first described 

by Davis in 1968 [1, 2]. It is possible to prolong the 

gastric residence time of drugs using these systems. 

Several techniques are used to design gastro 

retentive dosage forms. These include floating, 

swelling, inflation, adhesion, high-density systems 

and low density systems that increase the gastric 

residence time [3-5]. Gastric retention is useful for 

drugs which (i) act locally; (ii) have a narrow 

absorption window in the small intestinal region; 

(iii) unstable in the intestinal environment; (iv) low 

solubility at high pH environment [6]. Various 

dosage forms developed for gastric retention 

include, floating tablets, [7] floating beads, [8] 

pellets, [9] floating granules, [10] floating 

microspheres [11]. In this investigation, an attempt 

was made to formulate floating tablets of atenolol- 

___________________________________________________________ 

*Correspondence 

Rangasamy Manivannan 

Professor 

Department of Pharmaceutics, 

JKKMMRF’s – Annai JKK Sampooraniammal College of 

Pharmacy, 

B.Komarapalayam, Namakkal (Dist), 

Tamilnadu, India. 638183. 

Email: manivannan_biotech@yahoo.co.in 

-using different release retarding polymers along 

with a gas-generating agent. 

Atenolol is β-1 cardio selective adrenergic 

receptor blocker, widely used in the treatment of 

hypertension. The drug is insoluble in water and 

has half-life of 6-8 hours with oral bioavailability of 

50% due to smaller dose of drug (less than 50 mg). 

[12-14]. In this study, an attempt was made to 

design and formulate the floating matrix tablets of 

atenolol so as to increase its gastric retention 

thereby ensuring slower and complete release of 

atenolol. Also, attempts were made to assess the 

effect of hydroxylpropylmethyl cellulose (HPMC) 

K4M and K100M on the release rate of drug. Sodium 

bicarbonate and citric acid was used as a gas 

generating agent. 

2.0. MATERIALS AND METHODS 

2.1. Materials 

Atenolol was obtained as a gift sample from Kopran 

India Ltd. Various grades of Hydroxylpropylmethyl 

cellulose (HPMC) K4M was obtained from Colorcon 

Asia Ltd, GOA. PVP K30, Starch, Lactose, Sodium 

Bicarbonate, Citric Acid, Mg. Stearate were obtained 

as gift samples from Loba Chemical (Mumbai, 

India). 

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Manivannan et al, 

Extended Release Floating Tablets: Atenolol 

ISSN: 2230-9306 Available online at www.ijrapronline.com 

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2.2. Methods 

2.2.1 Preparation of floating tablet 

Atenolol was mixed with required quantity of 

polymer (HPMC K100M, HPMC K15M and HPMC 

K4M), sodium bicarbonate and lactose in mortar for 

5 min by using a spatula. Isopropyl alcohol was 

added drop wise till suitable mass for granulation 

was obtained. The wet mass was granulated 

through sieve 40#. The granules were dried at room 

temperature (35°C) for 1 h, and then blended with 

talc and magnesium stearate in the weight 

proportion as mentioned in [Table 1] and 

compressed on 10-station rotary tablet 

compression machine (Rimek, Kadi, India) using a 

6-mm standard concave die punch set. 

2.2.2 Floating capacity 

Floating characteristics of the prepared 

formulations were determined by using USP 2 

paddle apparatus at a paddle speed of 50 rpm in 

900 ml of a 0.1 N HCl solution (pH=1.2) at 37±0.5°C 

for 24 h. The time between the introduction of 

tablet and its buoyancy on the simulated gastric 

fluid (floating lag time) and the time during which 

the dosage form remain buoyant (floating duration) 

were measured. 

2.2.3 Drug content 

Twenty tablets from each batch were weighed and 

powdered. Powder equivalent to 125 mg of atenolol 

was accurately weighed and transferred into a - 

100 ml volumetric flask and dissolved in a suitable 

quantity of 0.1 N HCl. Five milliliters of the resulting 

solution was diluted to 100 ml with 0.1 N HCl to get 

a concentration in the range of 25 µg/ml. A portion 

of the sample was filtered through membrane filter 

and analyzed by Shimadzu UV-1700 UV/Vis doublebeam 

spectrophotometer (Kyoto, Japan) at 224 nm. 

2.2.4 In vitro dissolution studies 

The release rate of atenolol from floating tablets 

(n=3) was determined as per British 

Pharmacopoeia (BP) using dissolution Testing 

Apparatus 2 (paddle method). The dissolution test 

was performed using 900 ml of 0.1N HCl, at 

37±0.5°C and 50 rpm. A sample (5 ml) of the 

solution was withdrawn from the dissolution 

apparatus hourly for 24 h, and the samples were 

replaced with fresh dissolution medium. The 

samples were filtered through membrane filter and 

diluted to a suitable concentration with 0.1N HCl. 

Absorbance of these solutions was measured at 224 

nm using a Shimadzu UV-1700 UV/Vis double-beam 

spectrophotometer (Kyoto, Japan). Duration of time 

the tablets constantly float on dissolution medium 

was noted as total floating time. 

2.2.5 Physical characterization 

The fabricated tablets were characterized for its 

weight variation (n=20), hardness (n=6) by using 

Monsanto hardness tester, and % friability (n=20) 

by using Roche friabilator, Electrolab, Mumbai, 

India). 

Table 1: Composition of Atenolol Floating Matrix Tablet 

Batch 

Code 

Atenolol 

HPMC 

K100M 

HPMC 

K15M 

HPMC 

K4M 

NaHCO3 

Citric 

acid 

Lactose 

PVP 

k30 

Mg. 

stearate 

(1%) 

Talc 

(1%) 

F1 25 12.5 12.5 6.25 37.5 6.25 1 2 

F2 25 12.5 12.5 6.25 37.5 6.25 1 2 

F3 25 25 12.5 6.25 25 6.25 1 2 

F4 25 25 12.5 6.25 25 6.25 1 2 

F5 25 25 18.75 25 6.25 1 2 

F6 25 37.5 12.5 6.25 25 6.25 1 2 

F7 25 37.5 12.5 6.25 25 6.25 1 2 

F8 25 37.5 12.5 6.25 25 6.25 1 2 

F9 25 50 12.5 6.25 25 6.25 1 2 

F10 25 50 12.5 6.25 25 6.25 1 2 

* Quantities are in milligrams 

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ISSN: 2230-9306 

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2.2.6 Stability study 

Stability studies were carried out by ICH guidelines. 

All formulations were sealed in aluminum 

packaging coated inside with polyethylene. 

Samples were kept in humidity chamber at room 

temperature, refrigerator, 40°C/ 75% RH. Stability 

studies it was concluded that the tablets batch F 8 

were stable for period of 3 month. There was not 

observed any significant change in dissolution 

profile of tablet over period of study. 

2.2.7 DSC studies 

Differential scanning calorimeter (DSC) studies 

were performed to characterize formulation for 

excipients compatibility. Thermo grams were 

obtained for pure Atenolol and HPMC K 4M. Tablets 

of F8 were stored in an oven at 50 o C for 6 weeks 

and at end of this period thermo grams were taken. 

3.0 RESULTS AND DISCUSSION 

3.1 Floating capacity: 

Results of floating properties (Table 2) study reveal 

that all batches had good floating capability. This 

might be due to the presence of gas generating 

agent, i.e., sodium bicarbonate and citric acid. 

Incorporation of sodium bicarbonate helps to 

improve floating property by reacting with gastric 

fluid, when dosage form comes in contact and 

produce carbon dioxide gas which entrapped inside 

the hydrophilic matrices leads to increase in volume 

of dosage form resulting in lowering of density and 

dosage form starts to float. 

Table 2: Evaluation of physical parameters 

Parameters 

Batch 

Code 

Hardness 

(Kg / sq. 

cm.) 

Friability 

(%) 

Average 

Weight 

(mg) 

Drug 

Content 

(%) 

Volume 

(cc) 

Specific 

Gravity 

(gm/cc) 

Floating 

Lag Time 

(sec.) 

Total Floating 

Time (hrs.) 

F1 5 0.57 

103 ± 

1.92 

97.12 ± 

0.91 

0.0994 1.03 30 ± 5 < 5 

F2 6 0.4 

106 ± 

1.58 

99.13± 

0.84 

0.0994 1.04 95 ± 5 < 5 

F3 4.5 0.57 

103 ± 

2.70 

98.60 ± 

0.65 

0.1094 0.88 23 ± 9 > 24 

F4 4.5 0.86 

100 ± 

0.70 

99.62 ± 

1.21 

0.1094 1.04 12 ± 3 > 24 

F5 6 0.48 

102 ± 

1.48 

99.60 ± 

0.54 

0. 0994 1.04 128 ± 6 > 24 

F6 4 0.84 

114 ± 

2.06 

101.23 ± 

0.87 

0.1094 0.90 60 ± 11 > 24 

F7 5 0.32 

119 ± 

4.08 

100.03 

±0.57 

0.1227 1.11 103 ± 10 > 24 

F8 6 0.36 

111 ± 

1.09 

99.68 ± 

0.99 

0.0981 0.98 44 ± 8 > 24 

F9 6 0.16 

119 ± 

2.86 

97.13 ± 

0.93 

0.1094 0.98 83 ± 6 > 24 

F10 6 0.2 

120 ± 

0.44 

102.02 ± 

1.56 

0.1094 0.95 276 ± 4 > 24 

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All formulations except F1 – F2 were showed 

floating time of more than 24 hrs. The probable 

reason behind shorten total floating time of F1 – F2, 

might be the low concentration of polymers. It was 

also observed that as the total concentration of the 

polymers increases in final formulation, floating lag 

time increases. 

3.2 Drug content 

Atenolol (97%-102%) contents were found to be 

within the accept range. Additives in formulations 

did not have any effect on drug content (Table 2). 

3.3 In vitro dissolution studies 

In vitro release study, it was observed that the 

formulation F1 – F2 (1:0.5 ratio) showed faster dug 

release, i.e., 96.07%, 101.6% respectively in 2- 7 hr. 

This faster release was due to less polymer 

concentration. Formulations contain drug and 

polymer in ratio of 1:1(F 3-F 5) (Figure 1) showed 

drug release from 57.82%, 77.66%, 95.53% over a 

period of 24 hr. while the formulation (F5) contain 

drug and polymer in ratio of 1:1 without citric acid 

(increased concentration of sodium bicarbonate) 

showed less drug release, i.e., 57.82% over a period 

of 24 hr. This is due to fact that there is no 

generation of gas in absences of citric acid. But as 

the concentration of polymer increases in 

formulation F 6-F 8 (Figure 2), tablet showed batter 

drug release from 97.78%, 71.31%, and 99.53% 

over a period of 24 hr and maintain the matrix 

integrity up to 24 hrs. The formulation F8 showed 

highest % cumulative drug release, i.e., 99.5% 

which might be due to presence of low viscosity 

HPMC K4 M at appropriate proportion (drug : 

polymer as1:1.5). The in vitro performance of 

floating formulations has been reported to be 

greatly affected by physiological conditions such as 

food transport, gastrointestinal motility, and so on. 

The tablets of Atenolol are expected to be retained 

for longer duration in upper GIT. Three different 

types of polymers and their combinations were 

used to prepare floating matrix tablets. It was 

observed that the type of polymer influences the 

drug release pattern. A significantly higher rate and 

extent of drug release was observed from the 

batches based on HPMC K4 M. although HPMC K100 

M, HPMC K15 M, alone or in combination sustains 

the drug release for a longer time. Varying the 

amount of polymer from 1:1.5 to 1:2, in F9-F10 

there was slight difference on drug release. Drug 

release from HPMC K15 M was lesser owing to its 

high viscosity. 

% c u m u la t iv e r e le a s e 

120 

100 

80 

60 

40 

20 

% c u m u l a t i v e r e l e a s e 

0 

0 5 10 15 20 25 30 

120 

100 

80 

60 

40 

20 

time(hr) 

F1 F2 F3 F4 F5 

Figure 1: In vitro dissolution profile of F1-F5 

0 

0 5 10 15 20 25 30 

time(hr) 

F6 F7 F8 F9 F10 

Figure 2: In vitro dissolution profile of F6-F10 

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3.4 Physical characterization 

Hardness of various batches of prepared 

formulations (4 – 6 kg / sq cm.) and Friability (0.2 – 

0.86 %) indicates that the tablets having sufficient 

strength to withstand physical abrasion. Tablets of 

all batches pass the weight variation test as per the 

limits prescribed in IP. Results of specific gravity 

indicate that the formulations having density less 

than that of gastric fluid (less than 1), which cause 

formulation to float on the gastric content 

(Table 2). 

3.5 DSC studies 

DSC curves showed that there was no any 

incompatibility between Atenolol and HPMC K4M, 

and optimized batch (F8) (Figure 3). 

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ISSN: 2230-9306 

A] Atenolol; B] HPMC K4M; C] F8 

Figure3: DSC thermograms of pure drug, HPMC K 4 

M & F8 

4.0 CONCLUSION 

Floating tablets having different release profiles for 

drugs can be formulated using HPMC K15M and 

HPMC K4M (alone and in combination) to give 

controlled release of atenolol. Hence, this dosage 

form should be further evaluated for delivery of 

drugs from, a single dosage form, which could 

Available online at www.ijrapronline.com 

improve patient compliance and give better disease 

management. 

Acknowledgement 

Authors are very much thankful to, Dr. JKK 

Munirajah, M.Tech (Bolton), Chairmen, JKKM Group 

of Institution, Komarapalayam (TN) and Vama 

Pharma, Nagpur (MS) for providing necessary 

facilities to carry out this project. 

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