RGUHS J Pharm Sci_2_2_06.pdf

Design And Evaluation of Gastroretentive Floating 

Drug Delivery System of Metoprolol Tartrate 

M. Mohan Varma and P. Anita 

Shri Vishnu college of Pharmacy, Vishnupur, Bhimavaram-534202, A.P., India 

ABSTRACT 

Drugs that have narrow absorption window in the gastrointestinal tract (GIT) will have poor absorption. For 

these drugs, gastroretentive drug delivery systems offer the advantage in prolonging the gastric emptying time. 

Metoprolol tartrate is an antihypertensive drug,it has low elimination half life: 3–4 hrs.The floating tablets of 

metoprolol tartrate were prepared to increase the gastric retention and to improve the bioavailability of the 

drug. The rapid gastro-intestinal transit could result in incomplete drug release from the drug delivery system 

above the absorption zone leading to poor bioavailability of the drug. The floating tablets were formulated using 

HPMC K4M and HPMC K100M as the release retardant polymers, and sodium bicarbonate as the gas generating 

agent to reduce the floating lag time. The tablets were prepared by direct compression.The formulated tablets 

were evaluated for weight variation, hardness, friability, swelling index floating lag time, total floating time and 

dissolution rate in pH 1.2. The floating tablets extended the drug release up to 8 hrs. The drug-polymer interaction 

was evaluated by fourier transform infrared spectroscopy (FTIR). The FTIR study indicated the lack of drugpolymer 

interaction. The optimized formulation (F8), containing drug: HPMC K100M, at 1:4 ratio, showed very 

good result and extended the release up to 8 hours. The drug release from the optimized formulation followed 

first order kinetics (correlation coefficient, r value 0.981) and non-fickian diffusion (n=0.623). The similarity 

factor calculated for batch F8(optimized formulation) was 55.46%, and its dissolution profile was similar to the 

dissolution profile of the branded extended release tablet. 

Keywords: Metoprolol, Floating tablets, HPMC, Dissolution. 

INTRODUCTION 

Oral controlled release 1,2 drug delivery 

is a drug delivery system that provides 

the continuous oral delivery of drugs at 

predictable and reproducible kinetics for 

a predetermined period through out the 

course of GI transit and also the system can 

target the delivery of a drug to a specific 

region within the GI tract for either local 

or systemic action. Conventional oral 

controlled release dosage forms suffer from 

mainly two adversities: the short gastric 

retention time (GRT) and unpredictable 

gastric emptying time (GET). A relatively 

brief GI transit time of most drug products 

impedes the formulation of single daily 

dosage forms. Altering the gastric emptying 

can overcome these problems. Therefore, 

it is desirable, to formulate a controlled 

release dosage form that gives an extended 

GI residence time. Extended release dosage 

forms with prolonged residence time in 

stomach are highly desirable for drugs: that 

are locally active in stomach, that have an 

absorption window in the stomach or in the 

upper small intestine, that are unstable in 

the intestinal or colonic environment, have 

low solubility at high pH values. Various 

approaches have been pursued to increase 

the retention of an oral dosage form in the 

stomach. 3,4 These systems include: Floating 

systems, bioadhesive systems, swelling and 

expanding systems, high density systems. 

Floating Drug Delivery System (FDDS) has 

Original Article 

Received Date : 18-03-2012 

Revised Date : 18-05-2012 

Accepted Date : 01-06-2012 

DOI: 10.5530/rjps.2012.2.6 

Address for 

correspondence 

M. Mohan Varma 

Shri Vishnu college of Pharmacy, 

Vishnupur, 

Bhimavaram-534202, 

A.P.,India. 

mohan_pharm@rediffmail.com 

www.rjps.in 

38 RGUHS J Pharm Sci | Vol 2 | Issue 2 | Apr–Jun, 2012

M. Mohan Varma et al.: Design And Evaluation of Gastroretentive Floating Drug Delivery System of Metoprolol Tartrate 

a bulk density lower than gastric fluids and thus remain 

buoyant in the stomach for a prolonged period of time, 

without affecting the gastric emptying rate. 5,6 While the 

system is floating on the gastric contents, the drug is 

released slowly at a desired rate from the system. After 

the release of the drug, the residual system is emptied 

from the stomach. This, results in an increase in the 

GRT and a better control of the fluctuations in the 

plasma drug concentration. 

Based on the mechanism of buoyancy, two distinctly 

different technologies have been utilized in development 

of FDDS which are : effervescent system and the noneffervescent 

system. 7 Effervescent systems include 

use of gas generating agents, carbonates (e.g. sodium 

bicarbonate) and organic acid (e.g. citric acid and 

tartaric acid) present in the formulation to produce 

carbon dioxide (CO 2 ) gas, thus reducing the density 

of the system and making it float on the gastric fluid. 

The non-effervescent FDDS is based on mechanism 

of swelling of the polymer or mucoadhesion to the 

mucosal layer in the GI tract. The most commonly used 

excipients in non-effervescent FDDS are gel forming 

or highly swellable cellulose type hydrocolloids, 

polysaccharides and the matrix forming materials 

such as Polycarbonate, Polyacrylate, Polymethacrylate, 

Polystyrene as well as mucoadhesive polymer such as 

Chitosan and Carbopol. 

Metoprolol 8,9 is a β1 selective adrenergic receptor 

blocking agent. It is a widely used antihypertensive 

drug. Metoprolol tartrate is a water soluble drug, it is 

administered orally, initially at a dose of 50 mg, 3–4 

tissues/day gradually increased to a maximum dose 

of 200 mg/day in divided doses. It has an elimination 

half life of 3–4 hours and has an absorption zone from 

the upper intestinal tract. Efficacy of the administered 

dose may get diminished due to incomplete drug release 

from the device above the absorption zone. Therefore, 

it is a suitable drug for gastroretentive formulation. The 

gastroretentive drug delivery systems can be retained in 

the stomach and assist in improving the oral sustained 

delivery of drugs that have an absorption window in 

a particular region of the gastrointestinal tract. These 

systems help in continuously releasing the drug before it 

reaches the absorption window , thus ensuring optimum 

bioavailability. 

In the context of the above principles, a strong need was 

recognized for the design of a dosage form to deliver 

metoprolol in the stomach and to increase the efficiency 

of the drug, providing controlled release action. The 

drug is subjected to first pass metabolism and its oral 

bioavailability is 50%. The drug is mainly absorbed in the 

stomach and in the upper part of duodenum, hence it is 

ideally suited for the gastroretentive floating tablets. The 

objective of the study is to formulate Metoprolol tartrate 

floating tablets , to increase the gastric retention , extend 

the drug release and to improve its oral bioavailability. 

MATERIALS AND METHODS 

Metoprolol tartrate was a gift sample from Hetero 

Drugs Ltd, Hyderabad. HPMC K4M, HPMC K100M, 

microcrystalline cellulose (MCC), magnesium stearate, 

sodium bicarbonate and talc were procured from SD 

Fine Chemicals, Mumbai. All other chemicals used were 

of analytical grade. 

Estimation of metoprolol tartrate 

A spectrophotometric 3 method based on the measurement 

of absorbance at 221 nm in 0.1N HCl was used 

in the present study for the estimation of Metoprolol 

tartrate. The 100 mg of Metoprolol tartrate pure drug 

was dissolved in 100 ml of 0.1 N HCl (stock solution 

1000 μg/ml), from this 10 ml of solution was taken 

and the volume was adjusted to 100 ml with 0.1 N HCl 

(100 μg/ml). The above solution was subsequently 

diluted with 0.1N HCl to obtain the series of dilutions 

containing 2,4,6,8,10,12,16,20,24 and 30 μg/ml of 

Metoprolol tartrate solution. The absorbance of the 

above dilutions was measured at 221 nm by using 

the UV-spectrophotometer (Lab. India) using 0.1N 

HCl as the blank. Then a graph was plotted by taking 

concentration on x-axis and absorbance on y-axis which 

gives a straight line (Figure 1). 

Preparation of metoprolol tartrate 

floating tablets 

All the formulations were prepared by direct compression 4 

method using different viscosity grades of HPMC 

polymers in various ratios (designated as F-1 to F-8 

in Table 1). The metoprolol tartrate and all other 

ingredients were individually passed through sieve ≠ 60. 

All the ingredients were mixed thoroughly by triturating 

up to 15 min. The powder mixture was lubricated with 

talc. The single punch tablet machine (CADMACH) was 

used for the compression of the floating tablets. Use of 

ingredients in the formulation: Sodium bicarbonate was 

used as the gas generating agent to reduce the floating lag 

time. HPMC K4M and HPMC K100M were used as the 

release retardant polymer to obtain prolonged release of 

the drug up to 8 hours. Microcrystalline cellulose (MCC) 

was used as the diluent. Magnesium stearate and talc 

were used as the lubricants. The tablets were prepared 

by using the direct compression method. 

Evaluation of tablets 

The formulated tablets were evaluated for the following 

physicochemical characteristics 5 (Table 2): 

RGUHS J Pharm Sci | Vol 2 | Issue 2 | Apr–Jun, 2012 39


Table 1: Composition of different formulations 

Formulation 

No. 

Metoprolol 

tartrate (mg) 

Figure 1: Calibration curve of Metoprolol tartrate in 0.1 N HCl. 

HPMC K15M 

(mg) 

HPMC K100M 

(mg) 

NaHCO 3 

(mg) 

Mag. Stearate 

(mg) 

40 RGUHS J Pharm Sci | Vol 2 | Issue 2 | Apr–Jun, 2012 

Talc 

(mg) 

Microcrystalline cellulose 

(mg) 

F1 50 50 –– 45 3 3 154 

F2 50 100 –– 45 3 3 99 

F3 50 150 –– 45 3 3 49 

F4 50 200 –– 45 2.5 2.5 –– 

F5 50 –– 50 45 3 3 154 

F6 50 –– 100 45 3 3 99 

F7 50 –– 150 45 3 3 49 

F8 50 –– 200 45 2.5 2.5 –– 

TABLE 2: Quality Control Parameters of Metoprolol tartrate floating Tablets 

Formulation 

No. 

Avg. Weight (mg) 

(Mean ± S.D) 

(n =20) 

Hardness 

(kg/cm 2 ) 

(n =3) 

% Friability 

(Mean ± S.D) 

(n =20) 

% Drug content 

(mg) 

Buoyancy 

Lag time 

(min) 

Total 

floating 

time(hrs) 

F1 283 ± 0.6 7.2 ± 0.2 0.546 97 ± 0.7 4 8 + 

F2 320 ± 0.9 7.5 ± 0.2 0.612 99 ± 0.5 10 8 + 

F3 292 ± 0.4 8 0.702 100 ± 0.3 8.6 8 + 

F4 291 ± 0.4 7.6 ± 0.2 0.611 99 ± 0.4 6.1 8 + 

F5 286 ± 0.8 7.6 ± 0.2 0.625 99 ± 0.6 5.0 8 + 

F6 304 ± 0.8 7.3 ± 0.4 0.655 98 ± 0.5 3 8 + 

F7 294 ± 0.4 7.7 ± 0.5 0.711 99 ± 0.4 8.5 8 + 

F8 297 ± 0.3 8.0 0.827 100 ± 0.6 8 8 + 

Hardness 

Hardness of the tablet was determined by using the 

Monsanto hardness tester. The lower plunger was placed 

in contact with the tablet and a zero reading was taken. 

The plunger was then forced against a spring by turning a 

threaded bolt until the tablet fractured. As the spring was 

Matrix 

integrity 

compressed a pointer rides along a gauge in the barrel to 

indicate the force required for the tablet to break. 

Weight variation 

The 20 tablets were selected and weighed collectively and 

individually. From the collective weight, average weight


was calculated. Each tablet weight was then compared 

with average weight to ascertain whether it was within 

the permissible limits or not. Not more than two of the 

individual weights deviated from the average weight by 

more than 7.5% for 300 mg tablets and none by more 

than double that percentage. 

Friability test 

The 20 previously weighed tablets were placed in the 

friability apparatus, which was given 100 revolutions and 

the tablets were reweighed. The percentage friability was 

calculated by using the following formula, 

Percentage friability = initial weight-final weight/ 

initial weight × 100 

Drug content 

The 20 tablets of each formulation were weighed and 

powdered. The quantity of powder equivalent to 100 mg 

of Metoprolol tartrate was transferred in to a 100 ml 

volumetric flask and the volume was adjusted to 100 ml 

with 0.1N HCl. The sample was filtered to remove the 

insoluble excipients. Further 1ml of the above solution 

(filtrate) was diluted to 100 ml with 0.1N HCl and the 

absorbance of the resulting solution was observed at 

221 nm. 

In vitro buoyancy studies 

Figure 2: Swelling index of the floating tablets. 

The in vitro buoyancy was determined by floating lag 

time and total floating time as per the method described 

by Rosa et al. 10 The tablets were placed in a 100 ml beaker 

containing 0.1N HCl. The time required for the tablet to 

rise to the surface and float was determined as floating 

lag time (FLT) and the duration of the time the tablet 

constantly floats on the dissolution medium was noted 

as the total floating time respectively (TFT). 

Swelling index 

The swelling behavior of a dosage unit was measured 

by studying its weight gain. The swelling index (Table 3, 

Figure 2) of the tablets was determined by placing the 

tablets in the basket of the dissolution apparatus 

using dissolution medium as 0.1N HCl at 37 ± 0.5°C. 

After 0.5, 1, 2, 3, 4, 5, and 6 h, each dissolution basket 

containing tablet was withdrawn, blotted with tissue 

paper to remove the excess water and weighed on the 

analytical balance (Shimadzu, ELB300). The experiment 

was performed in triplicate for each time point. 

Swelling index was calculated by using the following 

formula. 6 

Swelling index 

( Wet weight of tablet − Dry weight of tablet 

) × 100 

% = 

Dry weight of tablet 

RGUHS J Pharm Sci | Vol 2 | Issue 2 | Apr–Jun, 2012 41 

( )


Table 3: Swelling index profile of Metoprolol tartrate 

floating tablets 

S.NO Formulation code Swelling index(%) 

1 F1 44.64 

2 F2 48.43 

3 F3 51.23 

4 F4 60 

5 F5 81.03 

6 F6 85.48 

7 F7 92.87 

8 F8 107.14 

Dissolution study 

The 900 ml of 0.1 HCl(pH 1.2) was placed in the 

vessel and the USP apparatus–II (paddle method) was 

assembled. The medium was allowed to equilibrate to 

temp of 37 + 0.5°C. The tablet was placed in the vessel 

and the vessel was covered, the apparatus was operated 

for 8 hours at 50 rpm. 3 At definite time intervals, 5 ml 

of the fluid was withdrawn; filtered and again 5 ml of 

the fresh fluid was replaced. Suitable dilutions were done 

with the blank dissolution fluid and the samples were 

analyzed spectrophotometrically (Lab, India) at 221 nm 

(Figure 3–6). 

Release kinetics 

The analysis of drug release mechanism from a 

pharmaceutical dosage form is an important but 

complicated process and is practically evident in the case 

of matrix systems. As a model-dependent approach, the 

dissolution data was fitted to four popular release models 10 

such as zero-order, first-order, diffusion and Peppa’s- 

Korsemeyer equations. The order of drug release from 

the matrix systems was described by using zero order 

kinetics or first orders kinetics. The mechanism of drug 

release from the matrix systems was studied by using 

Higuchi equation and Peppa’s- Korsemeyer equation. 

Zero order release kinetics 

It defines a linear relationship between the fraction of 

drug released versus time. Q = k o t. Where, Q is the 

fraction of drug released at time t and k o is the zero 

order release rate constant. A plot of the fraction of 

drug released against time will be linear if the release 

obeys zero order release kinetics. 

First order release kinetics 

Wagner assuming that the exposed surface area of a tablet 

decreased exponentially with time during dissolution 

Figure 3: Dissolution profile of Metoprolol tartrate floating tablets (F1, F2) formulations. 



Figure 4: Dissolution profile of Metoprolol tartrate floating tablets (F3, F4). 

Figure 5: Dissolution profile of Metoprolol tartrate floating tablets (F5, F6). 



process suggested that drug release from most of the 

slow release tablets could be described adequately by 

apparent first-order kinetics. The equation that describes 

first order kinetics is In (1–Q) = – K 1 t. Where, Q is the 

fraction of drug released at time t and k 1 is the first 

order release rate constant. Thus, a plot of the logarithm 

of the fraction of drug undissolved against time will be 

linear if the release obeys first order release kinetics. 

Higuchi equation 

It defines a linear dependence of the active fraction 

released per unit of surface (Q) on the square root of 

time. Q=K 2 t ½ . Where, K2 is the release rate constant. 

A plot of the fraction of drug released against square 

root of time will be linear if the release obeys Higuchi 

equation. 11 

Power law 

Figure 6: Dissolution profile of Metoprolol tartrate floating tablets (F7, F8 and Brand) formulations. 

In order to define a model, which would represent 

a better fit for the formulation, dissolution data was 

further analyzed by Peppa’s and Korsemeyer equation 

(Power Law). M t /M α = K.t n . Where, M t is the amount 

of drug released at time t and M α is the amount released 

at time α, thus the M t /M α is the fraction of drug released 

at time t, k is the kinetic constant and n is the diffusion 

exponent. A plot between log of M t /M α against log 

of time will be linear if the release obeys Peppa’s 

and Korsemeyer equation and the slope of this plot 

represents “n” value 12 . 

Similarity factor (f2 analysis) 

n f2 = 50 ∙ log { [1 + (1/n) ∑ (Rt T ) t=1 - t 2 ] –0.5 ∙ 100} 

Where ‘R t ’ and ‘T t ’ are the cumulative percentage drug 

dissolved at each of the selected n time point of the 

reference and test product respectively. The factor f2 is 

inversely proportional to the averaged squared difference 

between the two profiles, with emphasis on the larger 

difference among all the time points. 4 

FTIR STUDIES 

The FTIR studies were carried out to evaluate the drugpolymer 

interaction. The FTIR spectra of the drug 

(alone), polymer (alone) and the drug-polymer (physical 

mixture) were recorded by the potassium bromide pellet 

method 5 (Bruker model FTIR was used). 

RESULTS AND DISCUSSION 

Evaluation of tablets 

The objective of the present study was to prepare 

floating tablets of Metoprolol tartrate. These tablets 

were developed to prolong the gastric residence time and 

to increase the bioavailability of the drug. Metoprolol 

tartrate was chosen as a model drug because it is better 

absorbed in the stomach than the lower gastro intestinal 

tract. The tablets were prepared by direct compression 

technique, using polymers such as HPMC K 15M, HPMC 



K 100M and other standard excipients. Tablets were 

evaluated for physical characteristics such as hardness, 

floating capacity and weight variation. The in vitro 

release characteristics were evaluated for 8 hrs. Totally 

8 different formulations of Metoprolol tartrate were 

prepared by using two different polymers like HPMC 

K15 M, HPMC K100 M and diluent : microcrystalline 

cellulose in different concentrations (Table 1). All the 

formulations fulfilled the compendial specifications of 

the various quality control parameters (Table 2): weight 

variation, hardness, friability, drug content, floating lag 

time, total floating time and the matrix integrity. The 

values of hardness of the different formulations ranged 

from 7.2 to 8 kg/cm 2 . The values of friability of the 

different batches ranged from 0.546% to 0.827%. All 

the batches exhibited uniformity of drug content. The 

values of drug content of the different formulations 

ranged from 97% to 100%. The values of floating 

(buoyancy) lag time of all the formulations (Table 2) 

ranged from 3–10 minutes. The total floating time of 

all the formulations was 8 hours. All the formulations 

exhibited good matrix integrity. The sodium bicarbonate 

was used as a gas generating agent in order to float the 

tablet. The sodium bicarbonate induces CO 2 generation 

in the presence of dissolution medium (0.1N HCl). The 

gas generated is trapped and protected with in the gel 

formed by hydration of the polymer, thus decreasing 

the density of the tablet below 1 gm/mL, and the tablet 

becomes buoyant. 

Swelling studies 

Swelling is crucial in determining the release rate. 

A direct correlation between swelling and drug 

release was observed and the swelling indices were 

increased with increase in polymer concentration 6 

(Table 3, Figure 2). Among, all the formulations the 

F8 formulation containing HPMC K100M shows the 

best result of swelling index, where as the batch F1 

showed the least value of the swelling index. The values 

of swelling index of the different batches ranged from 

:44.64% to 107.14%. Based on the values of the swelling 

index, the different formulations can be arranged as 

:F8>F7>F6>F5>F4>F3>F2>F1. 

Dissolution study 

The dissolution studies of the floating tablets were 

conducted in 0.1N HCl (pH1.2) for 8 hours. The amount 

of drug released from all the formulations depends upon 

the concentration of the polymer used. HPMC K4M 

and HPMC K100M were used as the release retardant 

polymers, so that we can prolong the release of the water 

soluble drug, metoprolol tartrate. Sodium bicarbonate 

was used as the gas generating agent to reduce the 

floating lag time. The polymers: HPMC K4M and 

HPMC K100M showed good tablet integrity , swelling 

and extended the release of metoprolol tartrate. Sodium 

bicarbonate in the acidic environment reacts with the 

acid and produces carbon dioxide. The evoloved gas will 

get entrapped in the matrix leading to floating of the 

tablet. As the concentration of sodium bicarbonate was 

increased, the floating lag time was decreased. The higher 

concentration of sodium bicarbonate facilitates the drug 

release. Increase in sodium bicarbonate concentration 

increases the release rate. As the concentration of the 

polymer was increased in the different formulations, 

the rate of drug release was decreased. Similar results 

were obtained in the evaluation of floating tablets of 

atenolol, 3 ketoconazole 4 and ofloxacin. 5 Finally, the 

retardant effect of the polymer on the drug release 

can be indicated as: HPMC K100M > HPMC K15M 

(Figure 3–6). The dissolution rate of the marketed 

(branded) extended release tablet was evaluated (Figure 6). 

The value of the similarity factor was calculated. The 

similarity factor value for the optimized formulation, 

F8 (drug: HPMC K100M ratio, 1:4) is 55.46%, so its 

dissolution profile is similar to the dissolution profile of 

the branded extended release tablet. 

The values of n (diffusion exponent), K (release rate 

constant) and the dissolution parameters: T 25 (time taken 

to release 25% of the drug), T 50 (time taken to release 

50% of the drug) and T 75 (time taken to release 75% of 

the drug) computed for all the controlled release floating 

tablets and the marketed branded extended release tablet 

are represented in Table 4. Based on the values of T 25(hr), 

the release of the drug from the different formulations 

can be arranged as: F1>F2=F5>F3>F4=F6>F7>F8. 

Based on the values of T 50(hr), the release of the drug 

from the different formulations follows the order: 

F1=F3=F5=F6>F2>F4>F7>F8. The batches, F1 and 

F2 attained the value of T 75(hr) in 8 hours, the other 

formulations did not attain the value of T 75(hr) , even after 

8 hours of the dissolution study. The branded extended 

release tablet exhibited the values of T 25(hr) = 2.5 hour, 

T 50(hr) =7hour and T 75(hr) >8hours. 

The hydration rate of HPMC increases with an increase 

in the hydroxypropyl content. The solubility of HPMC 

is pH independent. In the present study ,HPMC was 

used as a hydrophilic matrix polymer because it forms a 

strong viscous gel on contact with the aqueous media, 

which may be useful in controlled delivery of highly 

water-soluble drugs. In an attempt to prolong the release 

of drug, the concentration of HPMC was increased. 

Faster release of the drug from the hydrophilic matrix 

was probably due to faster dissolution of the highly 

water-soluble drug from the core and its diffusion 

out of the matrix forming the pores for the entry of 

solvent molecules. Similar results were reported in 

the evaluation of floating tablets of hydrophilic drug, 



diltiazem HCl. 6 In vitro drug release studies revealed 

that the release of metoprolol tartrate from different 

formulations varies with the characteristics and the 

composition of matrix forming polymers as shown 

in Figure 5–8. These findings are in compliance with 

the ability of HPMC to form complex matrix network 

which leads to delay in the release of the drug from the 

device. 3 In the present investigation, the results indicated 

that as the polymer concentration and the viscosity of 

the polymer was increased, there was a reduction in the 

rate of drug release. Formulations containing higher 

methocel viscosity grades i.e., F5 to F8 showed slower 

drug release rates when compared to formulations with 

lower methocel viscosity grade i.e. F1 to F4 . 

Release kinetics 

The Table 5 enlists the coefficient of correlation (r) values 

of the different formulations. To examine the release 

mechanism of Metoprolol tartrate floating tablets, the 

results were analyzed according to Korsemeyer-Peppas 

equation. Release of Metoprolol from the optimized 

formulation (F8) was found to follow first order 

kinetics (correlation coefficient, r value of 0.981). The 

drug release from the formulations: F1,F2,F5,F6,F7,F8 

followed zero order kinetics (r > 0.9), where as the drug 

release from the formulations: F3,F4,F8 demonstrated 

first order kinetics (r > 0.9). The Higuchi plot showed 

an r valve of 0.986 for formulation F8, suggesting 

that the diffusion and erosion plays an important role 

in the controlled release. 10 The drug release from all 

the formulations depends on diffusion and erosion 

mechanism, as the Higuchi plot for all the formulations 

exhibited the r value > 0.9. The data was fitted to 

Korsemeyer equation; and the value of diffusion 

exponent ‘n’ (0.623) indicated that the drug release from 

the optimized formulation (F8) exhibited non-fickian 

diffusion. The n values of the different formulations 

ranged from 0.492 to 0.623. Hence, the drug release 

from all the floating formulations exhibited non-fickian 

diffusion (n > 0.45). The n value of the branded extended 

release tablet was 0.655, therefore the drug release from 

the brand also showed non-fickian diffusion (n>0.45). 

FTIR studies 

The FTIR studies of the pure drug, polymer (HPMC 

K100M) and the drug-polymer physical mixture was 

carried out to study the interaction between the drug 

and the polymer used. The FTIR spectrum of the 

pure drug (alone) and the polymer (alone): HPMC 

K100M are depicted in the Figure 7a and the Figure 7b 

respectively. The FTIR spectrum of the pure drug shows 

the characteristic FTIR peaks at 3342.05 cm –1 (O–H 

stretching), 3017.49 cm –1 (C–H aromatic stretching), 

1404.72 cm –1 (C=C aromatic stretching), 1179.5 cm –1 (C–N 

stretching), 2870.16 cm –1 (C–H stretching), 1421.05 cm –1 

(CH 2 bending). As all the FTIR peaks of the drug were 

observed in the drug: HPMC (1:4) physical mixture 

(Figure 7c), the FTIR studies 5 revealed the absence of 

drugpolymer interaction in the solid state. 

CONCLUSION 

Table 4: Dissolution Parameters of Metoprolol Tartrate Floating Tablets 

Formulation 

The best formulation F8 can successfully be employed 

as a controlled release floating drug delivery system. The 

effervescent based floating drug delivery is a promising 

approach to achieve in vitro buoyancy by using gel– 

forming polymer HPMC K100M and gas generating 

agent sodium bicarbonate. The floating matrix tablets 

Table 5: Release kinetics: Coefficient of correlation (r) values 

of different batches of Metoprolol tartrate floating tablets 

Formulation Zero order First order Higuchi’s Peppa’s 

F1 0.976 0.870 0.929 0.934 

F2 0.975 0.915 0.954 0.971 

F3 0.937 0.940 0.996 0.994 

F4 0.971 0.990 0.994 0.995 

F5 0.983 0.923 0.957 0.966 

F6 0.992 0.954 0.966 0.975 

F7 0.975 0.955 0.970 0.985 

F8 0.979 0.981 0.986 0.994 

BRAND 0.995 0.987 0.977 0.992 

Dissolution Parameters 

n K 0(mg/hr) K 1(hr-1) T 25(hr) T 50(hr) T 75(hr) 

F1 0.492 7.831 0.301 0.9 5 8 

F2 0.591 8.084 0.248 1 5.1 8 

F3 0.608 8.077 0.223 1.4 5 — 

F4 0.612 5.503 0.204 1.5 5.6 — 

F5 0.496 7.819 0.186 1 5 — 

F6 0.599 7.867 0.175 1.5 5 — 

F7 0.621 6.626 0.151 2 6 — 

F8 0.623 5.490 0.175 2.2 7 — 

BRAND 0.655 6.762 0.179 2.5 7 — 



Figure 7a: FTIR spectrum of metoprolol tartrate. 

Figure 7b: FTIR spectrum of HPMC K100M. 



Figure 7c: FTIR spectrum of drug: HPMC K 100M (1:4) physical mixture. 

(batch F8) containing drug: HPMC K 100M, at 1:4 

ratio could control the metoprolol release effectively for 

8 hours. The tablets demonstrated good floating time for 

8 hours. The FTIR study revealed the absence of the drugpolymer 

interaction. The floating tablets can control the 

fluctuations in the plasma drug concentration, increase 

the gastric residence time and eventually improve the 

bioavailability of metoprolol. 

ACKNOWLEDGEMENT 

The authors are thankful to the chairman sir, director 

sir,principal sir and the management of the shri vishnu 

college of pharmacy for providing the necessary facilities 

to carry out this work. 

REFERENCES 

1. Robinson JR, Lee VHL. Controlled drug delivery: Fundamentals and 

Applications, 2nd ed. Marcel Dekker, New York. 1987, pp. 24–36. 

2. Chein YW. Novel Drug Delivery Systems, 2nd ed., Marcel Dekker, 

New York.1992, pp. 4–56. 

3. Srivastava AK, Wadhwa S, Ridhurkar D, Mishra B. Oral sustained 

delivery of atenolol from floating matrix tablets-formulation and in vitro 

evaluation. Drug Dev. Ind. Pharm. 2005;31:367–74. 

4. Chandra Sekhar B, Shireesh Kiran R , Nagendra Babu B. Preparation 

and evaluation of gastro retentive floating tablets of Ketoconazole. 

Int. J. Pharma Res. Develop.2010;2:174–184. 

5. Pramod Patil, Someshwara Rao B, Kulkarni SV. Formulation and 

In Vitro Evaluation of Floating Matrix Tablets of Ofloxacin. Asian J. Res. 

Pharm. Sci. 2011;1:17–22. 

6. Khan T, Nazim S, Sheikh S, Sheikh A. Design and In vitro evaluation 

of floating diltiazem hydrochloride tablets based on gas formation. 

Int. J. Pharm. Bio. Sci. 2010;3:1263–1267. 

7. Gangadharappa HV, Pramod KT, Shiva Kumar HG. Gastric Floating 

Drug Delivery Systems: A Review. Ind. J. Pharm. Edu. Res.2007; 

41:295–305. 

8. Martindale:The Complete Drug reference, 34th edn., edited by 

S.C. Sweetman, Pharmaceutical Press, U.K., 2005; pp.957. 

9. Goodman Gilman’s The Pharmacological Basis of Therapeutics, 

10th ed, New York. 2001; p. 176. 

10. Rosa M, Zia H, Rhodes T. Dosing and testing in vitro of a bioadhesive 

and floating drug delivery system for oral application. Int. J. Pharm. 

1994;105:65–70. 

11. Higuchi T. Mechanism of Sustained-action medication. Theoretical 

Analysis of rate of release of solid drugs dispersed in solid matrices. 

J. Pharm. Sci. 1963;51:1145–1149. 

12. Peppas N.A. Analysis of Fickian and Non-Fickian drug release from 

polymers. Pharma Acta. Helv. 1985;60:110–111.

RGUHS J Pharm Sci_2_2_06.pdf

Create successful ePaper yourself

Delete template?

Save as template?