Formulation and Evaluation of Atenolol Floating Tablets using Polymers

 

Sathvik T, Yash Tyagi, Venkatesh, Shilpa, Mamtha, Pradnya B Patil*, Ayesha Sultana

N.E.T Pharmacy College, Raichur.

*Corresponding Author E-mail: pradnyap65@gmail.com

 

ABSTRACT:

Gastro-retentive floating drug delivery system of atenolol, an antihypertensive drug with an oral bioavailability of only 50% and other 25% is excreted unchanged in faces because of its poor absorption from lower gastro intestinal tract. To improve the oral bioavailability and therapeutic effectiveness of atenolol, the gastro retentive floating drug delivery system was deemed useful. The direct compression technique was used to make floating tablets (F1 to F3), to reduce the floating delay, a natural polymer okra gum and ethyl cellulose was used together with gas producing sodium bicarbonate. Evaluations were done on the powder blends, angle of repose, bulk density, tapped density, Hausner’s ratio and compressibility index. Pre-compressional study indicates good micrometric properties of powder blend. Additionally, formulated floating tablets were evaluated for weight variation, hardness, diameter, drug content, buoyancy lag time and total floating time, impact of hardness, In-vitro swelling behaviour and In-vitro drug release. Post-compressional parameters were within limits. The results indicated that gas powdered floating tablets of atenolol containing 125mg of okra gum provides a better release for 12h i.e. 84.16%. The order of drug release showed F3<F2<F1 The mechanism of drug release pattern of this optimized formulation was found to be diffusion controlled zero order kinetics. FT-IR study revealed the absence of drug polymer interaction and exists a scope for further in-vivo evaluation using suitable model.

 

KEYWORDS: Atenolol, Gastro-Retentive Floating System, Hypertension, Okra Gum, Ethyl Cellulose, In-Vitro Buoyancy.

 

 


INTRODUCTION:

Oral drug delivery is the preferred route of administration due to its natural, non-invasive nature compared to IV and IM routes. An ideal drug delivery system should require minimal dosing and release the drug at the site of action. However, low oral bioavailability of macromolecular drugs often results from enzymatic hydrolysis and poor membrane permeability.

 

Floating Drug Delivery Systems (FDDS) have been developed to enhance gastric retention and bioavailability by using low-density materials that remain buoyant in the stomach without affecting gastric emptying1,2. These systems may be floating inflation high density system and low-density system increase the gastric residence time and gastric retention is useful for the active disintegration3 FDDS can be categorized into non-effervescent4 and effervescent5 systems. Non-effervescent FDDS relies on polymer swelling mechanisms using hydrocolloids, cellulose derivatives, polysaccharides, and bio-adhesive polymers like chitosan and Carbopol. Effervescent FDDS generates carbon dioxide through reactions between sodium bicarbonate6 and acids like citric or tartaric acid, reducing system density and ensuring buoyancy.

 

FDDS can be formulated as tablets or capsules using excipients such as hydrocolloids, inert fatty materials, and buoyancy agents, making them suitable for drugs like antacids, anti-diabetics, antifungals, and anticancer7 agents. Atenolol, a beta-adrenergic blocker absorbed mainly in the stomach, benefits from FDDS by prolonging gastric residence time and enhancing bioavailability. A combination of ethyl cellulose (semisynthetic polymer) and okra gum (natural polymer) can be used to achieve this sustained drug release.

 

MATERIALS AND METHODS:

Materials:

Atenolol was obtained as a gift sample Anant Pharmaceuticals PVT Ltd., Thane, Maharashtra. Other chemicals ethyl cellulose, sodium bicarbonate, Talc, Microcrystalline cellulose, Magnesium stearate and other reagents were of analytical grade. Natural polymers as Okra gum obtained from okra seeds, local market.

 

Methods:

a)    Preparation of Okra Gum (Abelmoschus esculentus)

Okra gum is a sticky, mucilaginous, and pale yellowish coloured gum. The preparation of the gum is consisting of the four steps. The final step is quite lengthy and it takes up to weeks to complete.

1)    Washing: For the extraction of the mucilaginous gum from the okra, the okra was obtained from the local market and it was washed completely to remove the soil and dirt particles. Then it was dried to remove water. The okra was thinly sliced or it was chopped into the small pieces. The seeds were removed from the okra because consists it does not consist of mucilage.

2)    Filtration: After the cutting of the okra, the smaller pieces were soaked into the water overnight to extract out the mucilage. After thickening of the mucilage, the gummy material was filter out from rest part of okra by using muslin cloth.

3)    Precipitation: In the third step the precipitation of the gum was done. For the precipitation of the gum, the acetone was added at a ratio of 3 parts of acetone to one part of gum extract. This results in the precipitation of the gummy material.

4)    Drying: After the complete precipitation of the gum, it was separated and then it was dried in a hot air oven at 60℃, The gum was stored in the air tight container.

 

Evaluation of okra gum8

Okra gum was assessed and characterised by following methods

Physical Evaluation:

Observe the prepared gum formulation for appearance, odour and pH.

Swelling Index: The swelling index of the gum was carried out to find out the swelling capacity of the okra gum. The Swelling index of Okra gum was determined by placing one gram of powder in a measuring cylinder. The initial volume of the powder In a measuring cylinder was noted and then the volume was made up to 100 ml mark with 0.1N HCI (pH 1.2) at room temperature. The cylinder was stoppered shaken gently and set aside for some time.

 

𝑆𝐼 = (𝑤𝑡𝑤𝑜)/𝑤𝑡 × 100

 

where, S.l.= Swelling index, Wt= Height occupied by swollen gum after 24hrs, Wo = Initial height of the powder in graduated cylinder.

 

Evaluation of Powder Blend:

Pre-compression evaluation of powder blend of floating tablets of Atenolol:

Angle of repose (θ) 9

The fixed funnel method was employed to measure the angle of repose (θ) and it was calculated using the following formula: Tan θ = h/r. In which, θ is the angle of repose, h is the height of the cone and r is radius of the cone base. To measure the angle of repose, a funnel was fixed to a stand so that the lower tip of funnel was 2.5cm above the surface. A graph paper was placed on a flat surface. The powder blend was allowed to fall freely on the graph paper through the funnel (6.9 cm diameter), till the tip (8 mm diameter) of heap formed just touches the funnel. The radius of heap was noted and from this angle of repose was determined. If angle of repose less than 30°suggests free flowing properties of the material. The test was repeated thrice.

 

Angle of repose () = tan^ (−1) (ℎ/𝑟)……….………..(2)

 

Bulk Density:

The bulk density, as a measure used to describe packing materials or granules, was determined by transferring the accurately weighed powder to the graduated cylinder (50 ml) with the aid of a funnel. The powder was levelled carefully without compacting, and the unsettled volume was read. The volume was noted and bulk density (g/cm3) was determined as the ratio of weight of the sample to the volume occupied. The test was repeated thrice.

                             Weight of powder

Bulk Density = -------------------------------          ……..(3)

                                Bulk Volume

 

Tapped Density:

Sample was transferred in 50 ml graduated cylinder. Then cylinder was tapped mechanically by raising the cylinder and allowing it to drop under its own weight using mechanical tapped density tester. Cylinder was tapped for 100 times and tapped volume was measured. Tapped density in g/cm3 was calculated by the following formula:

                             Weight of powder

Tapped Density = -------------------------------          …..(4)

                                Tapped Volume

 

Carr’s Index:

Flowability of powder samples was also assessed from Carr’s Index (CI). The compressibility of sample blend was determined from their apparent bulk density and the tapped densities by using the following formula. The test was carried out in triplicate.

 

                         Tapped density- bulk density

%Compressibility=--------------------------- x 100    …..(5)

                                Tapped density

 

 

Hausner’s Ratio:

Hausner’s ratio is an indication of the flowability of powder and the ratio is greater than 1.25 is considered to be an indication of poor flowability. Hausner’s ratio was determined by the following equation. The test was done in triplicate.

                                   Tapped density

Hausner’s Ratio = ------------------------                …….(6)

                                  Bulk density

 

Formulation of floating tablets of Atenolol:

The floating tablets of Atenolol were prepared by direct compression method using 4 mm flat-faced punch of 12 station Rimek compression machine employing different polymers like okra gum and ethyl cellulose in varying concentrations in combination. For the preparation of floating tablets, weighed quantities of drug, natural polymers, diluents and gas forming agent (sodium bicarbonate) were taken in a mortar and pestle and thoroughly mixed. Then the powder blend was mixed with magnesium stearate and talc as flow promoters and compressed directly to give floating tablets. The formulae of different gastroretentive floating tablets of atenolol are given in the Table 1.

 

Table 1: Composition of floating tablets of Atenolol

Ingredients(mg)

F1

F2

F3

Atenolol

50

50

50

Okra gum

125

150

175

Ethyl cellulose

62.5

37.5

12.5

Sodium bicarbonate

50

50

50

Microcrystalline cellulose

6.5

6.5

6.5

Magnesium stearate

4

4

4

Talc

2

2

2

Total

300mg

300mg

300mg

 

Evaluation of gastroretentive floating tablets of atenolol:

Post Compression Evaluation:

All tablets were evaluated for various parameters related to physical characteristics, mechanical strength and drug release.

1. General appearance:

Morphological characters like shape, colour and texture were determined visually.

2. Thickness and Diameter:

Thickness and diameter of prepared tablets (10 no’s) were tested using Vernier callipers. The test was done in triplicates and average was determined.

 

3. Hardness:

The hardness of prepared tablets (5 no’s) was determined by using Monsanto hardness tester and measured in terms of kg/cm2. Test was done in triplicate.

 

4. Drug Content:

Weighed tablets (2 no’s) were powdered using a glass mortar and pestle. An accurately weighed quantity of powder equivalent to 20 mg of atenolol was taken into a 100 ml volumetric flask and dissolved in methanol (5 ml) while shaking for 10min. Further sample was diluted with 0.1N HCl and volume was made up to 100ml. The solution in the volumetric flask was filtered and the drug content was determined at 255nm by using UV-spectrophotometer against blank. The test was done in triplicate.

 

5. Friability:

The test was performed to assess the effect of friction and shocks, which may often cause tablet to chip, cap or break. Roche Friabilator was used for testing the friability of prepared tablets. 10 tablets were accurately weighed and placed in the Friabilator and operated for 100 revolutions. The tablets were de-dusted and reweighed.

 

Friability (F) was calculated using the following formula

                        w

%F = (W0 -    -----)  x 100                                 ………...(7)

                       w0

Where, W0 and W are the weight of the tablets before after the test respectively. The test was done in triplicate. The tablets that loose less than 1% weight were considered to be compliant.10

 

6. Weight Variation:

The weight variation test was done by (Shimadzu digital balance) weighing 20 tablets individually, calculating the average weight and comparing the individual tablet weights to the average. The percentage difference in the weight variation should be within the permissible limits (± 5%). The percent deviation was calculated using the following formula.

                       (Individual wt − Average wt)

% Deviation =  --------------------------------- X 100-----(8)

                                  (Average wt)

 

7. Swelling index:

Swelling of tablet involves the absorption of a liquid by tablet matrices resulting in an increase in weight and volume of tablet. The extent of swelling was measured in terms of % weight gain by the tablet. For each formulation batch, one tablet was weighed and placed in a beaker containing 200ml of 0.1 N HCl. After each time interval, the tablet was removed from beaker and weighed again up to 12 h.11.

 

Swelling Index % (S.I.) = (Wt − Wo)/Wo 100..........(9)

Where, S.I. = Swelling index, Wt = Weight of tablet at time t, Wo = Weight of tablet before placing in the beaker.

 

8. Floating or buoyancy lag time and total floating time:

The time taken for tablet to emerge on the surface of the medium is called the floating lag time (FLT) or buoyancy lag time (BLT) and duration of time the tablet constantly remains on the surface of the medium is called the total floating time (TFT). The buoyancy of the tablets was studied in USP type II dissolution apparatus at 37oC±0.5oC in 900ml of 0.1 N HCl (pH 1.2). The time of duration of floatation was observed visually12.

 

9. In-vitro Drug Release Studies:

In-vitro dissolution studies were conducted to determine the release pattern of the drug from atenolol floating tablet. Dissolution test for atenolol floating tablets was carried out using 8 station USP Type II dissolution test apparatus (Electro Lab, TDT-O8L, Mumbai). The dissolution studies were carried out in 900ml 0.1 N HCl (pH 1.2) at 37±0.5oC. The speed of the paddle was set at 100rpm. Sampling was done every 1 h interval. An aliquot of 5ml sample was withdrawn at each time interval and replaced with equal volume of fresh medium. The samples withdrawn after suitable dilution were analysed in the UV spectrophotometer at 255nm. The mean of three determinations was used to calculate the drug release from each formulation13.

 

10. Kinetic Study:

In order to analyse the release mechanism, several release models were tested such as zero order, first order, Higuchi’s and Korsmeyer-Peppas equations were applied to the in-vitro release data.

 

11. Fourier Transform Infrared Spectroscopy studies (FTIR):

The Pure drug and selected formulations (F1) were subjected for FTIR analysis to check the compatibility/interaction between the drug and excipients. The samples were scanned over a range of 4000-400 cm-1 using Fourier transformer infrared spectrophotometer. Spectra were analysed for drug carrier interactions.14

 

Result & Discussion:

Gastro-retentive dosage forms extend drug release duration, improve patient compliance, and reduce dosing frequency. Developing floating formulations for Biopharmaceutics Classification System (BCS) Class-III drugs, like Atenolol, can reduce toxicity and ensure controlled release. Atenolol, a cardio-selective β-blocker for hypertension and angina pectoris, has low gastrointestinal absorption and a bioavailability of 50%, necessitating a sustained-release formulation to minimize plasma fluctuations and improve absorption. This study formulated and evaluated floating tablets of Atenolol using natural okra gum, which is biodegradable, non-toxic, and hydrophilic.

 

Preformulation studies:

Preformulation studies were conducted for Atenolol to assess its purity, identification, and solubility. The melting point was determined using Thiel's apparatus and found to be 152ºC, consistent with the reported range of 151-155ºC. Identification was confirmed by UV spectrophotometry, with a principal peak observed at 255 nm, matching the standard value. Solubility studies indicated Atenolol's high solubility in acidic media, with saturation solubility of 25mg/ml in water and 290mg/ml in 0.1N HCl, aligning with reported values. 0.1 N HCl was chosen as the medium to mimic physiological conditions.

 

Preparation of okra gum:

Okra mucilage was extracted using an aqueous extraction technique, followed by gum precipitation with acetone. The precipitate was dried at 60℃ for 4 hours and sieved through mesh no. 80. Okra gum, a non-starch, linear water-soluble polysaccharide, exhibits swelling, binding, suspending, and taste-masking properties. The preparation of okra gum showed in fig 2.

 

 

Okra mucilage extraction

 

Dried okra mucilage powder

Fig 2: Okra gum

 

Physiological properties of okra gum:

Mucilage yield from okra pods was 0.46% w/w (Table 2). Its presence was confirmed by purple to violet and pink coloration with Molisch reagent and ruthenium red tests (Table 3). The sticky, yellowish gum turned dark brown after drying and remained stable with no unusual changes. The swelling index was 205, indicating good swelling capacity (Table 4).

 

Table 2: Percentage yield of okra mucilage.

Sl No.

Batches

Quantity of okra pods (gm)

Weight of mucilage after drying (gm)

Percentage yield (%)

1.

Batch 1

5000

23

46

2.

Batch 2

5000

22

44

Table 3: Results of identification test for mucilaginous substance.

S. No

Description

Observations

Results

1

Molisch’s test

Purple to violet colour ring appears

Presence of carbohydrates

2

Ruthenium test

Pink colour

Present of mucilage

 

Table 4: Evaluation of okra gum

Sl No.

Appearance

λmax

pH

Swelling index

1.

Dark

201nm

6.5

205

 

Pre-compressional evaluation of Atenolol floating tablets:

Pre-compression evaluation of atenolol floating tablets was conducted to ensure good flow properties for direct compression. Lubricants like magnesium stearate and talc were added due to the poor flow of natural polymers.

 

Angle of Repose of formulation F1to F3 atenolol floating tablet powders showed in range of 22.23±0.11° to 25.89±0.02°, indicating good flow, out of these formulations F1 showed the angle of repose at 22.3±0.11°.

 

Bulk and Tapped Density: Bulk density is in range of 0.769±0.04 to 0.909±0.02g/cm³ and tapped density is in the range of 0.869±0.03 to 1.05±0.02g/cm³, indicating that make the tablets to be floatable.

 

Carr’s Index values exhibited in between the range of 9.66±0.02% to 13.42±0.02%, showing good compressibility. The Hausner’s ratio exhibited in the range of 1.106±0.02 to 1.155±0.02, confirming good compressibility as shown in Table 5. Hence The powder blend was suitable for direct compression.

 

Formulation of gastro-retentive floating tablets of atenolol:

Floating tablets of atenolol with okra gum were prepared using direct compression in three formulations (F1-F3) with varying okra gum and ethyl cellulose quantities (Fig 1) The tablets underwent pre-compression and post-compression evaluations.

 

 

Fig 1: Formulated floating tablets

 

Post compression evaluation of atenolol floating tablets.

General Appearance:

Morphological characters like shape, colour and texture was determined visually. The tablets were Tan (light brown) coloured having spherical shape, sharp edges, flat rough surface on both sides. Since natural polymers were used the colour of polymer was easily visible and tablets were not completely white.

 

As the material was free flowing, tablets were obtained of uniform weight due to uniform die filling. The thickness was found in the range of 3.0±0.17 to 3.2±0.18 mm. Since natural polymers was used in the formulation and the thickness was more compared to tablets with synthetic polymers. The diameter of tablets was found to be 10±0.11 to 10.0±0.18mm and was uniform for all tablets.

Hardness of tablets was found in between 4.2±0.02 to 4.5±0.01kg/cm2. Hardness of the formulations F1, F2 and F3 showed 4.2±0.02, 4.3±0.03 and 4.5±0.01 respectively. Among all formulations F3 showed greater hardness.

 

The percentage friability of the prepared tablets was found in between 0.74±0.04 to 0.81±0.02% and it was well within the limits i.e. below 1%, an indication of good mechanical resistance of the tablet.

 

The percentage weight variation of each tablet from average was less than 5% which proved good uniformity. The assay for drug content was found to be 96.8±0.01-98±0.02mg which was within the acceptable limits.

 

Swelling index (%) was found in between 70 – 82% for all formulations. Among them F1, F2 and F3 showed 70.66±0.05, 76.66±0.03 and 81.66±0.04 respectively. The swelling index studies showed a gradual increase with increase in concentration of gum used. F3 exhibited maximum swelling index of 81.66%. Lowest swelling index was with F1 of 70.66%. Rate of hydration of okra gum varies. Hydration rate and viscosity of okra gum does not remain constant but changes with conditions like temperature, pH, solute, concentration, etc. Hence F1 showed least swelling index (%). The swelling index for all polymers was in the order F3> F2 > F1. Tablet composed of polymeric material build a gel layer around the tablet core when they come in contact with water. This gel layer governs the drug release kinetics. Swelling is important because the gel barrier is formed with water penetration. Swelling is also vital factor to ensure floating of tablet. It was observed that swelling index were increased with increasing gum concentration. Swelling was strong enough to avoid premature disintegration as swollen burst effect and retards the release of drug for a layer period of time. For floating of tablet there should be appropriate balance between swelling and water uptake. Post compressional parameters were given in Table 6.


 

Table 5: Pre-compression evaluation of powder blend of Atenolol floating tablets.

Formulation code

Angle of repose *(θ)

Bulk density* (g/cm3)

Tapped density* (g/cm3)

Carr’s Index* (%)

Hausner’s Ratio*

F1

22.23±0.11

 0.909±0.02

1.05±0.02

13.42±0.02

1.155±0.02

F2

24.16±0.06

 0.86±0.01

0.952±0.01

11.50±0.03

1.130±0.01

F3

25.89±0.02

 0.769±0.04

0.869±0.03

9.66±0.02

1.106±0.02

 

 


Table 6: Physiochemical data for post compression parameters of atenolol floating tablets.

Formulation Code

Thickness (mm)

Diameter (mm)

Hardness Test (kg/cm2)

Weight Variation (%)

Friability (%)

F1

3.1±0.20

10±0.11

4.2±0.02

3.125±0.01

0.74±0.04

F2

3.0±0.17

10±0.18

4.3±0.03

3.03±0.09

0.80±0.03

F3

3.2±0.18

10±0.19

4.5±0.01

3.22±0.1

0.81±0.02

 

 


Table 7: Data for post compression parameter of atenolol floating tablets.

FormulationCode

Drug Content*

Swelling index *(%)

F1

96.8±0.01

70.66±0.05

F2

97.9±0.02

76.66±0.03

F3

98±0.02

81.66±0.04

 

Floating or buoyancy test:

Gastro retentive floating tablets need to possess certain characteristics for floating. Therefore, experiments were conducted for buoyancy lag time as well as total floating time. The buoyancy of the tablets was studied in USP type II dissolution apparatus at 37oC±0.5oC in 900 ml of 0.1 N HCl (pH 1.2). The time required for the tablet to rise to the surface for floating was determined as the buoyancy lag time.

 

Sodium bicarbonate induces CO2 generation in the presence of hydrochloric acid. The gas generated is trapped and protected within the gel formed by hydration of the polymer, thus decreasing the density of the tablet below 1 gm/ml and the tablet becomes buoyant. The optimized concentration of sodium bicarbonate was found to be 5% of total tablet weight and it was maintained constant in all the floating tablets prepared. All floating tablets had buoyancy lag time in the range of 22±0.11 to 37±0.22 sec. All the tablets prepared were floated for 12 h. Formulations F1, F2 and F3 showed 22±0.11, 33±0.17 and 37±0.22 respectively. Among all formulations F1 has the best floating time than other formulations. The total floating time was found to be 12 h indicating a stable gel layer formation by natural polymer selected and sodium bicarbonate that persists for a longer time. The results of the buoyancy lag time and total floating time for the different Atenolol floating tablets is given in Table 8.

 

 

Table 8: Floating lag time and Total floating time of Atenolol floating tablets.

Formulation Code

Floating lag time (sec)*

Total floating time (hr)*

F1

22±0.11

12

F2

33±0.17

12

F3

37±0.22

12

 

 

In-vitro drug release studies:

In-vitro dissolution test was carried out for Atenolol floating tablets formulation F1, F2 and F3. and showed the drug release was in range of 84.16% to 66.74% of drug in 12h. The order of drug release from all formulations prepared was F1>F2>F3. F3 showed maximum controlled release of drug than other formulations. The results also indicated that the rate of release of the drug decreased as the amount of okra gum in the tablet increased (F1-84.16%, F2 – 72.15% and F3-66.74%). The slow release of drug with increase in polymer content may be due to formation of thick gel layer, causing the difficulty in drug diffusion through the matrix and thus decreasing the overall drug release from the matrix.

 

It was observed that the type of polymer influences the drug release pattern the percentage release profile was shown in Table 9 & Fig 2. A significantly higher rate and extent of drug release was observed from batches based on okra gum and sodium bicarbonate than based on ethyl cellulose. The combination of high percentage of okra gum and sodium bicarbonate formulations (F1, F2 and F3) were provide drug release for longer time, different concentration of ethyl cellulose did not affect the drug release.

 

A hydrophilic matrix-controlled release system is a dynamic system composed of polymer wetting, hydration and dissolution. At the same time, other soluble excipients or drug(s) will also wet, dissolve and diffuse while the insoluble ingredients will be held in place until the polymer erodes or dissolves. Since the diffusional release of atenolol drug may primarily be controlled by the gel thickness (diffusion layer), increasing polymer level tends to decrease drug release. The effect of increase in the polymer level on drug release, results in the increase in the thickness of the gel layer, which retards drug diffusion out of tablet. Given the complexity of these swellable floating systems other factors such as, differences in water penetration rate, water absorption capacity and swelling, polymer erosion and attrition which result from changes in the polymer content may contribute to this effect.

Table 9: Comparison of In-vitro release profile Atenolol floating tablets (F1, F2 and F3).

Time

% Drug Release

 

F1

F2

F3

0

0

0

0

1

16.79

15.58

14.99

2

21.64

20.42

18.03

3

32.46

25.84

23.44

4

36.07

31.25

28.24

5

42.56

34.86

30.66

6

49.63

39.06

34.86

7

52.31

42.67

38.46

8

58.8

51.09

45.08

9

69.7

57.72

49.88

10

76.3

63.72

54.7

11

81.17

67.33

61.32

12

84.16

72.15

66.74

 

 

Fig 2: Comparison of In-vitro release profile Atenolol floating tablets (F1, F2 and F3).

 

Kinetic study:

To investigate the mechanism of drug release from atenolol floating tablets, various kinetic models like zero order, first order, Higuchi’s and Korsmeyer-Peppas equations were applied to the in-vitro release data obtained from different formulations. As observed from Table 21, the values of correlation-coefficient (r2) for all the formulations were high enough to evaluate the drug dissolution behaviour. The value of release exponent (n) was found to be a function of polymer used and the physicochemical property of a drug molecule itself. –

 

When the data was plotted as per zero order kinetics, plots were obtained with high correlation coefficient values ranging from 0.9846 - 0.9826. First order plots showed low correlation coefficient values ranging from 0.9556- 0.9649. From the observations it was concluded that the selected formulations followed zero order release indicating that the dissolution rate of drug was independent of the amount of drug available for dissolution. When the drug release data was fitted to Higuchi equation, linear plots were obtained with high correlation coefficient values ranging from 0.9599 - 0.9473. The drug release was proportional to square root of time indicating that the drug release from all the floating tablets was diffusion controlled. The release data obtained were also put in Korsemayer-Peppas model in order to find out n values, which describe the drug release mechanism. The n values of different floating tablets were found in the range of 1.1514 – 1.0597, indicating non-fickian super case II type transport mechanism. Hence the above observations led us to conclude that, all the atenolol floating tablets followed diffusion controlled zero order kinetics.

 

To see influence of concentration of microcrystalline cellulose on release rate of atenolol were found that diffusion controlled zero order kinetics, plots were obtained with high correlation co-efficient values ranging from 0.9846-0.9824. It was also observed that the release rate was found to be influenced by MCC employed in the preparation of tablets. Good correlation was observed in between the concentration of MCC and release rate. The results of kinetic study are shown in Table 10.

 

Fourier Transform Infrared Spectroscopy studies (FTIR):

The IR spectra of pure drug, okra gum and optimised formulations F1 were studied in detail in order to ascertain whether there is any interaction of drug and excipients (Fig 3, Fig 4 & Fig 5). The drug excipient interaction study provides stability data of the drug and shelf-life of drug. The FTIR spectroscopy is the best method to evaluate the drug excipients incompatibility study. The study of FTIR spectroscopy indicated the characteristics peaks due pure atenolol have appeared without any change in their position after successful formulation of floating tablet. It indicates no chemical interaction between atenolol and excipient; hence the drug was found compatible with the excipient used.


 

Table 10: Kinetic profile of Atenolol floating tablets (F1 – F3)

Formulation code

Zero order

First order

Higuchi plot

Korsmeyer peppas plot

N

r2

N

r2

N

r2

N

r2

F1

6.6617

0.9846

0.0638

0.9556

25.396

0.9599

1.1514

0.7078

F2

5.5384

0.9844

0.0431

0.9713

21.06

0.95548

1.0928

0.7002

F3

4.9427

0.9826

0.0354

0.9649

18.75

0.9473

1.0597

0.698

 


 

Fig. 3: FTIR spectra of pure drug atenolol.

 

Fig 4 FTIR Spectra of Okra gum

 

Fig. 5: FTIR spectra of Atenolol floating tablet (F1).

 

CONCLUSION:

Atenolol floating tablets with better dissolution profiles could be successfully developed by using polymers and direct compression method. The floating tablets showed promising results which may prolong the time the medicine spends in stomach, without affecting the gastric emptying rate and controls variations in plasma drug concentrations thus eventually improve the drug’s bioavailability. Thus, it exists a scope for further in vivo evaluation using suitable models.

 

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Received on 21.01.2025      Revised on 05.03.2025

Accepted on 16.04.2025      Published on 08.07.2025

Available online from July 12, 2025

Asian J. Pharm. Tech. 2025; 15(3):217-225.

DOI: 10.52711/2231-5713.2025.00033

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