Formulation and Evaluation of Glipizide Effervescent Tablets

 

Ravindra M. Hanwate*

Associate Professor, Department of Pharmaceutics, Valmik Naik College of Pharmacy, Telwadi,

Kannad Dist. Chh. Sambahjinagar, Maharashtra, India.

*Corresponding Author E-mail: ravi_hanwate@yahoo.co.in

 

ABSTRACT:

The current study aims to create effervescent tablets of Glipizide that offer better elegance, comfort, and improved drug performance in treating diabetes compared to traditional tablets. Three versions of the effervescent Glipizide tablets (5mg each) were made using different combinations of ingredients. Using the wet granulation method, 60 tablets were made for each version, each weighing 700mg. The physical properties of both the granules and tablets were tested using established methods. Tests like angle of repose, Hausner ratio, Carr's index, loss on drying, and moisture content showed that the granules had good flow and compressibility. However, tests related to physical appearance and drug content did not clearly show which of the three tablet versions the best was. The friability of the tablets was 0. 71%, which is within the acceptable range set by USP? The average time it took for the tablets to break down was between 95 and 105 seconds. The potency test showed that F1 had 95%, F2 had 88%, and F3 had 97% of the expected drug content. The drug release followed a straight line over time. After 1.5hours, F3 released the highest amount of the drug, at 59%, showing better solubility. Since Glipizide is a drug that dissolves poorly in water, the effervescent tablet may help with the breakdown and release of the drug, leading to better absorption in the body.

 

KEYWORDS: Anti diabetics, Granulation, Dissolution, Effervescent, Drug solubility, flow property.

 

 


INTRODUCTION:

Effervescent tablets combine features of both solid and liquid medicines. When placed in water, they dissolve and turn into a liquid that can be easily taken. This makes the medicine more pleasant to drink, but it still keeps the benefits of solid tablets, like accurate dosing, long shelf life, and easy carrying.1 This form is becoming more popular because it's easy to take. The special design of the tablet causes it to float and then break apart when it comes into contact with water, creating a fizzy solution.2

 

However, making and storing these tablets involves several important factors. They are sensitive to chemical changes because the ingredients tend to absorb moisture easily. Even a small amount of water can start a reaction that keeps going until the medicine's quality is ruined.3 So, the production and storage of these tablets must be done in a controlled environment with the right humidity and temperature levels. Glipizide is a second-generation anti-diabetic medicine from the sulfonylurea group used to treat type II diabetes.4-5 People with type II diabetes have issues like too much glucose production by the liver, not enough insulin release, and resistance to insulin, which can cause mild to severe high blood sugar levels.6 Glipizide works by affecting the pancreatic beta cells. It partially blocks potassium channels in these cells, which causes the voltage-gated calcium channels to open. This leads to more calcium flowing into the cells, which helps release stored insulin.7-8 According to the Biopharmaceutics Classification System (BCS), Glipizide is a Class II drug, meaning its absorption is mainly limited by how well it dissolves in the digestive tract, which affects how much of it is absorbed into the body when taken by mouth. Previous research shows that techniques like reducing particle size, improving dispersion, and using cyclodextrin complexes can help improve both in vitro and in vivo absorption and bioavailability of Glipizide.9-10 Patients are usually advised to take one or two doses a day, with a maximum daily dose of up to 20mg. Also, studies show that how well Glipizide is absorbed in the body depends on the way it's formulated. Diabetes is a long-term condition, so the way it's treated and the medicines used should be easy to manage and fit into everyday life. Also, solid medicine forms, like tablets, can be hard for elderly and young patients to swallow. This problem is even bigger for people who have difficulty moving or eating.11-12 The study on making new medicines aimed to reduce the issues with how drugs dissolve in the stomach and intestines, and to create a better medicine form that makes it easier for patients to take over a long period, improving both their willingness to take the medicine and how well it works in the body.13-15

 

MATERIAL AND METHODS:

a.     Chemicals and reagents:

Glipizide was given as a free sample from JB Chemical in Thane. Corn starch, polyvinyl pyrrolidone, citric acid, Sodium bicarbonate, Lactose, Ascorbic acid, Sodium Saccharine, Congo red, Magnesium stearate, and Sodium Metabisulphite were bought from Merck India. All the reagents were of standard quality and purchased from local suppliers.

 

b.    Tablet formulation

Three versions of Glipizide 5mg tablets, named F1, F2, and F3, were made with different amounts of other ingredients. Each tablet weighed a total of 700mg, and the details are shown in Table 1. This study was done in the Pharmaceutics Laboratory at Valmik Naik College of Pharmacy in Kannad.

 

Table 1. Formulations of effervescent tablet. 16

Ingredients

F1

(mg)

F2

(mg)

F3

(mg)

Glipizide

5

5

5

Polyvinyl pyrrolidone K30

(PVP K30) (Binder)

90

95

100

Corn Starch

(Binder and Disintegrating agent)

110

115

120

Sodium bicarbonate

(Base and effervescent agent)

140

130

120

Citric acid (Acidifier)

40

35

30

Ascorbic acid(Acidifier)

50

45

40

Sodium Saccharine (Sweetener)

5.5

6

5

Lactose (Diluents)

226

243

260

Magnesium stearate (Lubricant)

14

12

10

Sodium Metabisulphite (Stabilizer)

3.5

3

4

Congo red cool (Coloring agent)

1

1

1

Raspberry flavor (drop)

1

1

1

Water (ml)

0.5

0.5

0.5

Total wt.

700

700

700

c.     Tablet preparation:17

50 Tablets were made using the wet granulation method. Ascorbic acid, citric acid and saccharine were mixed together using a mortar and pestle. Then, Glipizide was added to this mixture. The mixture was then combined with slurry made from warm water, polyvinyl pyrrolidone (PVP), and four-fifths of the starch used in the formulation. The wet mass was dried for one hour at 80 degrees Celsius. After drying, the hard mass was ground to make granules that could pass through a 60 mesh sieve. Next, saccharine, one-fifth starch, sodium metabisulphite, sodium bicarbonate, and magnesium stearate were mixed with the granules to form the final powder. This powder was then compressed using 13mm flat punches in a 15-ton manual hydraulic pellet press, applying a pressure of 10.05 tons during the tablet compression.

 

The angle of repose (θ) measurement:

A resting angle is the highest possible angle between the powder pile surface and the horizontal plane. It is indicative of the flow properties and friction force of the loose powder

 

θ=tan-1(H/R)

θ, the angle of repose; H, the height of pile; R, the radius of the base of the pile.

 

d.    Hausner's ratio:

It is the ratio of tapped density/bulk density related to inter particle friction could be used to predict powder flow properties. The Hausner's ratio was calculated by the formula as given below:

Hausner’sratio=Tappeddensity/Bulkdensity=Df/Do

 

e.     Carr's Index:

The indirect method of measuring powder flow from bulk densities, also known as percentage compressibility. Carr's index of each formulation was calculated according to the equation described by

Carr’s index = [(Df-Do) Df] ×100

Where, Do = bulk density; Df = Tapped density

 

f.      Loss on drying : LOD determination:

Powder equivalent to ten tablets was dried for 4 hours in a desiccators containing silica gel. LOD was calculated as

LOD= [(Wi-Wf)/WI] ×100%

Where Wi and Wf are the initial and final weights of the granules, respectively.

 

g.     Moisture content (MC) determination:

The percent moisture content was calculated using the equation.

 

Moisture Content = [(Wi-Wf)/Wf] ×100%

Where Wi and Wf are the initial and final weights of the granules, respectively.

 

h.    Organoleptic properties test: 18

Ten healthy volunteers were used for each formulation to test the color, smell, and taste of the 200 ml solution made from one effervescent tablet. Each volunteer gave informed consent before taking part in the test. For the color and smell tests, volunteers used the terms: Bad, moderate, good, or pleasant. For the taste test, they provided comments like Sweet, Bitter, Sour & Sweet, or Sour.

 

i.      Table hardness measurement: 19-20

The hardness of each tablet formulation was checked using a Monsanto Hardness Tester. This test measures how strong the tablet is, which the amount of force needed to crush it is. Ten tablets from each formulation were tested, and the results were recorded in kilograms. in kg.

Hardness average=Total hardness of all tablets /No. of tablets

 

j.      Tablet thickness and diameter determination:

The thickness and diameter of ten tablets for each formulation were evaluated using a calibrated dial caliper.

 

k.    Weight variation determination:

Twenty tablets were taken randomly for each formulation. Then, tablets individually measured the weight of tablets, and each tablet's deviation from the average weight was calculated.

 

l.      Friability (F) test:

Roche Friabilator was used to assess the friability of the tablet. 10 pre-weighed tablets for each formulation were placed in the Friabilator and were subjected to the100 revolutions. Tables have been polished using a soft muslin cloth and measured. The formula gives the friability (F)

F= [(Wi-Wf) /Wi]×100

Where Wi and Wf are the initial and final weights of the tablets, respectively.

 

m.   Measurement of effervescence time:

Single tablet was placed in a beaker containing 200 ml filtered water at 20°C±1°. When a clear solution is obtained, effervescence time has been recorded using a stopwatch. The average of five dimensions was calculated to compare the formulations for each formulation.21

 

n.    Determination of effervescent solution pH:

The pH was determined using the pH meter. Complete dissolution in 200 ml of purified water at 20±1°C, immediately after each tablet was dissolved.

 

o.     Tablet's potency determination:

The potency of tablets was determined using a UV spectrophotometer ((Shimadzu UV-1800 spectrophotometer, Shimadzu, Japan) at λmax = 270nm.

p.    Preparation of standard curve:

Glipizide mother solution was made to dissolve in water at strength of 10mg per ml. This solution was then diluted step by step to create concentrations of 1mg per ml, 0. 2mg per ml, 0. 06 mg per ml, 0. 024mg per ml and 0. 012mg per ml. After that, the absorbance was measured at a wavelength of 270nm using a UV spectrophotometer.

 

q.    Dissolution Studies:

The release of Glipizide from the tablet was tested using a USP Dissolution Apparatus II, which uses a paddle method. The temperature was maintained at 37±0.50C and the dissolution medium was 900ml of phosphate buffer with a pH of 6. 8. The paddle was set to rotate at 50 revolutions per minute throughout the test. At each of the times 5, 15, 30, 45, 60, and 90 minutes 5ml of sample was taken from the medium and the same amount of fresh medium was added back. The collected 5ml sample was diluted twice before measuring its absorbance. The absorbance was measured using a UV spectrophotometer at a wavelength of 270nm, with the phosphate buffer pH 6. 8 used as the reference. The raw data were then used to calculate how much drug was released and the percentage of that release at each time point. 21

 

RESULT:

The study shows three steps in quality assurance. First, it looked at the characteristics of granules, which helps understand how they flow, stick together, and can be pressed into shape. Second, it examined the physical features of the tablets. Third, it checked the parameters related to the amount of drug in the tablets.

 

 

Table 2.   Tablet granules of the formulations (F1, F2, and F3)

Granules parameter

F1

F2

F3

Angle of Repose

23.12⁰

27.24⁰

25.24⁰

Hausner ratio

1.16

1.16

1.17

Carrʼs index

14.325%

14.324%

14.931%

Loss on Drying

1.06512%

1.2832%

1.2832%

Moisture Content

1.08516%

1.3004%

1.3004%

 

 

 

The angle of repose of F1 was the least, and the angle for all formulation is less than 30º. Hausner ratio and carr's index for the formulations were almost the same. F3 showed a little bit of variation from the other two. Values of Loss on drying and Moisture content for F3 were smaller than the others in both cases. Whereas the LOD values for F2 and F3 were the same and the same on MC. The features of granules property are represented in table -2.

 

 

 

 

 

 

Table 3. Physical parameters of tablets of the three formulations (F1, F2, F3)

Tablets parameter

F1

F2

F3

Colour

Pleasant

Pleasant

Pleasant

Smell

Pleasant

Pleasant

Pleasant

Taste

Sour

Sour/sweet

Sour

Thickness (mean in mm)

4.04±0.01

4.07±0.02

4.06±0.01

Diameter (mean in mm)

12±0

13±0

13±0

Weight variation (mg)

702.35± 9.931

703.80± 16.732

704.80±9.217

Hardness (mean in Kg)

2.05±0.093

2.61±0.086

3.65±0.203

Friability

0.71%

0.73%

0.69%

Disintegration time (seconds)

105

90

100

pH of the effervescent solution

7.0±0.02

7.0±0.02

7.0±0.02

 

The model on the volunteer comment on the color and smell of three formulations was the same, but the mode of taste for F2 was sour and sweet, whereas, for F1 and F3, it was sour. The mean thickness of F1 and F2 was 4.05 mm, and the mean of F2 was 4.06. The mean diameter of the formulations was 13. The highest mean weight of 20 tablets was for F3, but the standard deviation was the highest for F2. The mean hardness of F1 and F3 was around 2.60 kg, but the hardness of F1 was 2.05 kg. The formulations showed a friability of around 0.7%. However, the mean disintegration time showed few deviations depending on the formulation. This time of F1, F2, and F3 was 105s, 90s, and 100s. The last physical parameter was to determine the pH of the effervescent solution. In all of the cases, the values were 7.0 ±02. The physical parameter of different formulations of Glipizide 5mg tablets are represented in Tabe-3.

 

Figure 1. The potency of effervescent tablets for the three formulations

 

The highest potency, 97.4%, was explored by F3 among the three formulations, as mentioned in Fig1. Moreover, the lowest potency was found for F2, with a value of 88.8%. According to Fig2, the regression line was very close to 1, indicating the linear relationship of absorbance with concentrations.

 

 

Figure 2: Standard Dose response curve of Glipizide

 

Figure 3. The cumulative percentage of drug dissolution from the tablets

 

As time passed, more of the drug dissolved in the different formulations, as shown in Figure 3. The measurements started at 5 minutes and went up to 90 minutes. At 5 minutes, only F3 had about 15% of the drug dissolved. By the end of the test, the total amount of drug dissolved was 48% for F1, 52% for F2, and 59 % for F3. F1 had the lowest amounts dissolved at most time points, while F3 had the highest total dissolution among the three.

 

DISCUSSION:

Most oral tablets and capsules are made to be chewed or swallowed. Even though effervescent forms look nice, there's no 5mg version of Glipizide in this form. Because the drug isn't very soluble in water and is easier for patients to take, we made three effervescent tablets instead. All three formulations had repose angles less than 30, meaning the granules flow very easily. The Hausner ratio was between 1.12 and 1.18, and the Carr index was between 11 and 15, which shows the powder flows well. These values were within the expected range, so the granules have good flow, but not excellent. Also, the moisture content was below 2.5%, which helps the granules flow smoothly. We kept the loss on drying (LOD) and moisture content (MC) around 1.3% to improve flow and reduce the risk of moisture being absorbed by hygroscopic ingredients like ascorbic acid and citric acid. The color and taste of the effervescent solution depend on the type and amount of coloring and flavoring added. Even though the color and flavor should match, a reddish color with a raspberry flavor in a certain amount was found to be pleasant by volunteers. The taste of the solution comes from the acids, bases, and sweeteners used in the formulation. Formulation F2 tasted sour and sweet, which may be better than the other two formulations' sour test. Though the formulations' hardness was less than 3, the determined friability was less than 1%. What is more, the effervescent time and solution pH of all the formulations were acceptable for the dosage form that had the least hardness. This could be because they used more of a disintegrating agent (corn starch) and a lubricating substance (magnesium stearate) compared to the others. However, the moisture content (MC) and loss on drying (LOD) of F1 were lower than the others, which might have affected the hardness. Testing the drug content in the tablets showed that F2 did not meet the USP and BP standards. This could be due to its higher weight variation. The other two formulations passed the USP specifications, with results within the range of 90%-100%. After confirming the dose-response relationship using UV absorbance, drug release patterns were tested. Glipizide is a drug that doesn't dissolve well in water, so its dissolution into the test medium might be low. After one and a half hours, F3 had the highest cumulative drug release, at 59. 2%. The lower amount of binder PVP in F3 might be the reason for this higher drug release. The drug release and dissolution from the three formulations were better than from regular tablets and floating effervescent tablets. This raises a question: does this new formulation offer any real therapeutic benefit compared to traditional Glipizide tablets? The effervescent dosage form starts releasing the drug through the physical breakdown of the tablet. Although the drug's interaction with water on a molecular level is not significant, the drug molecules spread into the medium, forming dispersion. This dispersion might lead to better dissolution and absorption, and increased permeability through the body's membranes. This study successfully developed a 5 mg Glipizide effervescent tablet that disintegrates within two minutes. It is more pleasant for patients due to its taste and appearance, and meets all other tablet requirements. Patients can easily adopt this formulation for long-term diabetes management.

 

CONCLUSION:

The research investigated the significant connection among syntheses and results on the test boundaries. Bubbly tablets offer appealing stylish qualities and improve the bioavailability of medications when contrasted with customary tablets. This bubbly definition will be more appealing choice for diabetic patients, particularly for patients with delayed enemy of diabetic treatment, and drug organizations overall can embrace this detailing after a fruitful bioequivalence study to assess the viability of the pre-arranged bubbly tablets.

 

ACKNOWLEDGMENTS:

Authors are thankful management of Valmik Naik College of Pharmacy, Telwadi Kannad for providing Lab facility. Authors are also thankful to JB Chemicals for providing gift sample of drug.

 

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Received on 17.07.2025      Revised on 08.11.2025

Accepted on 25.01.2026      Published on 15.04.2026

Available online from April 18, 2026

Asian J. Pharm. Res. 2026; 16(2):151-155.

DOI: 10.52711/2231-5691.2026.00023

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