Development of Zinc Gluconate Vitamin C Effervescent Tablet for Immunity Improvement and Management of COVID-19

 

Bagul Mahesh B.*, Surawase Rajendra K.

Department of Pharmaceutics, Loknete Dr. J. D. Pawar College of Pharmacy,

Manur, Tal. Kalwan - 423501, Dist. Nashik, (MH) India.

*Corresponding Author E-mail: bagulmahesh12245@gmail.com

 

ABSTRACT:

This look at aimed to increase the system of effervescent tablet containing zinc Gluconate and Ascorbic acid (vit c) combination to increase immunity and likely through reducing viral load and improving immunity of the patients. In this examine the formula turned into calculated exactly and then prepared by way of two distinct srtategies for compression and assessment. The flowability of powder and grannules turned into investigated effervescent tablet were produced by way of direct compression and wet granulation approach. The produced tablet have been then evaluated for appropriate hardness, friability ˂1%, effervescent time ˂ 3 minutes, solution PH ˂6, water content ˂ 0.5% and most beneficial content uniformity. The powder aggregate prepared for the direct compression technique had acceptable flowability however required a excessive compression force. Flowability and different physicochemical properties of this powder. Including compressibility and hardness have been progressed with the aid of granulation. The result of effervescent tablet produced by way of the moist granulation technique, which incorporate a higher percent of granulated content material have been higher than other method. The PVP-K30 binder solution is suitable to produced bubbling granules which are compressed into tablet, because of improvement in flowability and compactibility.

 

KEYWORDS: Zinc Gluconate, Vitamin C, Effervescent tablet, Immunity, Wet granulation method.

 

 

1. INTRODUCTION:

Effervescent include a soluble natural acid and an alkali metal carbonate salt that release Carban dioxide in contact with water. Effervescent tablet are typically made by way of compressing the active component with a combination of sodium bicarbonate and organic acid which includes citric acid and tartaric acid. The primary benefit of effervescent tablet in the rapid onset of movement because of quik production of buffered bubbling solution.

 

 

PVP-K30 is an powerful binder for effervescent tablet and can be used each in moist granulation and in direct compression low relative humidity (maximum 25% or much less) and moderate to cool temperatures (25°C ) Inside the production regions are essential to save you granules or tablet from sticking, picking up moisture in the air which might also cause product degradation.1,2 The patient must take vitamin c supplement at the same time to will increase immunity and minimized the disease burden. Zinc gluconate in aggregate with excessive dose of Ascorbic acid (1000mg) to boom the immunity and save you disease. The aim of this observe turned into to design broaden and evaluation of the effervescent tablet which comprise zinc gluconate and ascorbic acid (vitamin c aggregate.3,4

2. MATERIAL AND METHODS:

Material:

Chemicals:

Zinc gluconate pure drug was purchased from Chemkart Drug, Bhiwandi, Maharashtra, india. Vitamin c was purchased from fine chemicals Mumbai india. PVP-K30 was purchased from the fine chemicals, Mumbai, india. All the other reagents obtained from Research lab.

 

Instrumentation:

The work was accomplish on a UV- visible spectrophotometer (model uv-3000 Labindia), tablet compression machine was manufactrure by cemach machinaries LTD. Ahmadabad (model no. 8 station, D) the FTIR spectra of API and its excipients were secure by fourier transform infrared spectrophotometer (Aglient Technologies). All weighing was done on electronic precision balance (wenser PGB 220).

 

2.1 Methods:

Method of production of effervescent tablet:

Direct Compression:

The formulation material have been weighed in according to table no1. Sodium bicarbonate was dried at 100°c for 1 hour and combined with other additives for 15 mins. after preparing the number one aggregate, add sweetner or orange flavour have been handed via a 0.8 mm sieve and delivered to the aggregates and combined for 5 mins. Final the magnesium stearate lubricant was delivered and mixed with other material for about 2.5 mins again. The powder aggregate turned into then compressed into tablet the use of a tablet press machin ( Labindia) with a 20 mm punch at a most of 25% RH. In the end the tablet had been dried in an oven with air move at 50°C for 1 hour after which packed in plastic tubes after cooling.5,6

 

Wet Granulation:

According to table 1 mixture of sodium bicarbonate, citric acid passed through 35 mesh sieve much (˂ 0.5 mm) and mixed for 10 minutes. then 5% w/v PVP-K30 solution is isopropanol changed into added dropwise the usage of a pipette to the combination until an pasty mass formed. This wet mass passed through sieve no 10 and the ensuring grannules have been dried in an oven at 50°c until dry. The dried mass became then passed via 10 mesh sieve. at last magnesium stearate became brought to granules combination become compressed into tablet the use of tablet press system with a 20 mm punch at most 25% RH. The prepared tablet have been dried in an oven with air flow at 50°c for 90 minutes.

 

3. RESULT AND DISCUSSION:

3.1 Characterization of physicochemical properties of drug:

Organoleptic properties:

Color - white

Nature – amorphous powder

Odor - odorless

 

3.2. Pre-formulation study:

Physical constant:

Melting point of zinc gluconate was examine by capillary fusion method. It was found to be 131°c to 1400c.

 

Solubility profile of drug:

Solubility of zinc gluconate was determined by flask shaking method. It was insoluble in chloroform, slightly soluble in propylene glycol, and freely soluble in water, ether, ehanol, methanol.

 

Table No. 1. Composition of Zinc Gluconate vit c effervescent tablet.

Ingredients (mg)

F1

F2

F3

F4

F5

F6

F7

F8

Zinc Gluconate

40

40

40

40

40

40

40

40

Vitamin c

1000

1000

1000

1000

1000

1000

1000

1000

Sodium bicarbonate

60

60

60

60

60

60

60

60

Citric acid

384

576

768

384

384

450

450

450

Magnesium stearate

16

16

16

16

16

16

16

16

PVP-K30

50

100

150

200

250

300

350

400

Mannitol

30

30

30

30

35

35

35

35

 

Stability study of zinc gluconate with excipient:

Table no. 2. Compatibility study of drug with excipients:

Sr. No

Zinc gluconate +Excipient

Observation

Conclusion

Initial (color)

After 15 day

1

PVP-K30

white powder

No change

Compatible

2

Na bicarbonate

white powder

No change

Compatible

3

Citric acid

white powder

No change

Compatible

4

Mannitol

white powder

No change

Compatible

5

Mg stearate

white powder

No change

Compatible

6

Vitamin c

white powder

No change

Compatible

 

 

Characterization of Zinc Gluconate by differential scanning calorimetry:

 

Fig.1 DSC curve of Zinc gluconate

 

Discussion:

The thermal stability of Zinc gluconate was examined by differential scanning calorimetry (DSC). The activation energy of thermal degradation of zinc gluconate was -458.20 mcal and -196.16 mcal respectively. the melting point of zinc gluconate is observed in 144.990C. The result were in good agreement.

 

Refractive index of Zinc Gluconate:

In this work Abbe’s refractometer become used to measure refractive index of the zinc gluconate using a particular monochromatic light supply. The equipment is calibrated with water as a liquid. adjust the micrometer screw to attention the boundry between the bright and dark area. Adjust refractometer scale to area the cross cord of the telescop precisely at the boundry between the brightish and darkish areas. Repeat the identical manner for zinc gluconate liquid after the gadget is calibrated.

 

Discussion:

The refractive index of the zinc gluconate sample at 200C is 1.4130. the result is observed in good and acceptable limit.

 

Drug – Excipient study by FTIR:

the physical mixture of zinc gluconate, PVP-K30, Sodium bicarbonate, citric acid, mannitol, magnesium stearate, Ascorbic acid. Were kept under compatibility study for temperature 400C. ±75 RH for period of two weeks. without any significant physical changes. Therefore it is confirmed that all the active and inactive excipients which were kept under compatibility study are compatible with each other all these ingredients were selected and used in present work.9,10

 

 

 

Table no. 3. Interpretation of FTIR peak present in zinc gluconate                                                   

Sr. No

Frequency cm-1

Functional group

1

Above 3000

Hydroxy acid

2

2927

OH group of zinc gluconate

3

2839

OH

4

1597

RCOO – (asymetric streching)

5

1541

RCOO -

6

1429

RCOO (symetric stretching)

7

1199, 1160, 1095, 1056, 1025

C-O Bond (Asymetric streching),

O-C-C (symetric streching)

8

896, 696, 653

Carboxylate group (out of Plane)

 

Discussion:

The IR spectrum of the Zinc gluconate was recorded and the IR spectra of zinc gluconate show functional group as per the structure. The table gives the interpretation of the peak obtained in the IR spectra along with their corresponding functional group.

 

 

Fig.2 FTIR spectra of pure Zinc Gluconate

 

 

Fig.3 FTIR spectra of Zinc Gluconate with All Excipients

 

Pre-compression evaluation test:

Pre-formulation studies: prior to compression, effervescent grannules were evaluated for their characteristic pre-compression parameter, such as bulk density, tapped density, Hausner ratio, carr’s compressibility index and angle of repose.11,12,13

 

Table No. 4. Pre-compression evaluation of formulation (Tablet)

Flowability characteristic

F1

F2

F3

F4

F5

F6

F7

F8

Angle of Repose

43.2

38.9

36.5

37.2

36

34.6

34.1

26.2

Bulk density

0.66

0.68

0.67

0.69

0.70

0.71

0.72

0.75

Tapped density

0.84

0.83

o.81

0.83

0.83

0.82

0.81

0.82

% CI

21.4

18.1

17.4

17.8

16.5

14.4

13.2

8.5

Hausner ratio

1.27

1.22

1.21

1.22

1.2

1.17

1.15

1.09

 

Discussion:

The flowability study of all direct compression formulation (F1 to F7) show moderate and acceptable flowability. The best flowability is related to the formulation of wet granulation (F8). The formulation (F8) indicate that, the powder mixture posses good flow of powder and Compressibility properties.

Post-compression evaluation test:

Post-compression parameter like Effervescent time, Effervescent solution PH, Hardness, Friability, Thickness, weight variation, CO2 content, water content, content uniformity studies were performed.14,15.16

 

 

Table no.5. Post Compression Evaluation of formulation (Tablet)

Physicochemical evaluation

F1

F2

F3

F4

F5

F6

F7

F8

Effervescence time (s)

232.3±4

241.8±4

234.3±6

226.5±3

207.3±4

201.6±3

177.5±3

162.6±4

 PH

5.2±0.1

4.5±0.1

3.5±0.1

5.8±0.2

6.3±0.2

4±0.1

4.2±0.1

4.9±0.4

Hardness (kg/cm2)

19.16±0.2

19.61±0.6

28.35±0.5

38.22±0.3

28.45±0.3

29.42±0.8

39.22±0.4

49.03±0.5

Thickness (mm)

5.6±0.1

5.4±0.1

5.6±0.1

5.7±0.1

5.5±0.1

5.9±0.1

5.8±0.1

5.8±0.1

CO2 content(mg)

313±4.5

246±4.3

770±4.1

364±5.2

573±3.4

162±2

94±1.6

112±3.4

Water content (%)

0.05

0.06

0.09

0.06

0.05

0.13

0.12

0.2

Weight variation (mg)

1996±0.5

2005±1.2

1995±0.6

1998±0.8

2002±0.5

1998±0.6

2005±0.4

2001±0.7

Friability (%)

0.92

0.93

0.95

0.95

0.97

0.94

0.94

0.75

Content uniformity mg

493±7.5

494±12

494±7

492±10

493±8

499±7.7

500±9.5

499±9.1

 

Table no.6. In-vitro drug release of Zinc gluconate phosphate buffer PH 6.8

Time

Zinc gluconate

F1

F2

F3

F4

F5

F6

F7

F8

0 min

0

0

0

0

0

0

0

0

0

15min

37.57

39.38

40.88

46.11

45.32

46.04

47.20

46.12

45.31

30min

38.62

41.39

41.38

47.22

46.91

47.4

49.91

47.32

46.90

45min

40.33

42.46

42.84

48.22

48.20

48.33

50.92

48.20

48.21

60min

41.97

44.33

43.33

49.12

50

50.35

51.06

49.10

50

75min

42.73

45.25

44.25

51.13

51.07

51.72

52.22

51.12

51.05

 

Discussion:

The weight variation obtained for all formulation in the range of 1996 to 2005 mg. and the thickness of the tablet of all the formulation was found in range of 5.6 to 5.8mm which is in the good range. The hardness of the tablets of all the formulation was found in the range of 19.16±0.2 to 49.03±0.5 (2 to 5kg/ cm2) which is excellent or in the acceptable range. The friability was found to be in the range 0.75 to 0.97%. The effervescent time of the tablets of all formulation was found in 162.6±4 to 241.8±4 S which is good and acceptable range. The effervescent solution of PH of all tablet 3.5±0.1 to 6.3±0.2 which is in the good range. The CO2 content of all tablet was found in 94±1.6 to 770±4.1mg which is acceptable limit.

 

In-vitro Dissolution studies:

The release rate of zinc gluconate effervescent tablets became decided the use of USP dissolution testing apparatus 2 (paddle type). The dissolution medium used turned into 900ml of Phosphate buffer PH 6.8 which become maintained at 37±0.50C. the paddle speed changed into stored at 50rpm.17,18.

 

CONCLUSION:

This take a look at attempted to formulate and produced effervescent tablet containing zinc gluconate and vitamin c combination the usage of direct compression and wet granulation method. The end result of this have a look at display that each method are relevant however moist granulation is more suitable technique to produced zinc gluconate vit c bubbuling tablet. The approach is accomplished throughincluding a granulator approach to the powder aggregate to gain a wet mass. In this examine all assessment consequences are according with the pharmacopoeia standards.

·       The produced bubbling tablet by the wet granulation method were greater compact and uniform in content they did no longer have any of the processing troubles.

·       The advanced formulation is suitable for all physicochemical homes. Consisting of effervescent time much less than 3 min, PH less than 6, friablity under 1%, water content material beneath 0.5 % low weight variation.

·       The metalic taste of zinc gluconate become also masked by way of adding orange flavour as an awful lot as viable.

·       These tablet are very useful in control of COVID-19 due to the fact their ascorbic acid and zinc gluconate to growth immunity, indirect antiviral hobby, and limit the sickness burden.

 

ACKNOWLEDGEMENT:

We are grateful to the Teacher’s and Principal of Loknete Dr. J. D. Pawar College of Pharmacy, Manur, tal. Kalwan for their helpful guidance.

 

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Received on 18.05.2022         Modified on 27.07.2022

Accepted on 22.09.2022   ©AandV Publications All Right Reserved

Res.  J. Pharma. Dosage Forms and Tech.2022; 14(4):299-303.

DOI: 10.52711/0975-4377.2022.00049