Quality Evaluation of Generic Products of Metformin and Vildagliptin Tablets

 

Bhavana Habib*, Jyoti Mittha

D. S. T. S. Mandal’s College of Pharmacy, Solapur- 413004, Maharashtra, India.

*Corresponding Author E-mail: bhavanahabib55@gmail.com

 

ABSTRACT:

The aim of the present study was the evaluation and comparison between four different Metformin and Vildagliptin tablets which are commercially available in Indian market. These tablets were assessed for various pharmacopoeial quality control tests. Parameters including weight variation, hardness, friability, drug content, and disintegration time were evaluated. Results were within acceptable limits for all selected products (three generic and an innovator). These results show that the tested generic products were biopharmaceutically similar to the innovator formulation. Therefore, the consumer can select any one of these equivalent products as a substitute for innovator product in case of cost concern or unavailability.

 

KEYWORDS: Metformin, Vildagliptin, Quality Control, Weight Variation.

 

 


INTRODUCTION:

Diabetes mellitus type 2 (T2DM) is a chronic disease that requires a combination of anti-diabetic drugs to have different mechanism of action to reduce hyperglycemic level 1.

 

Metformin (1-carbamimidamido-N, N-dimethylmethanimidamide) is an antihyperglycemic agent of the biguanide class, used for the management of type 2 diabetes. It is prescribed to more than 120 million people worldwide. It lowers blood glucose concentrations in type 2 diabetes without causing hypoglycemia. It is commonly described as insulin sensitizer leading to decrease in insulin resistance and a clinically significant reduction of plasma fasting insulin levels 2.

 

Vildagliptin (2S-1-{2- [(3-hydroxyadamantan-1-yl) amino]acetyl} pyrrolidine-2-carbonitrile) is a new oral anti-hyperglycemic agent of the dipeptidyl peptidase-4(DPP-4) inhibitor. It acts by inhibiting the activation of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) by DPP-4. This inhibitory activity ultimately results in two- fold action where GLP-1 and GIP are present to potentiate the secretion of insulin by beta cells and supress glucagonsecretion by alpha cells in the islets of Langerhans in the pancreas3.

 

Drug products that are biopharmaceutically and chemically equivalent must be identical in their quality, strength, purity and active ingredient release profile. They must be in the same dosage form and intended for the same route of administration. Metformin hydrochloride and Vildagliptin used in combination used to treat hyperglycemic conditions in patients.

 

The use of Metformin and Vildagliptin tablets needs to monitor and ensure the quality of the various brands commercially available in the Indian market in order to assess their quality control. Additionally, if these brands are interchangeable and patients can safely switch from one brand to another or not and which is the best economically. Numerous Metformin and Vildagliptin tablets brands in Indian drug market today make a problem of alternative generic brands for physician and the pharmacist. Some studies in different countries compared the performance of innovator and generic products of metformin hydrochloride tablets 4-10. The results showed that there are some generic products which didn’t satisfy the pharmacopoeial specifications or some quality parameters. The present study aimed to evaluate and compare four different Metformin and Vildagliptin tablets brands by applying both official and unofficial method following the Indian pharmacopeia.

 

MATERIALS:

Metformin (MET) and Vildagliptin (VILDA) branded and generic tablets having label strength of 500 mg and 50 mg (Table 1) were purchased from a retail pharmacy in Solapur city, India. All tests were performed within product expiration dates. Metformin hydrochloride and Vildagliptin powder was a gift of Wockhardt Pharmaceuticals Pvt Ltd, Aurangabad, India. The reagents used were potassium dihydrogen orthophosphate and disodium hydrogen phosphate. All reagents used were of analytical grade. Distilled water was used throughout the work.

 

Table No 1. Details of tablet products compared in study

Code

Tablet Name

Manufacturer

Price (Rs)

A

Galvus Metformin 50mg/500mg (Branded)

Novartis Singapore Pharmaceutical Manufacturing Pvt Ltd.

300.0

B

Vildava MET 500 TAB (Generic)

Logos Pharma

67.50

C

Vildagliptin 50mg and Metformin HCl 500 mg tablets (Generic)

Swast Aaushadhi Seva

68.50

D

Leevia Metformin 50/500 (Generic)

Bioaltus Pharmaceuticals Pvt Ltd.

88.00

 

METHODS:

Quality Control Tests for MET and VILDA (500 mg/50 mg) tablets 11:

1.    General Appearance

The branded and generic tablets were assessed for their general appearance and observations were made for Color, Shape, Diameter, Thickness, and Odour.

 

2.    Thickness:

Thickness mainly depends upon die filling, physical properties of the material to be compressed under the compression force. The thickness of the tablet was measured using Vernier Caliper.

 

3.       Weight Variation

Individually weighed 20 tablets and calculated the average weight. Not more than two of individual weights deviate from the average weight by more than the percentage deviation shown in Table no 2 and none deviated by more than twice the percentage.

 

Table no 2. Limits of Weight Variation

No

Average weight of tablets (mg)

Maximum percentage deviation

1

80 or less

10%

2

80 to 250

7.5%

3

250 or more

5%

 

4.       Hardness:

Tablet requires a certain amount of strength or hardness to withstand mechanical shocks of handling in manufacture, packaging, and shipping tablets should be able to withstand reasonable abuse when in the hands of the consumer. The hardness of the tablet is defined as the force required in breaking a tablet in diametric compression test. In this test, a tablet was placed between two anvils and crushing strength that just causes the tablet to break is recorded. The hardness of tablets was determined for each formulation by Monsanto hardness tester. The hardness was measured in terms of kg/cm2. The optimum hardness regarded for uncoated tablet is 4-6 kg/cm2.

 

5. Friability:

Friability is the loss in weight of tablet due to removal of fine particles from their surface. A pre-weighed tablet sample (10 tablets) was placed in friabilator chamber and rotated for 100 revolutions. In each revolution, the tablets are carried up and are allowed to freely fall from a height of 6 inches. After 100 revolution, the tablets are removed from the chamber, dusted and reweighed. Friability is calculated by using the following formula:

 

                                Initial weight –Final weight

Friability =––––––––––––––––––––––––––––––––× 100

                                         Initial Weight

 

Limit: Maximum loss of weight not greater than 1 % is acceptable.

 

6. Disintegration Test:

The process of breakdown of a tablet into smaller particles is called disintegration. The in-vitro disintegration time of a tablet was determined using disintegration test apparatus as per IP specifications. Place one tablet in each of the 6 tubes of the basket and run the apparatus using Water. The time in seconds/ minutes taken for complete disintegration of tablets with no palpable apparatus was measured and recorded. The tablets pass the test if all of them have disintegrated.

 


Table No 3. Disintegration testing conditions and interpretation

No

Types of Tablet

Medium

Temperature

Limits

1

Uncoated

Water/ Buffer

37°±2°C

15 min as per individual monograph

2

Film Coated

Water

37°±2°C

30 min as per individual monograph

3

Sugar Coated

Water/ 0.1 N HCl

37°±2°C

60 min as per individual monograph

4

Dispersible Tablets

Water

25°±1°C

3 min as per individual monograph

5

Effervescent Tablets

Water

25°±5°C

0.5 min as per individual monograph

6

Enteric coated tablets

0.1 M HCl mixed with phosphate buffer

37°±2°C

2 hr in HCl: no disintegration and 60 min in buffer: disintegrate

 

Table no 4. Branded and Generic Drug Characteristics

Sr. No.

Code

Colour

Odour

Diameter in mm (mean ± S.D)

Thickness in mm (mean ± S.D)

Shape

1.

A

Cream

Characteristic

7 ± 0.5

6.05 ± 0.01

Oblong

2.

B

Cream

Characteristic

7 ± 0.5

6.00 ± 0.05

Oblong

3.

C

Orange

Characteristic

7 ± 0.5

6.10 ± 0.10

Oblong

4.

D

Orange

Characteristic

7 ± 0.5

6.00 ± 0.10

Oblong

 

 

7. Content Uniformity:

The Content Uniformity of Metformin and Vildagliptin in tablets was determined by RP-HPLC method.

 

20 Tablets were weighed and powdered. An accurately weighed quantity of tablet powder containing about 100 mg of Metformin and 10 mg of Vildagliptin was transferred to 100 ml volumetric flask and mixed with 70 ml methanol then diluted to 100ml with methanol. The solution was sonicated for 10 min and filtered through whatmann filter paper (no 41). 5 ml of the filtrate was diluted with methanol to 10 ml. 1.5 ml of resulting solution was further diluted with mobile phase to 10 ml. (Conc. about Metformin: 750µg/ml and Vildagliptin: 75µg/ml). Label claim: Each tablet contains 500 mg and 50 mg of Metformin and Vildagliptin respectively.

 

OBSERVATIONS:

Some of the physical characteristics of tablets are indicated in Table 4. During manufacturing of tablets, thickness of individual tablets depends on factors like fill weight and pressure applied for tablet compression. The thickness measurement results showed that values ranged from 6.00 to 6.10 mm in which product B and C measured the minimum and maximum average thickness among all brands. Thickness uniformity is one of the requirements for tablets as there might be effect on their acceptance by consumers and proper packaging of the products. IP stated that tablets thickness for a batch should be found within a ±5 % variation from the required thickness. The study revealed the closeness of tablets’ physical thickness as the maximum standard deviation was found to be 0.10.

 

Friability, Hardness and Disintegration time:

Hardness of a tablet is an important parameter for providing optimum effect in the body. If the tablet is very hard it will not disintegrate readily and may lead to failure to meet the specification. If the tablet is too soft, it will create difficulties during handling, packaging. Disintegration test is done to note the time a given tablet takes to break down in to the small particles. From Table 5, it is also clearly seen that the disintegration time of the studied brands ranged from 1.15 to 16.00 minutes. All brand products showed average disintegration time less than 15 minutes which is according to the IP specification for film coated tablets (less than 30 minutes). Brand C showed the fastest disintegration time (1.15 min) which might contribute for the rapid release of the contents during tablet dissolution process. On the other hand, brand D exhibited the relatively slow average disintegration time (16.00 minutes) compared with the other.

 

As depicted from Table 5, the active pharmaceutical ingredients for all Metformin hydrochloride and Vildagliptin tablet brands were within specifications and satisfied the assay requirement. IP limits 100 ± 5% of labeled claim for Metformin hydrochloride and Vildagliptin 500/50 mg tablets and the assay result for the samples varied between 97.00 and 104.00 %. Brand D had the maximum content and brand A contained the minimum amount of the claimed label.


 

Table no 5. Evaluation of Branded and Generic Drugs

Tablet Code

Weight Variation (mg)

Hardness in Kg/cm2 (mean ± S.D)

Friability in % (mean ± S.D)

Disintegration Time (Min)

Content Uniformity (%)

Metformin

Vildagliptin

A

Pass

4.33 ± 0.7636

0.4606 ± 0.003

15.25

98

98

B

Pass

4.83 ± 0.7637

0.5036 ± 0.008

13.28

101

97

C

Pass

2.51 ± 0.2961

0.5701 ± 0.013

01.15

104

98

D

Pass

2.30 ± 0.2880

0.4583 ± 0.001

16.00

104

101

 

RESULT AND DISCUSSION:

The various evaluation tests for tablets were performed and results were interpreted.

Sr. No

Parameters

Interpretation

IP Limit

Remarks

1

Shape

The shapes of all the types of tablets were found to be oblong.

-

-

2

Thickness

Thickness of all the types of tablets were found to be in the range of .0.3 to 0.9%

-

-

3

Hardness

The hardness of all types of tablets were found to be in the range 8.23 to 8.76 kg/cm2

More than 4kg/cm2

Passed

4

Friability

Friability test for all the types of tablets were found to be in the 0.4 to 0.6 %

Not more than 1%

Passed

5

Weight Variation

The weight variation tests for all the types of tablets were found to be in the deviation of 5%

Table no 2

Passed

6

Disintegration

Disintegration time for all the film coated tablets were found to be within limits

Not more than 30 min

Passed

7

Content Uniformity

The percentage purity of all the tablets were found to be in the limit.

95% to 105%

Passed

 


CONCLUSION:

Three generic brands of Metformin and Vildagliptin namely Vildava Met 500, Vildagliptin 50 mg and Metformin HCl 500 mg tablets, Leevia Metformin 50/500 together with innovative Galvus Metformin 50 mg/500mg have been subjected to analysis according to IP 2019 and the results have shown that all the tested generics satisfied the IP requirements in terms of identification, weight variation, disintegration and Content uniformity. Circulation of poor quality antidiabetic pharmaceutical products in the market compromises the therapeutic outcome of medication. Weak control of such products by regulatory bodies limit investment of major pharmaceutical companies into medicine research and development. Moreover, from healthcare practitioners’ point of view, there might be a concern of selection of one product among different available generic drug products in a market. Therefore, this study was carried out to investigate the quality of generic products and to evaluate their potential substitution with the innovator product.

 

ACKNOWLEDGEMENT:

The authors are thankful to Wockhardt Ltd, Aurangabad for providing gift samples of MET and VILDA API.

 

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

 

REFERENCES:

1.        Abu D, Mallah, Eyad andTawfiq. Method Development and Validation of Vildagliptin and Metformin HCl in pharmaceutical Dosage Form by Reversed Phase High performance Liquid Chromatography (RP-HPLC). Int J Pharma Sci Res. 2018;(9):2965-2972.

2.        Metformin [Internet]. Drug bank [Cited October 8, 2020] Avaiable from:https://go.drugbank.com/drugs/DB00331

3.        Vildagliptin [Internet]. Drug bank [Cited October 8, 2020]. Available from: https://go.drugbank.com/drugs/DB04876

4.        Samar Afifi et al. A Comparative Study for Evaluation of Different Brands of Metformin Hydrochloride 500 Mg Tablets Marketed in Saudi Arabia. Life Science Journal 2012;9(4)

5.        Akinleye Olusola et al. Comparative Evaluation of Physicochemical Properties of Some Commercially Available Brands of Metformin HCl Tablets in Lagos, Nigeria. Journal of Applied Pharmaceutical Science 02 (02); 2012: 41-44.

6.        Nigatu et al. Comparative in Vitro Evaluation of Different Brands of Metformin Hydrochloride Film Coated Tablets Marketed in Addis Ababa, Ethiopia. Asian Journal of Pharmaceutical Research and Development. 2020; 8(3):42-50.

7.        Emara et al. Comparative in vitro dissolution study on metformin market products using Different dissolution apparatuses. Int J Pharm Sci.2019; 11(9): 65-72.

8.        Mohammad Haroun et al. Comparative In-vitro Evaluation of Metformin HCl Extended Release Tablets Marketed in Syria.

9.        Srinivas Nandyala et al. Comparative Evaluation of Branded and Generic Medicines - Ranitidine and Metformin HCl. International Research Journal of Pharmacy and Medical Sciences (IRJPMS). 2018; 1(4), 24-28.

10.      Nour Mammari, Wehad Ibrahim, Mohammad Haroun. Comparative In-vitro Evaluation of Metformin HCl Extended Release Tablets Marketed in Syria. Research J. Pharm. and Tech. 2019; 12(7):3365-3370

11.      Indian Pharmacopoeia 2010; Volume 1: 187-198.

 

 

 

Received on 06.05.2021       Modified on 18.06.2021

Accepted on 23.07.2021   ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Ana. 2021; 11(4):255-258.

DOI: 10.52711/2231-5675.2021.00043