INTRODUCTION:

With the growth in pharmaceutical industries, number of pharmaceutical products (branded as well as generic) are increasing in market so to maintain its quality is the most primary concern for manufacturers¹. The same generic drug can be manufactured by different pharmaceutical companies, which may look like or different than original and sold under different brand name and different cost².

Generally, generic as well as branded product contains the same type and quantity of the active ingredient. So, a generic drug should be identical or bioequivalent to brand drug with respect to dosage form, safety, strength, route of administration, quality, performance characteristics and intended use³. But substandard drugs are also finding place in the market due to ignorance, neglectance and personal profit of pharmaceutical companies and these differ from original product in many aspects viz.

concentration, quality etc. So, to ensure safety and reliability of any pharmaceutical dosage form in terms of quality, pharmaceutical companies should maintain the pharmacopoeial standards as prescribed by pharmaceutical regulatory authorities during manufacturing of the drugs⁵. Therefore, quality control tests as per the standard official books like IP, USP, BP etc. during manufacturing and also on the final product should be performed^6-7.

The literature reveals that in many countries, people are suffering not because of diseases but their inability to meet cost of medication for their diseases⁸. So, the present study aims to throw away the blind belief of many people that branded drugs show better therapeutic activity than the generic drugs. The generic drugs are also bioequivalent to ethical drugs if all the quality control parameters are being maintained⁹. As per pharmaceutical standards, the parameters like weight variation, hardness, friability, disintegration, dissolution and content uniformity should be checked to assure the effectiveness of any drug¹⁰.

Metformin (molecular formula C₄H₁₁N₅, molecular weight, 129.167 gm/mol) is the most widely prescribed anti-diabetic used for treatment of type II (non insulin dependent diabetes mellitus) which basically acts by decreasing hepatic glucose production, intestinal glucose absorption, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization^11-14. Various brands of metformin are available in the market so the quality of the various brands commercially available should be ensured in order to assess their quality control which helps in the selection of brand of the drug.

Figure 1 Chemical structure of Metformin

MATERIAL AND METHODS:

Chemicals and reagents:

Pure Metformin hydrochloride was gifted as a free sample. Various brands of metformin (both branded and generic having label strength 500 mg were purchased from local market in Ambala region, Haryana, India. All tests were performed within product expiration dates. All used reagents or chemicals like potassium dihydrogen orthophosphate and sodium hydroxide pellets were of analytical grade. Distilled water was used throughout the work.

Table 1: Brand selected for analysis

S. No	Brand Name	Mfg. Date	Exp. Date	Price (in Rs.)
1	Brand A	11/2016	10/2019	29.19
2	Brand B	04/2017	03/2020	29.76
3	Brand C	06/2017	05/2020	19.70
4	Brand D	06/2017	05/2020	14.6

Instrumentation:

A double beam UV-Visible spectrophotometer (UV-1800, Shimadzu Japan) having 2 matched cells (1cm), an electronic analytical balance (Shimadzu AUX 220), Monsanto Hardness Tester, Friability Tester {Electro lab EF-2 friabilator (USP)}, Dissolution Apparatus {Electro lab TDT-08L Dissolution tester (USP)}, Disintegration Apparatus{ Electro lab ED-2L Disintegration tester (USP)} were used.

Methods used for assessment¹⁵

Visual Inspection:

Thickness of tablets (randomly selected) using Vernier caliper and visual parameters like shape, size, and color of the different brands of tablets were examined. Results are reported in Table 2. No defects in the color homogeneity/coat integrity etc. were observed with consistent thickness of all selected brands.

Table 2: Visual Parameters

Brand Name	Color	Shape	Texture	Thickness (mm)
A	White	Oval	Smooth	1 ± 0.027
B	White	Oval	Smooth	0.85± 0.056
C	White	Oval	Smooth	0.89± 0.043
D	White	Oval	Smooth	0.892± 0.018

Friability and Hardness Test:

Friability (abrasion) using Electro lab EF-2 friabilator (USP) at 100 revolutions for 4 min and hardness using Monsanto Hardness tester was evaluated using twenty tablets of each brand to determine their strength during chipping, abrasion, or breakage under condition of storage, transportation and handling before usage. Weight loss in case of friability using given formula and pressure required to crush the tablet in evaluating hardness is observed and results are reported in Table 2.

% Friability = [(Initial weight – Final weight)/Initial weight] × 100

Tablet passes the hardness test if crushing strength is between 4 kg/cm²-10 kg/cm² and friability should be not more than 1% as per USP.

Weight Variation (Uniformity of Weight):

Twenty tablets of each brand were individually weighed. The average weight was determined and the percentage (%) deviation of the individual tablets from the mean was determined (Table 3). Tablet meet USP standards if not more than 2 tablets are outside percentage limit and if no tablet differs by more than two times the percentage limit.

Average weight–Individual weight

% of weight = ------------------------------------------ x 100

variation Average weight

Disintegration Test:

Tablet disintegration was determined at 37°C using Electro lab ED-2L Disintegration tester (USP) of randomly selected six tablets of each brand in distilled water as well as in HCl to check whether the tablet disintegrates within a time when placed in liquid medium under the prescribed experimental condition (Table 3).

Dissolution Test:

Dissolution using ERWEKA dissolution apparatus was done using paddle method at 50rpm with phosphate buffer pH 6.8 (900mL) as dissolution medium (37±0.5 ⁰C) according to the prescribed procedure and absorbance of withdrawn samples were measured at 232 nm. The percentage of drug release is calculated (Table 4) using the formula and then plotted against the time in minutes (Figure 2)

% of drug release = Amount of drug release x 100

Drug content in tablet

Table 4: Dissolution studies

Time	% of drug release
	Brand A	Brand B	Brand C	Brand D
5	17.1	15.84	18	25.38
10	33.3	28.08	36.54	36.79
15	45.72	39.06	47.7	55.69
30	59.76	60.36	63.72	66.06
45	77.04	77.45	80.28	80.1
60	91.26	94.33	91.08	91.9

Figure 2: Drug Release.

Content Assay:

Analyzing drug content is necessary for ensuring the efficacy and potency and thus a mandatory parameter in quality control analysis.

Preparation of Standard Solution:

50 mg of standard pure drug was dissolved in phosphate buffer to get a solution of 500 µg/ml. 1 ml of the solution is further diluted to get working standard solution of 10 µg/ml.

Preparation of Calibration Curve:

Above solution was scanned in UV spectrum range between 200-400nm and wavelength of maximum absorbance was determined. Then appropriate aliquots were taken from standard stock solution and diluted with the solvent to get solution of 2, 4, 6, 8, 10, 12, 14, 16 and 18µg/ml. The absorbance of prepared solutions were observed and then plotted against their respective concentration to get the calibration graph (Figure 3). From the calibration graph, linearity equation is being determined for further calculations.

Fig 3: Linearity graph

Preparation of Sample Solution:

Twenty tablets from each brand are weighed individually and crushed. Powder equivalent to 200 mg was weighed and dissolved in phosphate buffer to prepare 1000 µg/ml. Further dilution was made to get final working dilution of 10µg/ml. Absorbance is then being observed at the selected λ_maxand the concentration is determined (Table5).

Table 5: Assay studies

Brands	Label Claim (mg)	Amount Found(mg)	%
Brand A	500	504.6	100.92
Brand B	500	498.3	99.66
Brand C	500	502.4	100.48
Brand D	500	499.1	99.82

DISCUSSION:

All the selected brands of metformin meet the desired quality and efficacy according to the USP standards. All the tablets are uniform, oval and smooth with approximate same thickness (Table 2). Weight variation results revealed that all brands selected complied with acceptance limits (Table 3) and deviation of individual tablet weights from the average weight is within the official specification (± 5%) as stipulated by USP. % friability is less than 1% in all brands with hardness in range of 5-9 kg/cm² indicated good friability and strength as per USP (Table 3). Disintegration time, less than 10 minutes, is indicative of good disintegration of all tablets and is as per the USP limits (within 30 minutes for uncoated tablets). Dissolution studies indicated that more than 75% drug got released within 45 min (Figure 2) indicating good efficacy of tablets. All the parameters tested thus assure that these brands although manufactured by different companies can be used interchangeably.

CONCLUSION:

From the present study, it can be concluded that quality assessment is an important criteria which is required for any pharmaceutical preparation to assure its efficacy and potency because it ensure that whether the different brands (generic as well as branded) of same drug are pharmaceutically equivalent or not and thus can be interchangeably used or not.

ACKNOWLEDGEMENT:

Authors are grateful to MM College of Pharmacy, Mullana for providing the necessary facilities.

CONFLICT OF INTERSEST:

The authors declared no conflict of interest.

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Received on 21.11.2018 Modified on 05.12.2018

Research J. Pharm. and Tech. 2019; 12(3): 1357-1360.

DOI: 10.5958/0974-360X.2019.00228.2

Brand	Average Weight	% Deviation allowed (± 5%)	Friability (%)	Hardness (kg/cm²)	Disintegration Time In water In HCl
A	643 mg ± 0.285	610.85-675.15	0.0777	6.6	09:12	07:59
B	555 mg ± 0.387	527.25-582.75	0.1081	7.7	07:30	05:58
C	529 mg ± 0.136	502.55-555.45	0.0751	5.7	08:13	06:46
D	590 mg ± 0.453	560.5-619.5	0.2538	8.5	08:50	05:45