INTRODUCTION:

The safety and efficacy of drug products can be guaranteed when their quality is reliable and reproducible from batch to batch[1]. The quality of medicines is an integral part of access in light of ensuring that the pharmaceutical products are fit for their intended use, comply with the requirement of the marketing authorization and do not expose consumers to risks. According to the United States Food and Drug Administration (FDA), bioavailability and bioequivalence of drug products, and drug product selection have emerged as critical issues in pharmacy and medicine during the last three decades[2]. The FDA has mandated that all generic drugs meet the same standards as the brand name drugs in strength, safety, purity and performance. However, there are substandard and/or counterfeit generic drugs that don’t satisfy the pharmacopoeial standards set for them.

Preliminary physicochemical assessment of drug products has a paramount importance in ensuring the quality of drug products. Generic drug products must satisfy the same standards of quality, efficacy and safety as those applicable to the innovator products. In vitro dissolution testing can be a valuable predictor of the in vivo bioavailability and bioequivalence of oral solid dosage forms [3].

Warfarin Sodium (figure 1) is a synthetic coumarin drug which depresses synthesis of prothrombin in the liver and interferes with the production of factors VII, IX, X, thereby minimizing intravascular clotting [4].

Figure 1: Structure of warfarin sodium

This study aims at evaluating the physicochemical properties of three brands of Warfarin Sodium tablets marketed in Syria.

MATERIALS AND METHODS:

Three commercial brands (A, B, C) of warfarin sodium were randomly selected. Warfarin sodium brands having label strength of 5 mg were purchased from registered pharmacies in Lattakia, Syria. All tests were performed within product expiration dates. The reagents used were sodium hydroxide (BDH Chemicals, UK) and potassium dihydro orthophosphate (BDH Chemicals, UK). Freshly distilled water was used throughout the work.

Hardness test:

Hardness of 10 tablets from each brand was measured individually by calibrated hardness apparatus. The standardized value for hardness ranges from 5–15kg/cm². After operating the procedure for 10 tablets of each sample, the mean value was calculated.

Friability test:

Tablets friability test apparatus was used for the determination of durability of the tablet at the time of production. Ten tablets were randomly selected and weighed for the purpose of friability test. Tablets were then placed into calibrated friabilator for 4 min at 25 r/min. The differences in weight were calculated as percentage friability by weighing the tablets again. The percentage (%) losses of 20 tablets were calculated as per the following equation:

Friability (%) = (W1 – W2)/W1 × 100

W1 = Weight of 20 tablets before friability test

W2 = Weight of 20 tablets after friability test

The loss should be less than 1% according to BP[5].

Weight Variation:.

Twenty tablets were selected from each of the brand and weighed individually using an analytical balance. The average weight of the tablets was calculated. Then % of weight variation is calculated by using the following formula

Individual weights- Average weights

% of Weight variation =------------------------------- X 100

Average weights

Not more than two of the individual weights deviated from the official standards USP pharmacopeia [6].

Calibration curve of warfarin sodium in NaOH at 308 nm:

A standard curve was created for Warfarin sodium using pure drug powder diluted to 5 known concentrations (range between 0.2 and 0.7mg/100ml). These standard curves were established to verify accurate analysis of the drug .

Uniformity of content:

10 tablets were taken from each brand. Each tablet was crushed and dissolved separately using a combination of manual agitation and sonication techniques in 50 ml of 0.1N NaOH. Then the samples were mixed well before filtration through a membrane filter. The samples of each solution were assayed for drug concentration using spectrophotometer at 308nm. The drug content was quantiﬁed by calculating the concentrations from the absorbance readings obtained through UV analysis.

Several measures were calculated in order to assess the amount and acceptability of variations in drug content. The measured drug content expressed as a percent of label claim was calculated for each tablet. Individual values for each tablet should be in the range of 95-105% Warfarin Sodium (proxy USP speciﬁcation for drug content).

Dissolution test:

Dissolution is the property or tendency of a drug to undergo solution, which affects the rate of drug absorption. Generally dissolution test is performed by using Dissolution Tester-USP to determine drug release pattern during a specific period of time [7]. 900 ml of phosphate buffer, pH 7.4 was used as dissolution medium. In general, a single tablet is placed in a basket fastened to the bottom of the shaft connected to a variable speed motor.

One tablet was put into the basket and stirred immediately at 50 revolutions per minute (rpm). The amount of dissolved Warfarin Sodium was determined from UV absorbance at the wavelength of maximum absorbance at about 308 nm. By measuring the absorbance, the percentage (%) of drug release was calculated [8]. All drug products have dissolution specification, Q, stated the USP, and for passing the test, Warfarin Sodium tablets must release 80% of drug within 30 minutes.

RESULTS AND DISCUSSION:

Hardness and friability tests:

Crushing strength test shows the ability of tablets to withstand pressure or stress during handling, packaging and transportation. It is a property of a tablet that is measured to assess its resistance to permanent deformation. This result also indicates that all brands passed standardized value for hardness ranges test of crushing strength/hardness (Table 1).

The result of tablet friability test shows that virtually all the tested brands had impressive friability values ranging from 0.21% to 0.81%w/w (Table 1). According to BP no batch should have a friability value greater than 1.0%w/w; therefore, all the brands passed the test.

Table.1. Hardness and friability of warfarin sodium tablets

Brand	Hardness (kg/cm²)±SD N=10	Friability(%) N=20
A	5.34±0.88	0.81
B	7.87±1.03	0.64
C	11.31±0.97	0.21

Weight Variation:

Table (2) shows the weight variation results of all brands of warfarin sodium. The data suggested that the test was positive for all the products as their average weight ranged within the lower limit and upper limit according to the standards of USP.

Table.2. Weight variation of Warfarin Sodium tablets

Brand	Measured weight mean (mg); N=20	Deviation range (%)	RSD (%)
A	199.7	-2.87 – 3.87	2.87
B	169.4	-1.98- 4.13	3.88
C	100.2	-3.44 – 4.76	5.01

Calibration curve of Warfarin Sodium in NaOH at 308 nm:

A linear relationship between the absorbance and the concentration of Warfarin Sodium in NaOH at 308 nm in the concentration range of 0.2-0.7mg/100ml is observed. The regression equation is Y= 1.1576X+0.0279 and the correlation coefﬁcients (r) of the linear regression of the calibration curves is 0.9988.

Uniformity of content:

The results obtained from the assessment of the percentage content of active ingredient in the three brands of warfarin sodium tablets showed that brands (A, B) gave values within the SP monograph specifications (95-105%) while brand C failed the test with values outside of proxy USP specification in all tablets (table 3).

Table.3. Content uniformity of warfarin sodium tablets

Brand	Measured drug content mean (mg); N=10	Percent of content mean (%); N=10	RSD (%)
A	4.95	99	2.67
B	4.84	96.8	4.11
C	4.61	92.2	5.87

Dissolution test:

Dissolution is the rate of mass transfer from the product to the bulk of solution[9]. One aim of dissolution testing is to guarantee the quality of the pharmaceutical product and prove consistency from one batch to another and no important change occurs during the stability study. Any change in dissolution could impact the efficacy of the pharmaceutical product.

In this study, brands (A, B) release at least 80% of drug within 30 minutes, so these brands passed USP specifications, While brand C failed this test (figure 2).

Figure 2: Dissolution profiles of warfarin sodium tablets

CONCLUSION:

From the above results, all the studied brands warfarin sodium of passed the test for friability (less than 1%). The values for hardness of all brands range between 5 – 15 kg/cm², so all brands passed this test. All brands passed the test for weight variation. Brands (A, B) gave values within the monograph specifications (95-105%), while brand C failed the test with values outside of proxy USP specification. In dissolution test brands (A, B) release at least 80% of drug within 30 minutes, so these brands passed USP specifications, While brand C failed this test.

REFERENCES:

1. Chow, S. Pharmaceutical Validation and Process Controls in Drug Development. J. Drug Information. 31: 1997: 1195-1201.

2. Miller, SW and Strom, JG. Drug Product Selection: Implications for the Geriatric Patient. The Consultant Pharmacist, 5:1990: 30-37.

3. Tiola, O.A and Pilpel, N. Effects of interacting variables on the disintegration and dissolution of metronidazole tablets. Pharmazie, 51: 1996: 987-989.

4. Lopez L. Prescribing individualized dosing of wafarin. Why so complicated. Drugs and therapy bulletin. 24: 2010.

5. British Pharmacopoeia, 2009.

6. United States Pharmacopeia, 2013.

7. Kishore, B.H., Venkareswararao, T., Sankar, K.R., Rao, B.S. Studies on dissolution rate of paracetamol tablets by using different polymers. J Glob Trends Pharm Sci, 2(1):2011: 1-10.

8. Ki-Kalakuntla, R., Veerlapati, U., Chepuri, M., Raparla, R. Effect of various super disintegrants on hardness, disintegration and dissolution of drug from dosage form. J. Adv. Sci. Res, 1(1): 2010: 15-19.

9. Aulton ME. Pharmaceutics: The Science of Dosage Form Design. Edinbourgh: Churchill Livingstone; 2001.

Received on 08.03.2017 Modified on 20.03.2017

Research J. Pharm. and Tech. 2017; 10(7): 2119-2121.

DOI: 10.5958/0974-360X.2017.00371.7