Evaluation of Marketed Formulation of Dapaglifoxin

Abstract

Dapagliflozin, commercially available as Forxiga, is a widely prescribed oral antidiabetic agent belonging to the class of sodium–glucose co-transporter 2 (SGLT2) inhibitors. It plays a crucial role in the management of type 2 diabetes mellitus by promoting urinary glucose excretion, thereby improving glycemic control. With the increasing availability of multiple marketed formulations, it becomes essential to evaluate their quality, safety, and therapeutic performance to ensure consistent patient outcomes. The present study focuses on the evaluation of marketed formulations of dapagliflozin tablets using standard pharmaceutical quality control parameters. The assessment includes physical characterization tests such as weight variation, hardness, thickness, and friability, which help determine the uniformity and mechanical strength of the tablets. These parameters are important because they influence the drug’s stability during handling, transportation, and storage. In addition to physical evaluation, chemical and performance-based tests were carried out. Drug content uniformity was analyzed to confirm that each tablet contains the appropriate amount of active pharmaceutical ingredient as per the labeled claim. Dissolution testing was performed to study the rate and extent of drug release in a simulated physiological environment. This test is particularly significant for dapagliflozin, as its therapeutic effectiveness depends on its ability to dissolve and become available for absorption within a specific time frame. The results obtained from the evaluation of marketed dapagliflozin formulations indicated that most of the tested brands complied with pharmacopeial standards. The tablets exhibited acceptable weight variation, adequate hardness, and low friability, suggesting good mechanical integrity. Drug content analysis showed that the formulations contained the active ingredient within the permissible limits, ensuring dose accuracy. Furthermore, dissolution studies demonstrated that the majority of the formulations released a significant percentage of the drug within the specified time intervals, indicating satisfactory in vitro performance. However, minor variations were observed among different brands, particularly in dissolution profiles, which could be attributed to differences in excipient composition, manufacturing processes, or formulation techniques. Such variations, although within acceptable limits, highlight the importance of continuous quality monitoring and comparative evaluation of marketed products. In conclusion, the evaluation of marketed dapagliflozin formulations confirms that they generally meet the required quality standards and are suitable for therapeutic use. Regular assessment of these formulations is essential to maintain consistency, ensure patient safety, and support effective diabetes management. This study emphasizes the role of systematic quality control testing in safeguarding the reliability of pharmaceutical products available in the market.

Keywords

Introduction

4. MATERIALS AND METHODS

4.1 Study Design

Comparative experimental study on five marketed brands of dapagliflozin tablets (10 mg).

4.2 Materials

• Tablet samples (5 brands)
• Phosphate buffer (pH 6.8)
• Distilled water
• Analytical reagents

4.3 Instruments

• Dissolution apparatus (USP Type II)
• Monsanto hardness tester
• Roche friabilator
• Digital balance
• Disintegration apparatus (Basket Rack Assembly)
• Vernier Caliper (Thikness and Diameter test)
• UV- Spectrophotometer

4.4 Evaluation Parameters

4.4.1 Weight Variation Test

The weight variation test is a basic quality control test performed on tablet dosage forms to ensure uniformity in the weight of individual tablets within a batch. It is an important parameter in pharmaceutical manufacturing because it indirectly indicates the uniform distribution of the active pharmaceutical ingredient, such as Dapagliflozin, in each tablet.

This test is based on the principle that if a tablet contains a uniform blend of drug and excipients, then tablets of consistent weight will also contain a consistent amount of the active drug. Any significant variation in tablet weight may lead to dose variation, which can affect therapeutic efficacy and patient safety.[4,6,7,23,24]

• 20 tablets weighed individually
• Average weight calculated
• % deviation determined

4.4.2 Hardness Test

The hardness test is an essential quality control parameter used to determine the mechanical strength of tablets. It measures the force required to break a tablet under compression. For tablet formulations containing drugs like Dapagliflozin, maintaining appropriate hardness is crucial to ensure proper handling, packaging, and therapeutic performance.

The test is based on applying a controlled force to a tablet until it breaks. The amount of force required to cause fracture is recorded as the tablet’s hardness, usually expressed in kilograms per square centimeter (kg/cm²) or Newtons (N).[4,10,23]

• Measured using Monsanto tester
• Expressed in kg/cm²

Hardness test

4.4.3 Friability Test

The friability test is an important quality control test used to evaluate the ability of tablets to resist mechanical shock, abrasion, and handling stress during manufacturing, packaging, and transportation. It is especially relevant for oral solid dosage forms containing drugs such as Dapagliflozin, where tablet integrity directly affects dose accuracy and patient compliance.[6,10]

• 20 tablets rotated at 25 rpm for 4 minutes
• % weight loss calculated

Friability test

4.4.4 Drug Content (Assay)

The drug content assay of Dapagliflozin is an essential analytical procedure used in pharmaceutical quality control to determine the amount of active pharmaceutical ingredient (API) present in a dosage form such as tablets. This assay ensures that the drug product contains the labeled amount of dapagliflozin and meets regulatory standards for safety, efficacy, and uniformity.[35]

Dapagliflozin belongs to the class of sodium–glucose co-transporter-2 (SGLT2) inhibitors, used in the treatment of type 2 diabetes mellitus. Because of its therapeutic importance, accurate and precise analytical methods are required for its quantification in bulk drug and formulations.[11,16]

Measurement

• Scan in range 200–400 nm
• Measure absorbance at λmax ≈ 225 nm

Quantitative estimation is commonly performed by UV–Visible spectrophotometry.

• Based on measurement of absorbance proportional to concentration (Beer–Lambert law)
• λmax for dapagliflozin: ~223–225 nm

Calculation: Formula

Drug Content (%) = (Absorbance of sample / Absorbance of standard) × 100

4.4.5 Dissolution Test

The dissolution test is a key quality control test used to determine the rate and extent to which the active pharmaceutical ingredient is released from a solid dosage form into a solution under standardized conditions. For oral tablets such as those containing Dapagliflozin, this test is very important because it directly reflects how the drug will become available for absorption in the body.[12,15]

The dissolution test is performed to:

• Evaluate the drug release profile from tablets
• Ensure batch-to-batch consistency in drug performance
• Predict in vivo bioavailability (how the drug behaves in the body)
• Support quality control and regulatory compliance

Conditions:

• Medium: pH 6.8 phosphate buffer
• Temperature: 37°C
• Speed: 50 rpm

Samples withdrawn at 5, 10, 15, 20 minutes.

Dissolution test

4.4.6 Disintegration Test

The disintegration test is a fundamental quality control test used to determine the time required for a tablet or capsule to break down into smaller particles when placed in a liquid medium under standardized conditions. For solid oral dosage forms such as those containing Dapagliflozin, this test ensures that the tablet will break apart properly after administration, which is an essential first step before drug dissolution and absorption.[7]

• Medium : 0.1N HCL or Phosphate Buffer at pH (6.8)
• Tempreture : 37°C ± 0.5°C.
• Speed : 30 ± 2 cycle / min.

4.4.7 Thickness and Diameter Test

The thickness and diameter test is an important physical evaluation parameter used in the quality control of tablet dosage forms. It ensures uniformity in tablet dimensions such as thickness and diameter, which indirectly reflects consistency in tablet weight, hardness, and overall manufacturing quality. For oral solid dosage forms like those containing Dapagliflozin, maintaining uniform tablet dimensions is essential for proper packaging, labeling, and patient acceptability.[4]

• Take five brands of Dapaglifoxin Tablet.
• Measure the Thikness and Diameter of tablet from Vernier Caliper apparatus.

Thickness and Diameter Test

4.4.8 UV Spectroscopy

UV spectroscopic analysis of Dapagliflozin tablets is a simple, cost-effective, and widely used method for estimating the drug content in pharmaceutical formulations. It is particularly valuable in routine quality control laboratories where rapid, accurate, and economical analysis is required without the need for sophisticated instrumentation [13,14]

Dapagliflozin is an oral antidiabetic drug that acts by selectively inhibiting the sodium–glucose co-transporter-2 (SGLT2) in the kidneys, thereby reducing glucose reabsorption and lowering blood glucose levels. From an analytical perspective, Dapagliflozin exhibits absorption in the ultraviolet (UV) region due to the presence of chromophoric groups in its chemical structure. This property makes it suitable for estimation using UV-visible spectrophotometry techniques [13,33].

For analysis, a standard stock solution is prepared by accurately weighing a known quantity of pure Dapagliflozin and dissolving it in a suitable solvent, such as methanol, to obtain a defined concentration (for example, 100 µg/mL). From this stock solution, serial dilutions are prepared to obtain working standard solutions within a linear concentration range (typically 2–20 µg/mL). These solutions are then scanned using a UV spectrophotometer over a wavelength range of 200–400 nm to determine the wavelength of maximum absorbance (λmax). For Dapagliflozin, the λmax is generally observed in the range of 223–225 nm, where the compound exhibits maximum absorbance and optimal sensitivity for quantitative analysis [13,14].

Uv spectroscopy test

5. RESULTS

5.1 Weight Variation

6. DISCUSSION

The present study was carried out to evaluate the quality of different marketed formulations of Dapagliflozin using standard pharmaceutical quality control tests including weight variation, hardness, friability, dissolution, disintegration, assay, and cost analysis. Overall, all tested brands showed acceptable results within pharmacopeial limits, indicating satisfactory manufacturing quality and performance. In the weight variation test, all formulations showed minimal deviation, ranging from ±0.77% to ±1.15%. This indicates good uniformity in tablet weight and suggests that the mixing and compression processes during manufacturing were well controlled. Among all brands, FORXIGA showed the least variation, reflecting high consistency, while DAPASACH and DAPALIFT showed slightly higher but still acceptable variation. DAPAWICH had a higher average weight (309 mg), which may be due to formulation differences such as higher excipient content.[4,6,7,23]

The hardness test results showed considerable variation between brands, ranging from 3.5 kg/cm² to 10 kg/cm². VOAGE exhibited the highest hardness, indicating strong mechanical strength, while DAPALIFT showed the lowest hardness. Although higher hardness improves tablet durability, excessively hard tablets may delay disintegration. Conversely, lower hardness may improve disintegration but increase the risk of breakage during handling. Therefore, an optimal balance is necessary for effective performance.

In the friability test, all formulations showed values below 1%, ranging from 0.42% to 0.50%. This confirms that all tablets possess good resistance to mechanical stress during packaging and transportation. VOAGE demonstrated the lowest friability, indicating better structural integrity, while DAPASACH showed the highest but still acceptable value.[12,15,22,34]

The dissolution study revealed that all formulations released more than 90% of the drug within 30 minutes. DAPALIFT showed the highest release (97%), while DAPASACH showed slightly lower release (92%). These results indicate good drug release characteristics across all brands, suggesting effective formulation design and compliance with dissolution standards. The similarity in dissolution profiles also suggests that the generic brands are comparable to the innovator product FORXIGA.

The assay (drug content) results ranged from 97.8% to 99.2%, confirming that all brands contain the correct amount of active pharmaceutical ingredient within acceptable limits (typically 95–105%). VOAGE showed the highest drug content, indicating accurate dosing and good manufacturing control.

The cost analysis highlighted a significant difference between branded and generic products. FORXIGA was the most expensive, while generic formulations such as DAPASACH and DAPLIFT were much more affordable. Despite lower cost, generics demonstrated comparable quality parameters, making them a cost-effective alternative for long-term diabetes management.[31,2,25]

Overall, the study concludes that all evaluated dapagliflozin formulations meet standard quality requirements. The slight variations observed among brands are likely due to differences in excipients and manufacturing processes, but they do not significantly affect the overall performance. These findings support the use of generic formulations as reliable and economical alternatives to branded products in the management of type 2 diabetes mellitus.

7. CONCLUSION

The present study was conducted to evaluate and compare the quality of five marketed formulations of Dapagliflozin available in India, namely FORXIGA, DAPASACH, VOAGE, DAPALIFT, and DAPAWICK. The evaluation was performed using standard pharmaceutical quality control parameters including weight variation, hardness, friability, dissolution profile, drug content (assay), disintegration behavior, and cost analysis. The findings provide a clear understanding of how different brands perform in terms of quality, performance, and economic value.[4]

Overall, all tested formulations complied with official pharmacopeial standards, indicating that the marketed products are of acceptable quality and suitable for therapeutic use. The weight variation results showed minimal deviations across all brands, confirming good uniformity in tablet manufacturing and accurate dose distribution. This is important because consistent weight generally reflects uniform distribution of the active ingredient, ensuring reliable therapeutic outcomes.[6]

The hardness test revealed variation among brands, with values ranging from low to high mechanical strength. While VOAGE showed higher hardness, indicating strong tablets that can withstand handling stress, DAPALIFT showed comparatively lower hardness. However, all formulations remained within acceptable limits, suggesting a balanced compromise between strength and disintegration ability.[25]

Friability results were also found to be satisfactory for all brands, with values well below the 1% limit. This confirms that all tablets possess adequate resistance to abrasion and mechanical stress during packaging, transport, and handling. Such results ensure that the tablets maintain their physical integrity until they reach the patient.

The dissolution studies demonstrated that all formulations released more than 90% of the drug within 30 minutes. This indicates good drug release behavior and suggests that the tablets are likely to provide effective bioavailability under physiological conditions. Minor differences observed between brands may be attributed to variations in excipients and manufacturing techniques, but these differences do not appear to significantly affect overall performance.[31]

Drug content analysis further confirmed that all brands contained the active ingredient within the acceptable range of 95–105%. This ensures dose accuracy and reliability of therapeutic action across all formulations. VOAGE showed slightly higher drug content, while others remained close to the standard value, indicating good manufacturing quality control across all products.[33]

The cost analysis highlighted a clear economic difference between innovator and generic formulations. FORXIGA was significantly more expensive compared to its generic counterparts. However, the quality parameters of generic brands such as DAPASACH and DAPALIFT were comparable to the innovator product. This suggests that generic formulations provide a cost-effective alternative without compromising quality or therapeutic efficiency, making them more accessible for long-term diabetes management.[33].

In conclusion, the study demonstrates that all evaluated dapagliflozin formulations are pharmaceutically equivalent in terms of quality, performance, and drug release characteristics. The slight variations observed among brands are within acceptable limits and are unlikely to affect clinical outcomes. These findings strongly support the use of generic formulations as reliable and economical alternatives to branded products. Continuous monitoring and quality assessment of marketed formulations remain essential to ensure consistent drug performance, patient safety, and effective management of type 2 diabetes mellitus.[25,31]

REFERENCES

1. McGraw-Hill Education. Harrison’s Principles of Internal Medicine. 21st ed. New York: McGraw-Hill; 2022.
2. American Diabetes Association. Standards of Care in Diabetes—2025. Diabetes Care. 2025;48(Suppl 1):S1–S350.
3. AstraZeneca Pharmaceuticals LP. Forxiga (dapagliflozin) Prescribing Information. 2023.
4. Aulton ME, Taylor KMG. Aulton’s Pharmaceutics: The Design and Manufacture of Medicines. 6th ed. London: Elsevier; 2022.
5. Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill; 2023.
6. United States Pharmacopeial Convention. United States Pharmacopeia and National Formulary (USP 47–NF 42). Rockville, MD; 2024.
7. Indian Pharmacopoeia Commission. Indian Pharmacopoeia. 9th ed. Ghaziabad: IPC; 2022.
8. Medicines and Healthcare Products Regulatory Agency. British Pharmacopoeia. London; 2024.
9. European Directorate for the Quality of Medicines. European Pharmacopoeia. 11th ed. Strasbourg; 2023.
10. Lachman L, Lieberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. 4th ed. New Delhi: CBS Publishers; 2013.
11. Allen LV. Pharmaceutical Calculations. 16th ed. Philadelphia: Wolters Kluwer; 2020.
12. Sinko PJ. Martin’s Physical Pharmacy and Pharmaceutical Sciences. 7th ed. Philadelphia: Wolters Kluwer; 2017.
13. Beckett AH, Stenlake JB. Practical Pharmaceutical Chemistry. 4th ed. New Delhi: CBS Publishers; 2018.
14. Chatwal GR, Anand SK. Instrumental Methods of Chemical Analysis. 5th ed. Mumbai: Himalaya Publishing House; 2019..
15. United States FDA. Guidance for Industry: Dissolution Testing of Immediate Release Solid Oral Dosage Forms. FDA; 1997.
16. ICH Harmonised Guideline Q2(R2). Validation of Analytical Procedures. International Council for Harmonisation; 2023.
17. ICH Harmonised Guideline Q6A. Specifications: Test Procedures and Acceptance Criteria. ICH; 2000.
18. ICH Harmonised Guideline Q1A(R2). Stability Testing of New Drug Substances and Products. ICH; 2003.
19. Rang HP, Dale MM, Ritter JM, Flower RJ. Rang & Dale’s Pharmacology. 9th ed. Elsevier; 2020.
20. Tripathi KD. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers; 2019.
21. Katzung BG. Basic and Clinical Pharmacology. 15th ed. McGraw-Hill; 2021.
22. Shargel L, Yu ABC. Applied Biopharmaceutics & Pharmacokinetics. 7th ed. McGraw-Hill; 2016.
23. Remington JP. Remington: The Science and Practice of Pharmacy. 23rd ed. Pharmaceutical Press; 2020.
24. Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. 8th ed. Pharmaceutical Press; 2017.
25. World Health Organization. WHO Guidelines for Quality Assurance of Pharmaceuticals. WHO; 2018.
26. Sweetman SC. Martindale: The Complete Drug Reference. 40th ed. Pharmaceutical Press; 2020.
27. Bailey CJ, Day C. SGLT2 inhibitors: mechanisms and clinical applications. Diabetes Therapy. 2019;10(2):701–715.
28. Zinman B, et al. Empagliflozin cardiovascular outcome trial. N Engl J Med. 2015;373:2117–2128.
29. Wiviott SD, et al. Dapagliflozin and cardiovascular outcomes. N Engl J Med. 2019;380:347–357.
30. Heerspink HJL, et al. Renal outcomes with dapagliflozin. Lancet Diabetes Endocrinol. 2020;8(7):582–593.
31. US FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. 2024.
32. Indian Journal of Pharmaceutical Sciences. Evaluation of marketed tablet formulations. Various issues.
33. Journal of Pharmaceutical Analysis. Analytical methods for dapagliflozin estimation.
34. International Journal of Pharmacy and Pharmaceutical Sciences. Studies on dissolution profile comparison.
35. World Health Organization. Technical Report Series No. 1010. WHO; 2018.