International Journal of Drug Delivery Technology
Volume 15, Issue 2

Design, Optimize and Evaluate Dapagliflozin Sustained Release Microspheres using Box-Behnken Design 

Anushree Chauhan1, Ganesh Prasad Mishra1,2*, Surbhi Gupta3 

1Faculty of Pharmacy, Department of Pharmacy, Swami Vivekanand Subharti University, Meerut, Uttar Pradesh, India

2Dr Prafulla Chandra Ray Subharti College of Pharmacy, 20th Milestone, Bijnor-Haridwar Road, Near Chandok, Bijnor, Uttar Pradesh, India

3Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India 

Received: 28th Mar, 2025; Revised: 4th May, 2025; Accepted: 24th May, 2025; Available Online: 25th Jun, 2025 

ABSTRACT

This study aimed on optimizing dapagliflozin microspheres for sustained release to improve efficacy over the marketed product. Microspheres were formulated by a Solvent Evaporation method involving sodium alginate, ethyl cellulose and HPMC K 100. The process was optimized through Box- Behnken statistical experimental model, adjusting polymer concentration, surfactant amount and rotational speed. Seventeen formulations were formulated and the optimized formulation (F2) was investigated for its micromeritic characteristics, SEM, in-vitro release, kinetic modeling, and stability. FT-IR study showed no negative correlation among the drug and polymers. F2 exhibited maximum yield (81.78%), entrapment efficiency (82.21%) with optimum particle size (278.69 μm). Increased concentration of polymer improved yield and efficiency of drug entrapment while stirring rate decreased particle size. SEM analysis revealed rough, porous and spherical microspheres, and the release was sustained, with 98.02% of the drug released over 20 hours. The optimized microspheres showed prolonged drug release under gastrointestinal conditions, offering increased efficacy and potentially enhancing patient adherence by lowering dosing compared to the marketed product.

Keywords: Dapagliflozin, Box- Behnken, Independent, Dependent variables

How to cite this article: Anushree Chauhan, Ganesh Prasad Mishra, Surbhi Gupta. Design, Optimize and Evaluate Dapagliflozin Sustained Release Microspheres using Box-Behnken Design. International Journal of Drug Delivery Technology. 2025;15(2):465-71. doi: 10.25258/ijddt.15.2.13

REFERENCES

  1. Ginsberg HN, MacCallum PR. The Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus Pandemic: Part I. Increased Cardiovascular Disease Risk and the Importance of Atherogenic Dyslipidemia in Persons with the Metabolic Syndrome and Type 2 Diabetes Mellitus. CardioMetabolic Syndrome Journal. 2009;4(2):113-119.
  2. Nihad AH, Nazish B, Raid GA, Hany H, Amr EH. Oral Modified Release Multiple-Unit Particulate Systems: Compressed Pellets, Microparticles and Nanoparticles. Journal of Pharmaceutics. 2018;10(4):1-23
  3. Pise AG, Ghuse H, Zade S, Tiwaskar GH. Development and Assessment of a Nutritional Supplement Formulation for Diabetes Mellitus. International Journal of Drug Delivery Technology. 2024;14(2):759-767.
  4. Prasad BSG, Gupta VRM, Devanna N, Jayasurya K. Microspheres as drug delivery system- a review. Journal of Global Trends in Pharmaceutical Sciences. 2014;5(3):1961-1972.
  5. McMurray JV, Solomon SD, Inzucchi SE, Kober L. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. The New England Journal of Medicine. 2019;381(21):1995-2008.
  6. Rafaela ZC, Aline BM, Fabio SM, Paulo RDO, Larissa SB. In Vitro Dissolution Profile of Dapagliflozin: Development, Method Validation, and Analysis of Commercial Tablets. International Journal of Analytical Chemistry. 2017;1-6.
  7. Anderson SL. Dapagliflozin efficacy and safety: a perspective review. Therapeutic Advances in Drug Safety. 2014;5(6):242-254.
  8. Raymond CR, Paul JS, Marian EQ. Handbook of Pharmaceutical Excipients. 6th ed. Pharmaceutical Press; 2009. p. 262-267.
  9. Maskova E, Kateřina K, Bahijja TRA, Driton V, Eva V, Jaroslav T, Josef M. Hypromellose – A traditional pharmaceutical excipient with modern applications in oral and oromucosal drug delivery. Journal of Controlled Release. 2020;324:695-727.
  10. Sahoo CK, Rao SRM, Sudhakar M. HPMC a biomedical polymer in pharmaceutical dosage forms. Journal of Chemical and Pharmaceutical Sciences. 2015;8(4):875-881.
  11. Grumezescu AM. Oral Controlled and Sustained Drug Delivery Systems, Drug Targeting and Stimuli Sensitive Drug Delivery Systems. 2018.
  12. Jadach B, Swietlik W, Froelich A. Sodium Alginate as a Pharmaceutical Excipient: Novel Applications of a Well-known Polymer. Journal of Pharmaceutical Sciences. 2022;111(5):1250-1261. d
  13. Prajapati B, Atara S. Development of an Optimized Budesonide Delivery System: A ControlledRelease Approach for Targeting the Colon. International Journal of Drug Delivery Technology. 2024;14(4):1971-80
  14. Ahmed R, Jeyabalan G, Goyal PK. Evaluation of Hypo-glycemic and Anti-oxidant potential of Caesalpinia sappan Leave in STZ Induced Diabetic Rats. International Journal of Drug Delivery Technology. 2024;14(4):1945-53.
  15. Mante GV, Gupta KR, Hemke AT. Estimation of Dapagliflozin from its Tablet Formulation by UV-Spectrophotometry. Pharm Methods. 2017;8(2):102-107.
  16. Bhadauria RS, Agarwal V. Development and Validation of UV Spectroscopic Method for Simultaneous Estimation of Dapagliflozin and Saxagliptin in marketed formulation. Journal of Drug Delivery and Therapeutics. 2019;9(4):1160-1164.
  17. Segall AI. Preformulation: The use of FTIR in compatibility studies. Journal of Innovations in Applied Pharmaceutical Science. 2019;4(3):01-06.
  18. Chandira M, Venkateswarlu BS, Shankarro JA, Bhowmik D, Jayakar B, Narayana TV. Formulation and Evaluation of Extended-release tablets containing Metformin HCl. International Journal of ChemTech Research. 2010;2(2):1320-1329.
  19. Rai SY, Ravikumar P. Development and Evaluation of Microspheres Based Topical Formulation using Design of Experiments. Indian Journal of Pharmaceutical Sciences. 2016;78(2):182-192.
  20. Kujur A, Daharwal SJ. Box–Behnken Design Based Optimization of Process Variables for the Green Synthesis of 18-Beta–Glycyrrhetinic Acid Silver Nanoparticles and Evaluation of its Antioxidant, Antimicrobial Activity. International Journal of Drug Delivery Technology. 2023;13(2):501-509.
  21. Wong YC, Tan YP, Taufiq Y.H, Ramli I. An Optimization Study for Transesterification of Palm Oil using Response Surface Methodology (RSM). Sains Malaysiana. 2015;44(2):281–290.
  22. Rajesh M, Kumar BK, Sundaram SM, Pippala MK. Formulation and Evaluation of Metformin Hydrochloride Microspheres by Solvent Evaporation Method. International Journal for Pharmaceutical Research Scholars. 2013;2(1):121-127.
  23. Kalpna DD, Mohd. S, Prakash J, Prasad DN. Preparation of Controlled Release Metformin Hydrochloride Loaded Chitosan Microspheres and Evaluation of Formulation Parameters. Journal of Drug Delivery and Therapeutics. 2018;8(5):378-387.
  24. Chandira M, Venkateswarlu BS, Shankarro JA, Bhowmik D, Jayakar B, Narayana TV. Formulation and Evaluation of Extended-release tablets containing Metformin HCl. International Journal of ChemTech Research. 2010;2(2):1320-1329..
  25. Kumar S, Singh SP, Verma NK. Preformulation study of metformin Hydrochloride (Antidiabetic drug). International Journal of Research in Pharmaceutical and Nano Sciences. 2020;9(4):224-240.
  26. Modekar SD, Mohale DS, Kochar NI, Chandewar AV. Box-Behnken Design for Formulation, Characterization and In-vivo Antidiabetic Activity of Pioglitazone Loaded Nanostructured Lipid Carriers. International Journal of Drug Delivery Technology. 2023;13(4):1465-1470.
  27. Prasanthi D, Yanmanagandla D, Sripada RD. Formulation and Evaluation of Linagliptin Mucoadhesive Microspheres. International Research Journal of Pharmacy. 2018;9(5):11-17.
  28. Chalo CSL, Robinson JR, Lee VHL. Sustained Release Drug Delivery Systems. In: Gennaro AR. Remington: The Science and Practice of Pharmacy, Vol 2. Easton, PA: Mack Publishing Company, 17th edition; 1995:1660-1675.
  29. Das AK, Battu S, Shivaramkrishnan M, Suchutra D, Vishwanath BA, Kumar D. Formulation of Amorphous Ternary Solid Dispersion of Poorly Soluble Drug-Dapagliflozin. International Journal for Research Trends and Innovation. 2022;7(11):2456-3315.
  30. Maheshwari R, Todke P, Kuche K, Raval N, Tekade R. Dosage Form Design Considerations, Micromeritics in Pharmaceutical Product Development, Volume 1, 599-635. 2018.
  31. Kesharvani S, Jaiswal P, Mukerjee A, Singh A. Formulation and Evaluation of Metformin Hydrochloride Loaded Floating Microspheres. International Journal of Pharmacy and Pharmaceutical Sciences. 2020;12(2):74-82.