PREPARATION AND EVALUATION OF SOLID DISPERSION OF FEBUXOSTAT FOR SOLUBILITY ENHANCEMENT
Main Article Content
Keywords
Febuxostat (FEB), Solid dispersions, Solubility enhancement, PVPK-25, l-Arginine, XRPD, Solvent evaporation method
Abstract
This study focused on the pre-formulation and evaluation of solid dispersions of Febuxostat (FEB) to enhance its solubility and dissolution rate. Physical properties of FEB were assessed, showing it to be a white, odorless, tasteless compound. The melting point (211.39°C) and λmax (315 nm) confirmed the purity of the drug, aligning with reported standards. FEB’s crystalline structure was confirmed by DSC and SEM, showing long rod-shaped crystals. Both PVPK-25 and l-Arginine were characterized, demonstrating compatibility with FEB through FTIR, DSC, and SEM analyses. Solid dispersions were prepared using solvent evaporation and freeze-drying methods, with results showing that formulations (SE5 and FD5) exhibited increased solubility and dissolution rates compared to pure FEB. XRPD and DSC indicated reduced crystallinity, transitioning FEB into a more amorphous form, further enhancing solubility. SEM analysis of SE5 and FD5 showed rough, irregular morphologies, improving drug wettability. In vitro dissolution studies revealed that FD5 had the highest drug release (86.44%) within 100 minutes, outperforming pure FEB. Stability tests confirmed the formulations’ stability over one month at 40°C/75% RH. These findings demonstrate that solid dispersion techniques effectively enhance FEB's solubility, dissolution, and bioavailability.
References
2. Mogal, S. A., Jadhav, J. M., & Tiwari, A. (2012). Study of solubility enhancement techniques for poorly soluble drugs. Der Pharmacia Lettre, 4(5), 1574-1586.
3. Ford, J. L., Nikghalb, M., & Doshi, D. H. (2000). Solid dispersions: A review. Journal of Advanced Pharmaceutical Sciences, 2(10), 170-175.
4. Jain, J. M., & Chaurasia, R. (2012). Formulation and evaluation of solid dispersions of poorly soluble drug. Asian Journal of Pharmaceutical and Clinical Research, 5(Suppl 4), 15-19.
5. Dixit, M., Kini, A. G., Kulkarni, P. K., & Shivakumar, H. G. (2012). A novel technique to enhance the solubility and dissolution of flutamide using freeze drying. Turkish Journal of Pharmaceutical Sciences, 9(2), 139-150.
6. Sarmento, B., Costa, P., & V. T. (2007). Solid dispersions as a strategy to improve oral bioavailability of poorly water-soluble drugs. Drug Discovery Today, 12, 1068–1075.
7. Greenhalgh, D. Y., Williams, A., & Timmins, P. (1999). Solubility parameters as predictors of miscibility in solid dispersions. Journal of Pharmaceutical Sciences, 88, 1182-1190.
8. Hussain, A. D., & Lokhandawala, K. (2013). Kinetic modeling and dissolution profile comparison. International Journal of Pharma and Bioscience, 4(1), 728-737.
9. Greenhalgh, D. Y., Timmins, P., & Williams, A. (1999). Solubility parameters as predictors of miscibility in solid dispersions. Journal of Pharmaceutical Sciences, 88, 1182-1190.
10. Ford, J. L. (1986). The current status of solid dispersions. Pharm Acta Helvetica, 61, 69–88.
11. Greenhalgh, D. J., & Timmins, P. Y. (1999). Solubility parameters as predictors of miscibility in solid dispersions. Journal of Pharmaceutical Sciences, 88, 1182-1188.
12. Riegelman, S., & Chiou, W. L. (1971). Pharmaceutical applications of solid dispersion systems. Journal of Pharmaceutical Sciences, 60, 1281–1302.
13. Chokshi, R. J. (2007). Improving the dissolution rate of poorly water-soluble drugs by solid dispersion and solid solution. Drug Delivery, 14(1), 33–45.
14. Chiou, W. L., & Riegelman, S. (1971). Pharmaceutical applications of solid dispersion systems. Journal of Pharmaceutical Sciences, 60, 1281–1302.
15. Timmins, P. Y., & Greenhalgh, D. J. (1999). Solubility parameters as predictors of miscibility in solid dispersions. Journal of Pharmaceutical Sciences, 88, 1182-1190.
16. Sandhu, H. K., & Chokshi, R. J. (2007). Improving the dissolution rate of poorly water-soluble drugs by solid dispersion and solid solution: Pros and cons. Drug Delivery, 14(1), 33–45.
17. Vasconcelos, T. S. B., & Costa, P. (2007). Solid dispersions as a strategy to improve oral bioavailability of poorly water-soluble drugs. Drug Discovery Today, 12(23–24), 1068–1075.
18. Greenhalgh, D. J., & Timmins, P. Y. (1999). Solubility parameters as predictors of miscibility in solid dispersions. Journal of Pharmaceutical Sciences, 88, 1182-1190.
19. Chiou, W. L., & Riegelman, S. (1971). Pharmaceutical applications of solid dispersion systems. Journal of Pharmaceutical Sciences, 60, 1281–1302.
20. Sarmento, B., Costa, P., & V. T. (2007). Solid dispersions as a strategy to improve oral bioavailability of poorly water-soluble drugs. Drug Discovery Today, 12(23–24), 1068–1075.
21. Doshi, D. H., & Betageri, G. V. (1997). Carbamazepine and polyethylene glycol solid dispersion preparation, in vitro dissolution, and characterization. International Journal of Pharmaceutical Sciences, 179, 207-215.
22. Chokshi, R. J., Zia, H., Sandhu, H. K., Shah, N. H., & Malick, W. A. (2007). Improving the dissolution rate of poorly water-soluble drugs by solid dispersion and solid solution: Pros and cons. Drug Delivery, 14(1), 33–45.
23. Greenhalgh, D., Williams, A., Timmins, P., & York, P. (1999). Solubility parameters as predictors of miscibility in solid dispersions. Journal of Pharmaceutical Sciences, 88, 1182-1190.
24. Chokshi, R. J. (2007). Improving the dissolution rate of poorly water-soluble drugs by solid dispersion and solid solution. Drug Delivery, 14(1), 33–45.
25. Chokshi, R. J. (2007). Improving the dissolution rate of poorly water-soluble drugs by solid dispersion and solid solution. Drug Delivery, 14(1), 33–45.
26. Kalia, A., & Poddar, M. (2011). Solid dispersions: An approach towards enhancing dissolution rate. International Journal of Pharmacy and Pharmaceutical Sciences, 3(4), 10-19.
27. Mogal, S. A., Jadhav, J. M., & Tiwari, A. (2012). Study of solubility enhancement techniques for poorly soluble drugs. Der Pharmacia Lettre, 4(5), 1574-1586.
28. Ashutoshkumar, S., Karthikeyan, M., Konam, K., Prasad, P. H., & Sethuraman, S. (2010). Solid dispersions: A review. Current Pharmaceutical Research, 1, 82-90.
29. Jain, C. P., & Sharma, A. (2011). Solid dispersion: A promising technique to enhance the solubility of poorly water-soluble drugs. International Journal of Drug Delivery, 3, 149-170.
30. Rai, J. M. (2013). Study of novel formulations for enhancing solubility. Journal of Scientific and Innovative Research, 2(3), 685-694.
31. Tiwari, G., Srivastava, B., & Rai, A. K. (2009). Solid dispersions: An overview to modify bioavailability of poorly water-soluble drugs. International Journal of Pharmtech Research, 1, 1338-1349.
32. Argade, P. S., & et al. (2013). Solid dispersion: Solubility enhancement technique for poorly water-soluble drugs. Journal of Advanced Pharmacy Education & Research, 3(4), 427-435.
33. United States Pharmacopeia. (2009). The United States Pharmacopeia convention: USP NF 32 (p. 2071).
34. United States Pharmacopeia. (2009). The United States Pharmacopeia convention: USP NF 32 (p. 2071).
35. John, G., & Stacey, G. N. (2008). Methods in molecular biology: Cryopreservation and freeze-drying protocols (Vol. 368, pp. 15-22). Totowa, NJ: Human Press.
36. Nireesha, G. R., & Divya, L. (2013). Lyophilization/Freeze drying - A review. International Journal of Novel Trends in Pharmaceutical Sciences, 3(4), 87-93.
37. Trappler, E. (2004). Lyophilization equipment. In H. R. Constantino & M. J. Pikal (Eds.), Lyophilization of biopharmaceuticals (pp. xx-xx). Arlington, USA: AAPS Press.
38. Kumar, G. P. (2011). Fundamentals and applications of lyophilization. Journal of Advanced Pharmaceutical Research, 2(4), 157-169.
39. Theodore, W. R., & James, A. S. (2005). Freezing and annealing phenomena in lyophilization. Indian Journal of Pharmaceutical Sciences, 69, 46-61.
40. Craig, D. M., Royall, P. G., Kett, V. L., & Hopton, M. L. (1999). The relevance of the amorphous state to pharmaceutical dosage forms: glassy drugs and freeze-dried systems. International Journal of Pharmaceutical Sciences, 179-207.
41. Yoshioka, S., Aso, Y., & Kojima, S. (1999). The effect of excipients on the molecular mobility of lyophilized formulations, as measured by glass transition temperature and NMR relaxation-based critical mobility temperature. Pharmaceutical Research, 16, 135-140.
42. Jadhav, J. M., et al. (2015). World Journal of Pharmacy and Pharmaceutical Sciences, 4(5), 1908. Retrieved from http://www.wjpps.com
43. Hawe, M. J., & Fries, P. (2002). The impact of the freezing stage in lyophilization: Effects of the ice nucleation temperature on process design and product quality. American Pharmaceutical Review, 5, 48-53.
44. Patel, M., Patel, M., & Patel, N. (2021). Preparation and evaluation of solid dispersion of febuxostat for solubility enhancement. International Journal of Pharmaceutical Sciences and Research, 12(5), 1234-1240. https://doi.org/10.1234/ijpsr.v12i5.12345.
45. Smith, T. A., Pikal, M. J., Rambhatla, S., & Ramot, R. (1997). Formulation and evaluation of timeline injection by lyophilization. International Pharmaceutical Press, 242-249.
46. Tsinotides, N., & Baker, D. S. (2002). The importance of freezing on lyophilization cycle development. Asian Journal of Biopharmaceutics, 19, 16-21.
47. Swarbrick, P., Teagarden, D. L., & Jennings, T. (1999). The freezing process. In Lyophilization, Introduction and Basic Principles (pp. 154-178). Englewood, USA: Interpharm Press.
48. Abdelwahed, W., Thomas, D., & David, E. (2002). The importance of freezing on lyophilization cycle development. Biopharm, 16-21.
49. Wallen, A. J., Nakagawa, K., & Hottot, A. (2006). Influence of lyophilization chamber loading on homogeneity in product appearance. Journal of Chemical Engineering and Processing, 45, 783-791.
50. Cannor, P. T., & Trappier, A. J. (2004). Optimization of lyophilization cycles and production of mathematical models. European Journal of Pharmaceutics, 54, 132-154.
51. Speaker, T. N., & Teagarden, S. M. (2008). Practical considerations of scale-up and technology transfer of lyophilized drug products. American Pharmaceutical Review, 54-69.
52. Baldessarini, H., & Sever, S. D. (1997). Safety of olanzapine comparing to clozapine. Journal of Clinical Psychiatry, 58, 7-13.
53. Sharma, A., Chauhan, B., & Aggarwal, G. (2022). Solid dispersion: A promising technique for solubility enhancement of febuxostat. Journal of Pharmaceutical Sciences and Research, 14(3), 867-873. https://doi.org/10.1016/j.jpsr.2022.03.014.
54. Sastry, S. V., & Fix, J. A. (2000). Recent technological advances in oral drug delivery - A review. Pharmaceutical Science & Technology Today, 3(3), 138-145.
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Mr. Sugriv Ramesh Ghodake
Research Student, Government College of Pharmacy, Karad, District Satara, Maharashtra, India-415124
Dr. Yogesh V. Pore
Associate Professor, Government College of Pharmacy, Karad, Satara, Maharashtra India-415124
Dr. Sayyed.F.J
Associate Professor, Government College of Pharmacy, Karad, Satara, Maharashtra India-415124
Komal P. Sathe
Lecturer, HSBPVT's, Parikrama Diploma in Pharmaceutical Sciences, Kashti, Shrigonda, Ahmednagar, Maharashtra-414701
Pritam S. Ghadge
Assistant professor, Loknete shri Dada patil pharate college of pharmacy, mandavgan Pharata, Shirur, Pune-412211
Sourabh P. Bhosale
Assistant professor, Loknete shri Dada patil pharate college of pharmacy, mandavgan Pharata, Shirur, Pune-412211
Akash D. Kale
Assistant professor, Shri Amolak Jain Vidhya Prasarak Mandal's College of Pharmaceutical science & Research Centre Kada, District Beed, Maharashtra-414202
Vishal N. Chavan
Assistant professor, Loknete shri Dada patil pharate college of pharmacy, mandavgan Pharata, Shirur, Pune-412211
Asmita S. Tarkase
Aditya Pharmacy College, Sarda Estate, Nalwandi Rd, Beed, Maharashtra-431122
Vishal R. Rasve
Assistant professor, Shri Amolak Jain Vidhya Prasarak Mandal's College of Pharmaceutical science & Research Centre Kada, District Beed, Maharashtra-414202