SOLUBILITY ENHANCEMENT OF RITONAVIR BY HOT MELT EXTRUSION

  • Sanjeevani Desai Tatyasaheb Kore College of Pharmacy Warananagar, India
  • John Disouza
  • Kiran Musle
  • Hoshmani Avinash

Abstract

Objective: The enhancement of oral bioavailability of poorly water-soluble drugs remains one of the most challenging aspects of drug development. Therefore formulation approaches are being explored to enhance bioavailability of poorly water-soluble drugs. The aim of the present study was to prepare and characterize solid solution of water insoluble anti-HIV drug (Ritonavir).

Methods: There are various techniques such as micronization, solubilization, salt formation, complexation with polymers, change in physical form, use of prodrug and drug derivatization, alteration in pH, the addition of surfactants, and others are used by which the dissolution and bioavailability of sparingly soluble drugs can be improved. Among the various approaches, the solid dispersion (SD) technique has often proved to be the most successful in improving the dissolution and bioavailability of the poorly soluble drug. Solid Solution were prepared by Hot Melt Extrusion technique at 1:1.5, 1:2 (Ritonavir: Soluplus) and 1:1.5:0.5 (Ritonavir: Soluplus: Leutrol F68/leutrol 127/TPGS) ratios respectively. Solid Solution was evaluated for Saturation solubility, dissolution rate, XRD, FTIR, DSC and SEM.

Results: Among all prepared Solid solution systems, the systems which contain 1:2 ratios of Ritonavir and Soluplus, has shown 13 fold increases in solubility than pure Ritonavir. DSC, XRD and SEM results shown to change from crystalline to amorphous form for all ratios of Ritonavir.

Conclusion: From the above results, it was concluded that the improved drug dissolution could be achieved by formulating Ritonavir as a solid solution with the polymers such as Soluplus. The low hygroscopicity and low glass transition temperature of Soluplus make it particularly suitable for hot melt extrusion.

Keywords: Solid solutions, Hot melt extrusion, Bioavailability, Soluplus

Downloads

Download data is not yet available.

References

1. Sharma DK, Joshi SB. Solubility enhancement strategies for poorly water-soluble drugs in solid dispersions: a review. Asian J Pharm 2007;1:9-19.
2. Chiou WL, Riegelman S. Pharmaceutical application of solid dispersion. J Pharm Sci 1971;60:1281-302.
3. Amidon GL, Lennernas H, Shah VP, Crison JR. A Theoretical basis for a biopharmaceutic drug classification-the correlation of in-vitro drug product dissolution and in-vivo bioavailability. Pharm Res 1995;12:413-20.
4. Sharma D, Soni M, Kumar S, Gupta GD. Solubility enhancement–Eminent role in poorly soluble drugs. Res J Pharm Technol 2009;2:220-4.
5. Choksi RJ, Zia H. Hot melt extrusion technique: a review. Iran J Pharm Res 2004;3:16-23.
6. Ghebre-Selassie I, Martin C. Pharmaceutical extrusion technology. Marcel Dekker, Inc; 2003. p. 197-200.
7. Breitenbach J. Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm 2002;54:107-17.
8. Khatry S, Abbulu K. Melt extrusion-An overview. Res J Pharm Technol 2011;3:685-703.
9. Repka MA, Battu SK. Pharmaceutical application of hot melt extrusion part: part–I. Drug Dev Ind Pharm 2007;33:909-26.
10. Repka MA, Battu SK, Upadhyay SB, Summa S, Crowley MM, Zhang F, et al. Pharmaceutical application of hot melt extrusion part–II. Drug Dev Ind Pharm 2007;33:1043-57.
11. Razavialavi SA, Gholami Z. Twin screw extruder and effective parameters on the HDPE extrusion process. World Academy Sci Eng Technol 2009;37:49-58.
12. Dressman J, Leuner C. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000;50:47-60.
13. Rupal J, Kaushal J, Setty C, Patel D. Preparation, and evaluation of the solid dispersion of Aceclofenac. Int J Pharm Sci Drug Res 2009;1:32-5.
14. Choudhary D, Kumar S, Gupta GD. Enhancement of solubility and dissolution of Glipizide by solid dispersion (kneading) technique. Asian J Pharm Sci 2009;3:245-51.
15. Hardung H, Djuric D, Ali S. Combining HME and solubilization: surplus-the solid solution. Drug Delivery Technol 2010;10:20-7.
16. Zhu Y, Shah N, Malic A, McGinity J. Controlled release of a poorly water drug from hot melt extruder containing acrylic polymers. Drug Dev Ind Pharm 2006;32:569-83.
17. Desai S, Doke A, Disouza J. Development, and evaluation of anti-fungal topical niosomal gel formulation. Int J Pharm Pharm Sci 2011;3:224-31.
18. Patterson J, James M, Forster A, Rades T. Melt extrusion and spray drying of carbamazepine and dipyridamole with polyvinylpyrrolidone/vinyl acetate copolymers. Drug Dev Ind Pharm 2008;34:95-106.
19. Forster A, Hempenstall J, Tucker I, Rades T. Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int J Pharm 2001;226:147-61.
20. Timpe C, Forschung L. Strategies for formulation development of poorly water soluble drug candidates-A recent perspective. Am Pharm Rev 2007;10:104-9.
Statistics
1046 Views | 1754 Downloads
How to Cite
Desai, S., J. Disouza, K. Musle, and H. Avinash. “SOLUBILITY ENHANCEMENT OF RITONAVIR BY HOT MELT EXTRUSION”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 3, Mar. 2016, pp. 309-12, https://innovareacademics.in/journals/index.php/ijpps/article/view/9681.
Section
Original Article(s)