SOLUBILITY ENHANCEMENT OF RIVAROXABAN BY SOLID DISPERSION WITH POLYETHYLENE GLYCOL 4000

Authors

  • RUCHITA KUMARI PATRA Royal College of Pharmacy and Health Sciences, Berhampur-2, Odisha
  • AJIT KUMAR ACHARYA Royal College of Pharmacy and Health Sciences, Berhampur-2, Odisha
  • ANJAN KUMAR MAHAPATRA Royal College of Pharmacy and Health Sciences, Berhampur-2, Odisha
  • PADALA NARASIMHA MURTHY Royal College of Pharmacy and Health Sciences, Berhampur-2, Odisha https://orcid.org/0000-0001-9649-7848

DOI:

https://doi.org/10.22159/ijap.2023v15i2.46687

Keywords:

solid dispersions, dissolution rate, PEG 4000, hydrophilic carriers, physicochemical characterization

Abstract

Objective: The aim of the work was to enhance the dissolution rate of rivaroxaban by preparing its solid dispersions (SDs) using hydrophilic carrier PEG 4000.

Methods: The SDs of rivaroxaban with PEG 4000 were prepared at 1:1, 1:2 and 1:3 w/w ratios by physical mixing, melting and solvent evaporation techniques. The prepared solid dispersions were characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC).

Results: Both solubility and dissolution rate of the drug in these formulations were increased. The used hydrophilic carriers showed more than two fold increase in dissolution rate in their prepared solid dispersions by melting or solvent evaporation techniques. The pure drug rivaroxaban as the pure drug shows a dissolution rate of nearly 39 % after 60 m, where as the solid dispersions by melting or solvent evaporation showed 90% of dissolution after 60 m. The FTIR spectroscopic and DCS thermal studies showed the compatibility of rivaroxaban and absence of well-defined drug polymer interactions, though shift in peaks observed due to formation of new bonds.

Conclusion: Formulation of solid dispersions of drug with hydrophilic carriers is a successful approach for solubility or dissolution rate enhancement of low soluble drug(s). In this work for solubility enhancement of rivaroxaban the hydrophilic carrier PEG 4000 showed significant solubility enhancement.

Downloads

Download data is not yet available.

References

Choi Min-Jong, Woo Mi Ran , Choi Han-Gon , Jin Sung Giu. Effects of Polymers on the Drug Solubility and Dissolution Enhancement of Poorly Water-Soluble Rivaroxaban. Int J Mol Sciences.2022 Aug 22; 23(16): 9491.

Chen N, Di P, Ning S, Jiang W, Jing, Q, Ren G, Liu Y, Tang Y, Xu Z, Liu G. Modified rivaroxaban microparticles for solid state properties improvement based on drug-protein/polymer supra molecular interactions. Powder. Technol. 2019; 344: 819–829.

Choi, MJ, Kim JS, Yu HS, Woo MR, Choi JE, Baek KH, Kim JO, Choi YS, Choi HG, Jin SG. Comparison of the physicochemical properties, aqueous solubility, and oral bioavailability of rivaroxaban loaded-high pressure-homogenized and Shirasu porous glass membrane emulsified solid self nanoemulsifying drug delivery systems. J. Mol. Liq. 2021; 23: 117057.

Mahapatra AK, Murthy PN, Erla RR, Soujany SP, Patra RK. An updated Review on Technical Advances to Enhance Dissolution rate of Hydrophobic Drugs. Int. Res. J. Pharm. 2012, 3(10).

A. K. Mahapatra, P. N. Murthy, R. K. Patra, S. Panda, R. K. Rautray. Comparative interaction of β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin with fenofibrate: Phase-solubility behavior and dissolution rates. Lat. Am. J. Pharm. 31 (9): 1302-9 (2012).

Anjan K. Mahapatra, P. N. Murthy , Jagannath Sahoo, Siba Prasad Pradhan, Ruchita Kumari Patra. Dissolution Enhancement and Solid state Characterization of Fenofibrate Solid Dispersions with Polyethylene Glycol 6000 and 8000. J. Pharm. Res. 2011, 4(6), 1802-1805.

A. K. Mahapatra , P. N. Murthy , S. Biswal , J. Sahoo , S. P. Pradhan (2010) Dissolution Enhancement and Physicochemical Characterization of Fenofibrate in Solid Dispersions with Polyethylene Glycol 4000 and 20000, Int J Pharm Sci Tech.,Vol-4,Issue-1:21-31

Zhang X, Xing H, Zhao Y, Ma Z. Pharmaceutical dispersion techniques for dissolution and bioavailability enhancement of poorly water-soluble drugs. Pharmaceutics 2018: 10: 74.

Ohara, Kitamura S, Kitagawa T, Terada K. Dissolution mechanism of poorly water- soluble drug from extended-release solid dispersion system with ethylcellulose and hydroxypropyl methylcellulose. Int J Pharm. 2005; 302: 95-102.

Yalkowsky S. Techniques of solubilization of drugs. Drugs and the pharmaceutical sciences (Volume 12). Yalkowsky S. (Ed). Marcel Dekker, 1981 New York vii.

Noyes AA and Whitney WR. The rate of solution of solid dispersion substances in their own solutions. J Am Chem Soc. 1897; 19: 930-934.

Martin A. Physical pharmacy and pharmaceutical sciences; 5th (edn), Philadelphia, 2006; 232-276 and 420-432.

Park C, Lee BJ. Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs. Eur J Pharm Biopharm. 2013; 85: 799-813.

Yanzhuo Z, Zhuangzhi Z, Tongying J , Jinghai Z , Zhanyou W , Siling W. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan. J Control Release. 2010; 145: 257-263.

Teofilo V, Bruno S, Paulo C. Solid dispersions as strategy to improve oral bioavailability of poor water-soluble drugs. Drug Discovery Today, 2007; 12:23-24.

Ahmad Z, Maurya N, Mishra KS, Khan I. Solubility enhancement of poorly water-soluble drugs: A review. Int. J. Pharm. Technol. 2011; 3(1): 807-823.

Daisy S, Mohit S, Sandeep K, GD Gupta. Solubility enhancement-eminent role in poorly soluble drugs. Research J. Pharm. and tech. 2009; 2(2):220-224.

Amidon GL, Lennerneas 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: 413-420.

Granero GE., Ramachandran C, and Amidon GL. Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate solutions, Drug Dev. Ind. Pharm., 2005, 31: 917–922.

Alkufi HK , Rashid AM. Enhancement of the Solubility of Famotidine Solid Dispersion Using Natural Polymer by Solvent Evaporation. Int. J. Appl. Pharm. 2021, 13 (3): 193-198.

Hardikar SR, Mulla SS. “Optimization of Formulation of Solid Dispersion of Furosemide by Factorial Design”. Int J Pharm Pharm Sci. 2020, 12(4): 43-48.

Kaur J, Aggarwal G, Singh G, Rana AC. Improvement of Drug Solubility Using Solid Dispersion. Int J Pharm Pharm Sci. 2012, 4(2): 47-53.

Published

22-12-2022

How to Cite

PATRA, R. K., ACHARYA, A. K., MAHAPATRA, A. K., & MURTHY, P. N. (2022). SOLUBILITY ENHANCEMENT OF RIVAROXABAN BY SOLID DISPERSION WITH POLYETHYLENE GLYCOL 4000. International Journal of Applied Pharmaceutics, 15(2). https://doi.org/10.22159/ijap.2023v15i2.46687

Issue

Section

Original Article(s)