Polymers in Medicine

Polim. Med.
Index Copernicus (ICV 2022) – 121.55
MEiN – 70
Average rejection rate – 39.13%
ISSN 0370-0747 (print)
ISSN 2451-2699 (online) 
Periodicity – biannual

Download PDF

Polymers in Medicine

2018, vol. 48, nr 2, July-December, p. 69–75

doi: 10.17219/pim/102976

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Creative Commons BY-NC-ND 3.0 Open Access

The preparation and physicochemical characterization of eprosartan mesylate-laden polymeric ternary solid dispersions for enhanced solubility and dissolution rate of the drug

Abid Mehmood Yousaf1,A,C,D, Sundas Zulfiqar2,B, Yasser Shahzad1,C,E, Talib Hussain1,E, Tariq Mahmood2,C,E, Muhammad Jamshaid2,F

1 Department of Pharmacy, COMSATS University Islamabad, Lahore Campus, Pakistan

2 Faculty of Pharmacy, University of Central Punjab, Lahore, Pakistan

Abstract

Background. Eprosartan mesylate is a poorly water-soluble drug. It does not dissolve well in the aqueous gastrointestinal fluid, which means it is not absorbed well via the oral route, because a drug can cross cell membranes when it is dissolved in the gastrointestinal fluid.
Objectives. The purpose of this research was to enhance the aqueous solubility and dissolution rate of eprosartan mesylate using the solid dispersion technique. Enhancing the solubility and dissolution leads to better absorption via the oral route.
Material and Methods. A number of eprosartan mesylate-laden polymeric solid dispersions were prepared with hydroxypropyl methylcellulose (HPMC) and polysorbate 80 by means of the solvent evaporation technique. The impact of the weight ratios of the constituents on the solubility and dissolution rate was studied in comparison with the plain drug. The formulation presenting the optimal solubility and dissolution underwent the solid-state characterization using X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR).
Results. Both polysorbate 80 and HPMC positively affected the solubility and dissolution of eprosartan mesylate.
Conclusion. In particular, a ternary solid dispersion consisting of eprosartan mesylate, HPMC and polysorbate 80 at a weight ratio of 1:4.2:0.3 showed the highest solubility (36.39 ± 3.95 mg/mL) and dissolution (86.19 ±4.09% in 10 min). Moreover, the drug was present in the amorphous form in the solid dispersion with no covalent drug–excipient interactions.

Key words

amorphous, hydroxypropyl methylcellulose, aqueous solubility, eprosartan mesylate, polymeric solid dispersions

References (34)

  1. Vijaya Santhi D, Reddy NH, Sumalatha N, Jothieswari D. A novel estimation of eprosartan mesylate in pure and in tablet formulations by simple UV method. Res J Pharm Technol. 2011;4(7):1069–1072.
  2. Satheesh B, Pulluru SK, Nitin K, Saravanan D. Simultaneous determination of eprosartan, hydrochlorothiazide, and their related compounds in pharmaceutical dosage forms by UPLC. J Liq Chromatogr Relat Technol. 2011;34(17):1885–1900.
  3. Israili Z. Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. J Hum Hypertens. 2000;14(S1):S73–S86.
  4. Hedner T, Himmelmann A; the Eprosartan Multinational Study Group. The efficacy and tolerance of one or two daily doses of eprosartan in essential hypertension. J Hypertens. 1999;17(1):129–136.
  5. McClellan KJ, Balfour JA. Eprosartan. Drugs. 1998;55(5):713–718, discussion 719–720.
  6. Sareen S, Mathew G, Joseph L. Improvement in solubility of poor water-soluble drugs by solid dispersion. Int J Pharm Investig. 2012;2(1):12–17.
  7. Derosa G, Ragonesi P, Mugellini A, Ciccarelli L, Fogari R. Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: A randomized, double-blind, placebo-controlled 12-month study. Hypertens Res. 2004;27(7):457–464.
  8. Dézsi CA. The different therapeutic choices with ARBs. Which one to give? When? Why? Am J Cardiovasc Drugs. 2016;16(4):255–266.
  9. Joe JH, Lee WM, Park YJ, et al. Effect of the solid-dispersion method on the solubility and crystalline property of tacrolimus. Int J Pharm. 2010;395(1):161–166.
  10. Yan YD, Sung JH, Kim KK, et al. Novel valsartan-loaded solid dispersion with enhanced bioavailability and no crystalline changes. Int J Pharm. 2012;422(1–2):202–210.
  11. Cho JH, Kim YI, Kim DW, et al. Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet. Eur J Pharm Sci. 2014;54(Suppl C):1–7.
  12. Dave RH, Patel HH, Donahue E, Patel AD. To evaluate the change in release from solid dispersion using sodium lauryl sulfate and model drug sulfathiazole. Drug Dev Ind Pharm. 2013;39(10):1562–1572.
  13. Hwang du H, Kim YI, Cho KH, et al. A novel solid dispersion system for natural product-loaded medicine: Silymarin-loaded solid dispersion with enhanced oral bioavailability and hepatoprotective activity. J Microencapsul. 2014;31(7):619–626.
  14. Leane MM, Sinclair W, Qian F, et al. Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant. Pharm Dev Technol. 2013;18(2):359–366.
  15. Yousaf AM, Kim DW, Kim JO, et al. Characterization of physicochemical properties of spray-dried solid dispersions loaded with unmodified crystalline fenofibrate. Curr Pharm Anal. 2015;11(2):139–144.
  16. Shahzad Y, Sohail S, Arshad MS, Hussain T, Shah SNH. Development of solid dispersions of artemisinin for transdermal delivery. Int J Pharm. 2013;457(1):197–205.
  17. Yousaf AM, Mustapha O, Kim DW, et al. Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate. Int J Nanomedicine. 2016;11:213–221.
  18. Yousaf AM, Kim DW, Kim DS, et al. Influence of polyvinylpyrrolidone quantity on the solubility, crystallinity and oral bioavailability of fenofibrate in solvent-evaporated microspheres. J Microencapsul. 2016;33(4):365–371.
  19. Yousaf AM, Kim DW, Oh YK, Yong CS, Kim JO, Choi HG. Enhanced oral bioavailability of fenofibrate using polymeric nanoparticulated systems: Physicochemical characterization and in vivo investigation. Int J Nanomedicine. 2015;10:1819–1930.
  20. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today. 2007;12(23):1068–1075.
  21. Ming-Thau S, Ching-Min Y, Sokoloski TD. Characterization and dissolution of fenofibrate solid dispersion systems. Int J Pharm. 1994;103(2):137–146.
  22. Modi A, Tayade P. Enhancement of dissolution profile by solid dispersion (kneading) technique. AAPS PharmSciTech. 2006;7(3):E87–92.
  23. Patel T, Patel L, Patel T, Makwana S, Patel T. Enhancement of dissolution of fenofibrate by solid dispersion technique. Int J Res Pharm Sci. 2010;1(2):127–132.
  24. Craig DQ. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2002;231(2):131–144.
  25. Shah V, Konecny J, Everett R, McCullough B, Noorizadeh AC, Skelly J. In vitro dissolution profile of water-insoluble drug dosage forms in the presence of surfactants. Pharm Res. 1989;6(7):612–618.
  26. Shah VP, Noory A, Noory C, et al. In vitro dissolution of sparingly water-soluble drug dosage forms. Int J Pharm. 1995;125(1):99–106.
  27. Hugo M, Kunath K, Dressman J. Selection of excipient, solvent and packaging to optimize the performance of spray-dried formulations: Case example fenofibrate. Drug Dev Ind Pharm. 2013;39(2):402–412.
  28. Taylor LS, Zografi G. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm Res. 1997;14(12):1691–1698.
  29. Doherty C, York P. Accelerated stability of an X-ray amorphous frusemide-polyvinylpyrrolidone solid dispersion. Drug Dev Ind Pharm. 1989;15(12):1969–1987.
  30. Konno H, Handa T, Alonzo DE, Taylor LS. Effect of polymer type on the dissolution profile of amorphous solid dispersions containing felodipine. Eur J Pharm Biopharm. 2008;70(2):493–499.
  31. Gupta P, Kakumanu VK, Bansal AK. Stability and solubility of celecoxib-PVP amorphous dispersions: A molecular perspective. Pharm Res. 2004;21(10):1762–1769.
  32. Tanno F, Nishiyama Y, Kokubo H, Obara S. Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions. Drug Dev Ind Pharm. 2004;30(1):9–17.
  33. Dangre PV, Godbole MD, Ingale PV, Mahapatra DK. Improved dissolution and bioavailability of eprosartan mesylate formulated as solid dispersions using conventional methods. Ind J Pharm Edu Res. 2016;50(3):S209–217.
  34. Ahn JS, Kim KM, Ko CY, Kang JS. Absorption enhancer and polymer (vitamin E TPGS and PVP K29) by solid dispersion improve dissolution and bioavailability of eprosartan mesylate. Bull Korean Chem Soc. 2011;32(5):1587–1592.
© Wroclaw Medical University