IMPROVEMENT OF SOLUBILITY AND DISSOLUTION RATE OF TICAGRELOR SOLID DISPERSIONS BY DIFFERENT METHODS

Main Article Content

Md Abdul Khader
Roshan S

Keywords

Ticagrelor, solid dispersion, fusion (melt) method, poloxamer 188, platelet aggregation inhibitor.

Abstract

Introduction: The current study is aimed at enhancing the solubility and release rates of ticagrelor (TGL), an oral antiplatelet agent by adopting solid dispersion (SD) technique.


Material and Methods: Forty formulations of TGL SD prepared by solvent evaporation method(TGL1-TGL20) and fusion(melt) method(TGL20-TGL40) using varying ratios of water soluble carriers(poloxamer 188, labrafil M1944, PEG 8000and gelucire 44/14).All the formulations evaluated for pre compression parameters,% practical yield,% drug content and drug dissolution. The optimized formulation further subjected to characterization by FTIR, PXRD and SEM studies.


Results: The solubility of ticagrelor(TGL) checked in various polymers indicate that  pure drug exhibited maximum solubility in  phosphate  buffer(0.152 mg/ml) while drug and poloxamer 188 mixture exhibited maximum solubility of 3.8 mg/ml in phosphate buffer . The SD formulation TGL35 containing poloxamer 188 exhibited maximum solubility of 6.992±0.04 mg/ml which is 46 folds that of pure drug. Similar enhancement trends observed in % drug content, %practical yield and in-vitro dissolution rates of TGL35 (99.55% in 60 minutes) when compared to pure drug. FTIR study displayed the compatibility amongst drug and polymer used. The XRD and SEM studies showed TGL35 existed in amorphous state which fetched in better drug release rates of SD formulation in comparison to pure drug.


Conclusion: The results indicate that the formulation technology employed with a potential of enhancing bioavailability and solubility of ticagrelor.

Abstract 130 | pdf Downloads 158

References

1. Win Loung Chiou, Riegelman S.Pharmaceutical applications of solid dispersion systems. J Pharm Sci 1971; 60(9):1281-1302.
2. Aftab M, Pralhad T. Enhancement of dissolution profile by solid dispersion (kneading) technology. AAPS Pharm Sci Tech 2006; 7: 68-71.
3. Vasconcelos T, Sarmento B, Costa P. Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 2007; 12(23-24):1068-1075.
4. Youn YS.Improved intestinal delivery of salmoncalcitonin by Lys18 amine specific PEGylation: Stability, permeability, pharmacokinetic behavior vivo hypocalcemic efficacy. J Contr Release 2006; 114:334–42.
5. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001; 409(6817): 202–7.
6. Bambace NM, Levis JE, Holmes CE. The effect of P2Y-mediated platelet activation on the release of vegf and endostatin from platelets. Platelets 2010; 21: 85–93.
7. Beigi R, Kobatake E, Aizawa M, Dubyak GR. Detection of local ATP release from activated platelets using cell surface-attached firefly luciferase. Am J Physiol 1999; 276: 267–78.
8. Cattaneo M, Schulz R, Nylander S. Adenosine-mediated effects of ticagrelor: evidence and potential clinical relevance. J Am CollCardiol. 2014; 63: 2503–09.
9. Wijeyeratne YD, Joshi R, Heptinstall S. Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes. Expert Rev Clin Pharmacol 2012;5(3):257–69.
10. Pandya, Darshana & Patel, Madhavi & Ghediya, Ravi & Shah ,Anamik & Ranjan, Khunt. UV-Vis spectrophotometric assay determination of oral antiplatelet ticagrelor drug in pharmaceutical formulation: Application to content uniformity. J Chem Pharm Res 2016; 316-21.
11. Arora SC, Sharma PK, Irchhaiya R, Khatkar A, Singh N, Gagoria J. Development, characterization and solubility study of solid dispersions of Cefuroxime Axetil by the solvent evaporation method.J Adv Pharm Technol Res 2010;1(3):326-29.
12. Enose AA, Dasan PK, Sivaramakrishnan H, Shah SM. Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection. Int J Pharm 2014; 1–13.
13. Saravanan M, Natraj KS, Ganesh KS. The effect of tablet formulation and hardness on in vitro release of cephalexin from Eudragit L100 based extended release tablets. Biol Pharm Bull 2002; 25: 4541-45.
14. Afrasim M, Shivakua HG. Formulation of Sustained-release diltiazem matrix tablets using hydrophilic gum blends.Trop J Pharm Res 2010; 9: 283-91.
15. Mohammadi H, Hemanath Kumar V. Formulation and Evaluation of Solid Dispersion Incorporated Fast Disintegrating Tablets of Tenoxicam Using Design of Experiment. Int J Pharm Sci Drug Res 2019; 11(1):35-44.
16. Vanshiv SD, Rao MRP, Sonar GS. Physicochemical characterization and in vitro dissolution of Domperidone by solid dispersion technique. Ind J Pharm Edu Res 2009; 43(1):86-90.
17. Subhash Katore, Bidkar SJ, Dama GY. Formulation& Evaluation of Ciprofloxacin Solid Dispersion Controlled Release Floating Capsules for Solubility Improvement. Indian J Pharm Biol Res 2017; 5(3):7-16.
18. Batra V, Shirolkar VS, Mahaparale PR. Solubility and dissolution enhancement of glipizide by solid dispersion technique. Ind J Pharm Edu Res. 2008; 42(4):373-78.
19. Yadav B, Tanwar YS.Development, Characterization and In Vitro Evaluation of Flurbiprofen Solid Dispersions using Polyethylene Glycols as Carrier. J App Pharm Sci 2016; 6(04): 060-66.
20. Mohammadi G, Barzegar-Jalali Azim, Khosro A. Development and Characterization of Solid Dispersion for Dissolution Improvement of Furosemide by Co grinding Method. Adv Pharm Bull 2014; 4(4): 391-99.
21. Soliman MS, Khan MA. Preparation and in vitro characterization of a semi-solid dispersion of flurbiprofen with Gelucire44/14 and Labrasol. Pharmazie 2005;60(4): 288-93.
22. Thenge R, Mahajan SS, Mahajan NM, Adhao V, Ajmire PV. Formulation and Evaluation of Buccoadhesive Drug Delivery System for Lovastatin. JDDT 2019;9(2);6-2.
23. Ganesh R, Suresh K, Jawahar, Senthil V, Nagasamy D. Preparation and evaluation of sustained release matrix tablet of diclofenac sodium using natural polymer. J Pharm Sci Res 2010; 2: 360-68.