DESIGN, OPTIMIZATION, AND CHARACTERIZATION OF A NOVEL AMORPHOUS SOLID DISPERSION FORMULATION FOR ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF TICAGRELOR

ABHISHEK SRIVASTAVA; MOHAMMAD AHMAD KHAN; SIMRATA BEDI; UMA BHANDARI

doi:10.22159/ijap.2023v15i4.47618

Authors

ABHISHEK SRIVASTAVA Formulation Research and Development, Sun Pharmaceutical Industries Ltd. Gurugram-122015 Haryana, India. Department of Pharmacology, SPER, Jamia Hamdard University, New Delhi-110062, India https://orcid.org/0009-0005-8639-2491
MOHAMMAD AHMAD KHAN Department of Pharmacology, SPER, Jamia Hamdard University, New Delhi-110062, India
SIMRATA BEDI Formulation Research and Development, Sun Pharmaceutical Industries Ltd. Gurugram- 122015 Haryana, India
UMA BHANDARI Department of Pharmacology, SPER, Jamia Hamdard University, New Delhi-110062, India

DOI:

https://doi.org/10.22159/ijap.2023v15i4.47618

Keywords:

BCS Class-IV drug, Amorphous solid dispersion, Hot melt extrusion, Ticagrelor

Abstract

Objective: The study aims to enhance the solubility and dissolution of ticagrelor by formulating an amorphous solid dispersion using the hot melt extrusion technique.

Methods: Solubility of ticagrelor is very limited in water and buffers of pH 1.2 to 6.8, which is one of the prime reasons for its low oral bioavailability. Amorphous solid dispersions were prepared using the Hot Melt Extrusion technique using different polymers, plasticizers, and surfactants. The formulation is optimized based on the level of polymer in the formulation. The final formulation of Ticagrelor Amorphous Solid Dispersion is made with a drug-polymer ratio of 1:3, keeping the plasticizer level at 10% of the polymer along with a surfactant Sodium Lauryl Sulfate.

Results: The formulation showed an increase in solubility of 193.95-times in water, 50.71-times in 0.1 N HCl, 332.74-times in pH 4.5 acetate buffer, and 85.20-times in pH 6.8 phosphate buffer as compared to the pure drug. The drug release of the final formulation was found to be 70.0±4.4%, 55.4±1.1%, 35.5±2.1%, and 30.0±0.8% at 90 min, while the reference product showed a release of 9.4±1.1%, 20.7±0.5%, 8.4±0.3%, and 7.8±0.2% at 90 min in water, 0.1 N HCl, pH 4.5 acetate buffer and pH 6.8 Phosphate Buffer respectively. The drug release of the final formulation was found to be 99.1±3.8% at 60 min in 0.2% w/v Polysorbate-80 in water.

Conclusion: In the present study, the amorphous solid dispersion of the poorly-soluble drug ticagrelor was successfully prepared. The polymer, Plasdone S630, is considered the most suitable with ticagrelor for formulating amorphous solid dispersion using Hot Melt Extrusion technology to increase the solubility and dissolution of the drug.

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References

Daeihamed M, Dadashzadeh S, Haeri A, Akhlaghi MF. Potential of liposomes for enhancement of oral drug absorption. Curr Drug Deliv. 2017;14(2):289-303. doi: 10.2174/1567201813666160115125756, PMID 26768542.

Kim SJ, Lee HK, Na YG, Bang KH, Lee HJ, Wang M. A novel composition of ticagrelor by solid dispersion technique for increasing solubility and intestinal permeability. Int J Pharm. 2019;555:11-8. doi: 10.1016/j.ijpharm.2018.11.038, PMID 30448313.

Bayoumi AA. Enhancement of solubility of a poorly soluble antiplatelet aggregation drug by cogrinding technique. Asian J Pharm Clin Res. 2018;11(10):340-4. doi: 10.22159/ajpcr.2018.v11i10.27136.

Niazi M, Wissmar J, Berggren AR, Karlsson C, Johanson P. Development strategy and relative bioavailability of a pediatric tablet formulation of ticagrelor. Clin Drug Investig. 2019;39(8):765-73. doi: 10.1007/s40261-019-00800-w, PMID 31140114.

Spina E, Barbieri MA, Cicala G, Bruno A, de Leon J. Clinically relevant drug interactions between newer antidepressants and oral anticoagulants. Expert Opin Drug Metab Toxicol. 2020;16(1):31-44. doi: 10.1080/17425255.2020.1700952, PMID 31795773.

Sharma R, Kumar P, Prashanth SP, Belagali Y. Dual antiplatelet therapy in coronary artery disease. Cardiol Ther. 2020;9(2):349-61. doi: 10.1007/s40119-020-00197-0, PMID 32804330.

Mehata AK, Dehari D. Bradford assay as a high-throughput bioanalytical screening method for conforming pathophysiological state of the animal. J Drug Delivery Ther. 2020;10(1-s):105-10. doi: 10.22270/jddt.v10i1-s.3921.

Bhide P, Nachinolkar R. Formulation development and characterization of meclizine hydrochloride fast dissolving tablets using solid dispersion technique. Int J App Pharm. 2018;10(4):141-6. doi: 10.22159/ijap.2018v10i4.26493.

Bhairav BA, Jagtap LR, Saudagar RB. Solubility and dissolution enhancement of pioglitazone using solid dispersion technique. Int J Curr Pharm Sci. 2017;9(5):186-93. doi: 10.22159/ijcpr.2017v9i5.22326.

Jagdale S, Dangat Y, Kuchekar B. Improvement of dissolution rate of ramipril by solid dispersion technique and development of buccal patch. Int J Pharm Pharm Sci. 2012;4:309-18.

Emara LH, Abdelfattah FM, Taha NF. Hot melt extrusion method for preparation of ibuprofen/sucroester WE15 solid dispersions: evaluation and stability assessment. J Appl Pharm Sci. 2017;7(8):156-67.

Khaleel NY, Abdulrasool AA, Ghareeb MM, Hussain SA. Solubility and dissolution improvement of ketoprofen by solid dispersion in polymer and surfactant using solvent evaporation method. J Acad Sci IJPPS. 2011;3:431-5.

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. J Pharm (Cairo). 2014;2014:105382. doi: 10.1155/2014/105382, PMID 26556187.

Baghel S, Cathcart H, O’Reilly NJ. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci. 2016;105(9):2527-44. doi: 10.1016/j.xphs.2015.10.008, PMID 26886314.

Mehata AK, Dehari D, Priya V, Muthu MS. Drug-releasing textile materials: current developments and future perspectives. Fiber and textile engineering in drug delivery systems. Elsevier; 2023. p. 1-38.

Yadav M, Sarolia J, Vyas B, Lalan M, Mangrulkar S, Shah P. Amalgamation of solid dispersion and melt adsorption technique: improved in vitro and in vivo performance of ticagrelor tablets. AAPS PharmSciTech. 2021;22(8):257. doi: 10.1208/s12249-021-02138-z, PMID 34676463.

Schittny A, Huwyler J, Puchkov M. Mechanisms of increased bioavailability through amorphous solid dispersions: a review. Drug Deliv. 2020;27(1):110-27. doi: 10.1080/10717544.2019.1704940, PMID 31885288.

Malviya R, Srivastava P, Bansal M, PKJIJPSR S. Improvement of dissolution behavior of paracetamol using solid dispersion technique. IJPSR. 2010;1:95-9. http://dx.doi.org/10.13040/IJPSR.0975-8232.1(7).95-99.

Tian Y, Jones DS, Donnelly C, Brannigan T, Li S, Andrews GP. A new method of constructing a drug–polymer temperature–composition phase diagram using hot-melt extrusion. Mol Pharm. 2018;15(4):1379-91. doi: 10.1021/acs.molpharmaceut.7b00445, PMID 29205040.

Shin SC, Kim J. Physicochemical characterization of solid dispersion of furosemide with TPGS. Int J Pharm. 2003;251(1-2):79-84. doi: 10.1016/s0378-5173(02)00586-0, PMID 12527177.

Dehari D, Mehata AK, Priya V, Parbat D, Kumar D, Srivastava AK. Luliconazole nail lacquer for the treatment of onychomycosis: formulation, characterization and in vitro and ex vivo evaluation. AAPS PharmSciTech. 2022;23(6):175. doi: 10.1208/s12249-022-02324-7, PMID 35750993.

Alwan RM, Raja NA, Alhagiesa AW. Formulation and optimization of lyophilized selexipag nanocrystals to improve the saturation solubility and dissolution rate. Syst Rev Pharm. 2020;11(11):596-605.

Roychowdhury R, Kara DD, Rathnanand M. Hot-melt extrusion technique: A novel continuous manufacturing method for enteric-coated pellets. J Appl Pharm Sci. 2021;11(7):13-9.

Li Y, Pang H, Guo Z, Lin L, Dong Y, Li G. Interactions between drugs and polymers influencing hot melt extrusion. J Pharm Pharmacol. 2014;66(2):148-66. doi: 10.1111/jphp.12183, PMID 24325738.

Kumar A, Singh P, Nanda A. Hot stage microscopy and its applications in pharmaceutical characterization. Appl Microsc. 2020;50(1):12. doi: 10.1186/s42649-020-00032-9, PMID 33580349.

Aparna A, Kumar YS, Bhikshapathi DVRN. Formulation and in vivo evaluation of ticagrelor self-nanoemulsifying drug delivery systems. Pharm Nanotechnol. 2021;9(1):61-9. doi: 10.2174/2211738508666200708150151, PMID 32640972.

Mehata AK, Dehari D, Ayyannan SR, Muthu MS. X-ray powder diffraction spectroscopy as a robust tool in early predicting bioavailability of pharmaceutical formulation containing polymorphic drug substance. Drug Deliv Lett. 2020;10(3):250-4. doi: 10.2174/2210303110999200519074306.

Kumar Mehata A, Bharti S, Singh P, Viswanadh MK, Kumari L, Agrawal P. Trastuzumab decorated TPGS-g-chitosan nanoparticles for targeted breast cancer therapy. Colloids Surf B Biointerfaces. 2019;173:366-77. doi: 10.1016/j.colsurfb.2018.10.007, PMID 30316083.

Patel JR, Carlton RA, Yuniatine F, Needham TE, Wu L, Vogt FG. Preparation and structural characterization of amorphous spray-dried dispersions of tenoxicam with enhanced dissolution. J Pharm Sci. 2012;101(2):641-63. doi: 10.1002/jps.22800, PMID 22095696.

Maggi L, Canobbio A, Bruni G, Musitelli G, Conte U. Improvement of the dissolution behavior of gliclazide, a slightly soluble drug, using solid dispersions. J Drug Deliv Sci Technol. 2015;26:17-23. doi: 10.1016/j.jddst.2015.01.002.

Saha SK, Joshi A, Singh R, Jana S, Dubey K. An investigation into solubility and dissolution improvement of alectinib hydrochloride as a third-generation amorphous solid dispersion. J Drug Deliv Sci Technol. 2023;81:104259. doi: 10.1016/j.jddst.2023.104259.