Biopharmaceutics considerations for direct oral anticoagulants

References

• Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the european respiratory society (ERS): the task force for the diagnosis and management of acute pulmonary embolism of the european society of cardiology (ESC). Eur Heart J. 2020;41(4):543–603.
   PubMed Web of Science ®Google Scholar
• Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis. 2008;25(1):52–60.
   PubMed Web of Science ®Google Scholar
• Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e44S–e88S.
   PubMed Web of Science ®Google Scholar
• Verheugt FWA, Granger CB. Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet. 2015;386(9990):303–310.
   PubMed Web of Science ®Google Scholar
• Raiola A, Tenore GC, Ritieni A, et al. In vitro bioaccessibility, bioavailability, and plasma protein interaction of new oral anticoagulants in the presence of macronutrients. Curr Pharm Biotechnol. 2018;19(12):982–989.
   PubMed Web of Science ®Google Scholar
• Kubitza D, Becka M, Voith B, et al. Safety, pharmacodynamics, and pharmacokinetics of single doses of Bay 59-7939, an oral, direct factor Xa inhibitor. Clin Pharmacol Ther. 2005;78(4):412–421.
   PubMed Web of Science ®Google Scholar
• Kubitza D, Becka M, Roth A, et al. Dose-escalation study of the pharmacokinetics and pharmacodynamics of rivaroxaban in healthy elderly subjects. Curr Med Res Opin. 2008;24(10):2757–2765.
   PubMed Web of Science ®Google Scholar
• Raghavan N, Frost CE, Yu Z, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009;37(1):74–81.
   PubMed Web of Science ®Google Scholar
• Ogata K, Mendell-Harary J, Tachibana M, et al. Clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel factor Xa inhibitor edoxaban in healthy volunteers. J Clin Pharmacol. 2010;50(7):743–753.
   PubMed Web of Science ®Google Scholar
• Härtter S, Sennewald R, Nehmiz G, et al. Oral bioavailability of dabigatran etexilate (pradaxa®) after co-medication with verapamil in healthy subjects. Br J Clin Pharmacol. 2013;75(4):1053–1062.
   PubMed Web of Science ®Google Scholar
• Frost C, Nepal S, Wang J, et al. Safety, pharmacokinetics and pharmacodynamics of multiple oral doses of apixaban, a factor Xa inhibitor, in healthy subjects. Br J Clin Pharmacol. 2013;76(5):776–786.
   PubMed Web of Science ®Google Scholar
• Matsushima N, Lee F, Sato T, et al. Bioavailability and safety of the factor Xa inhibitor edoxaban and the effects of quinidine in healthy subjects. Clin Pharmacol Drug Dev. 2013;2(4):358–366.
   PubMed Web of Science ®Google Scholar
• Miller CS, Grandi SM, Shimony A, et al. Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol. 2012;110(3):453–460.
   PubMed Web of Science ®Google Scholar
• Salazar CA, del Aguila D, Cordova EG. Direct thrombin inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in people with non-valvular atrial fibrillation. Cochrane Database Syst Rev. 2014;2014(3):CD009893.
   Web of Science ®Google Scholar
• Bai Y, Deng H, Shantsila A, et al. Rivaroxaban versus dabigatran or warfarin in real-world studies of stroke prevention in atrial fibrillation: systematic review and Meta-analysis. Stroke. 2017;48(4):970–976.
   PubMed Web of Science ®Google Scholar
• Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132(13):1365–1371.
   PubMed Web of Science ®Google Scholar
• Yu YB, Liu J, Fu GH, et al. Comparison of dabigatran and warfarin used in patients with non-valvular atrial fibrillation meta-analysis of random control trial. Medicine. 2018;97(46):e12841.
   Google Scholar
• Khodashahi M, Rezaieyazdi Z, Sahebari M. Comparison of the therapeutic effects of rivaroxaban versus warfarin in antiphospholipid syndrome: a systematic review. Arch Rheumatol. 2020;35(1):107–116.
   PubMed Web of Science ®Google Scholar
• Aprovação de medicamento genérico contendo rivaroxabana [Internet]. Brasília: Agência Nacional de Vigilância Sanitária (Anvisa); [cited 2021. Aug 17]. Available from: https://consultas.anvisa.gov.br/#/medicamentos/25351595763201604/?substancia=23863.
   Google Scholar
• FDA approves first generics of Eliquis [Internet]. Rockville (MD): Food and Drug Administration; [cited 2021. Aug 17]. Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-eliquis.
   Google Scholar
• European Medicines Agency (EMA). Committee for medicinal products for human use (CHMP). guideline on the investigations of bioequivalence. London: EMA; 2010.
   Google Scholar
• Food and Drug Administration (FDA). M9 biopharmaceutics classification System-Based biowaivers, guidance for industry. Rockville: FDA; 2021.
   Google Scholar
• Fifty-first report of the WHO Expert Committee on specifications for pharmaceutical preparations. Geneva: WHO; 2017.
   Google Scholar
• Agência Nacional de Vigilância Sanitária (Anvisa). Resolução da diretoria colegiada RDC n° 37, de 3 de agosto de 2011. Dispõe sobre o guia Para isenção e substituição de estudos de biodisponibilidade relativa/bioequivalência e dá outras providências. Brasília: Anvisa; 2011.
   Google Scholar
• Amidon GL, Lennernäs H, Shah VP, et al. A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12(3):413–420.
   PubMed Web of Science ®Google Scholar
• Agência Nacional de Vigilância Sanitária (Anvisa). Instrução normativa n° 10, de 29 de setembro de 2016. Lista de fármacos candidatos à bioisenção baseada no sistema de classificação biofarmacêutica (BCS) e dá outras providências. Brasília: Anvisa; 2016.
   Google Scholar
• Wu CY, Benet LZ. Predicting drug disposition via application of BCS: transport/absorption/ elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm Res. 2005;22(1):11–23.
   PubMed Web of Science ®Google Scholar
• Lennernäs H. Animal data: the contributions of the ussing chamber and perfusion systems to predicting human oral drug delivery in vivo. Adv Drug Deliv Rev. 2007;59(11):1103–1120.
   PubMed Web of Science ®Google Scholar
• Sachan NK, Bhattacharya A, Pushkar S, et al. Biopharmaceutical classification system: a strategic tool for oral drug delivery technology. Asian J Pharm. 2009;3(2):76–81.
   Google Scholar
• Kawabata Y, Wada K, Nakatani M, et al. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int J Pharm. 2011;420(1):1–10.
   PubMed Web of Science ®Google Scholar
• Sieger P, Cui Y, Scheuerer S. pH-dependent solubility and permeability profiles: a useful tool for prediction of oral bioavailability. Eur J Pharm Sci. 2017;105:82–90.
   PubMed Web of Science ®Google Scholar
• Xue X, Cao M, Ren L, et al. Preparation and optimization of rivaroxaban by self-nanoemulsifying drug delivery system (SNEDDS) for enhanced oral bioavailability and no food effect. AAPS PharmSciTech. 2018;19(4):1847–1859.
   PubMed Web of Science ®Google Scholar
• Yamazaki S, Costales C, Lazzaro S, et al. Physiologically-based pharmacokinetic modeling approach to predict rifampin-mediated intestinal P-glycoprotein induction. CPT Pharmacometrics Syst Pharmacol. 2019;8(9):634–642.
   PubMedGoogle Scholar
• Zheng C, Li Y, Peng Z, et al. A composite nanocarrier to inhibit precipitation of the weakly basic drug in the gastrointestinal tract. Drug Deliv. 2020;27(1):712–722.
   PubMed Web of Science ®Google Scholar
• Yu LX, Amidon GL, Polli JE, et al. Biopharmaceutics classification system: the scientific basis for biowaiver extensions. Pharm Res. 2002;19(7):921–925.
   PubMed Web of Science ®Google Scholar
• Stangier J, Rathgen K, Stähle H, et al. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol. 2007;64(3):292–303.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Highlights of prescribing Information – Pradaxa^® (dabigatran etexilate mesylate) capsules for oral use. Rockville: FDA; 2010.
   Google Scholar
• Mekaj YH, Mekaj AY, Duci SB, et al. New oral anticoagulants: their advantages and disadvantages compared with vitamin K antagonists in the prevention and treatment of patients with thromboembolic events. Ther Clin Risk Manag. 2015;11:967–977.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency (EMA). CHMP assessment report for pradaxa. London: EMA, 2008.
   Google Scholar
• Eisert WG, Hauel N, Stangier J, et al. Dabigatran: an oral novel potent reversible nonpeptide inhibitor of thrombin. Arterioscler Thromb Vasc Biol. 2010;30(10):1885–1889.
   PubMed Web of Science ®Google Scholar
• Remko M. Molecular structure, lipophilicity, solubility, absorption, and polar surface area of novel anticoagulant agents. J Mol Struct THEOCHEM. 2009;916(1-3):76–85.
   Web of Science ®Google Scholar
• Remko M, Broer R, Remková A. A comparative study of the molecular structure, lipophilicity, solubility, acidity, absorption and polar surface area of coumarinic anticoagulants and direct thrombin inhibitors. RSC Adv. 2014;4(16):8072–8084.
   Web of Science ®Google Scholar
• Remko M, Remková A, Broer R. Theoretical study of molecular structure and physicochemical properties of novel factor Xa inhibitors and dual factor XA and factor IIA inhibitors. Molecules. 2016;21(2):185.
   Web of Science ®Google Scholar
• Ishiguro N, Kishimoto W, Volz A, et al. Impact of endogenous esterase activity on in vitro P-glycoprotein profiling of dabigatran etexilate in caco-2 monolayers. Drug Metab Dispos. 2014;42(2):250–256.
   PubMed Web of Science ®Google Scholar
• Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–295.
   PubMed Web of Science ®Google Scholar
• Blech S, Ebner T, Ludwig-Schwellinger E, et al. The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans. Drug Metab Dispos. 2008;36(2):386–399.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Clinical pharmacology and biopharmaceutics review(s). Application number: 22-512. Center for Drug Evaluation and Research. Rockville: FDA; 2010.
   Google Scholar
• Stangier J, Stähle H, Rathgen K, et al. Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects. Clin Pharmacokinet. 2008;47:47–59.
   PubMed Web of Science ®Google Scholar
• Stangier J, Eriksson BI, Dahl OE, et al. Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol. 2005;45(5):555–565.
   PubMed Web of Science ®Google Scholar
• Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost. 2009;15(1_suppl):9S–16S.
   PubMed Web of Science ®Google Scholar
• Mueck W, Stampfuss J, Kubitza D, et al. Clinical pharmacokinetic and pharmacodynamic profile of rivaroxaban. Clin Pharmacokinet. 2014;53(1):1–16.
   PubMed Web of Science ®Google Scholar
• Ingrasciotta Y, Crisafulli S, Pizzimenti V, et al. Pharmacokinetics of new oral anticoagulants: implications for use in routine care. Expert Opin Drug Metab Toxicol. 2018;14(10):1057–1069.
   PubMed Web of Science ®Google Scholar
• Weinz C, Buetehorn U, Daehler HP, et al. Pharmacokinetics of Bay 59-7939-an oral, direct Factor Xa inhibitor-in rats and dogs. Xenobiotica. 2005;35(9):891–910.
   PubMed Web of Science ®Google Scholar
• Weinz C, Schwarz T, Kubitza D, et al. Metabolism and excretion of rivaroxaban, an oral, direct factor xa inhibitor, in rats, dogs, and humans. Drug Metab Dispos. 2009;37(5):1056–1064.
   PubMed Web of Science ®Google Scholar
• Gnoth MJ, Buetehorn U, Muenster U, et al. In vitro and in vivo p-glycoprotein transport characteristics of rivaroxaban. J Pharmacol Exp Ther. 2011;338(1):372–380.
   PubMed Web of Science ®Google Scholar
• Wang L, Zhang D, Raghavan N, et al. In vitro assessment of metabolic Drug-Drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos. 2010;38(3):448–458.
   PubMed Web of Science ®Google Scholar
• He K, Luettgen JM, Zhang D, et al. Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor. Eur J Drug Metab Pharmacokinet. 2011;36(3):129–139.
   PubMed Web of Science ®Google Scholar
• Zhang D, He K, Herbst JJ, et al. Characterization of efflux transporters involved in distribution and disposition of apixaban. Drug Metab Dispos. 2013;41(4):827–835.
   PubMed Web of Science ®Google Scholar
• Vakkalagadda B, Frost C, Byon W, et al. Effect of rifampin on the pharmacokinetics of apixaban, an oral direct inhibitor of factor Xa. Am J Cardiovasc Drugs. 2016;16(2):119–127.
   PubMed Web of Science ®Google Scholar
• Bathala MS, Masumoto H, Oguma T, et al. Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans. Drug Metab Dispos. 2012;40(12):2250–2255.
   PubMed Web of Science ®Google Scholar
• Mendell J, Chen S, He L, et al. The effect of rifampin on the pharmacokinetics of edoxaban in healthy adults. Clin Drug Investig. 2015;35(7):447–453.
   PubMed Web of Science ®Google Scholar
• Partida RA, Giugliano RP. Edoxaban: pharmacological principles, preclinical and early-phase clinical testing. Future Cardiol. 2011;7(4):459–470.
   PubMedGoogle Scholar
• Chai F, Sun L, Ding Y, et al. A solid self-nanoemulsifying system of the BCS class IIb drug dabigatran etexilate to improve oral bioavailability. Nanomedicine. 2016;11(14):1801–1816.
   PubMed Web of Science ®Google Scholar
• Cho JH, Kim JC, Kim HS, et al. Novel dabigatran etexilate hemisuccinate-loaded polycap: physicochemical characterisation and in vivo evaluation in beagle dogs. Int J Pharm. 2017;525(1):60–70.
   PubMedGoogle Scholar
• Ge L, He X, Zhang Y, et al. A dabigatran etexilate phospholipid complex nanoemulsion system for further oral bioavailability by reducing drug-leakage in the gastrointestinal tract. Nanomed Nanotechnol Biol Med. 2018;14(4):1455–1464.
   Web of Science ®Google Scholar
• Xu H. Profiling ester prodrug activation: an activity based protein profiling (abpp) approach [dissertation]. Ann Arbor (MI): University of Michigan; 2015.
   Google Scholar
• Perzborn E, Strassburger J, Wilmen A, et al. In vitro and in vivo studies of the novel antithrombotic agent Bay 59-7939-an oral, direct Factor Xa inhibitor. J Thromb Haemost. 2005;3(3):514–521.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Highlights of prescribing Information - Xarelto^® (rivaroxaban) tablets, for oral use. Rockville: FDA; 2011.
   Google Scholar
• Food and Drug Administration (FDA). Clinical pharmacology and biopharmaceutics review(s). Application number: 022406Orig1s000. Center for Drug Evaluation And Research. Rockville: FDA; 2010.
   Google Scholar
• European Medicines Agency (EMA). CHMP assessment report for xarelto. London: EMA; 2008.
   Google Scholar
• Package insert of Xarelto 1 mg/mL granules for oral suspension [Internet]; [cited 2021 Oct 01]. Available from: https://www.medicines.org.uk/emc/product/12108/smpc#AUTHDATE.
   Google Scholar
• Stampfuss J, Kubitza D, Becka M, et al. The effect of food on the absorption and pharmacokinetics of rivaroxabana. Int J Clin Pharmacol Ther. 2013;51(7):549–561.
   PubMed Web of Science ®Google Scholar
• Brew CT, Blake JF, Mistry A, et al. Use of QSPR modeling to characterize in vitro binding of drugs to a gut-restricted polymer. Pharm Res. 2018;35(4):89.
   PubMed Web of Science ®Google Scholar
• Metre S, Mukesh S, Samal SK, et al. Enhanced biopharmaceutical performance of rivaroxaban through polymeric amorphous solid dispersion. Mol Pharm. 2018;15(2):652–668.
   PubMed Web of Science ®Google Scholar
• Vertzoni M, Kersten E, Van der Mey D, et al. Evaluating the clinical importance of bacterial degradation of therapeutic agents in the lower intestine of adults using adult fecal material. Eur J Pharm Sci. 2018;125:142–150.
   PubMed Web of Science ®Google Scholar
• Willmann S, Zhang L, Frede M, et al. Integrated population pharmacokinetic analysis of rivaroxaban across multiple patient populations. CPT Pharmacometrics Syst Pharmacol. 2018;7(5):309–320.
   PubMedGoogle Scholar
• Wingert NR, dos Santos NO, Campanharo SC, et al. In vitro dissolution method fitted to in vivo absorption profile of rivaroxaban immediate-release tablets applying in silico data. Drug Dev Ind Pharm. 2018;44(5):723–728.
   PubMed Web of Science ®Google Scholar
• Abouhussein DMN, Bahaa El Din Mahmoud D, Mohammad FE. Design of a liquid nano-sized drug delivery system with enhanced solubility of rivaroxaban for venous thromboembolism management in paediatric patients and emergency cases. J Liposome Res. 2019;29(4):399–412.
   PubMed Web of Science ®Google Scholar
• Chen N, Di P, Ning S, et al. Modified rivaroxaban microparticles for solid state properties improvement based on drug-protein/polymer supramolecular interactions. Powder Technol. 2019;344:819–829.
   Web of Science ®Google Scholar
• Kapourani A, Vardaka E, Katopodis K, et al. Rivaroxaban polymeric amorphous solid dispersions: moisture-induced thermodynamic phase behavior and intermolecular interactions. Eur J Pharm Biopharm. 2019;145:98–112.
   PubMed Web of Science ®Google Scholar
• Demir H, Gulsun T, Ozkan MH, et al. Assessment of dose proportionality of rivaroxaban nanocrystals. AAPS PharmSciTech. 2020;21(6):1–11.
   Web of Science ®Google Scholar
• Sherje AP, Jadhav M. β-Cyclodextrin-based inclusion complexes and nanocomposites of rivaroxaban for solubility enhancement. J Mater Sci Mater Med. 2018;29:186.
   PubMed Web of Science ®Google Scholar
• Takács-Novák K, Szoke V, Völgyi G, et al. Biorelevant solubility of poorly soluble drugs: rivaroxaban, furosemide, papaverine and niflumic acid. J Pharm Biomed Anal. 2013;83:279–285.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Highlights of prescribing Information - Eliquis^® (apixaban) tablets, for oral use. Rockville: FDA; 2012.
   Google Scholar
• Pinto DJP, Orwat MJ, Quan ML, et al. 1-[3-Aminobenzisoxazol-5'-yl]-3-trifluoromethyl-6-[2'-(3-(R)-hydroxy-N-pyrrolidinyl)methyl-[1,1']-biphen-4-yl]-1,4,5,6-tetrahydropyrazolo-[3,4-c]-pyridin-7-one (BMS-740808) a highly potent, selective, efficacious, and orally bioavailable inhibitor of blood coagulation factor Xa . Bioorg Med Chem Lett. 2006;16(15):4141–4147.
   PubMed Web of Science ®Google Scholar
• European Medicines Agency (EMA). Assessment report for eliquis. London: EMA; 2010.
   Google Scholar
• Byon W, Nepal S, Schuster AE, et al. Regional gastrointestinal absorption of apixaban in healthy subjects. J Clin Pharmacol. 2018;58(7):965–971.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Clinical pharmacology and biopharmaceutics review(s). Application number: 202155Orig1s000. Center for Drug Evaluation and Research. Rockville: FDA; 2012.
   Google Scholar
• Padrini R. Clinical pharmacokinetics and pharmacodynamics of direct oral anticoagulants in patients with renal failure. Eur J Drug Metab Pharmacokinet. 2019;44(1):1–12.
   PubMed Web of Science ®Google Scholar
• Song Y, Wang X, Perlstein I, et al. Relative bioavailability of apixaban solution or crushed tablet formulations administered by mouth or nasogastric tube in healthy subjects. Clin Ther. 2015;37(8):1703–1712.
   PubMed Web of Science ®Google Scholar
• Song Y, Chang M, Suzuki A, et al. Evaluation of crushed tablet for oral administration and the effect of food on apixaban pharmacokinetics in healthy adults. Clin Ther. 2016;38(7):1674–1685.
   PubMed Web of Science ®Google Scholar
• Asati Amit V, Salunkhe Kishor S, Chavan Machindra J, et al. Solubility enhancement of BCS classified IV drug-apixaban by preparation and evaluation of mesoporous nanomatrix. Int J Pharm Sci Res. 2020;11:880–890.
   Google Scholar
• Byon W, Garonzik S, Boyd RA, et al. Apixaban: a clinical pharmacokinetic and pharmacodynamic review. Clin Pharmacokinet. 2019;58(10):1265–1279.
   PubMed Web of Science ®Google Scholar
• Food and Drug Administration (FDA). Highlights of prescribing Information - Savaysa^® (edoxaban) tablets for oral use. Rockville: FDA; 2015.
   Google Scholar
• Furugohri T, Isobe K, Honda Y, et al. DU-176b, a potent and orally active factor Xa inhibitor: in vitro and in vivo pharmacological profiles. J Thromb Haemost. 2008;6(9):1542–1549.
   PubMed Web of Science ®Google Scholar
• Pharmaceuticals and Medical Devices Agency (PMDA). Review report: Lixiana^® tablets 15 mg and 30 mg. Pharmaceuticals and medical devices agency. Tokyo: PMDA; 2011.
   Google Scholar
• Food and Drug Administration (FDA). Clinical pharmacology and biopharmaceutics review(s). Application number: 206316Orig1Orig2s000. Center for Drug Evaluation and Research. Rockville: FDA; 2014.
   Google Scholar
• Parasrampuria DA, Kanamaru T, Connor A, et al. Evaluation of regional gastrointestinal absorption of edoxaban using the enterion capsule. J Clin Pharmacol. 2015;55(11):1286–1292.
   PubMed Web of Science ®Google Scholar
• Avdeef A, Fuguet E, Llinàs A, et al. Equilibrium solubility measurement of ionizable drugs – consensus recommendations for improving data quality. Admet Dmpk. 2016;4(2):117–178.
   Google Scholar
• Iga K, Ogawa Y. Effect of buffer species, pH and buffer strength on drug dissolution rate and solubility of poorly-soluble acidic drugs: experimental and theoretical analysis. J Takeda Res. 1196;55:173–187.
   Google Scholar
• Levis KA, Lane ME, Corrigan OI. Effect of buffer media composition on the solubility and effective permeability coefficient of ibuprofen. Int J Pharm. 2003;253(1-2):49–59.
   PubMedGoogle Scholar
• Benet LZ, Broccatelli F, Oprea TI. BDDCS applied to over 900 drugs. AAPS J. 2011;13(4):519–547.
   PubMed Web of Science ®Google Scholar
• Tsume Y, Mudie DM, Langguth P, et al. The biopharmaceutics classification system: subclasses for in vivo predictive dissolution (IPD) methodology and IVIVC. Eur J Pharm Sci. 2014;57:152–163.
   PubMed Web of Science ®Google Scholar
• Tubic-Grozdanis M, Bolger MB, Langguth P. Application of gastrointestinal simulation for extensions for biowaivers of highly permeable compounds. AAPS J. 2008;10(1):213–226.
   PubMed Web of Science ®Google Scholar
• Murray L, Arias A, Li J, et al. Innovative in vitro methodologies for establishing therapeutic equivalence. Rev Panam Salud Publica. 2016;40(1):23–28.
   PubMed Web of Science ®Google Scholar
• Parasrampuria DA, Truitt KE. Pharmacokinetics and pharmacodynamics of edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting Factor Xa . Clin Pharmacokinet. 2016;55(6):641–655.
   PubMed Web of Science ®Google Scholar
• Solanki PV, Uppelli B, Dhokrat PA, et al. Investigation on polymorphs of apixaban, an anticoagulant drug: study of phase transformations and designing efficient process for their preparation. World J Pharm Res. 2015;3:663–677.
   Google Scholar
• Zhai J, Chen Z, Liu X, et al. Solubility measurement, model evaluation and thermodynamic analysis of rivaroxaban polymorphs in organic solvents. J Chem Thermodyn. 2017;104:218–229.
   Web of Science ®Google Scholar
• European Medicines Agency (EMA). Assessment report: apixaban accord. London: EMA, 2020.
   Google Scholar
• Yan Y, Li A, Si Z, et al. Solubility measurement, correlation and molecular simulation of dabigatran etexilate mesylate polymorphs in five Mono-solvents. J Mol Liq. 2020;314:113676.
   Web of Science ®Google Scholar
• Bodhuri P, Weeratunga G, inventors; Apotex Pharmachem Inc., assignee. POLYMORPHIC FORM OF 5 CHLORO N {[(5S) 2 OXO 3 [4 (3 OXOMORPHOLIN 4 YL)PHENYL]OXA-ZOLIDIN 5 YL]-METHYL}THIOPHENE 2 CARBOXAMIDE. United States patent US 20100168111 A1. 2010. July 01.
   Google Scholar
• Grunenberg A, Lenz J, Braun GA, et al., inventors; Bayer Schering Pharma Aktiengesellschaft, assignee. POLYMORPHOUS FORM OF 5-CHLORO-N-({(5S)-2-OXO-3[4-(3-OXO-4-MORPHOLINYL)-PHENYL-1,3-OXAZOLIDINE-5-YL}-METHYL)-2-THOPHENE CARBOXAMIDE. United States patent US 8,188,270 B2. 2012. May 29.
   Google Scholar
• European Directorate for the Quality of Medicines and HealthCare (EDQM). Monograph of Rivaroxaban tablets. European Pharmacopoeia 10.6, 2021.
   Google Scholar
• Rowe RC, Sheskey P, Quinn M. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical Press; 2009.
   Google Scholar
• Page A, Etherton-Beer C. Choosing a medication brand: excipients, food intolerance and prescribing in older people. Maturitas. 2018;107:103–109.
   PubMed Web of Science ®Google Scholar
• Butler JM, Dressman JB. The developability classification system: application of biopharmaceutics concepts to formulation development. J Pharm Sci. 2010;101:2271–2280.
   Google Scholar
• Kasim NA, Whitehouse M, Ramachandran C, et al. Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol Pharmaceutics. 2004;1(1):85–96.
   PubMed Web of Science ®Google Scholar
• Pajouhesh H, Lenz GR. Medicinal chemical properties of successful central nervous system drugs. NeuroRx. 2005;2(4):541–553.
   PubMedGoogle Scholar
• Giulia C, Giuseppe E. Molecular descriptors for polarity: the need of going beyond polar surface area. Future Med Chem. 2016;8:2013–2016.
   PubMed Web of Science ®Google Scholar
• Wang J, Skolnik S. Permeability diagnosis model in drug discovery: a diagnostic tool to identify the most influencing properties for gastrointestinal permeability. Curr Top Med Chem. 2013;13(11):1308–1316.
   PubMed Web of Science ®Google Scholar
• Palm K, Stenberg P, Luthman K, et al. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharm Res. 1997;14(5):568–571.
   PubMed Web of Science ®Google Scholar
• Hughes JD, Blagg J, Price DA, et al. Physiochemical drug properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett. 2008;18(17):4872–4875.
   PubMed Web of Science ®Google Scholar
• Sun H, Chow ECY, Liu S, et al. The caco-2 cell monolayer: usefulness and limitations. Expert Opin Drug Metab Toxicol. 2008;4(4):395–412.
   PubMed Web of Science ®Google Scholar
• Hodin S, Basset T, Jacqueroux E, et al. In vitro comparison of the role of p-glycoprotein and breast cancer resistance protein on direct oral anticoagulants disposition. Eur J Drug Metab Pharmacokinet. 2018;43(2):183–191.
   PubMed Web of Science ®Google Scholar
• Gong IY, Mansell SE, Kim RB. Absence of both MDR1 (ABCB1) and breast cancer resistance protein (ABCG2) transporters significantly alters rivaroxaban disposition and Central nervous system entry. Basic Clin Pharmacol Toxicol. 2013;112(3):164–170.
   PubMed Web of Science ®Google Scholar
• Jarc T, Novak M, Hevir N, et al. Demonstrating suitability of the caco-2 cell model for BCS-based biowaiver according to the recent FDA and ICH harmonised guidelines. J Pharm Pharmacol. 2019;71(8):1231–1242.
   PubMed Web of Science ®Google Scholar