Synthesis, characterization and thermoanalytical study of Valsartan, Candesartan Cilexetil and Olmesartan medoxomil co-crystals

• Grant number: 18/24378-6
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2019
• End date: May 31, 2021
• Field of knowledge: Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
• Principal Investigator: Flávio Junior Caires
• Grantee: Flávio Junior Caires
• Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil
• Associated researchers: Daniel Rinaldo ; Joop ter Horst

Abstract

The low aqueous solubility and low oral bioavailability of the active pharmaceutical ingredients (APIs) are the main constraints during the development of new products. Several approaches have been used to improve the aqueous solubility of poorly soluble drugs, but the success of such approaches depends on the physical and chemical nature of the molecules being developed. The co-crystallization of drugs offers a great opportunity for the development of new solid forms of drugs with higher physicochemical properties, such as melting point, compaction capacity, solubility, stability, bioavailability and permeability, preserving the pharmacological properties of the APIs. The co-crystals are multicomponent systems, wherein two components, one the active pharmaceutical ingredient and the other a coformer are present in stoichiometric ratio and maintained through non-covalent interactions in the crystal structure.Thus, the present project aims at the synthesis, thermoanalytical studies, characterization, solubility determination and comparative dissolution of the co-crystals obtained from the drug valsartan, candesartan cilexetil and Olmesartan medoxomil, drugs that present serious problems of solubility and bioavailability. The cocrystals will be obtained by the mechanochemical method (Liquid assisted Grinding (LAG) and without solvent), with the aid of a ball mill, by the slurry method and also by crystallization in solution using solvents and / or solvent mixtures. The optimization of the synthesis method and the characterization of the cocrystals that are obtained will be performed using the following techniques: crystallisation system (Crystal 16); thermomicroscopy (hot stage coupled to a optical microscope); differential scanning calorimetry (DSC); simultaneous thermogravimetric analysis and differential scanning calorimetry (TG-DSC); Fourier transform infrared spectroscopy (FTIR); density functional theory (DFT) calculation; solid state nuclear magnetic resonance spectroscopy (NMR); powder/single crystal X-ray diffraction; Experiments will be performed to determine the solubility and the comparative dissolution tests. Thus, it is expected to obtain cocrystals that are able to provide improvements in physicochemical properties and therefore to provide an innovative approach to improve the bioavailability of these drugs. (AU)

Scientific publications

(29)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERNANDES, RICHARD PEROSA; EKAWA, BRUNO; FERREIRA, LAURA TEOFILO; CARVALHO, ANA CARINA SOBRAL; TEIXEIRA FREIRE, RAFAEL; CAIRES, FLAVIO JUNIOR. Classification of beer by thermogravimetric and chemometric techniques. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, MAR 2021. (13/09022-7, 18/24378-6, 17/14936-9)

NUNES, WILHAN DONIZETE GONCALVES; RUSSO, HELENA MANNOCHIO; BOLZANI, VANDERLAN DA SILVA; CAIRES, FLAVIO JUNIOR. Thermal characterization and compounds identification of commercialStevia rebaudianaBertoni sweeteners and thermal degradation products at high temperatures by TG-DSC, IR and LC-MS/MS. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, AUG 2020. (18/24378-6, 14/50926-0, 13/07600-3, 16/16970-7)

DE ALMEIDA, AMANDA COSMO; FERREIRA, PATRICIA OSORIO; TORQUETTI, CAROLINA; EKAWA, BRUNO; SOBRAL CARVALHO, ANA CARINA; DOS SANTOS, EVERTON CARVALHO; CAIRES, FLAVIO JUNIOR. Mechanochemical synthesis, characterization and thermal study of new cocrystals of ciprofloxacin with pyrazinoic acid and p-aminobenzoic acid. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, NOV 2019. (13/09022-7, 18/24378-6, 17/14936-9)

FERREIRA, PATRICIA OSORIO; DE MOURA, ANIELE; DE ALMEIDA, AMANDA COSMO; DOS SANTOS, EVERTON CARVALHO; KOGAWA, ANA CAROLINA; CAIRES, FLAVIO JUNIOR. Mechanochemical synthesis, thermoanalytical study and characterization of new multicomponent solid forms of norfloxacin with saccharin. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 147, n. 3, p. 1985-1997, FEB 2022. (18/24378-6, 17/14936-9, 13/09022-7)

NUNES, WILHAN DONIZETE GONCALVES; RUSSO, HELENA MANNOCHIO; BOLZANI, VANDERLAN DA SILVA; CAIRES, FLAVIO JUNIOR. Thermal characterization and compounds identification of commercialStevia rebaudianaBertoni sweeteners and thermal degradation products at high temperatures by TG-DSC, IR and LC-MS/MS. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 146, n. 3, p. 1149-1155, NOV 2021. (13/07600-3, 18/24378-6, 16/16970-7, 14/50926-0)

DE MOURA, ANIELE; GAGLIERI, CAROLINE; DA SILVA-FILHO, LUIZ CARLOS; CAIRES, FLAVIO JUNIOR. Mechanochemical synthesis, characterization and thermoanalytical study of a new curcumin derivative. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 146, n. 2, p. 587-594, OCT 2021. (18/24378-6, 18/14506-7, 13/07296-2)

NASCIMENTO, A. L. C. S.; ASHTON, G. P.; PARKES, G. M. B.; EKAWA, B.; FERNANDES, R. P.; CARVALHO, A. C. S.; IONASHIRO, M.; CAIRES, F. J.. Novel solid-state compounds of heavy rare-earth (III) picolinates. A pyrolytic study using: TG-DSC-IR, HSM-MS and GC-MS. JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS, v. 144, NOV 2019. (18/24378-6, 17/14936-9)

TEIXEIRA, JOSE AUGUSTO; FERNANDES, RICHARD P.; ISQUIBOLA, GUILHERME; GASPARI, ANA P. S.; MACHADO, ANTONIO E. H.; CAIRES, FLAVIO J.; IONASHIRO, MASSAO. Synthesis, thermal behavior in oxidative and pyrolysis conditions, spectroscopic and DFT studies of some alkaline earth metals p-aminobenzoate complexes using TG-DTA, DSC, PXRD and EGA (TG-FTIR) techniques. Thermochimica Acta, v. 711, p. 12-pg., 2022-05-01. (18/24378-6, 13/09022-7, 13/07296-2, 17/14936-9)

MACHADO, RAFAEL DE GODOI; GAGLIERI, CAROLINE; ALARCON, RAFAEL TURRA; DE MOURA, ANIELE; DE ALMEIDA, AMANDA COSMO; CAIRES, FLAVIO JUNIOR; IONASHIRO, MASSAO. Cobalt selenate pentahydrate: Thermal decomposition intermediates and their properties dependence on temperature changes. Thermochimica Acta, v. 689, JUL 2020. (18/24378-6, 17/14936-9, 18/03460-6)

DE ALMEIDA, AMANDA COSMO; TORQUETTI, CAROLINA; FERREIRA, PATRICIA OSORIO; FERNANDES, RICHARD PEROSA; DOS SANTOS, EVERTON CARVALHO; KOGAWA, ANA CAROLINA; CAIRES, FLAVIO JUNIOR. Cocrystals of ciprofloxacin with nicotinic and isonicotinic acids: Mechanochemical synthesis, characterization, thermal and solubility study. Thermochimica Acta, v. 685, MAR 2020. (13/09022-7, 18/24378-6, 17/14936-9)

DE MOURA, ANIELE; BENEDITO JUNIOR, JOSE; SOBRAL CARVALHO, ANA CARINA; CAIRES, FLAVIO JUNIOR. Green synthesis of a Schiff base ligand and its Co(II), Cu(II) and Zn(II) complexes: thermoanalytical and spectroscopic studies. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. N/A, p. 14-pg., 2022-04-12. (18/24378-6, 13/07296-2)

NUNES, W. D. G.; TEIXEIRA, J. A.; DO NASCIMENTO, A. L. C. S.; EKAWA, B.; IONASHIRO, M.; CAIRES, F. J.. Thermal analysis (TG-DSC, DSC-microscopy and EGA) and characterization of heavy trivalent lanthanides and yttrium isonicotinates. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 138, n. 1, p. 309-319, OCT 2019. (18/24378-6, 17/14936-9)

DE MOURA, ANIELE; GAGLIERI, CAROLINE; ALARCON, RAFAEL TURRA; FERREIRA, LAURA TEOFILO; VECCHI, RAFAEL; ROVIS SANCHES, MARIANA LIESSA; DE OLIVEIRA, RODRIGO CARDOSO; VENTURINI, JAMES; DA SILVA-FILHO, LUIZ CARLOS; CAIRES, FLAVIO JUNIOR. A New Curcuminoids-Coumarin Derivative: Mechanochemical Synthesis, Characterization and Evaluation of Its In Vitro Cytotoxicity and Antimicrobial Properties. CHEMISTRYSELECT, v. 6, n. 41, p. 11352-11361, NOV 8 2021. (13/07296-2, 18/03460-6, 18/14506-7, 18/24378-6)

FERREIRA, PATRICIA OSORIO; DE ALMEIDA, AMANDA COSMO; DOS SANTOS, EVERTON CARVALHO; DROPPA JUNIOR, ROOSEVELT; FERREIRA, FABIO FURLAN; KOGAWA, ANA CAROLINA; CAIRES, FLAVIO JUNIOR. A norfloxacin-nicotinic acid cocrystal: Mechanochemical synthesis, thermal and structural characterization and solubility assays. Thermochimica Acta, v. 694, DEC 2020. (18/24378-6, 17/14936-9, 13/09022-7)

EKAWA, BRUNO; DIOGO, HERMINIO P.; CASTRO, RICARDO A. E.; CAIRES, FLAVIO J.; EUSEBIO, M. ERMELINDA S.. Coamorphous Systems of Valsartan: Thermal Analysis Contribution to Evaluate Intermolecular Interactions Effects on the Structural Relaxation. Molecules, v. 28, n. 17, p. 13-pg., 2023-09-01. (18/24378-6)

NASCIMENTO, ANDRE L. C. S.; FERNANDES, RICHARD P.; CHARPENTIER, MAXIME D.; TER HORST, JOOP H.; CAIRES, FLAVIO J.; CHORILLI, MARLUS. Co-crystals of non-steroidal anti-inflammatory drugs (NSAIDs): Insight toward formation, methods, and drug enhancement. PARTICUOLOGY, v. 58, p. 227-241, OCT 2021. (13/09022-7, 18/23357-5, 18/24378-6)

DE MOURA, ANIELE; GAGLIERI, CAROLINE; TERCIOTTI, LUIZ OCTAVIO; RINALDO, DANIEL; CAIRES, FLAVIO JUNIOR. Mechanochemical method: a powerful tool to obtain omega-poly(ethylene glycol)-functionalized structures and curcumin analogues. NEW JOURNAL OF CHEMISTRY, v. 47, n. 19, p. 9-pg., 2023-04-18. (18/24378-6, 13/07296-2)

FERREIRA, PATRICIA O.; DE ALMEIDA, AMANDA C.; COSTA, GIOVANNA DE P.; TORQUETTI, CAROLINA; BAPTISTA, JOAO A.; EUSEBIO, M. ERMELINDA S.; CAIRES, FLAVIO J.; CASTRO, RICARDO A. E.. Norfloxacin Cocrystals: Mechanochemical Synthesis and Scale-up Viability Through Solubility Studies. Journal of Pharmaceutical Sciences, v. 112, n. 8, p. 10-pg., 2023-08-01. (22/00239-2, 18/24378-6, 20/07724-8)

DE ALMEIDA, AMANDA COSMO; FERREIRA, PATRICIA OSORIO; TORQUETTI, CAROLINA; EKAWA, BRUNO; SOBRAL CARVALHO, ANA CARINA; DOS SANTOS, EVERTON CARVALHO; CAIRES, FLAVIO JUNIOR. Mechanochemical synthesis, characterization and thermal study of new cocrystals of ciprofloxacin with pyrazinoic acid and p-aminobenzoic acid. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 140, n. 5, p. 11-pg., 2019-11-06. (17/14936-9, 13/09022-7, 18/24378-6)

DE MOURA, ANIELE; GAGLIERI, CAROLINE; DA SILVA-FILHO, LUIZ CARLOS; CAIRES, FLAVIO JUNIOR. Mechanochemical synthesis, characterization and thermoanalytical study of a new curcumin derivative. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, JUL 2020. (18/24378-6, 13/07296-2, 18/14506-7)

TORQUETTI, CAROLINA; FERREIRA, PATRICIA OSORIO; DE ALMEIDA, AMANDA COSMO; FERNANDES, RICHARD PEROSA; CAIRES, FLAVIO JUNIOR. Thermal study and characterization of new cocrystals of ciprofloxacin with picolinic acid. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, FEB 2021. (13/09022-7, 18/24378-6, 17/14936-9, 15/19863-4)

FERREIRA, PATRICIA OSORIO; DE MOURA, ANIELE; DE ALMEIDA, AMANDA COSMO; DOS SANTOS, EVERTON CARVALHO; KOGAWA, ANA CAROLINA; CAIRES, FLAVIO JUNIOR. Mechanochemical synthesis, thermoanalytical study and characterization of new multicomponent solid forms of norfloxacin with saccharin. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, MAR 2021. (18/24378-6, 17/14936-9, 13/09022-7)

FERNANDES, RICHARD PEROSA; EKAWA, BRUNO; FERREIRA, LAURA TEOFILO; CARVALHO, ANA CARINA SOBRAL; TEIXEIRA FREIRE, RAFAEL; CAIRES, FLAVIO JUNIOR. Classification of beer by thermogravimetric and chemometric techniques. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 147, n. 4, p. 3063-3069, FEB 2022. (17/14936-9, 13/09022-7, 18/24378-6)

CARVALHO, A. C. S.; ZANGARO, G. A. C.; FERNANDES, R. P.; EKAWA, B.; NASCIMENTO, A. L. C. S.; SILVA, B. F.; ASHTON, G. P.; PARKES, G. M. B.; IONASHIRO, M.; CAIRES, F. J.. Lornoxicam drug-A new study of thermal degradation under oxidative and pyrolysis conditions using the thermoanalytical techniques, DRX and LC-MS/MS. Thermochimica Acta, v. 680, OCT 2019. (18/24378-6, 17/14936-9, 08/10449-7, 13/09022-7)

FERNANDES, RICHARD PEROSA; CARNEIRO SOARES DO NASCIMENTO, ANDRE LUIZ; SOBRAL CARVALHO, ANA CARINA; TEIXEIRA, JOSE AUGUSTO; IONASHIRO, MASSAO; CAIRES, FLAVIO JUNIOR. Mechanochemical synthesis, characterization, and thermal behavior of meloxicam cocrystals with salicylic acid, fumaric acid, and malic acid. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 138, n. 1, p. 765-777, OCT 2019. (18/24378-6, 17/14936-9)

EKAWA, BRUNO; SOBRAL CARVALHO, ANA CARINA; FERNANDES, RICHARD PEROSA; CARNEIRO SOARES DO NASCIMENTO, ANDRE LUIZ; CAIRES, FLAVIO JUNIOR. Synthesis, thermoanalytical and spectroscopic studies of trivalent lanthanides (Eu-Ho) complexes with the valsartan ligand. Thermochimica Acta, v. 686, APR 2020. (13/09022-7, 18/24378-6, 17/14936-9)

TORQUETTI, CAROLINA; FERREIRA, PATRICIA OSORIO; DE ALMEIDA, AMANDA COSMO; FERNANDES, RICHARD PEROSA; CAIRES, FLAVIO JUNIOR. Thermal study and characterization of new cocrystals of ciprofloxacin with picolinic acid. JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY, v. 147, n. 2, p. 1299-1306, JAN 2022. (18/24378-6, 17/14936-9, 13/09022-7, 15/19863-4)

ZANGARO, GEORGIA A. C.; CARVALHO, ANA C. S.; EKAWA, BRUNO; DO NASCIMENTO, ANDRE L. C. S.; NUNES, WILHAN D. G.; FERNANDES, RICHARD P.; PARKES, GARETH M. B.; ASHTON, GAGE P.; IONASHIRO, MASSAO; CAIRES, FLAVIO J.. Study of the thermal behavior in oxidative and pyrolysis conditions of some transition metals complexes with Lornoxicam as ligand using the techniques: TG-DSC, DSC, HSM and EGA (TG-FTIR and HSM-MS). Thermochimica Acta, v. 681, NOV 2019. (18/24378-6, 17/14936-9)

FERREIRA, LAURA TEOFILO; MANNOCHIO-RUSSO, HELENA; ISQUIBOLA, GUILHERME; FERNANDES, RICHARD PEROSA; DE MOURAC, ANIELE; BOLZANI, VANDERLAN DA SILVA; CAIRES, FLAVIO JUNIOR. Thermal and degradation study of candesartan under pyrolysis and oxidizing conditions. JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS, v. 173, p. 9-pg., 2023-06-17. (18/24378-6, 13/07600-3, 14/50926-0)