Cocrystallization of axitinib with carboxylic acids: preparation, crystal structures and dissolution behavior

Abstract

Axitinib (AXI) is an oral selective tyrosine kinase inhibitor used for the treatment of early to advanced renal cell carcinoma. However, the clinical efficacy of AXI is severely limited by...

Two anhydrous forms and one monohydrate of a cocrystal of axitinib and glutaric acid: characterization, property evaluation and phase transition study

“…Both AXI-GA·H 2 O and AXI-GA I retain the supramolecular synthon between the pyrazole and amide groups of AXI (N–H⋯O hydrogen bond), which is consistent with previously reported cocrystals of AXI. 33 The main difference between them is that the acid–acid R 2 2 (8) homosynthons of GA remain in AXI-GA I , but are replaced by the GA-H 2 O hetero supramolecular synthons in AXI-GA·H 2 O . In addition, AXI-GA I demonstrates stronger hydrogen bonds between AXI and GA (O2–H2A⋯N1, 2.592(2) Å, 171.8°) compared with AXI-GA·H 2 O (O6–H6A⋯N1, 2.623(4) Å, 165.0°).…”

“…To date, six anhydrous forms, sixty-six solvates and at least seven salts and three cocrystals of AXI have been discovered, but the polymorphism of AXI salts or cocrystals has not been reported yet. 27–33 In this work, we obtained two polymorphs and one monohydrate of a cocrystal of AXI with glutaric acid. Although glutaric acid isn't included in the GRAS (generally recognized as safe) list, it has been widely applied in the pharmaceutical field as an important intermediate material and is commonly used as a CCF for cocrystal screening.…”

Novel multi-component crystals of berberine with improved pharmaceutical properties

“…Recently, many attempts have been made to elucidate this relationship. To the best of our knowledge, the main influencing factors include the packing index (Zhang et al, 2020), intermolecular interactions (Zhao et al, 2020), lattice energy (Guo et al, 2018), the affinity of the counter-ion to the solvent (Ren et al, 2021), the pH of the solution (Alhalaweh, et al, 2012), the molar ratio of the drug to counter-ion in the product (Yu et al, 2021), the common ion effect (Devarapalli et al, 2021) and so on. A combination of these factors has frequently been found to affect the solubility of a drug.…”

A novel drug–drug cocrystal of tegafur and myricetin: optimized properties of dissolution and tabletability

“…A fixed-dose combination (FDC) is a drug product that combines two or more active pharmaceutical ingredients (APIs) in a single dosage form. 1 A FDC exhibits great a superiority for the improvement of efficacy, safety and patient compliance, medicinal cost reduction and intellectual property value of drugs, which have been commonly used in the treatment of complex diseases such as cancer, diabetes, cardiovascular diseases and so on. 2,3 A multi-component crystal containing two or more APIs is an emerging and effective approach to achieve FDCs, that is, various APIs are crystallized in the same lattice at a fixed stoichiometric ratio via noncovalent bonds such as hydrogen bonds to generate a drug-drug cocrystal or salt.…”

“…A fixed-dose combination (FDC) is a drug product that combines two or more active pharmaceutical ingredients (APIs) in a single dosage form. 1 A FDC exhibits great a superiority for the improvement of efficacy, safety and patient compliance, medicinal cost reduction and intellectual property value of drugs, which have been commonly used in the treatment of complex diseases such as cancer, diabetes, cardiovascular diseases and so on. 2,3…”