01635nas a2200157 4500008004100000245009500041210006900136260000800205300001200213490000700225520106700232100002401299700001901323700002401342856011101366 2020 eng d00aCrystal structure of a 1:1 co-crystal of the anti-cancer drug gefitinib with azelaic acid 0 aCrystal structure of a 11 cocrystal of the anticancer drug gefit cJUN a884-8880 v763 a

In the title co-crystal, C22H24ClFN4O3·C9H16O4, gefitinib (GTB; systematic name: quinazolin-4-amine) co-crystallizes with azelaic acid (AA; systematic name: nona-nedioic acid). The co-crystal has the monoclinic P21/n centrosymmetric space group, containing one mol-ecule each of GTB and AA in the asymmetric unit. A structure overlay of the GTB mol-ecule in the co-crystal with that of its most stable polymorph revealed a significant difference in the conformation of the morpholine moiety. The significant deviation in the conformation of one of the acidic groups of azelaic acid from its usual linear chain structure could be due to the encapsulation of one acidic group in the pocket formed between the two pincers of GTB namely, the morpholine and phenyl moieties. Both GTB and AA mol-ecules form N-H⋯O, O-H⋯N, C-H⋯O hydrogen bonds with C-H⋯F close contacts along with off-stacked aromatic π-π inter-actions between the GTB mol-ecules.

1 aGeorge, Christy, P.1 aSangtani, Ekta1 aGonnade, Rajesh, G. uhttps://library.ncl.res.in/content/crystal-structure-11-co-crystal-anti-cancer-drug-gefitinib-azelaic-acid02855nas a2200181 4500008004100000022001400041245017200055210006900227260000800296300001400304490000700318520213300325100002002458700002302478700002402501700002402525856012402549 2025 eng d a1528-748300aCocrystals of the highly potent sickle cell anemia drug voxelotor with trimesic acid: a substantial enhancement in in vitro dissolution performance at physiological pH0 aCocrystals of the highly potent sickle cell anemia drug voxeloto cMAY a4405-44250 v253 a

Global Blood Therapeutic's (GBT's) Voxelotor is an investigational oral therapy for treating sickle cell anemia. It functions by increasing the affinity between hemoglobin and oxygen, thereby preventing the sickling of red blood cells and altering the disease's pathology. The US FDA has approved Voxelotor for the treatment of sickle cell anemia and granted it an orphan drug status. However, Voxelotor is classified as a BCS class II, indicating poor water solubility. The current study explores the enhancement of Voxelotor's water solubility by forming cocrystals with trimesic acid (TMA). Novel cocrystals, cocrystal solvates, and hydrates of Voxelotor (Vox) with trimesic acid (TMA) have been developed to improve their solubility. The new solids were characterized using PXRD, DSC, TGA, XPS, HSM, and single-crystal X-ray diffraction studies, and the intermolecular interactions were quantified using Hirshfeld surface analysis. Detailed crystallographic analysis revealed strong O-H center dot center dot center dot N hydrogen bonding interactions between Vox and TMA, primarily involving the COOH functional group of TMA and the pyridine or pyrazole groups of Vox. Additionally, TMA molecules participate in further hydrogen bonding-either with themselves or with solvates, including hydrates, through mono- or dimeric O-H center dot center dot center dot O H-bonding synthons. In vitro solubility studies demonstrated a significant increase in the solubility of Voxelotor in the Vox-TMA cocrystals compared to the pristine drug at physicochemical pH 4.5 and 6.8. Stability studies confirmed that the nonsolvated multicomponent crystal retains their structural integrity under nonambient conditions without undergoing polymorphic phase transitions. In contrast, the solvated crystals, including hydrates, undergo phase transitions within the temperature range of 100-130 degrees C, losing solvents and converting into one of the nonsolvated cocrystal forms. These findings suggest that the novel Vox-TMA cocrystals have the potential to enhance the therapeutic performance and clinical utility of Voxelotor.

1 aKhan, Akram, A.1 aShaikh, Tabrez, R.1 aGeorge, Christy, P.1 aGonnade, Rajesh, G. uhttps://library.ncl.res.in/content/cocrystals-highly-potent-sickle-cell-anemia-drug-voxelotor-trimesic-acid-substantial