Mechanosynthesis of Stable Salt Hydrates of Allopurinol with Enhanced Dissolution, Diffusion, and Pharmacokinetics

Richu Bagya, V.S.; Pandey, N.; Ghosh, A.; Srivastava, A.; Puram, P.K.; Meka, S.T.; Chernyshev, V.V.; Sanphui, P.

Авторы: Richu Bagya Varsa S., Pandey Noopur, Ghosh Animesh, Srivastava Anubha, Puram Pavan Kumar, Meka Sai Teja, Chernyshev Vladimir V., Sanphui Palash
Журнал: ACS Omega
Том: 8
Номер: 37
Год издания: 2023
Первая страница: 34120
Последняя страница: 34133
DOI: 10.1021/acsomega.3c05263
Аннотация: Allopurinol (ALO) is a medication that treats goutand kidney stones by lowering uric acid synthesis in the blood. Thebiopharmaceutics classification system (BCS) IV drug exhibitspoor aqueous solubility, permeability, and bioavailability. Toovercome the bottlenecks of ALO, salts with maleic acid (MLE)and oxalic acid (OXA) were synthesized using the solvent-assistedgrinding method. The novel multicomponent solids werecharacterized by PXRD, DSC, TGA, FT-IR, and SEM images.The crystal structures of these salts with variable stoichiometrywere obtained using Rietveld refinement from the high-resolutionPXRD data. The proton from the dicarboxylic acid is transferred tothe most basic pyrimidine “N” of ALO. The N−H···N hydrogenbondedALO homodimer is replaced by the N+−H···O− ionicinteractions in ALO−OXA (2:1:0.4) and ALO−MLE (1:1:1) salt hydrates. The organic salts improved solubility and dissolution upto 5-fold and the diffusion permeability up to 12 times compared to the native drug in a luminal pH 6.8 phosphate buffer medium.The salt hydrates were exceptionally stable during storage at 30 ± 5 °C and 75 ± 5% relative humidity. Superior dissolution anddiffusion permeability of the ALO−MLE salt resulted in improved pharmacokinetics (peak plasma concentration) that offers apromising solid dosage form with enhanced bioavailability and lower dosage formulation.
Добавил в систему: Чернышев Владимир Васильевич

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Mechanosynthesis of Stable Salt Hydrates of Allopurinol with Enhanced Dissolution, Diffusion, and Pharmacokineticsстатья

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