Synthesis and characterization of ataluren-cyclodextrins complexes

An inclusion complex formation with cyclodextrin (CD) is a promising method for enhancing solubility and bioavailability of medicines. Ataluren (ALN) is a reading-through drug for overriding premature stop codons that is practically insoluble in water. By incresing the solubility of this molecule in aqueous me- dia, its bioavailability in its oral dosage form may be improved. Inclusion complexes of ALN with alpha (alpha CD), beta ( BCD), gamma (gamma CD), hydroxypropyl beta (HPBCD), randomly methylated beta (RMBCD) and sulfobutyl ether beta (SBECD) cyclodextrins were prepared. Phase solubility studies, Job's plot, Proton nu- clear magnetic resonance (1H -NMR), Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and Fourier transform Infrared (FTIR) analysis were used for the characterization of the inclusion com- plexes. The phase solubility profiles are AL type but each cyclodextrin behaves differently in interaction with ALN. The Job's plot revealed 1:1 stoichiometry in ALN -CD complexes. The stability constants of ALN with alpha CD, BCD, gamma CD, HPBCD, RMBCD, and SBECD were 35 M - 1 , 674 M - 1 , 163 M - 1 , 132 M - 1 , 324 M - 1, and 232 M - 1 respectively. All CDs increased ALN solubility in aqueous media and RMBCD showed the maximun value of 121.0 times increment of ALN solubility in aqueous media.(c) 2022 Elsevier B.V. All rights reserved.

Automated summary

Inclusion complexes of Ataluren (ALN) with different cyclodextrins (CDs) were prepared to enhance solubility and bioavailability. Various characterization techniques were used, including phase solubility studies, Job's plot, 1H-NMR, DSC, XRD, and FTIR analysis. The stability constants of ALN with different CDs were determined, and all CDs improved the solubility of ALN in aqueous media, with RMBCD showing the highest increase.