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Physicochemical characterization and molecular modeling study of host–guest systems of aripiprazole and functionalized cyclodextrins

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Abstract

Aripiprazole (ARP), an innovative atypical antipsychotic drug, exhibits very low aqueous solubility, affecting its dissolution and absorption and high lipophilicity. Its complexation with cyclodextrins (CDs) was designed to improve drug solubility and consequently its bioavailability. The inclusion complexes of aripiprazole with two β-cyclodextrin derivative, namely random methyl-β-cyclodextrin (RAMEB) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin, were obtained and investigated both in solution and in solid state. The kneading method was used to prepare the inclusion complexes, and they were characterized with different analytical techniques, including thermal analysis, powder X-ray diffractometry, universal attenuated total reflectance Fourier-transform IR spectroscopy and UV spectroscopy. The stoichiometry of both APR/CDs inclusion complexes was found as 1:2 by employing continuous variation method. Benesi–Hildebrand equation was used for the apparent constant stability determination. Structural studies of the inclusion complexes were carried out using molecular modeling techniques in order to explain the complexation mechanism. The results of the studies demonstrate that the physicochemical properties of the kneaded products are different from ARP, testifying the inclusion complexes formation between aripiprazole and CDs when the kneading method is used. The solubility of the drug substance was improved upon complexation with CDs; higher increase in ARP solubility was noticed in the presence of RAMEB.

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Authors and Affiliations

  1. Faculty of Industrial Chemistry and Environmental Engineering, Politehnica University of Timișoara, 2 Victoriei Square, 300006, Timisoara, Romania

    Ionuț-Mihai Tănase & Ionuț Ledeți

  2. Department of Drug Analysis, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timisoara, Romania

    Laura Sbârcea

  3. Department of Analytical Chemistry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timisoara, Romania

    Adriana Ledeți & Carmen Axente

  4. Research Center for Thermal Analysis in Environmental Problems, Faculty of Chemistry-Biology-Geography, West University of Timisoara, 16 Pestalozzi Street, Timisoara, Romania

    Gabriela Vlase

  5. Faculty of Physics, West University of Timişoara, 4 Vasile Pârvan Blvd, 300223, Timisoara, Romania

    Paul Barvinschi

  6. Department of Physical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy Craiova, 2-4 Petru Rares Str., 200349, Craiova, Romania

    Renata-Maria Văruţ

  7. Department of Dermatopharmacy and Cosmetology, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timisoara, Romania

    Anca Dragomirescu

  8. Department of Physical Chemistry, Faculty of Pharmacy, “Victor Babeş” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, 300041, Timisoara, Romania

    Ionuț Ledeți

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  1. Ionuț-Mihai Tănase
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  2. Laura Sbârcea
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Correspondence to Laura Sbârcea.

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Tănase, IM., Sbârcea, L., Ledeți, A. et al. Physicochemical characterization and molecular modeling study of host–guest systems of aripiprazole and functionalized cyclodextrins. J Therm Anal Calorim 141, 1027–1039 (2020). https://doi.org/10.1007/s10973-020-09549-3

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