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β-Cyclodextrin inclusion complexes of lisinopril and zofenopril

physicochemical characterization and compatibility study of lisinopril-β-cyclodextrin with lactose

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Abstract

Lisinopril is an angiotensin-converting enzyme inhibitor, exhibiting reduced absorption and bioavailability following oral administration and instability in the presence of lactose. Zofenopril, one of the newest therapeutic agents of the same class, is a highly lipophilic drug with low water solubility. Inclusion complexes between the drug substances and β-cyclodextrin (β-CD) were obtained to improve their solubility, bioavailability, and stability. The purpose of this study was to investigate the guest–host interaction of lisinopril dihydrate (LIS) and zofenopril calcium (ZOF) with β-CD in solid state and in aqueous solution in order to prove the formation of inclusion complexes between the components. The inclusion complexes were prepared using the kneading method, and they were investigated with different analytical technique, including thermal analysis, powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy (FTIR), and UV spectroscopy. All these techniques revealed that LIS and ZOF form inclusion complexes with β-CD both in solution and in solid state. The stoichiometry of the inclusion complexes was found to be 1:1 for both drug substances, and the apparent constant stability was calculated as 615.86 and 375.85 M−1 for LIS and ZOF, respectively. The compatibility between the binary system LIS/β-CD and lactose 1:1 (m/m) has been studied by means of thermogravimetry/derivative thermogravimetry, differential thermal analysis and FTIR spectroscopy. As a result of the encapsulation of LIS in the β-CD cavity, the stabilization of drug substance in the presence of lactose has been realized.

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Authors and Affiliations

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

    Laura Sbârcea, Lucreţia Udrescu & Zoltan Szabadai

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

    Ionuţ Ledeţi

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

    Adriana Fuliaş

  4. Cantacuzino National Research and Development Institute for Microbiology and Immunology, 103, Splaiul Independentei, 050096, Bucharest, Romania

    Claudiu Sbârcea

  5. Department of Infectious Diseases, National Institute for Infectious Diseases “Prof. Dr. Matei Balş”, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

    Claudiu Sbârcea

Authors
  1. Laura Sbârcea
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  2. Lucreţia Udrescu
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  3. Ionuţ Ledeţi
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  4. Zoltan Szabadai
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  5. Adriana Fuliaş
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  6. Claudiu Sbârcea
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Correspondence to Adriana Fuliaş.

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Sbârcea, L., Udrescu, L., Ledeţi, I. et al. β-Cyclodextrin inclusion complexes of lisinopril and zofenopril. J Therm Anal Calorim 123, 2377–2390 (2016). https://doi.org/10.1007/s10973-015-5045-7

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  • DOI: https://doi.org/10.1007/s10973-015-5045-7

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