Physico-chemical characterization and in vitro/in vivo evaluation of loratadine: dimethyl-β-cyclodextrin inclusion complexes

A. Szabados-Nacsa, P. Sípos, T. Martinek, I. Mándity, G. Blazsó, A. Balogh, P. Szabó-Révész, Z. Aigner

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Abstract

A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in class II of the Biopharmaceutical Classification System, was investigated. It is an ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable. Inclusion complexes were prepared by kneading method, containing loratadine (LOR) and dimethyl-β-cyclodextrin (DIMEB) in two different molar ratios in an attempt to achieve better dissolution and therefore the better bioavailability of loratadine. The formation and physicochemical properties of the inclusion complexes were investigated by means of dissolution tests, pH-dependent solubility studies, electrospray ionization mass spectrometry and diffusion-ordered 1H NMR spectroscopy. The in vivo efficiency of the complexes was examined in rat animal experiments to confirm the better in vitro dissolution. The instrumental examinations proved the presence of total complexes in 1:1 ratio in both compositions. However, the in vitro pH-dependent solubility results, the in vivo blood levels and the greater pharmacological effect prove that excess DIMEB is needed to achieve the pH-independent and complete solubility of LOR, and therefore better and more consistent bioavailability.

Original languageEnglish
Pages (from-to)294-300
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume55
Issue number2
DOIs
Publication statusPublished - May 15 2011

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Loratadine
Cyclodextrins
Solubility
Biological Availability
Dissolution
Electrospray ionization
Electrospray Ionization Mass Spectrometry
Histamine Antagonists
Nuclear magnetic resonance spectroscopy
Mass spectrometry
Rats
Animals
Blood
Magnetic Resonance Spectroscopy
Pharmacology
Derivatives
In Vitro Techniques
Chemical analysis
Pharmaceutical Preparations
Experiments

Keywords

  • DIMEB inclusion complex
  • DOSY
  • ESI-MS
  • In vivo examination
  • Loratadine
  • PH-independent solubility

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmaceutical Science
  • Spectroscopy
  • Clinical Biochemistry

Cite this

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abstract = "A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in class II of the Biopharmaceutical Classification System, was investigated. It is an ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable. Inclusion complexes were prepared by kneading method, containing loratadine (LOR) and dimethyl-β-cyclodextrin (DIMEB) in two different molar ratios in an attempt to achieve better dissolution and therefore the better bioavailability of loratadine. The formation and physicochemical properties of the inclusion complexes were investigated by means of dissolution tests, pH-dependent solubility studies, electrospray ionization mass spectrometry and diffusion-ordered 1H NMR spectroscopy. The in vivo efficiency of the complexes was examined in rat animal experiments to confirm the better in vitro dissolution. The instrumental examinations proved the presence of total complexes in 1:1 ratio in both compositions. However, the in vitro pH-dependent solubility results, the in vivo blood levels and the greater pharmacological effect prove that excess DIMEB is needed to achieve the pH-independent and complete solubility of LOR, and therefore better and more consistent bioavailability.",
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AU - Szabados-Nacsa, A.

AU - Sípos, P.

AU - Martinek, T.

AU - Mándity, I.

AU - Blazsó, G.

AU - Balogh, A.

AU - Szabó-Révész, P.

AU - Aigner, Z.

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N2 - A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in class II of the Biopharmaceutical Classification System, was investigated. It is an ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable. Inclusion complexes were prepared by kneading method, containing loratadine (LOR) and dimethyl-β-cyclodextrin (DIMEB) in two different molar ratios in an attempt to achieve better dissolution and therefore the better bioavailability of loratadine. The formation and physicochemical properties of the inclusion complexes were investigated by means of dissolution tests, pH-dependent solubility studies, electrospray ionization mass spectrometry and diffusion-ordered 1H NMR spectroscopy. The in vivo efficiency of the complexes was examined in rat animal experiments to confirm the better in vitro dissolution. The instrumental examinations proved the presence of total complexes in 1:1 ratio in both compositions. However, the in vitro pH-dependent solubility results, the in vivo blood levels and the greater pharmacological effect prove that excess DIMEB is needed to achieve the pH-independent and complete solubility of LOR, and therefore better and more consistent bioavailability.

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