Functional evaluation of loratadine–cyclodextrin complexes: comprehensive solid-state characterisation, biopharmaceutical assessment and stability profiling
- 1University of Zagreb, Faculty of Science, Department of Chemistry Horvatovac 102a 10000 Zagreb Croatia +385 1 4606 191
- 2Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences Sienkiewicza 112 90-363 Lodz Poland
- 3University of Zagreb, Faculty of Pharmacy and Biochemistry, Department of Pharmaceutical Technology A. Kovačića 1 Zagreb Croatia
Abstract
Loratadine (LOR) is a poorly water-soluble antihistaminic drug whose solubility can be significantly enhanced in water and biorelevant media through inclusion complexation with β-cyclodextrins (β-CDs), as we have shown previously. In this work, we investigated the biopharmaceutical properties and chemical stability of LOR : β-CDs 1 : 1 and 1 : 2 complexes in the solid state, prepared by two different methods: (i) solvent-free mechanochemical grinding in a high-energy vibrational mill, and (ii) spray-drying, as a traditional solvent-based technique. Altogether, 16 different systems were prepared using LOR, β-CD and its derivatives, namely hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RM-β-CD), and sulfobutylether-β-cyclodextrin (SBE-β-CD). Detailed solid-state characterization by differential scanning calorimetry (DSC), X-ray powder diffraction, ATR-FTIR and solid-state NMR was performed, indicating different levels of drug amorphization. Biopharmaceutical evaluation via in vitro dissolution testing and in vitro permeability assay across biomimetic membranes revealed that LOR dissolution and permeability depend on CD's type, LOR-to-CD molar ratio, and the method used for complex preparation. The influence of β-CDs on LOR stability under stress conditions, including photostability and accelerated stability studies, was determined using UHPLC-HR MS/MS. The structures of degradation products, including five previously unknown, were proposed. Obtained complexes, especially those prepared by grinding, demonstrated great potential for further formulation development.
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BibTeX
@article{pocrnic2026functional,
title = {{Functional evaluation of loratadine–cyclodextrin complexes: comprehensive solid-state characterisation, biopharmaceutical assessment and stability profiling}},
author = {Marijana Pocrnić and Marek J. Potrzebowski and Mario Jug and Nives Galić},
journal = {RSC advances},
year = {2026},
month = oct,
doi = {10.1039/d6ra08083a},
url = {https://europepmc.org/article/PMC/PMC13670038},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Functional evaluation of loratadine–cyclodextrin complexes: comprehensive solid-state characterisation, biopharmaceutical assessment and stability profiling
AU - Marijana Pocrnić
AU - Marek J. Potrzebowski
AU - Mario Jug
AU - Nives Galić
PY - 2026
DA - 2026/10/15
JO - RSC advances
DO - 10.1039/d6ra08083a
UR - https://europepmc.org/article/PMC/PMC13670038
AB - Loratadine (LOR) is a poorly water-soluble antihistaminic drug whose solubility can be significantly enhanced in water and biorelevant media through inclusion complexation with β-cyclodextrins (β-CDs), as we have shown previously. In this work, we investigated the biopharmaceutical properties and chemical stability of LOR : β-CDs 1 : 1 and 1 : 2 complexes in the solid state, prepared by two different methods: (i) solvent-free mechanochemical grinding in a high-energy vibrational mill, and (ii) spray-drying, as a traditional solvent-based technique. Altogether, 16 different systems were prepared using LOR, β-CD and its derivatives, namely hydroxypropyl-β-cyclodextrin (HP-β-CD), randomly methylated-β-cyclodextrin (RM-β-CD), and sulfobutylether-β-cyclodextrin (SBE-β-CD). Detailed solid-state characterization by differential scanning calorimetry (DSC), X-ray powder diffraction, ATR-FTIR and solid-state NMR was performed, indicating different levels of drug amorphization. Biopharmaceutical evaluation via in vitro dissolution testing and in vitro permeability assay across biomimetic membranes revealed that LOR dissolution and permeability depend on CD's type, LOR-to-CD molar ratio, and the method used for complex preparation. The influence of β-CDs on LOR stability under stress conditions, including photostability and accelerated stability studies, was determined using UHPLC-HR MS/MS. The structures of degradation products, including five previously unknown, were proposed. Obtained complexes, especially those prepared by grinding, demonstrated great potential for further formulation development.
SN - 2046-2069
ER -