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Published on: August 15, 2016
Etodolac/cyclodextrin formulations: physicochemical characterization and in vivo pharmacological studies
Brunella Cappello1, Clelia di Maio, Maria Iervolino
1Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II, Napoli, Italy. cappello@unina.it
Background:
The formulation of nonsteroidal anti-inflammatory drugs with cyclodextrins (CDs) has demonstrated to be a suitable strategy to increase drug aqueous solubility, dissolution rate, and gastric tolerance.
Aim:
We investigated the effects of the CDs on the physicochemical and pharmacological properties of Etodolac (ET), a practically water-insoluble nonsteroidal anti-inflammatory drug, to individuate a drug formulation with optimized pharmacokinetics and pharmacodynamics.
Methods:
The interactions in solution of ET with beta-CD, hydroxypropyl-beta-CD (HP-beta-CD), and gamma-CD were studied by (13)C-NMR spectroscopy and phase solubility method. Solid binary systems, prepared by physical mixing and freeze-drying, were characterized by differential scanning calorimetry, X-ray analysis and Fourier transform infrared spectroscopy, and dissolution studies. An in vivo pharmacological investigation (analgesic activity and gastric tolerance studies) was performed on freeze-dried ET/CD formulations.
Results:
(13)C-NMR and phase solubility studies demonstrated the ability of CDs to complex with ET and increase drug solubility. ET/CD interactions at the solid state occurred at the molecular level only for freezed-dried samples. All binary systems, mainly those containing HP-beta-CD and gamma -CD, showed a significantly improved dissolution profile of ET. In vivo pharmacological studies evidenced an improvement of analgesic activity and a reduction of gastrolesivity of ET/CD-tested formulations with respect to ET alone.
Conclusions:
The formulation of ET with CDs demonstrates relevant pharmaceutical potential in view of decreasing dose and side effects of ET. For industrial applications, HP-beta-CD appears to be the best partner for ET, as it is less expensive than gamma-CD and gives rise to higher drug solubilization than beta-CD.
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