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Stability and enzymatic studies with omeprazole:hydroxypropyl-β-cyclodextrin

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Abstract

Omeprazole (OME) exhibits low stability to light, heat and humidity. In stress conditions OME stability should improve under inclusion complex form with hydroxypropyl-β-cyclodextrin (HPβCD). Stability of OME, its physical mixture (PM) with HPβCD and OME:HPβCD inclusion complex was assessed during 60 days. The inclusion complexes were prepared by kneading and freeze-drying techniques and characterized by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). A molecular modelling was also held to predict the most probable tridimensional conformation of inclusion complex OME:HPβCD. The inhibitory activity of free and complexed OME on selected enzymes, namely, papain (protease model of the proton pump) and acetylcholinesterase (enzyme present in cholinergic neurons and also involved in Alzheimer’s disease) was compared. The results obtained show that HPβCD do not protect against OME degradation, in any prepared powder, in the presence of light, heat and humidity. This may indicate that the reactive group of OME is not included in the HPβCD cavity. This fact is supported by molecular modelling data, which demonstrated that 2-pyridylmethyl group of OME is not included into the cyclodextrin cavity. In relation to enzymatic assays it was observed that free OME and OME in the binary systems showed identical inhibitory activity on papain and acethylcolinesterase, concluding that HPβCD do not affect OME activity on these two enzymes.

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Acknowledgments

The authors would like to thank Laboratórios Medinfar for the kind donation of Omeprazole and Doctor R. Guedes for the help with the molecular simulation.

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Authors and Affiliations

  1. CQB, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1649-016, Lisbon, Portugal

    Margarida Ramos, Luísa Serralheiro & Fátima Fazão

  2. i Med.UL, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal

    Paulo Salústio & Helena Marques

Authors
  1. Margarida Ramos
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  2. Paulo Salústio
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  3. Luísa Serralheiro
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  4. Fátima Fazão
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  5. Helena Marques
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Correspondence to Helena Marques.

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Ramos, M., Salústio, P., Serralheiro, L. et al. Stability and enzymatic studies with omeprazole:hydroxypropyl-β-cyclodextrin. J Incl Phenom Macrocycl Chem 70, 407–414 (2011). https://doi.org/10.1007/s10847-010-9884-3

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  • DOI: https://doi.org/10.1007/s10847-010-9884-3

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