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

• Autor(es): Ramos, Margarida ; Salústio, Paulo ; Serralheiro, Luísa ; Frazão, Fátima ; Marques, Helena
• Data: 2010
• Identificador Persistente: http://hdl.handle.net/10451/3863
• Origem: Repositório da Universidade de Lisboa
• Assunto(s): Omeprazole; Hydroxypropyl-b-cyclodextrin; Inclusion complex; Stability; Enzymatic activity
• Tipo de Documento: Artigo
• Idioma: Inglês

Descrição

The original publication is available at www.springerlink.com. A publicação original está disponível em www.springerlink.com Omeprazole (OME) exhibits low stability to light, heat and humidity. In stress conditions OME stability should improve under inclusion complex form with hydroxypropyl-b-cyclodextrin (HPbCD). Stability of OME, its physical mixture (PM) with HPbCD and OME:HPbCD inclusion complex was assessed during 60 days. The inclusion complexes were prepared by kneading and freezedrying 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:HPbCD. 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 HPbCD 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 HPbCD 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 HPbCD do not affect OME activity on these two enzymes.