Skip to Main content Skip to Navigation
Theses

Évaluation d'une forme galénique à base d'alpha cyclodextrine et d'huile végétale pour l'administration par voie orale de molécules actives peu solubles dans l'eau

Abstract : The general aim of this thesis was the study of the potential of beads, made of α-cyclodextrin and soybean oil, for the oral delivery of poorly water soluble drugs. We have first verified that it was possible to encapsulate in beads, active molecules (progesterone and indomethacin), other than retinoid and diazepam, with a high drug loading and a satisfying yied. The study of the behaviour of freeze-dried naked beads, in terms of stability and drug release in simulated gastro-intestinal fluids, allowed to propose a mechanism for the release of the encapsulated drug, involving several steps: i) hydration of the freeze-dried beads, ii) dissolution of α-CD hydrophilic matrix, iii) release of oily droplets containing the active drug and then of the fraction of drug dissolved in oil, following a partition phenomenon, iiii) fragmentation of the weakened beads and at last the total release of oil. The presence of bile salts in the medium accelerates both the release and the dissolved amount, by weakening the beads and reducing the partition coefficient value of the active molecule between oil and digestive medium.We have shown in vitro as well as in vivo that it is possible to modulate the release of a model drug from the same initial formulation, according to the degree of organization of the system (dry emulsion, naked beads, coated beads obtained by an additional amount of α-cyclodextrine to the preformed naked beads). In vivo studies in rats have highlighted that dry emulsion behaves as a fast release formulation, the coated beads as a sustained release formulation and the naked beads as an intermediate one. Finally, the release of the encapsulated drug can also be modulated by modifying the drying method of the beads. Compared to freeze-drying, oven-drying modifies the properties of the beads by increasing their resistance in simulated gastro-intestinal fluids and sustaining the release of the encapsulated drug.
Complete list of metadata

https://tel.archives-ouvertes.fr/tel-00769948
Contributor : ABES STAR :  Contact
Submitted on : Friday, January 4, 2013 - 2:16:07 AM
Last modification on : Saturday, June 25, 2022 - 8:31:39 PM
Long-term archiving on: : Friday, April 5, 2013 - 5:50:34 AM

File

VA_Hamoudi_Mounira_ChA_rifa_13...
Version validated by the jury (STAR)

Identifiers

  • HAL Id : tel-00769948, version 1

Collections

Citation

Mounira Cherifa Hamoudi. Évaluation d'une forme galénique à base d'alpha cyclodextrine et d'huile végétale pour l'administration par voie orale de molécules actives peu solubles dans l'eau. Médecine humaine et pathologie. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA114826⟩. ⟨tel-00769948⟩

Share

Metrics

Record views

1010

Files downloads

1876