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Prérsenrért o

A Mr Philippe Maincent, professeur de pharmacie galénique et biopharmacie à la faculté de pharmacie de Nancy ∑8∑+

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∑8,, ∑ ∑- ∑, (9 ∑⇌ ∑ □ A Madame Lucie Manache-Alberici, pharmacien industriel ∑ , (9 8

8,,∑⇌

A Madame Sylvie Gigleux, DR INSERM

∑8∑+

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∑8,, ∑ ∑, ∑ ∑ , (9 : A Madame Anne Sapin-Minet, maître de conférence du laboratoire de pharmacie galénique et biopharmacie à la faculté de pharmacie de Nancy ∑8∑+

8(□□

∑8,, ∑ ∑, ∑ ∑ , (9 : A Madame Roudayna Diab, maître de conférence du laboratoire de pharmacie galénique et biopharmacie à la faculté de pharmacie de Nancy A l'équipe du PSD de Sanofi-Aventis à Budapest ∑8∑ ,( ∑∑9∑ ∑8∑ A la Therapeutic Research Unit de M.S. Roberts du Princess Alexandra Hospital à Brisbane

A ma famille...

∑8∑□□⇌ □ □∑(∑, □:

A mes amis...

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FDA : Food and Drug Administration

FeSSIF : Fed State Simulated Intestinal Fluid (fluide intestinal simulé nourri) GRAS : Generally Recognised As Safe (généralement reconnu comme sûr)

10HCPT : 10-hydroxycamptothécine

HLB : Hydrophile-Lipophile Balance (Balance hydrophile/lipophile)

HMG-CoA : 3-hydroxy-3-methylglutaryl-Coenzyme A

HPLC : High Performance Liquid Chromatography (chromatographie liquide haute performance)

HPMC : HydroxyPropyl MéthylCellulose

HPT1 : Human Peptide Transporter 1

ICH : International Conference on Harmonisation

IM : intramusculaire

IV : intraveineuse

IVIVC : corrélation UNIVUVERIUNIVUSTE

IVIVR : relation UNIVUVERIUNIVUSTE

LCT : Long Chains Triglycerides

LDH : lactate déshydrogénase

LFDS : Low Frequency Dielectric Spectroscopy

LUV : Large Unilamellar vesicles (grands liposomes unilamellaires) MCT : MonoCarboxylate Transporter (partie I); Medium Chains Triglycerides (patie II)

MDR1 : Multi Drug Resistance 1

MLV : Multilamellar Vesicle (grands liposomes multilamellaires)

MRP: Multidrug Resistance associated Protein

MS : Degré molaire moyen de substitution

2 MVV : MultiVesicular Vesicles (liposomes multivesiculaires)

NP : NanoParticule

OATP : Organic Anion Transporting Polypeptide

OCT : Organic Cation Transporter

PAMAM : polyamidoamine

PAT: Proton/Amino acid Transporters

PCA : Precipitation with a Compressed Antisolvent

PEG : polyéthylène glycol

PEPT : peptide transporter 1

PG : propylène glycol

PGA : Poly(acide glycolique)

Pgp : glycoprotéine P

PLA : acide polylactique

PLA-TPGS NPs : nanoparticules d'acide polylactique-vitamine E TPGS PLA-TPGS/MMT NPs : nanoparticules de poly(lactide)-vitamine E TPGS/montmorillonite

PLGA : poly(acide lactique-co-glycolique)

PLGA/MMT Nps : nanoparticules de poly(acide lactique-co-glycolique)-montmorillonite

PM : poids moléculaire

PVP : polyvinyl pyrrolidone RESAS : Rapid expansion from supercritical to aqueous solution

RH : relative humidity

SEDDS : Self Emulsifying Drug Delivery System

SEOF : Self-emulsifying oil formulations

SEM : Scanning electron microscopy : microscopie à balayage électronique

SFL : spray freezing into liquid

SLC : solute carrier

3

SLN : solid lipid nanoparticules

SMEDDS : Self micro Emulsifying Drug Delivery System S-SEDDS : supersaturated Self Emulsifying Drug Delivery System SUV : Small unilamellar vesicles (petits liposomes unilamellaires) TPGS : D-α-Tocopheryl Polyethylène Glycol 1000 Succinate

UGTs : UDP-glucuronosyltransférases

USP : United States Pharmacopeia

UV : ultra violet

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LISTE DES ABRÉVIATIONS ........................................................................A..................................................1

RÉSUMÉ : ........................................................................A........................................................................A............5

INTRODUCTION ........................................................................A.....................................................................10

PARTIE 1 : ABSORPTION INTESTINALE ........................................................................A.......................13

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1.2.1 Energies mises en cause. ..............................................................................................................................67

1.2.2 Degré de substitution ...................................................................................................................................68

1.2.3 pH et état d'ionisation ..................................................................................................................................68

1.2.4 Température ................................................................................................................................................68

1.2.5 Méthode de préparation et additifs ...............................................................................................................70

1.2.5.1 Effets de la méthode de préparation .....................................................................................................70

1.2.5.2 Effets d'additifs variés .........................................................................................................................71

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1.4.1 Effet sur la solubilité et la dissolution de la molécule ..................................................................................73

1.4.2 Effets sur la biodisponibilité de la molécule ................................................................................................75

1.4.3 Effet des CD sur la sécurité d'utilisation .....................................................................................................75

1.4.4 Effets sur la stabilité des molécules .............................................................................................................76

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1.3.2 Statut légal .....................................................................................................................................................81

1.3.3 Statut des brevets ...........................................................................................................................................81

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ES MICRO-ÉMULSIONS ........................................................................l.............................................................83

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ES SYSTÈMES AUTO-ÉMULSIFIANTS SEDDS (SELF EMULSIFYIG DRUG DELIVERY SYSTEM) ..............................85

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3.2.1 Huiles ............................................................................................................................................................86

3.2.2 Tensioactifs ...................................................................................................................................................87

3.2.2.1 Définition ..............................................................................................................................................87

3.2.2.2 Balance hydrophile/lipophile HLB .......................................................................................................88

3.2.2.3 Utilisation dans les SEDDS ...................................................................................................................90

3.2.3 Co-solvants / co-tensioactifs ..........................................................................................................................90

3.6.1 Avantages des SEEDS ...................................................................................................................................94

3.6.2 Paramètres influençant l'absorption ...............................................................................................................98

3.6.2.1 Influence du véhicule huileux ..............................................................................................................100

quotesdbs_dbs41.pdfusesText_41

[PDF] test de dissolution pharmacopée européenne

[PDF] formule de l'accélération

[PDF] résolution de problèmes 4ème

[PDF] équation allométrique définition

[PDF] allométrie définition

[PDF] oeuvre in situ de daniel buren

[PDF] formule brute du sorbitol

[PDF] formule semi développé de l'acide lactique

[PDF] pyruvate formule

[PDF] butanol formule

[PDF] formule semi développée isomère c4h10o

[PDF] formule semi développée c4h10

[PDF] formule semi développée du butane

[PDF] c4h10o isomers

[PDF] schéma d'analyse des champs de force st2s