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Abstract Most of the new chemical entities (NCE) under development are intended to be used as solid dosage forms originating an effective and reproducible in vivo plasma concentration after their oral administration. Unfortunately, an increasing number of new chemical entities emerging from drug discovery and reaching drug development are poorly or very poorly water soluble. Therefore, an urgent need has always existed to improve the dissolution, solubility and consequently the oral bioavailability of these poorly water-soluble drugs. Flutamide is the only nonsteroidal antiandrogen presently recommended for monotherapy of prostate cancer. The low bioavailability of FLT after oral formulations may be due to poor wettability, low aqueous solubility, poor permeability and rapid first pass hepatic extraction .The inadequate absorption of FLT through the gastrointestinal tract (GIT) may not be due to its inability to permeate the intestinal epithelium, but to its low concentration at the absorption surface. Formulations that produce higher concentrations of FLT in solution at the absorption site may overcome the solubility-mediated bioavailability deficiencies. Peptide drugs are attracting an increasing interest with a better understanding of their role in physiopathology, as with the progress in biotechnology and biochemical synthesis. However, the use of peptides and proteins in medicine has been limited by low oral bioavailability which results from their poor stability to proteolytic and hydrolytic degradation, low permeability across barriers, and short biologic half-life. Most therapeutic peptides are still being administered by the parenteral route because of their insufficient absorption from the gastrointestinal tract. The objective of this thesis is to improve the drug targeting and enhance the oral bioavailability of Flutamide and Albumin which are of low bioavailability and require innovative formulation approaches to reach a sufficiently high bioavailability after their oral administration. This thesis is divided into two parts: Part One: Development of Controlled Release Formulations of Flutamide. Part one is subdivided into two chapters: Chapter One: Preparation and Evaluation of Immediate-Release Flutamide Formulae using the Lyophilization Monophase Solution Technique. Chapter Two: Preparation and Evaluation of Controlled-Release Flutamide- Chitosan Microparticles. Part Two: Preparation and Evaluation of Chitosan Nanoparticles as Oral Controlled Release Drug Delivery System for Proteins and Peptide Drugs. 215 Part One Development of Controlled Release Formulations of Flutamide Chapter One Preparation and Evaluation of Immediate-Release Flutamide Formulae using the Lyophilization Monophase Solution Technique The aim of this chapter is to formulate FLT lyophilized dispersions in order to improve the drug aqueous solubility, dissolution rate and to facilitate faster onset of |