الفهرس 
Title: A pharmaceutical study on certain centrally acting drug
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Abstract
Major depressive disorder (MDD) is the most common mood disorder. Depressive disorders are chronic and both relapse and recurrence are seen frequently. Agomelatine, a novel antidepressant drug, is a melatonin analogue with a potent agonistic action on melatonin MT1 and MT2 receptors. It also has serotonin 5-HT2C receptor antagonistic activity. Although agomelatine is rapidly and well absorbed ( >75%) after oral administration, it is subjected to an extensive hepatic first pass metabolism leading to a low absolute bioavailability ( <5%). Moreover, it has a liver toxicity as it raises liver transaminase enzymes. The oral dose of agomelatine is 25 to 50 mg daily. The aim of this study was to deliver agomelatine through transdermal route and to reduce its dose (hence increasing its absolute bioavilablity). The work in this thesis is divided into three chapters as follows: Chapter 1: Formulation and optimization of agomelatine microemusions using D-optimal mixture design. Chapter 2: Formulation and optimization of agomelatine cubosomes using Box behnken design. Chapter 3: Bioavailability study of agaomelatine optimum microemusion gel formula and cubosomal formula. Chapter 1: Formulation and optimization of agomelatine MEs using D-optimal mixture design. Microemulsions are optically isotropic and thermodynamically stable systems consisting of oil, water, surfactants and cosurfactant. Preliminary screening was carried out to select proper ingredients combinations and then, the design expert software was utilized to optimize the microemulsion formulations. The independent variables of the employed mixture design were capryol 90 as an oily phase (X₁), cremophor RH40 and transcutol HP in a ratio of (1:2) as Smix (X₂) and water (X₃). The dependent variables were globule size, optical clarity, Q₁, Q₂₄ and ER