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The discussion of the doctoral thesis by Masters/ Shereen Mohammad Sameh El Mancy – assistant teacher in department of Pharmaceutics and industrial pharmacy – Faculty of Pharmacy The discussion of the doctoral thesis by Masters/ Shereen Mohammad Sameh El Mancy – assistant teacher in department of Pharmaceutics and industrial pharmacy – Faculty of Pharmacy – October 6 University was held on Monday 7/1/2013 in the seminar hall in Faculty of Pharmacy – Cairo University. Under the title of: “Improvement of the Performance of Some Hydrophobic Drugs Using Lipid-Based Drug Delivery Systems” Under the supervision of: - Prof. Dr. Alia A. Badawi. Professor of Pharmaceutics - Faculty of Pharmacy - Cairo University. - Prof. Dr. Wedad S. Sakran. Professor of Pharmaceutics - Faculty of Pharmacy - Helwan University. The committee of discussion consisted of: - Prof. Dr. Alia A. Badawi. Professor of Pharmaceutics - Faculty of Pharmacy - Cairo University. - Prof. Dr. Wedad S. Sakran. Professor of Pharmaceutics - Faculty of Pharmacy - Helwan University. - Prof. Dr. Omaima Naeem. Professor of Pharmaceutics - Faculty of Pharmacy - Cairo University. - Prof. Dr. Soheir El Nahas. Professor of Pharmaceutics - Faculty of Pharmacy – October 6 University. English Abstract The objective of the study was to develop and formulate two class II hydrophobic drugs in lipid-based formulations to improve their performance. Therefore, the work in this thesis is divided into two parts. Part I: Improvement of the microbiological activity of topical ketoconazole using microemulsion systems. The aim of this part was to formulate and evaluate microemulsion formulae for topical delivery of ketoconazole (KTZ) with improved microbiological activity. MEs containing KTZ were developed after screening of different oils, surfactants and cosurfactants to find out the most suitable components ratio for formulation of KTZ microemulsions. Different ME formulae containing KTZ were prepared using Labrafil M 2125 or IPM as oily phase, Tween 80/ isopropanol in ratio of 3:1 as S/Cos and water. The prepared KTZ MEs were subjected to different characterization tests. Screening of the microbiological activity of the prepared KTZ MEs was performed using agar diffusion method and the results showed that the prepared KTZ MEs showed wider zones of inhibition when compared to a marketed product (Nizoral® cream). Assessment of the rheological behavior revealed that all KTZ MEs showed Newtonian flow. Accelerated stability study was performed for six KTZ MEs at 5±1 ºC and 40±0.2 ºC for 3 months and drug content was analyzed every month using HPLC. All samples showed good stability at 5±1 ºC, while the samples stored at 40±0.2 ºC showed decrease of KTZ content by time. KTZ showed good stability in ME formula containing 10% water, 60% S/Cos and 30% IPM (I6B) when compared to Nizoral® cream. Formula (I6B) showed good stability during storage at ambient conditions for 6 months. Part II: Formulation and Characterization of Glibenclamide Self-Microemulsifying Drug Delivery Systems. The work in this part aimed to formulate glibenclamide (GBL) in self-emulsifying drug delivery systems (SMEDDSs) through screening of different excipients to improve its dissolution and consequently enhance its hypoglycemic activity. Based on the screening study Capryol 90, Labrafac PG and stearic acid were selected as oily phase and Cremophor RH40 was selected as surfactant and different GBL SMEDDSs containing 1% GBL were prepared. The prepared formulae were evaluated by different tests such as visual inspection, robustness to dilution and phase separation study, and assessment of self-emulsification efficiency. The rheological properties of the prepared GBL SEDDSs exhibited Newtonian flow with viscosity values in the range (155.9 – 485.0 cP). The in-vitro dissolution study revealed that formulae prepared using Capryol 90 showed the fastest dissolution profile when compared to the other GBL SMEDDS formulae as well as a marketed product (Daonil® tablet). The hypoglycemic activity of the selected GBL formulae was evaluated in comparison to a marketed product (Daonil® tablet) in normal rats using intraperitoneal glucose tolerance test. The results revealed that GBL SMEDDS formulae SE3 (prepared using Capryol 90: Cremophor RH40 in ratio of 40:60) and SE9 (prepared using Labrafac PG: Cremophor RH40 in ratio of 30:70) significantly enhanced the hypoglycemic activity when compared to a marketed product (Daonil® tablet).