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Abstract
Diacerein (D) is an insoluble chondroprotective agent intended for the treatment of osteoarthritis (OA). After oral administration, D cannot be completely absorbed from the digestive tract and thus results in undesirable side effects. Different techniques have been proved to enhance the bioavailability of insoluble drugs, among which are particle size reduction and self emulsifying drug delivery systems (SEDDS). SEDDS improve the bioavailability by increasing the saturation solubility of the active pharmaceutical agent (API) and size reduction increases the effective surface area and improve the drug dissolution and absorption rates. This work aimed at preparing D in a novel self nanoemulsifying self nanosuspension system (SNESNS) combining the advantages of SEDDS and nanosuspensions (NS) to improve the D saturated solubility, in vitro dissolution profile, its lymphatic absorption and its bioavailability. The work in this thesis is divided into two chapters: Chapter I: Formulation and evaluation of diacerein self Nano Emulsifying Self Nanosuspensions (D - SNESNS). Chapter II: In vivo portal blood and lymphatic absorption study of diacerein self Nano emulsifying self Nanosuspensions D SNESNS. Chapter I: Formulation and evaluation of diacerein self Nano emulsifying self Nanosuspensions (D - SNESNS) After screening D saturated solubility in different oily vehicles and examining different combinations to construct pseudo - ternary phase diagrams, five combinations with different ratios were able to form self nanoemulsifying drug delivery systems (SNEDDS), namely; maisine 35 - 1 / Polysobate 80 / transcutol HP, maisine 35 - 1 / cremophore El / Transcutol HP, triacetin / polysorbate 80 / transcutol HP, triacetin / cremophore El / transcutol HPand triacetin / labrasol / transcutol HP. Maisine-based systems were chosen for further formulation and evaluation for their superior solubilizing power and their ability for lymphatic targeting