الفهرس | Only 14 pages are availabe for public view |
Abstract The aim of any drug delivery system is to deliver a therapeutic amount of a drug to the correct site in the body, so that the anticipated drug concentration can be attained promptly, and then maintained. Recently, a vast attention has been paid to the development of new drug delivery systems. The nanosized drug delivery systems are among the dosage forms, which were emerged to achieve the objective of an enhanced drug delivery to the site of action, a modified drug release, a more proficient administration of the drugs by different routes, and hence improved therapeutic effect and patient compliance. The objective of the present study was to prepare a nanosized formulation using different polymers. Diosmin (DSN) is a natural flavonoid glycoside that can be extracted from numerous plant sources or can be derived from the flavonoid hesperidin. DSN shows various pharmacological activities including anti-inflammatory, anti-hyperlipidemic, hepatoprotective, anti-ulcerative colitis and anti-ulcer activities. DSN is a poorly water soluble compound, exhibiting a low dissolution rate in the gastrointestinal tract (GIT) fluids and a hindered uptake from the GIT wall. Plasma concentrations were faintly improved when DSN was administered as a micronized form owing to the influence of particle size reduction. Further size reduction to the nanosize is a promising approach to enhance the solubility and the penetration of the poorly water soluble drugs. Nanocrystallization is a universal tool to enhance the drugs bioavailability through the enhancement of their solubility and dissolution rate. Yet, there is an important factor that controls the quality of nanocrystals (NCs), which is the selection of the appropriate stabilizer that prevents crystal growth and particles enlargement. NCs can be stabilized by steric or electrostatic stabilizers. The combination of both types can be employed. In our study, we used the combination of steric and electrostatic stabilizers. Chitosan (CS) was selected as an electrostatic stabilizer that imparts many in vitro and in vivo advantages to DSN NCs owing to lack of toxicity, biocompatibility and most importantly its mucoadhesive and permeability enhancing capabilities. Consequently, it is expected to increase the residence time of the drug in GIT, and hence the rate of absorption preventing uncontrollable drug precipitation in the GIT. To fulfill the required goals, this thesis comprises of the following two chapters : The first chapter: to formulate, in vitro characterize, and optimize DSN NCs. The second chapter: to assess the therapeutic efficacy of the selected DSN NCs against ferrous sulfate-induced liver injury in rats. |