Formulation of multiparticulate drug delivery systems of gliclazide using natural polymeric materials / Ebtesam Wahman Hammam Elsayed ; Supervised Nadia M. Mursi , Laila H. Emara

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutics

Multiparticulate drug delivery systems offer numerous advantages over the single-unit dosage forms. For example, they show flexibility in modulation of drug release, excellent dose-weight proportionality and reduction in intra-or inter-subject variation in the bioavailability of many drugs.Design of Experiments(DOE)is a structured, organized method for determining the relationship between factors affecting a process and the output of that process. DOE is an excellent tool that allows systematically manipulating factors according to a pre-specified design.Gliclazide(GLZ)is a second-generation sulphonylurea, oral antidiabetic drug. It exhibits low solubility and high permeability (Biopharmaceutical Classification System, BCS, class II). The low water-solubility of gliclazide leads to a slow dissolution rate. Therefore, dissolution is considered as the rate-limiting step for gliclazide absorption. It exhibits high inter-subject variation in its absorption. Oral administration of a single dose of gliclazide results in a varying maximum plasma concentration that ranges from 2.2 mg/L to 8 mg/L within 2hoursto 8 hours. This variability in the absorption was attributed to both the physicochemical properties of gliclazide as well as the formulation administered.The recommended dose of gliclazide is much lower in case of the modified release dosage forms compared to the immediate release ones.The aim of the present study was to optimize the formulation of multiparticulate drug delivery systemsof gliclazide in order to overcome the problems of its slow dissolution and inter-subject variation and to reduce the total amount of drug administered.The optimization was carried out employing a design of experiments and response surface methodology. In addition, a biorelevant dissolution testing methodology wasestablished and utilized for evaluating the optimized formulations

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