الفهرس 
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Abstract
Diabetes mellitus (DM) type II is a chronic progressive disease which is defined by hyperglycemia due to inadequate blood glucose control caused by insulin resistance. Insulin resistance is prominent among type II diabetics and it is also appeared in over 50% of people who are not suffering from diabetes but have ischemia or transient ischemic stroke. Insulin resistance increased risk of evidence of vascular diseases due to hypertension and hyperinsulinemia. Pioglitazone hydrochloride reduces cardiovascular diseases includes strokes in persons with type II DM who take the medication and also lowers risk of stroke in people who have prediabetes, diabetes mellitus and insulin resistance. Pioglitazone hydrochloride is used to treat of type II Diabetes mellitus. It is class II drug according to Biopharmaceutical classification system (BCS) with poor water solubility and high permeability. Its solubility is dependent on pH values; it is highly soluble in acidic pH and weakly soluble in alkaline pH. This relates to simple dissolution in stomach pH, which may then results in precipitation when it transferred to duodenum because of higher pH. The goal of this research is to develop an oral in-situ gelling liquid Pioglitazone dosage form with gastro-retention or prolonged release. To be suitable for oral administration, the produced liquid dosage form should have an appropriate viscosity. Combination of an alginate-based in-situ gelling system with a solid dispersion (SD) formula was made using the pH-dependent polymer Eudragit L100 in two concentrations. In the alginate solution, a solid dispersion is suspended. 2 Pharmaceutical Technology department, Faculty of Pharmacy, Tanta University, Tanta, Egypt Abstract 1. Preparation of sPreparation of solid dispersion formulations for lowering olid dispersion formulations for lowering dissolutidissolution rate of Pon rate of Pioglitazone hydrochlorideioglitazone hydrochloride Because Pioglitazone hydrochloride is extremely soluble in acidic pH, it appears that lowering its solubility in the stomach is required for gastro-retentive drug delivery from in-situ gel system. This was accomplished through enteric coating of drug particles with Eudragit L100 as a polymer using solid dispersion approach by solvent evaporation technique; drug and Eudragit L100 are dissolved in ethanol. SD formulations are in percentage of Pioglitazone: Eudragit L100 is SD1 (1:2) and SD 2 (1:3). characterization of solid dispersion formulations of Pioglitazone hydrochloride The pure Pioglitazone, Eudragit L 100 and SD formulations were characterized by fourier-transform infrared spectrophotometry (FTIR), differential scanning calorimetry (DSC) and in vitro dissolution studies. These characterization techniques confirmed that SD formulations lower dissolution rate of drug. DSC for solid dispersion formulations showed that melting transition of Pioglitazone disappeared which is showing that lowering crystallinity of the drug and its presence as molecular dispersion in polymeric matrix. FTIR spectra which are the sum of the separate spectra of components indicated the absence of chemical interaction. The diffractogram of SD formulations revealed no changes in the diffraction pattern. Dissolution behavior of unprocessed pioglitazone and its SD formulations with Eudragit L100 were studied. The dissolution of unprocessed Pioglitazone hydrochloride reflected its very rapid dissolution as 3 Pharmaceutical Technology department, Faculty of Pharmacy, Tanta University, Tanta, Egypt Abstract shown from recorded percentage amount released after ten minutes (% Q10) and percentage dissolution efficiency (% DE) values being 102.44% and 103.55%, respectively. SD formulations lowered dissolution pattern of Pioglitazone compared with unprocessed drug. 2. InIn--situsitu gelling system preparation for lowering dissolution gelling system preparation for lowering dissolution rate of SD formulationsrate of SD formulations and gastroand gastro--retentive drug delivery retentive drug delivery systems of pioglitazonesystems of pioglitazone Sustained release formula is needed to achieve a prolonged effect with less fluctuation in drug plasma concentration levels, so it could be very useful to develop a gastro-retentive oral liquid pioglitazone dosage form which is transfers into gel in stomach. Meanwhile, oral liquid dose formulations are more convenient especially for geriatric patients who have difficulty in swallowing and consistent pattern of release of drug from created gel will limit fluctuations in plasma concentration. Oral in-situ gel forming liquids are novel drug sustaining release techniques. These are polymeric solutions that are liquid outside the body and change to gel after administration inside the body. Various environmental triggers such as pH changes or temperature or increasing electrolyte concentration; initiate the in-situ gelation. Because of the known mucoadhesive characteristics of sodium alginate, alginate in-situ gel producing liquid provides a gastro-retentive dosage form; it ought to be capable to penetrate deeply in the mucus layer which is near to epithelial cell lining to develop a support for produced gel; in order to have high mucoadhesion capabilities. 4 Pharmaceutical Technology department, Faculty of Pharmacy, Tanta University, Tanta, Egypt Abstract In-situ gelling systems were produced through addition of accurate weighted quantities of SD2 formulation to the prepared concentrations of sodium alginate solutions (1%, 2% and 3%). characterization of in-situ gel formulations of Pioglitazone hydrochloride Flow properties, viscosity and gel forming capacity of all in-situ gel formulations were determined. These formulations have shear thinning non-Newtonian flow which means that the formulations become more liquid when shaken to allow convenient pouring of the required volume. Viscosity rises with rising concentration of sodium alginate and this leads to larger opportunity for entanglement in a chain of mucin in the presence of high concentration of the polymer. Gel-forming capacity gives a prediction for ability of liquid system to convert into gel when it becomes in appropriate condition. Liquid containing 1% w/v alginate produced soft gel mass that became relatively firm via increasing of the alginate concentration to 2% and 3%. w/v. Release profiles of drug and all in-situ gel formulations were tested and indicated decrease in drug release of in-situ gelling systems compared to unprocessed drug. In conclusion, in-situ gelling systems of Pioglitazone hydrochloride offer a controlled release of drug through modulating composition of it.