الفهرس 
GENERAL INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Surfactants are well known as permeation enhancers. Span 60 microparticles encapsulated different concentrations of metformin HCl was prepared by using rapid congeal melting technique. Electron scanning microscopy showed a smooth surface but fewer round microparticles. The actual drug content is nearly equal in the different particle sizes microparticles. Differential scanning calorimetry results indicated the molecular distribution of the drug molecules with no evidence of drug thermal degradation. The drug release profile from the microparticles has, in each case, burst and incomplete drug release. The drug partition coefficient is markedly enhanced as a result of its molecular dispersion in span 60 indicating the increase of the drug lipophilicity as a result of its encapsulation in the polar part of the surfactant. The non-everted sac was used to study the drug permeability after solving its critic points. Compared to pure drug the permeability profile of the drug increased from span 60 microparticles encapsulated drug with total permeation of 68 % and drug absorption enhancement of 253 %. The drug permeation enhancement mechanism was suggested to be molecular dispersion of the drug in the matrix which is emulsified by tween 80 and this leads to increasing the hydrophilic Paracellular pathway of the drug. Considering the emulsification system of the Gastro Intestinal Tract )GIT(, which emulsifies the span 60 instead of tween 80, a huge improvement of the biopharmaceutics classification system class III permeability and consequently bioavailability could be expected. Also, this study will open the door to the use of the same technique for enhancing the drug absorption mechanisms by Paracellular pathway for rapid and complete pharmacological effect After proving the Paracellular pathway enhancement of the drug, the objective of this investigation was to improve the pharmacodynamics of the well-known anti-diabetic class III drug (Metformin HCl) by using an industrial granulation technique. The granulating agent used is span 60 due to its low melting point and solid stat at room temperature. Different granulation factors were studied by using multi-levels factorial experimental design to determine the optimized formula for industrial processing. Electron scanning microscopy showed the aggregation of the drug-coated crystals, which is reflected in reducing the drug release process. Differential scanning calorimeter )DSC( indicated there is no change in the crystallinity of drug and the presence of the granulating agent in the prepared drug granules. The non-everted intestinal sac was used to evaluate the intestinal permeation enhancement of the granulating agent used. As a simulation to the effect of the bile salt, tween 80 was added. The results showed a marked increase in the apparent permeability of the drug because of the addition of tween 80 comparing to the drug alone. This may be due to inhibition of the activity of P-gp. The apparent permeability of the drug from drug granules is markedly increased than both drug itself and drug plus tween. This effect is reflected in the total amount of drug-permeated. Lowering of the blood glucose level of diabetic male rats was used as a pharmacodynamics marker for the selected prepared granules comparing to the pure drug and drug plus tween 80. The pharmacodynamics effect of the drug plus tween 80 was 20% higher than the drug alone. The pharmacodynamics effect of the drug granules was 43% increase compared to the pure drug. That is due to the Paracellular pathway enhancement of the drug by using span 60 as a granulating agent. This technique could be suggested to solve the permeability problem of class III drugs.