الفهرس 
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Abstract
In the preparation of tablets by wet granulation, intra- and inter-granular migration of soluble, low-dosage drugs or colored additives upon drying of their wet granules may represent a serious problem. As a result, excessive dose variation may occur within the same batch of tablets especially in case of highly potent, low dose drugs. Also, the migration of the color may give rise to a tablet with a mottled appearance. The main objective of this investigation was to study the various factors affecting this phenomenon, as well as, finding out the most important measures to minimize the problem. Thus, two water soluble, low dose, colored drugs were selected for the study, which are: cyanocobalamin and riboflavin sodium phosphate. In this thesis, the effect of formulation and manufacturing variables on cyanocobalamin and riboflavin sodium phosphate migration was studied separately. This was achieved through the use of different diluents (lactose monohydrate and anhydrous dibasic calcium phosphate), different binders (PVP k25, MC, HPMC and gelatin) and different drying temperatures (50 and 70°C). This was followed by compression of some selected lactose granules into tablets, with studying their physical characters. Also, the bioavailability of riboflavin sodium phosphate from some selected tablet batches was studied in human. The obtained results revealed that, increasing the binder solution viscosity decreases the intergranular migration of the two studied vitamins. Both drugs showed mostly higher migration at a drying temperature of 50°C than at 70°C. At the same time, lactose showed less migration for cyanocobalamin than dibasic calcium phosphate. While for riboflavin sodium phosphate, the migration was higher in case of using lactose as a major diluent. Using 10 % w/w gelatin, as a binder in the wet granulation method, and 70ºC as the drying temperature of the wet granules, minimized the migration of both drugs. For the prepared tablets, mottling was extensively observed for batches (of both drugs) prepared with low viscous binder solutions, while, it diminishes on using highly viscous binder solutions. Also, for both drugs, tablets prepared with 10 % w/w gelatin showed the most uniform drug distribution, but had slower dissolution rate, and higher disintegration time, compared to the other batches. On the other hand, tablets prepared with 0.5 % w/w MC, showed highest friability percentage, least hardness value, least disintegration time. The in vivo study revealed a lower excretion rate, higher T max and good correlation with the in vitro data for riboflavin sodium phosphate tablets prepared with 10 % gelatin. While, those prepared with 0.5 % w/w MC exhibited higher excretion rate and lower T max.