EFFECT OF MODE OF INCORPORATION OF DISINTEGRANTS ON THE CHARACTERISTICS OF FLUID-BED WET-GRANULATED TABLETS

A full factorial experimental design was employed to investigate the e ffects of mode of disintegrant incorporation and concentration in wet- granulated paracetamol tablets manufactured by top-spray fluid-bed. Di sintegrants (croscarmellose sodium, sodium starch glycolate, or crospo vidone) were incorporated either intragranularly, extragranularly, or distributed equally between the two phases. The results were analysed by a general quadratic equation and response surfaces generated. On ex amining the results for dissolution studies the combined mode resulted in significantly faster dissolution rates than did the extragranular mode which, in turn, was superior to the intragranular mode of inclusi on. These results were reflected in the disintegration studies where t he combined mode exhibited the shortest disintegration times for all t he disintegrants. Tablet crushing strength was not affected by the mod e of incorporation of concentration of the disintegrants. Main as well as interaction effects between the types, mode of incorporation and p ercent disintegrant employed were significant (P < 0-05) for disintegr ation time and percent release at 15 min. Croscarmellose sodium exhibi ted the shortest while crospovidone displayed significantly (P < 0.05) longer disintegration times. Formulations containing crospovidone did not meet official compendial (USP XXII) requirements of 80% in 30 min . In general, croscarmellose sodium and sodium starch glycolate were f ound to be less sensitive to the mode of incorporation than crospovido ne.