Effect of Compression Force; Humidity and Disintegrant Concentration on the Disintegration and Dissolution of Directly Compressed Furosemide Tablets using Croscarmellose Sodium as Disintegrant

ABSTRACT

PURPOSE: The effect of compression force; relative humidity and disintegrant concentration on furosemide dissolution in directly compressed furosemide/Avicelr-tablets was studied. METHODS: Mixtures of furosemide (12.5 percent w/w); Ac-Di-Solr (0; 0.625 percent to 10 percent w/w) and Avicelr PH200 (qs to 100 percent w/w) were prepared in a Turbularmixer at 69 rpm for 10 min. Tablets were stored for 6 months under conditions similar to the four climatic zones recognized by ICH. Tablet hardness; disintegration time and dissolution were measured. RESULTS: At the same compression force; disintegration time decreased as the disintegrant concentration increased above 0.625 percent w/w but an increase in compression force resulted in increased tablet crushing strength and apparent density; both of which prolonged the disintegration time. This effect was less significant when the disintegrant concentration was above 1.25 percent. However; storage under high relative humidity conditions (mediterranean or subtropical; hot and humid climate) caused softening of tablets leading to the spontaneous disintegration of tablets containing high concentrations of Ac-Di-Solr . CONCLUSION: Fast disintegration of tablets within 1-2 min is a prerequisite for improving the dissolution of furosemide. This was attributed to an increase in the speed at which the maximum surface area of the sparingly water-soluble drug is exposed to the dissolution medium. Ac-Di-Solr was an efficient disintegrant for furosomide tablets at low concentrations of 1.25 percent -10 percent because it rapidly released the hydrophobic drug particles from tablets. However; tablets containing 10 percent disintegrant must be protected from atmospheric moisture because storage at 60-70 percent relative humidity led to softening of tablets