Effect of compression force, humidity and disintegrant concentration on the disintegration and dissolution of directly compressed furosemide tablets using croscarmellose sodium as disintegrant

摘要

Purpose: The effect of compression force, relative humidity and disintegrant concentration on furosemide dissolution in directly compressed furosemide/Avicel?-tablets was studied. Methods: Mixtures of furosemide (12.5% w/w), Ac-Di-Sol? (0, 0.625% to 10% w/w) and Avicel? PH200 (qs to 100% w/w) were prepared in a Turbula?mixer 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% 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%. 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-Sol? . 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-Sol? was an efficient disintegrant for furosomide tablets at low concentrations of 1.25% -10% because it rapidly released the hydrophobic drug particles from tablets. However, tablets containing 10 % disintegrant must be protected from atmospheric moisture because storage at 60-70 % relative humidity led to softening of tablets.