• Evaluation of the functional equivalence of different sources of super disintegrants in pharmaceutical tablets

      Shah, Umang Subodh; Augsburger, Larry L. (1996)
      Disintegrants are substances included in tablet formulations to cause the compressed tablet to break apart and promote drug dissolution when placed in an aqueous environment. In the past two decades, three categories of newer disintegrants have come into widespread use. These substances are chemically modified starch (sodium starch glycolate), chemically modified cellulose (croscarmellose sodium) and a synthetic polymer (crospovidone). Because of their high efficiency at low levels of addition compared to traditional starch, these substances are often called "super disintegrants." One objective of this dissertation was to identify among different sources of disintegrants of each type meeting NF standards, differences in physical properties thought to be related to functionality. A second objective was to develop standard performance tests and use those tests to determine the hypothesized relationship between these physical differences and disintegrant functionality. Dissolution was performed on a model tablet formulation of hydrochlorothiazide using either an insoluble filler (dicalcium phosphate dihydrate) or a soluble filler (spray-dried lactose) and test disintegrants at a 1% level. Disintegrants tested exhibited significant differences in the rate and extent of liquid uptake and in the ability to develop axial and radial disintegrating forces. Lowering the pH altered the rate and extent of liquid uptake of sodium-starch glycolate and croscarmellose sodium. Since there are no ionizable groups in crospovidones, lowering the pH did not affect their liquid uptake performance. Sources of crospovidone containing larger particle size fractions showed greater rate of liquid uptake, however crospovidones with greater porosity showed greater extent of liquid uptake. Liquid uptake study on sieve fractions of crospovidones showed greater rate and extent of uptake for larger sieve cuts, whereas smaller sieve cuts of starch glycolates showed greater rate and extent of liquid uptake. For tablets containing water-insoluble filler dicalcium phosphate, disintegration times for sources of crospovidone containing larger particle size were lower and showed correspondingly faster dissolution rates. The rate of disintegration and dissolution followed the same rank order as the extent of liquid uptake. However, when the filler was changed to spray-dried lactose, although the disintegration of all tablets containing different sources of crospovidone was faster than in the insoluble filler, no significant differences were detected in either the disintegration times or dissolution amongst the disintegrants from different sources. Tablets containing croscarmellose sodium or sodium starch glycolate from different sources, in either filler showed no significant differences in disintegration times and their corresponding rates of dissolution were also not different, indicating that dissolution of hydrochlorothiazide is the rate limiting step. This study indicates that liquid uptake study, particle size and porosity should be included in crospovidone monographs, whereas liquid uptake studies and/or settling volume studies in a low pH medium should be included in compendial monographs for sodium starch glycolate and croscarmellose sodium. (Abstract shortened by UMI.)