title: Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet.
abstract: An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab® concentration, DiPac®/Xylitab® ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability <10%) could be produced. The expansion coefficient (n) and the exponential rate constant (k) for disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab® and/or Xylitab®, magnesium stearate, and Explotab® suggested that the amount of Explotab® was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel® and Explotab®, which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone® XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol® showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.
authors.affiliation: Food and Drug Administration, CDER, Office of Generic Drugs, Rockville, MD 20855, USA. huijeong.jung@fda.hhs.gov
authors.forename: Huijeong Ashley
authors.initials: HA
authors.lastname: Jung
authors.forename: Larry L
authors.initials: LL
authors.lastname: Augsburger
mesh_terms: D017610:Calcium Compounds / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods*; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D011134:Polysaccharides / Q000737:chemistry; D017640:Silicates / Q000737:chemistry*; D013213:Starch / Q000031:analogs & derivatives / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
chemical_list: D017610:Calcium Compounds; D005079:Excipients; D011134:Polysaccharides; D017640:Silicates; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid; C038963:dipac; D013213:Starch; C048390:sodium starch glycolate; C031293:calcium silicate