title: Disintegration of highly soluble immediate release tablets: a surrogate for dissolution.
abstract: The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria.
authors.affiliation: Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical Science, Food and Drug Administration, 10903 New Hampshire Avenue, LS Bldg 64, Silver Spring, Maryland 20993-002, USA.
authors.forename: Abhay
authors.initials: A
authors.lastname: Gupta
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hunt
authors.forename: Rakhi B
authors.initials: RB
authors.lastname: Shah
authors.forename: Vilayat A
authors.initials: VA
authors.lastname: Sayeed
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D002626:Chemistry, Pharmaceutical; D012995:Solubility; D013607:Tablets / Q000737:chemistry*
chemical_list: D013607:Tablets