Influence of compaction on the intrinsic dissolution rate of modified acetaminophen and adipic acid crystals

Abstract Previous work has shown that aqueous crystallization of acetaminophen in the presence of p -acetoxyacetanilide or adipic acid in the presence of n -alkanoic acids (carbon number ⩾ 6) modifies the dissolution rate of free floating crystals per unit surface area in the USP Apparatus 2 (crystal intrinsic dissolution rate, i.e., crystal-IDR). The present work measures and compares the corresponding dissolution rates of compacted discs per unit surface area of disc (disc intrinsic dissolution rate, i.e., disc-IDR). The differences between the crystal IDRs (by factors of 1–2.4) of the acetaminophen samples almost disappeared with the disc-IDRs. This result confirms that crystal habit is the major factor which determines the intrinsic dissolution rate of acetaminophen crystals, rather than crystal energetics. On the other hand, differences between the crystal-IDRs of the adipic acid samples persisted, although somewhat reduced, among the disc-IDRs. This result confirms that the crystal energetics is the major factor which determines the intrinsic dissolution rate of adipic acid crystals. Significant changes in the dissolution behavior after compaction of the adipic acid samples suggest that compaction alters the nature, concentration and/or profile of the crystal defects that determine the crystal energetics. Implications in using the disc method for intrinsic dissolution rate measurement are discussed.