Cyclodextrin-Induced Change in Crystal Habit of Acetylsalicylic Acid in Aqueous Solution

The present work refers to a method to selectively modify the crystal habit of acetylsalicylic acid (ASA) through the use of the cyclic oligosaccharide derivatives 2-hydroxybutyl-β-cyclodextrin (HB-β-CD) and 2,6-di- O -methyl-β-cyclodextrin (DM-β-CD) as a growth inhibitor. ASA crystallized in plate crystals in solutions containing only drug. On the other hand, the addition of HB-β-CD or DM-β-CD markedly changed the crystal habit of the drug to needle crystals that elongated along the crystallographic b -axis. The habit modification of these CDs was attributable to the suppression of the crystal growth of ASA toward the c -axis direction, which is perpendicular to the {001} surface and consisted of phenyl and methyl groups of ASA. These results suggested that HB- and DM-β-CDs inhibited the access of ASA to the {001} face due to the inclusion complex formation with the drug and/or due to the adsorption of the amphiphilic hosts on this face. These CDs can work as a tailor-made additive and may be useful for control of crystal habits of drugs.