Imiquimod/β-Cyclodextrin Inclusion Complex: Experimental and Theoretical Studies

Imiquimod (IMQ), an immune response modifier, is used for topical treatment of basal cell carcinoma and actinic keratosis. The very poor aqueous solubility of imiquimod gives rise to difficulties in designing aqueous formulations with this drug. One approach that is widely used to enhance drug solubility is complexation with cyclodextrins. The formation of the inclusion complex between IMQ and beta-cyclodextrin was investigated in solution and in solid state. IMQ aqueous solubility was improved in the presence of citric acid. The experimental results and molecular modeling indicated the formation of the inclusion complex in aqueous solution of citric acid pH 3.0; however, the low apparent stability constant suggested weak interaction between beta-cyclodextrin and IMQ which hampered the use of this approach to improve imiquimod aqueous solubility and the development of an aqueous formulation containing IMQ in the same concentration as in the commercial product.