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 β-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 β-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.

Benzbromarone (BZB) is a drug that has diuretic activity and is used in the gout treatment. Its therapeutic efficiency is decreased by its low water solubility (11.8 mg L-1) and highly hydrophobic aspect (logP 2.7), which are responsible for affecting its intestinal absorption and bioavailability. BZB inclusion complex (IC) aims at increasing the drug solubility in water and reduce adverse effects resulting in more efficient formulations. The coprecipitation encapsulating method was used to obtain the IC of BZB in β-cyclodextrin (β-CD) and the complex (BZB@β-CD) was characterized via physical-chemical analysis. A comparative study of time-dependent density functional theory (TD-DFT) and configuration interaction singles (CIS), along with “our own N-layered integrated molecular orbital and molecular mechanics” (ONIOM) method, has been carried out on the UV-Vis absorption of BZB and BZB@β-CD. The qualitative description of the simulated spectrum, given by ONIOM(CIS:PM6), is in accord with the formation of BZB@β-CD. It only became possible when phosphate buffer (pH 7.4) was used to prepare the solutions, since the complex formation did not occur in deionized water or buffered acid. Furthermore, by using the Job plot, the Scatchard method and fluorescence, it was possible to conclude that the complex molecular stoichiometry was 1:1 (1 BZB to 1 β-CD).