Background: Malaria is still a dangerous disease that impacts specifically Africa, Asia, and
Latin America. The development of therapies to overcome the parasite infection is an important challenge
nowadays. The medicine primaquine (PQ) is used in the treatment, although several side effects and low
oral bioavailability are reported.
Objective: This work focused on the preparation and characterization of a complex between PQ and 2-
hydroxypropyl-β-cyclodextrin (HPCD), besides performing release tests of this formulation.
Methods: PQ:HPCD complexes were prepared at 1:1 and 1:2 molar ratios, by the lyophilization method.
The association between PQ and HPCD was tested using UV-vis, infrared (FTIR), differential scanning
calorimetry (DSC), scanning electron microscopy and NMR techniques (chemical shift, Job Plot, DOSY,
and ROESY). Tests were also conducted to evaluate drug release before and after complexation with
Results: Results showed that there was a weak interaction of PQ with HPCD, forming non-inclusion
complexes. These results were supported by FTIR results and spatial correlations between hydrogens from
PQ with the external HPCD hydrogens. A 1:2 PQ:HPCD preferred molar ratio was determined by DSC
and Job Plot experiments and the time to release 96% of the drug was 21.2 h slower after complexation.
Conclusion: Conclusion indicate that PQ interacts poorly with HPCD, probably due to its hydrophilic
character, as well as to its interaction with the external rim of HPCD. Our results demonstrate that there
was a significant improvement in the release time after the complexation process, which could lead to an
increase in the activity of the drug.