Resumo:
Biperiden Hydrochloride (BPR) is a drug indicated as an adjuvant in the treatment of Parkinson’s
disease, assisting in managing symptoms such as tremors and muscle stiffness. However, it has a
large amount of side effects, in addition to low water solubility and first-pass effect, limiting its
bioavailability. One way to overcome these limitations is the use of an association of the drug with
cyclodextrins (CDs) in supramolecular host-guest systems. Thus, in the present work,
supramolecular systems linked by non-covalent interactions, formed by the association of guest
molecules, β-cyclodextrin (βCD) and Hydroxypropyl-β-Cyclodextrin (HPβCD), with the drug
BPR, were investigated. Solid state inclusion compounds for both systems (βCD:BPR e
HPβCD:BPR) were prepared by lyophilization and characterized previously by infrared absorption
spectroscopy (FTIR-ATR). In solution, isothermal titration calorimetry (ITC) was used to obtain
the stoichiometric coefficients (n), the association constants (Ka) and the thermodynamic
parameters involved in the process. Still in solution the phase solubility diagram was utilized to
study the inclusion process on the solubility of the BPR. According to the ITC results, the
formation process of inclusion compounds, both the HPβCD:BPR and the βCD:BPR system, was
spontaneous and exothermic, however, the latter obtained a higher Ka, indicating stronger
interactions between species. Furthermore, the ITC results indicated values of n corresponding to
a 1:1 stoichiometry for the βCD:BPR system while for the HPβCD:BPR system fractional values
of n were observed, suggesting the formation of multiple equilibria in solution. The 2D-ROESY
correlation maps confirmed the inclusion of BPR for both systems, and also demonstrated the
existence of stronger interactions between BPR and βCD. Additionally, solubility studies indicated
that the solubility of inclusion compounds is superior in comparison with the free BPR drug, taking
by example the AL-type solubility profile obtained for the two systems under study.
