Abstract
Fosinopril, the unique phosphinic acid derivative among the angiotensin-converting enzyme inhibitors, is a poorly water-soluble and highly lipophilic substance, exhibiting poor bioavailability following oral administration. The inclusion complex between the drug substance and hydroxypropyl-β-cyclodextrin (HPBCD) was obtained in order to improve its solubility and, consequently, its bioavailability. The aim of this study was to investigate the thermoanalytical behavior of fosinopril sodium (FOS), of the inclusion complex between FOS and HPBCD (FOS/HPBCD) and its physical mixture with some pharmaceutical excipients commonly used in solid dosage forms. The analytical techniques used for this purpose have been thermogravimetry/derivative thermogravimetry (TG/DTG), differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FT-IR). Non-isothermal methods have been employed to determine the kinetic parameters using DTG data. The DTA curves of inclusion complex FOS/HPBCD and its 1:1 (m/m) physical mixtures with excipients (magnesium stearate, talc and starch) indicated a possible interaction of the inclusion complex (IC) with magnesium stearate and talc. FT-IR data and the values of the activation energy (E a) for physical mixture did not evidence any incompatibility between the IC and excipients. Concerning FOS, the thermoanalytical results and the value of E a for the binary mixture of drug with magnesium stearate confirmed the incompatibility between the two substances reported in the literature. Therefore, as a result of the encapsulation of FOS in the HPBCD cavity, the stabilization of drug substance in the presence of magnesium stearate has been realized.
Published Version
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