Physicochemical and dissolution properties of ezetimibe–aspirin binary system in development of fixed-dose combinations

Abstract

The objective of this work was to investigate binary pharmaceutical mixtures of ezetimibe (EZT) and aspirin (ASA) in order to identify whether the occurrence of eutectic in this system has an effect on EZT dissolution improvement. Ezetimibeaspirin (EZT-ASA) solid dispersions prepared by grinding in the whole range of compositions were characterized using differential scanning calorimetry (DSC) for purpose to describe solid-liquid phase equilibrium diagram. The occurrence of interactions between ingredients was excluded by Fourier transform infrared spectroscopy and X-ray powder diffractometry. Dissolution studies have shown that the mixtures containing from 10 to 60 mass% of EZT (53.5 mass% of EZT in eutectic composition) have released ezetimibe faster than a sample of pure drug. Moreover, ASA is released more quickly from all obtained dispersions than from powder alone. Our studies have shown that obtained mixtures are useful to obtain the fixeddose combinations, capable to deliver these two APIs together in a single system with enhanced dissolution of EZT and ASA.

Studies of the Formation and Stability of Ezetimibe-Cyclodextrin Inclusion Complexes

“…Similar results can be found in the literature [ 32 ]. The spectrum of ezetimibe corresponds with the literature data obtained experimentally [ 29 , 33 ]. The spectrum is characterized by the following bands: 3437.5 and 3275.2 cm −1 (O-H), 2928 cm −1 (C-H); 1730.6 cm −1 (C = O), 1509.7 cm −1 (C = C arom.…”

You cannot fight the pressure: Structural rearrangements of active pharmaceutical ingredients under magic angle spinning

“…After 88 days, an additional 1 H‐ 13 C FSLG HECTOR NMR spectrum with the same resolution in the indirect dimension revealed changes in the 1 H NMR chemical shifts. Górniak et al [ 28 ] and Knapik‐Kowalczuk et al [ 27 ] already showed by DSC that EZI has only one endothermic peak at 164°C, [ 28 ] which corresponds to the melting point, making changes due to elevated temperatures unlikely. A comparison of XRPD powder patterns (Figure 6) of EZI before MAS, which should represent the state of the initial 1 H‐ 13 C FSLG HECTOR NMR spectrum, and after MAS, representing the new spectrum, showed no differences in peak positions, so no completely new phase of EZI has formed.…”