New Perspectives for Fixed Dose Combinations of Poorly Water-Soluble Compounds: a Case Study with Ezetimibe and Lovastatin

作者：Riekes Manoela K; Engelen Axel; Appeltans Bernard; Rombaut Patrick; Stulzer Hellen K; Van den Mooter Guy

来源：Pharmaceutical Research, 2016, 33(5): 1259-1275.

DOI：10.1007/s11095-016-1870-z

• co-amorphous systems
• ezetimibe
• fixed dose combinations
• lovastatin
• ternary solid dispersions

Aiming to improve the dissolution rate of ezetimibe (EZE) and lovastatin (LOV) in a fixed dose combination (FDC), co-amorphous systems and ternary solid dispersions were prepared by quench cooling and spray drying, respectively.
Formulations were characterized through X-ray diffraction, modulated differential scanning calorimetry, infrared spectroscopy, scanning electron microscopy and laser diffraction, and evaluated by 'in vitro' dissolution. Stability studies were conducted at different conditions during 30 days with the ternary solid dispersion composed of 75% of SoluplusA (R) (ELS 1:1 75%).
Single phase co-amorphous systems made up of the pure drugs were not able to increase the dissolution rate of EZE and LOV. However, ternary solid dispersions achieved high dissolution for both compounds, especially when SoluplusA (R) was used as carrier. The dissolution efficiency increased up to 18 (EZE) and 6 (LOV) times in ternary solid dispersions, compared to the crystalline drugs. ELS 1:1 75% preserved its amorphous state during 30 days, in different stability conditions.
A spray dried ternary solid dispersion able to enhance the dissolution rate of two poorly soluble, therapeutically complementary drugs, is reported for the first time. These promising results open new perspectives for the development of more advanced FDCs.

• 出版日期2016-5