Abstract
In this study, the phase diagram of the ternary system of ezetimibe–simvastatin–fenofibrate was established. It has been proven that the ternary composition recommended for the treatment of mixed hyperlipidemia forms a eutectic system. Since eutectic mixtures are characterized by greater solubility and dissolution rate, the obtained result can explain the marvelous medical effectiveness of combined therapy. Considering that another well-known method for improving the aqueous solubility is amorphization, the ternary system with eutectic concentration was converted into an amorphous form. Thermal properties, molecular dynamics, and physical stability of the obtained amorphous system were thoroughly investigated through various experimental techniques compared to both: neat amorphous active pharmaceutical ingredients (considered separately) and other representative concentrations of ternary mixture. The obtained results open up a new way of selecting the therapeutic concentrations for combined therapies, a path that considers one additional variable: eutecticity.
Highlights
Mixed hyperlipidemia is a significant risk factor for the development of cardiovascular diseases.[1]
One can distinguish (i) statins, which inhibit 3hydroxy-3-methylglutaryl coenzyme A reductase, and thereby block the cholesterol synthesis;[4,5] (ii) fibrates, which activate peroxisome proliferator-activated receptors leading to induce the transcription of genes facilitating lipid metabolism;[6] and (iii) cholesterol absorption inhibitors working in the intestinal brush border membrane such as ezetimibe (EZB).[7]
The obtained results together with the differential scanning calorimetry (DSC) curves of neat active pharmaceutical ingredients (APIs) are presented in panels a, c, and e of Figure 2
Summary
Mixed hyperlipidemia is a significant risk factor for the development of cardiovascular diseases.[1] Dietary modification and increased physical activity are the first recommended therapy to modify the abnormal level of the lipids in the bloodstream.[2] in many cases, lifestyle changes are not enough to overcome this problem. Besides a healthy diet, regular physical activity, alcohol abstinence, and smoking cessation, the use of lipid-lowering drugs is needed.[3]. There are many active pharmaceutical ingredients (APIs) reducing the level of serum triglycerides and cholesterol. Combined drug therapy is recommended.[9]
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