Carmen Cristescu

Comparative Solid-State Stability of Perindopril Active Substance vs. Pharmaceutical Formulation

This paper presents the results obtained after studying the thermal stability and decomposition kinetics of perindopril erbumine as a pure active pharmaceutical ingredient as well as a solid pharmaceutical formulation containing the same active pharmaceutical ingredient (API). Since no data were found in the literature regarding the spectroscopic description, thermal behavior, or decomposition kinetics of perindopril, our goal was the evaluation of the compatibility of this antihypertensive agent with the excipients in the tablet under ambient conditions and to study the effect of thermal treatment on the stability of perindopril erbumine. ATR-FTIR (Attenuated Total Reflectance Fourier Transform Infrared) spectroscopy, thermal analysis (thermogravimetric mass curve (TG—thermogravimetry), derivative thermogravimetric mass curve (DTG), and heat flow (HF)) and model-free kinetics were chosen as investigational tools. Since thermal behavior is a simplistic approach in evaluating the thermal stability of pharmaceuticals, in-depth kinetic studies were carried out by classical kinetic methods (Kissinger and ASTM E698) and later with the isoconversional methods of Friedman, Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa. It was shown that the main thermal degradation step of perindopril erbumine is characterized by activation energy between 59 and 69 kJ/mol (depending on the method used), while for the tablet, the values were around 170 kJ/mol. The used excipients (anhydrous colloidal silica, microcrystalline cellulose, lactose, and magnesium stearate) should be used in newly-developed generic solid pharmaceutical formulations, since they contribute to an increased thermal stability of perindopril erbumine.

Perindopril Induces TSP-1 Expression in Hypertensive Patients with Endothelial Dysfunction in Chronic Treatment

Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment. As a conclusion, patients under treatment with Perindopril had increased plasma levels of TSP-1 compared with other hypertensive patients and with the control group. The results of this study confirms the pleiotropic properties of Perindopril: anti-proliferative, anti-inflammatory, with effects showed by quantifying a single biomarker: TSP-1.

Short-term rosuvastatin therapy influence on restored endothelial function in hypertensive patients

Methods: 47 patients with essential hypertension received 20 mg respectively 10 mg of rosuvastatin depending on the degree of endothelial dysfunction, the ADMA levels and ??respectively the values of carotid IMT. Endothelium-dependent flow-mediated vasodilatation (FMD), plasma ADMA levels and carotid ITM were determined. Results: At 6 months the rosuvastatin therapy, FMD was improved in both groups (p < 0,001), dependent on the dose after the first 3 months. A decreased a plasma ADMA levels and values of carotid IMT were found in patients who received 20 mg rosuvastatin. We found a medium statistically negative correlation between the %FMD changes and the plasma ADMA changes (for the first group p 1⁄4 0, 0125 and r 1⁄4 0, 5121; for the second group p1⁄4 0, 0058 and r 1⁄4 0, 5455), respectively between the FMD changes and the carotid IMT changes (for the first group p 1⁄4 0, 0152 and r 1⁄4 0, 4998, for the second group p 1⁄4 0, 0000 and r 1⁄4 0, 8000). Between the values of carotid IMT-changes and the plasma ADMA changes levels we found a medium statistically positive correlation after 6 months of treatment (for the first group p 1⁄4 0, 0376 and r 1⁄4 0, 4359, for the second group p1⁄4 0, 0101 and r 1⁄4 0, 5136). Conclusion: Short-term rosuvastatin therapy contributes in essential hypertensive patients with endothelial dysfunction to a significant increase % FMD and reduction on ADMA levels and carotid IMT progression.