- Mitigation of radiation myelopathy and reduction of microglial infiltration by Ramipril, ACE inhibitor. [Journal Article]
- SCSpinal Cord 2018 Jun 14
- CONCLUSIONS: Ramipril reduced the rate of paralysis even at the paralysis-inducing radiation doses. It also significantly delayed the onset of paralysis. Neuroinflammation and endothelial cell damage may be the key mediators of radiation injury. Ramipril can be readily translatable to clinical application as a mitigatory of radiotherapeutic toxicity.
- Challenges in Simultaneous Determination of Hydrochlorothiazide and Ramipril in Human Plasma: Application to a Bioequivalence Study SHRHPB. [Journal Article]
- JCJ Chromatogr Sci 2018 Jun 12
- An isotope dilution selective and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method has been developed for the simultaneous determination of hydrochlorot...
An isotope dilution selective and sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method has been developed for the simultaneous determination of hydrochlorothiazide (HCTZ) and ramipril in human plasma through a new concept of periodical polarity switching. Extraction of HCTZ, ramipril and their deuterated analogs as internal standards (ISs) was carried out from 150 μL of human plasma by solid-phase extraction method. Chromatographic separation of analytes was performed on Hypurity C18 (150 mm × 4.6 mm, 5 μ) column under gradient conditions with methanol:0.2% (v/v) formic acid in water as the mobile phase. The method was validated over a concentration range of 0.750-300 ng/mL for HCTZ and 0.125-80.0 ng/mL for ramipril. The mean extraction recovery for analytes and ISs were >(86.0%), consistent across all four QC levels. The challenges to evaluate matrix effect and continuous reproducibility of method during long analytical run was studied and resolved. Processed samples, freeze-thaw, long-term and whole blood stability were evaluated for both the analytes. The method was applied to support a bioequivalence study of 25 mg of HCTZ and 5 mg of ramipril tablet formulation in nine healthy Indian subjects. Assay reproducibility was demonstrated by reanalysis of 42 incurred samples.
- Natural deep eutectic solvents as eco-friendly and sustainable dilution medium for the determination of residual organic solvents in pharmaceuticals with static headspace-gas chromatography. [Journal Article]
- JPJ Pharm Biomed Anal 2018 Jun 04; 158:262-268
- Reported here is a simple and rapid static headspace gas chromatography (SHS-GC) method for the determination of trace solvents including ethanol, isopropanol, n-butanol, 1,4-dioxane, tetrahydrofuran...
Reported here is a simple and rapid static headspace gas chromatography (SHS-GC) method for the determination of trace solvents including ethanol, isopropanol, n-butanol, 1,4-dioxane, tetrahydrofuran, acetonitrile, methanol and acetone which commonly used in drug production process. Natural deep eutectic solvents (NADESs) are firstly used as the matrix medium for this method, which provided high sensitivity for residual solvents detection. With the optimized method, validation experiments were performed and the data showed excellent linearity for all the solvents (R2 ≥ 0.999, n = 7). The limits of detection (LOD) for ethanol, isopropanol, n-butanol, 1,4-dioxane, tetrahydrofuran, acetonitrile, methanol and acetone are 0.09, 0.08, 0.07, 0.11, 0.06, 0.10, 0.12 and 0.08 μg g-1, respectively. Accuracy was checked by a recovery experiment at three different levels, and the recoveries of the tested solvents were ranged from 94.3% to 105.4%. The relative standard deviation (RSD) of each solvent for intra- and inter-day precision is in the range of 0.85 to 3.65 and 1.51 to 4.53, respectively. The developed approach can be readily used for determination of the residual solvents in six active pharmaceutical ingredients including pramipexole dihydrochloride, rivaroxaban, lisinopril, ramipril, imatinib mesylate and sitagliptin.
- Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial. [Journal Article]
- PlosPLoS One 2018; 13(6):e0196962
- CONCLUSIONS: In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction.
- The binding of Captopril to Angiotensin-I Converting Enzyme triggers signaling pathways activation. [Journal Article]
- AJAm J Physiol Cell Physiol 2018 Jun 06
- Hypertension is a global health problem and ACE inhibitors are largely used to control this pathology. Recently, it has been shown that ACE can also act as a transducer signal molecule when its inhib...
Hypertension is a global health problem and ACE inhibitors are largely used to control this pathology. Recently, it has been shown that ACE can also act as a transducer signal molecule when its inhibitors or substrates bind to it. This new role of ACE could contribute to understanding some of the effects not explained by its catalytic activity only. In this study we investigated signaling pathways activation in Chinese hamster ovary (CHO) cells stably expressing ACE (CHO-ACE) under different treatments. We also investigated gene modulation after 4h and 24h captopril treatments. Our results demonstrated that CHO-ACE cells when stimulated with AngI, ramipril or captopril led to JNK and ERK1/2 phosphorylation. To verify any physiological role at endogenous level we made use of primary cultures of mesangial cells from spontaneously hypertensive rats (SHR) and Wistar rats. Our results showed that ERK1/2 activation occurred only in primary cultures of mesangial cells from SHR rats upon captopril stimulation suggesting that this signaling pathway is differentially regulated during hypertension. Our results also showed that captopril treatment leads to decrease of COX2, interleukin 1β and β-arrestin 2 gene expression level.Our findings strengthen the fact that in addition to the blockage of enzymatic activity, ACE inhibitors also trigger signaling pathways activation and this may contribute to their beneficial effects in the treatment of hypertension and other pathologies.
- Achieved diastolic blood pressure and pulse pressure at target systolic blood pressure (120-140 mmHg) and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials. [Journal Article]
- EHEur Heart J 2018 Jun 04
- CONCLUSIONS: Compared to a DBP of 70 to <80 mmHg, lower and higher DBP was associated with a higher risk in patients achieving a SBP of 120 to <140 mmHg. Associations of DBP and PP to risk were similar notably at controlled SBP. These data suggest at optimal achieved SBP, risk is still defined by low or high DBP. These findings support guidelines which take DBP at optimal SBP control into consideration.
- Effects of the concomitant administration of xanthine oxidase inhibitors with zofenopril or other ACE-inhibitors in post-myocardial infarction patients: a meta-analysis of individual data of four randomized, double-blind, prospective studies. [Journal Article]
- BCBMC Cardiovasc Disord 2018 Jun 05; 18(1):112
- CONCLUSIONS: Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.
- A comparative study between hot-melt extrusion and spray-drying for the manufacture of anti-hypertension compatible monolithic fixed-dose combination products. [Journal Article]
- IJInt J Pharm 2018 Jul 10; 545(1-2):183-196
- The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (F...
The purpose of this work was to investigate the application of different advanced continuous processing techniques (hot melt extrusion and spray drying) to the production of fixed-dose combination (FDC) monolithic systems comprising of hydrochlorothiazide and ramipril for the treatment of hypertension. Identical FDC formulations were manufactured by the two different methods and were characterised using powder X-ray diffraction (PXRD) and modulated differential scanning calorimetry (mDSC). Drug dissolution rates were investigated using a Wood's apparatus, while physical stability was assessed on storage under controlled temperature and humidity conditions. Interestingly both drugs were transformed into their amorphous forms when spray dried, however, hydrochlorothiazide was determined, by PXRD, to be partially crystalline when hot melt extruded with either polymer carrier (Kollidon® VA 64 or Soluplus®). Hot melt extrusion was found to result in significant degradation of ramipril, however, this could be mitigated by the inclusion of the plasticizer, polyethylene glycol 3350, in the formulation and appropriate adjustment of processing temperature. The results of intrinsic dissolution rate studies showed that hot-melt extruded samples were found to release both drugs faster than identical formulations produced via spray drying. However, the differences were attributable to the surface roughness of the compressed discs in the Wood's apparatus, rather than solid state differences between samples. After a 60-day stability study spray dried samples exhibited a greater physical stability than the equivalent hot melt extruded samples.
- Low temperature fused deposition modeling (FDM) 3D printing of thermolabile drugs. [Journal Article]
- IJInt J Pharm 2018 Jul 10; 545(1-2):144-152
- Fused deposition modelling (FDM) is the most commonly investigated 3D printing technology for the manufacture of personalized medicines, however, the high temperatures used in the process limit its w...
Fused deposition modelling (FDM) is the most commonly investigated 3D printing technology for the manufacture of personalized medicines, however, the high temperatures used in the process limit its wider application. The objective of this study was to print low-melting and thermolabile drugs by reducing the FDM printing temperature. Two immediate release polymers, Kollidon VA64 and Kollidon 12PF were investigated as potential candidates for low-temperature FDM printing. Ramipril was used as the model low melting temperature drug (109 °C); to the authors' knowledge this is the lowest melting point drug investigated to date by FDM printing. Filaments loaded with 3% drug were obtained by hot melt extrusion at 70 °C and ramipril printlets with a dose equivalent of 8.8 mg were printed at 90 °C. HPLC analysis confirmed that the drug was stable with no signs of degradation and dissolution studies revealed that drug release from the printlets reached 100% within 20-30 min. Variable temperature Raman and solid state nuclear magnetic resonance (SSNMR) spectroscopy techniques were used to evaluate drug stability over the processing temperature range. These data indicated that ramipril did not undergo degradation below its melting point (which is above the processing temperature range: 70-90 °C) but it was transformed into the impurity diketopiperazine upon exposure to temperatures higher than its melting point. The use of the excipients Kollidon VA64 and Kollidon 12PF in FDM was further validated by printing with the drug 4-aminosalicylic acid (4-ASA), which in previous work was reported to undergo degradation in FDM printing, but here it was found to be stable. This work demonstrates that the selection and use of new excipients can overcome one of the major disadvantages in FDM printing, drug degradation due to thermal heating, making this technology suitable for drugs with lower melting temperatures.
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- PATHOMORPHOLOGY OF THE MYOCARDIUM, KIDNEY AND LIVER IN SPONTANEOUSLY HYPERTENSIVE RATS TREATED WITH SHORT AND LONG-TERM USE RAMIPRIL AND CANDESARTAN. [Journal Article]
- GMGeorgian Med News 2018; (276):135-143
- Choosing a method of treating arterial hypertension remains an urgent problem today. For effective therapy, it is necessary to select hypotensive drugs that not only effectively reduce the pressure, ...
Choosing a method of treating arterial hypertension remains an urgent problem today. For effective therapy, it is necessary to select hypotensive drugs that not only effectively reduce the pressure, but also contribute to the restoration of the structure of tissues sensitive to oscillations of arterial pressure. The purpose of this study was to conduct a comparative analysis of the effect of angiotensin 2-candesartan receptor antagonist and angiotensin converting factor ramipril on pathomorphological changes in the myocardium, kidney, and liver in SHR lines that received treatment for 7 days (short) and 21 days (prolonged therapy ) The study was conducted on 20 spontaneously hypertensive rats with a mass of 248.0-441.0 g. The rabbit was administered at a dose of 5 mg / kg and candesartan 4 mg / kg, respectively. The period of short-term therapy was 7 days and long-term-21 days. For the evaluation of morphological changes in the heart, kidney, liver, frozen cross sections were stained using Ramonovsky-Giemsa method (H and E). The data obtained indicate a more significant effect of candesartan on myocardium and kidney. Ramipril had a negative effect on the renal tubules, increasing the degree of atrophy. Treatment with ramipril and candesartan, especially with long-term use, reduced the hydropic swelling of hepatocytes.