Lercanidipine Hydrochloride

The International Council for Harmonisation of Tech. Requirements for Pharmaceuticals for Human Use (ICH) guidelines are commonly used in the pharmaceutical industry to assess drug degradationWhile most studies focus on anal. protocols like impurity isolation and stability assessment, they often neglect detailed structural characterization of degradants thus potentially limiting the development of new chem.The present study investigates the degradation profile of Lercanidipine hydrochloride (LER.HCl), an antihypertensive drug belonging to the calcium channel blocker class with a dihydropyridine moiety, under ICH-guided acidic hydrolytic conditions and subsequent detailed characterization of the isolated degradation products.The acid-mediated hydrolytic condition (at 60 °C for 12 h) led to degradation of LER HCl (20.3 %) to five degradation products (LER-P1- 3.2 %, LER-P2- 4.3 %, LER-P3-5.5 %, LER-P4- 2.1 % and LER-P5-5.2 %).The compounds were initially detected by a simple mass-compatible UHPLC-MS and tentatively characterized by HRMS.The reaction mixture was separated using preparative HPLC with high recovery percentage (>90 %) and their structures were characterized comprehensively using a variety of techniques including 1D (¹H, ¹³C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy, FT-IR spectroscopy, and Single Crystal X-ray Diffraction (SC-XRD).LER-P1, previously identified as a process impurity with min. characterization data, was thoroughly characterized using advanced spectroscopic techniques.Moreover, the exhaustive characterization of LER-P2, LER-P3, LER-P4, and LER-P5 (which were not reported in previous LER degradation studies) confirmed the transformation of dihydropyridine ring to cyclohexenone with multiple chiral centers under acidic hydrolysis.The proposed mechanisms rationalized all structures, aiming to connect the thorough characterization of new degradation products with their transformation process.The present study provides a guideline about systematic investigations of the stress-induced degradation of pharmaceutical candidates.

Chronic inflammation is a well-recognized contributor to hypertension pathogenesis. However, the role of targeting inflammation in hypertension treatment, particularly through modulation of inflammatory markers like interleukin-6 (IL-6), remains less understood. We investigated the effects of antihypertensive medications with and without IL-6-lowering properties on long-term blood pressure (BP) control in a multi-ethnic cohort in the Netherlands.

Participants from HELIUS cohort receiving hypertension treatment were followed over six years. BP control at follow-up was determined using WHO criteria. Due to unavailability of IL-6 data, a literature review was conducted to classify antihypertensives based on their IL-6-lowering properties - a proxy approach. Logistic regression models were used to assess associations between the IL-6-lowering potential of antihypertensives and BP control, both within and between antihypertensive classes. Effect modification by ethnicity was explored.

A total of 1510 participants were included (mean age 57 years, 62 % women). Within the calcium channel blocker (CCB) class, medications with IL-6-lowering properties (amlodipine and barnidipine) were associated with superior BP control (aOR 1.41, 95 % confidence interval 1.05-1.90) compared to other CCBs (lercanidipine, nifedipine, verapamil, clevidipine, diltiazem). No significant associations were observed within angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs), between different antihypertensive drug classes, nor across ethnic groups.

Amlodipine and barnidipine were associated with better BP control compared to other CCBs. Our findings provide an important starting point for understanding the role of IL-6 in hypertension management. Further studies are warranted to confirm these observations by directly measuring IL-6 levels and investigating underlying mechanisms.