Stress Degradation Studies of Ramipril by a Validated Stability-Indicating Liquid Chromatographic Method

Abstract

Ramipril is an angiotensin-converting enzyme inhibitor which has chemical structure susceptible to degradation, therefore in this work forced degradation studies of ramipril were carried out by a developed and validated stability-indicating liquid chromatographic method. Stress testing was performed on drug substance under hydrolysis (0.1 N HCl, water and 0.1 N NaOH), oxidation (3% H 2 O 2 ), heat (70ºC) and photolysis (UV and VIS radiation). The drug was degraded under acidic, neutral, alkaline, oxidation and thermal stress conditions but it was stable under photolysis. Chromatographic separation of ramipril from its degradation products was achieved on a RP-18 column, using a mobile phase consisting of methanol -tetrahydrofuran -phosphate buffer (pH 2.4; 0.01M) (55:5:40, v/v/v) at a flow rate of 1.0 mL min −1 and UV detection at 215 nm. The assay was linear for ramipril concentrations of 50-300 µg/mL. The developed method was stability indicating, specific, accurate and precise for ramipril determination. This method was used to quantify ramipril in tablets. The results showed that the method described here is suitable for quantitative determination and the stability study of ramipril.

The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products

“…The exact molecular weight may be obtained using this method for RMP before and after exposure to the heating stress induced by HME. As an example, as shown in Figure 3a, the mass spectrum of pure RMP was tested after thermal treatment at 100°C for two hours on a hotplate, considered to be similar to the HME The trace in the positive mode ionisation showed the presence of a peak with a molecular ion at m/z 399.2291 (elemental composition C 23 H 31 N 2 O 4 calculated with +/-0.7mDa accuracy, Figure 3b) matching the formula of the suggested RMP degradation product (RMP-DKP) (Angeli and Trezza, 2009;De diego et al, 2010;Hogan et al, 2000).…”

“…In this work, we report, for the first time, the development of inline Raman spectroscopic analysis in combination with multivariate data analysis to monitor RMP drug content and RMP degradation product during HME processing. In the literature, several studies have shown RMP instability at different pH values, and under application of heat stress is ramipril-diketopiperazine (RMP-DKP) (De diego et al, 2010). Due to thermal sensitivity, RMP processing by HME represents a real challenge.…”

Palm Kernel Meal Activated Carbon via Glass Wool-Pyrolysis Method for Ceftriaxone Adsorption

“…Roca et al (2011) suggest that β-lactam antibiotics such as CFT will undergo thermal decomposition gradually at a temperature of 60°C-100°C following pseudo-firstorder kinetics. Meanwhile, at room temperature (23 ± 2°C), structurally, CFT is very stable for up to 4 days (De Diego et al, 2010). However, in the acid-base treatment, there were (hyperchromic and bathochromic) shifts in the peak of the CFT, which indicated that it was unstable (Figure 4).…”

Development and Validation of Stability-Indicating Ultra High-Performance Liquid Chromatography for Ramipril Analysis in Pharmaceutical Dosage Forms and its Application in Lipid-based Formulations

“…Partition coefficient (log p) of RMP is 3.41 and its pka is 3.17. RMP is a highly challenging compound which poses stability problems in acidic and alkaline media and it is sensitive to heat, moisture and mechanical stress [8][9][10] .…”