DSC, FT-IR, NIR, NIR-PCA and NIR-ANOVA for determination of chemical stability of diuretic drugs: impact of excipients

Abstract

It is well known that drugs can directly react with excipients. In addition, excipients can be a source of impurities that either directly react with drugs or catalyze their degradation. Thus, binary mixtures of three diuretics, torasemide, furosemide and amiloride with different excipients, i.e. citric acid anhydrous, povidone K25 (PVP), magnesium stearate (Mg stearate), lactose, D-mannitol, glycine, calcium hydrogen phosphate anhydrous (CaHPO4) and starch, were examined to detect interactions. High temperature and humidity or UV/VIS irradiation were applied as stressing conditions. Differential scanning calorimetry (DSC), FT-IR and NIR were used to adequately collect information. In addition, chemometric assessments of NIR signals with principal component analysis (PCA) and ANOVA were applied.Between the excipients examined, lactose and starch did not show any interactions while citric acid, PVP, Mg stearate and glycine were peculiarly operative. Some of these interactions were shown without any stress, while others were caused or accelerated by high temperature and humidity, and less by UV/VIS light. Based on these results, potential mechanisms for the observed interactions were proposed Finally, we conclude that selection of appropriate excipients for torasemide, furosemide and amiloride is an important question to minimize their degradation processes, especially when new types of formulations are being manufactured.

Active Neutralizing Mats for Corrosive Chemical Storage

“…The major thermal transitions of all compounds are presented in Table 2 , including the thermal behavior of MIRCAP CT 85-H. When compared to pure citric acid [ 32 ], MIRCAP CT 85-H DSC curve presents two extra peaks, at 58.6 °C and 420.9 °C, attributed to the melting and decomposition, respectively, of hydrogenated palm oil used in the encapsulation process. It was also observed that due to the presence of hydrogenated palm oil, the citric acid decomposition of MIRCAP CT 85-H started approximately 10 °C above the decomposition temperature of pure citric acid.…”

Starch Nanoparticles for Enhancement of Oral Bioavailability of a Newly Synthesized Thienopyrimidine Derivative with Anti-Proliferative Activity Against Pancreatic Cancer

“…It was observed that the two endothermic peaks of the physical mixture sample showed significant inconsistency with samples before the mixing. Such broadening observed in the physical mixture spectrum may be due to the interactions between the hydrogen bonding between OH (hydrogen donor) of starch, and hydrogen bond acceptors in the pyrimidine and piperazine rings of the TPD, 89 , 90 which in turn increase moisture content. It was reported that increasing moisture content results in decreasing the peak temperature of the starch.…”

An Insight into the Degradation Processes of the Anti-Hypertensive Drug Furosemide

“…Starch, which is highly hygroscopic, can absorb water and be a reservoir of water for hydrolysis processes [ 20 , 21 ]. To complicate the scenario, other excipients, such as lactose, magnesium stearate, and talc, could react with molecules containing amino groups and cause a browning phenomenon [ 22 , 23 , 24 , 25 , 26 ], as well as cocrystallization with compounds such as urea [ 27 ].…”