DSC, FT-IR and NIR with Chemometric Assessment Using PCA and HCA for Estimation of the Chemical Stability of Oral Antidiabetic Drug Linagliptin in the Presence of Pharmaceutical Excipients

Abstract

Pharmaceutical excipients should not interact with active substances, however, in practice, they sometimes do it, affecting the efficacy, stability and safety of drugs. Thus, interactions between active substances and excipients are not desirable. For this reason, two component mixtures of oral antidiabetic drug linagliptin (LINA) with four excipients of different reactivity, i.e., lactose (LAC), mannitol (MAN), magnesium stearate (MGS) and polyvinylpyrrolidone (PVP), were prepared in a solid state. A high temperature and a high humidity of 60 °C and 70% RH, respectively, were applied as stressors in order to accelerate the potential interactions between LINA and excipients. Differential scanning calorimetry (DSC) as well as Fourier transform infrared (FT-IR) and near infrared (NIR) spectroscopy were used to estimate the changes due to potential interactions. In addition, chemometric computation of the data with principal component analysis (PCA) and hierarchical cluster analysis (HCA) was applied to adequately interpret the findings. Of the excipients used in the present experiment, all of them were not inert in relation to LINA. Some of the interactions were shown without any stressing, whereas others were observed under high-temperature/high-humidity conditions. Thus, it could be concluded that selection of appropriate excipients for LINA is very important question to minimize its degradation, especially when new types of formulations with LINA are being developed and manufactured.

Compatibility study of mirtazapine with several excipients used in pharmaceutical dosage forms employing thermal and non-thermal methods

“…2a) does not reveal the presence of new signals that cannot be attributed to either MRTHH or pure Lact. In addition to the signals of the API's, a few peaks specific to the excipient [37] are worth mentioning, such as the sharp signal determined by the stretch of the O-H bonds (3522 cm −1 ), as well as the intense band seen at 1031 cm −1 associated with the stretching vibration of the C-O-C bonds.…”

“…In the case of the MRTHH + MgSt mixture, the FTIR spectrum (Fig. 2c) displays the characteristics of the components, the most intense spectral signals being correlated to the presence of the excipient [37]. These include the stretching vibrations of the C-H bonds (2916 and 2851 cm −1 ), as well as the vibrations associated with the carboxylate ion group (1574 and 1456 cm −1 ).…”

Modafinil-excipient compatibility study using differential scanning calorimetry

“…[ 22 ] However, there are many published articles concerning its incompatibility with pharmaceutical ingredients due to its hydrophobic nature, the presence of the positively charged magnesium ion, and its strong surface energetic behavior. [ 23 24 25 ] Gelucire 48/16 is a member of the Gelucire family, is a mixture of mono, di, and triglycerides with PEG esters of fatty acids, working as nonionic surfactants and used in lipid-based formulations to increase solubility and bioavailability of poorly soluble drugs. [ 26 ] However, there is a lack of research data regarding their compatibility behavior toward drugs.…”