Hydroxypropyl methylcellulose (hypromellose) is a widely known excipient commonly used in the preparation of drug formulations. It can interact with some active pharmaceutical ingredients (APIs), thereby contributing to a reduction in crystallinity, serve as a solvent for API or form stable dispersion with no tendency to aggregation. The aim of the present study was to investigate the effect of hypromellose on the solubility, miscibility and amorphization of paracetamol in mixture with this polymer. Homogenized mixtures of paracetamol with hypromellose were studied using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier transform infrared (FT-IR) and Raman methods to obtain a deeper insight into the interactions between ingredients in solid state including phase diagram construction for crystalline API and amorphous polymer. A DSC study revealed potential interaction between ingredients resulting in reduced paracetamol crystallinity. This was proved using heating-cooling-heating test to confirm paracetamol amorphization. FT-IR and Raman investigations excluded chemical reaction and hydrogen bonding between ingredients. The phase diagram developed facilitates predictions on the solubility of API in polymer, on the mutual miscibility of ingredients and on the temperature of mixture glass transition.

As amorphization may improve the solubility and bioavailability of a drug substance, the aim of this work was to assess to what extent the crystallinity of caffeine (CAF) and theophylline (TF) can be reduced by homogenization with a polymeric excipient. To realize this purpose, the physical mixtures of both methylxanthines with hydroxypropyl methylcellulose (HPMC) were examined using differential scanning calorimetry (DSC), hot-stage microscopy (HSM), Fourier-transform infrared (FTIR) and Raman spectroscopy. Moreover, phase diagrams for the physical mixtures were calculated using theoretical data. Results of DSC experiments suggested that both CAF and TF underwent amorphization, which indicated proportional loss of crystallinity for methylxanthines in the mixtures with HPMC. Additionally, HSM revealed that no other crystalline or amorphous phases were created other than those observed for CAF and TF. FTIR and Raman spectra displayed all the bands characteristic for methylxanthines in mixtures with HPMC, thereby excluding changes in their chemical structures. However, changes to the intensity of the bands created by hydrogen bonds imply the formation of hydrogen bonding in the carbonyl group of methylxanthines and the methyl polymer group. This is consistent with data obtained using principal component analysis. The findings of these studies revealed the quantities of methylxanthines which may be dissolved in the polymer at a given temperature and the composition at which methylxanthines and polymer are sufficiently miscible to form a solid solution.

Reliable interpretation of the changes occurring in the samples during their heating is ensured by using more than one measurement technique. This is related to the necessity of eliminating the uncertainty resulting from the interpretation of data obtained by two or more single techniques based on the study of several samples analyzed at different times. Accordingly, the purpose of this paper is to briefly characterize thermal analysis techniques coupled to non-thermal techniques, most often spectroscopic or chromatographic. The design of coupled thermogravimetry (TG) with Fourier transform infrared spectroscopy (FTIR), TG with mass spectrometry (MS) and TG with gas chromatography/mass spectrometry (GC/MS) systems and the principles of measurement are discussed. Using medicinal substances as examples, the key importance of coupled techniques in pharmaceutical technology is pointed out. They make it possible not only to know precisely the behavior of medicinal substances during heating and to identify volatile degradation products, but also to determine the mechanism of thermal decomposition. The data obtained make it possible to predict the behavior of medicinal substances during the manufacture of pharmaceutical preparations and determine their shelf life and storage conditions. Additionally, characterized are design solutions that support the interpretation of differential scanning calorimetry (DSC) curves based on observation of the samples during heating or based on simultaneous registration of FTIR spectra and X-ray diffractograms (XRD). This is important because DSC is an inherently non-specific technique. For this reason, individual phase transitions cannot be distinguished from each other based on DSC curves, and supporting techniques are required to interpret them correctly.

The aim of this study was to learn to what extent the selected instrumental techniques, differential scanning calorimetry (DSC), as well as Fourier-transform infrared (FTIR) and Raman spectroscopies, can be used to detect both organic or inorganic magnesium compounds in the dietary supplements and medicinal products. Besides magnesium compounds as the active pharmaceutical ingredients (APIs), the preparations contain also other organic and inorganic APIs and several excipients. The study will be extended over the analysis of the products manufactured by various firms but containing the same API at different levels. In this way, it will be possible to assess the impact of excipients on the DSC scans and the FTIR and Raman spectra of a dominant constituent present in a studied preparation. The study on thirty commercially available dietary supplements and medicinal products has shown that in the majority of cases the DSC, FTIR and Raman techniques could be used for the detection of APIs in these commercial products. This was possible with the aid of the endothermic DSC peaks and the so-called matching factors of the FTIR and Raman spectra to those of substances used as standards. Both the complex composition and low levels of API in the studied preparations have been identified as the factors which have a strong impact on the usefulness of the three techniques for the detection of APIs in the dietary and medicinal products.

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.