Date Published: May 15, 2019
Publisher: Springer International Publishing
Author(s): Przemysław Talik, Joanna Piotrowska, Urszula Hubicka.
The aim of the study was to examine the influence of non-freezing water (NFW) contents bound to hydroxypropyl methylcellulose (HPMC) or hydroxypropyl cellulose (HPC) binary mixtures using acetylsalicylic acid (ASA) as a model moisture-sensitive ingredient. Polysaccharides with significantly different physicochemical properties were mixed with acetylsalicylic acid at a ratio 1:1 (w/w). The measurements of NFW contents of hydrated samples were carried out using differential scanning calorimetry (DSC). In the method used, the dry mass normalized dependency of melting enthalpy (ΔH) and respective contents of water was found to be linear. NFW values were calculated after extrapolation ΔH to 0. For stability studies, HPC/ASA and HPMC/ASA mixtures were stored at 40°C and 75% RH for 5 weeks in the climatic chamber. The ASA hydrolysis was investigated using UV-Vis spectrophotometry. The amounts of NFW calculated for raw HPMC 3 cP and 100,000 cP were 0.49 and 0.42 g g−1, while for polymer and ASA mixtures, prepared from HPC type LF (126 cP) and MF (6300 cP) as well as from HPMC 3 cP and 100,000 cP were 0.23, 0.28 g g−1, 0.21 g g−1, and 0.33 g g−1 respectively. The measured NFW values were connected with appropriate concentrations of unhydrolyzed ASA.
Chemical stability is an important factor of the drug quality because it is directly related to purity, efficacy, and safety of pharmacotherapy. In most drugs, the stability of a medicinal product as a whole depends not only on the properties of the active pharmaceutical ingredient (API), but also on the formulation and/or method of manufacture. One of the most important concepts in drug design is understanding the intrinsic stability of the API molecule and its degradation pathways. The most frequently encountered mechanism of drug degradation is hydrolysis, oxidation, and to some extent, photolysis (1). However, in multi-component heterogeneous systems, the degradation of the API can be more complex and may be the result of more than one factor – for example, hydrolysis with further oxidation, or vice versa . It can be also possible that interactions between API molecules and excipients may be non-specific and thus less understandable. For that reason, drug stability is a constant interest of many research teams [2–6].
A section of typical DSC curve showing crystallization and melting events, obtained from hydrated raw hydroxypropyl methylcelluloses 3 cP is shown in Fig. 1.Fig. 1A representative DSC curve of crystallization and melting of hydroxypropyl methylcelluloses (3 cP) sample
In this study, we examined the influence of viscosity and contents of non-freezing water on the stability of acetylsalicylic acid as a model moisture sensitive ingredient.