Quality control of pharmaceutical excipients during storage and processing
The structure of pharmaceutical excipients as a function of storage time and temperature was analyzed by small- and wide-angle X-ray scattering using the SAXSpace system.
Pharmaceutical formulation is a process in which different chemical substances (excipients), including an active pharmaceutical ingredient (API), are combined to produce a final product. Many pharmaceutical formulations contain excipients (e.g. lipids, stearates), which exhibit self- assembled, nano-sized structures and which can be easily monitored using small-angle X-ray scattering (SAXS).
Aging or disruption of the pharmaceutical product does typically not involve changes in the material’s crystalline structure (analyzed by XRD). In fact aging of the product can be rather related to changes of its self-organized, nano-sized structures, which can only be studied by SAXS.
Another important aspect for pharmaceutical production is the structural characterization of the prod-uct as a function of temperature. Structural changes, occurring during melting and recrystallization of the sample, can be studied precisely and quickly with the SAXSpace system. When operated in line-collimation mode, SAXSpace ensures that a large (i.e. representative) sample volume is irradiated and the structure of the entire sample can be analyzed. Furthermore, the measurement is not affected by air bubbles which may form during recrystallization of the molten sample.
Experimental and Results
A pharmaceutical excipient was measured with the SAXSpace system (exposure time: 5 min) before and after storage at room temperature. Significant aging effects are visible especially in the SAXS region: the scattering curve of the excipient measured after storage indicates a change of the self-assembled structure, known as lipid phase separation (Fig. 1).
Fig. 1 SWAXS curves of the excipient before (red curve) and after (blue curve) storage; aging effects are mainly visible in SAXS region.
For studying temperature-dependent structural changes, the aged excipient sample was heated above its melting point and recrystallized. The SWAXS profiles (Fig. 2) indicate no structure change, yet during recrystallization bubbles have formed in the sample holder. If the sample would have been measured in point collimation, the X-ray beam might not have hit the sample. Using line collimation, the scattering results of the sample could be obtained despite the presence of bubbles in the sample.
Fig. 2 SWAXS curves of the aged excipient (blue curve) and after recrystallization (green curve).