Elevate drug performance with XRPD insights
Amorphous solid dispersions (ASDs) offer a promising approach to enhance the bioavailability of drugs made with poorly water-soluble active pharmaceutical ingredients (APIs). However, a major challenge in formulating ASDs lies in maintaining the long-term physical stability of the amorphous state.
On October 24, we will host an “Ask an Expert!” webinar featuring Alex Mathers from UCT Prague. Mathers will present a case study on the characterization and stability assessment of polyvinyl alcohol (PVA)-based ASDs, emphasizing the crucial role of X-ray powder diffraction (XPRD) as an analytical technique.
Read this blog for an introduction to this research, and register for the webinar if you would like to learn more – such as the importance of phase diagram construction, and the influence of water uptake on the long-term physical stability of ASDs.
Why crystallinity matters to drug performance
ASDs consist of APIs dispersed in a polymer matrix, typically in an unstable amorphous form. In this state, drugs are more soluble and have greater bioavailability, making them easier for the body to absorb. However, when the amorphous form recrystallizes—where its atomic and molecular structures shift into a more ordered arrangement—bioavailability decreases.
Therefore, understanding and evaluating the stability of ASDs is a key concern in pharmaceutical formulation. In his study, Mathers investigated the long-term stability of two APIs—indomethacin (IND) and naproxen (NAP)—in PVA-based dispersions with differing glass-forming abilities (GFA). GFA reflects how easily a compound forms an amorphous structure, making this experiment valuable for predicting whether an API will remain amorphous or recrystallize over time.
The strength of XRPD for pharmaceutical applications
XRPD is a powerful technique for analyzing the structure of crystalline materials. When X-rays are directed at a powdered sample, they scatter in various directions upon interacting with the atoms in the crystal matrix. By measuring the angles and intensities of the scattered X-rays, the atomic arrangement of the material can be determined.
One of the key advantages of XRPD is its non-destructive nature, enabling multiple assessments of the same sample during stability studies. This capability provides a dynamic perspective on the amorphous-to-crystalline transformation without altering the sample itself. In long-term studies, such as the one presented by Dr. Mathers, where samples are analyzed over 12 to 24 months, the ability of XRPD to monitor changes in physical stability without damaging the sample is invaluable.
Key insights provided by XRPD
Mathers employed XRPD to differentiate between amorphous and crystalline phases. The analysis confirmed that indomethacin remained entirely amorphous in PVA extrudates, even at high API concentrations of up to 50%, after 24 months of storage. In contrast, naproxen showed significant recrystallization.
As a complement to the XRPD analyses, differential scanning calorimetry (DSC) was used to quantify these phases over time. The results indicated that 22.5–23.5% of the amorphous naproxen remained in each of the samples after 12 months, providing a clear and quantifiable measure of recrystallization. Such insights can assist researchers in adjusting formulation parameters to mitigate crystallization.
Conclusions from the case study
XRPD is a powerful tool for distinguishing between amorphous and crystalline phases, quantifying recrystallization, and providing non-destructive analyses. In this case study, XRPD played a crucial role in assessing the stability of PVA-based solid dispersions of indomethacin and naproxen, offering valuable insights into their behavior and informing formulation adjustments to enhance stability.
With XRPD, the development of more stable and effective ASD formulations becomes more precise and predictable, ultimately leading to improved therapeutic outcomes.
To learn more about Mathers’ case study and the advantages of XRPD, register for our upcoming Ask an Expert webinar!