At the Respiratory Drug Delivery (RDD) conference in April 2020, Quotient Sciences [1] presented a poster describing the development of an X-ray diffraction (XRD) method for the quantification of active pharmaceutical ingredient (API) recrystallized from amorphous API in a low-dose dry powder inhaler (DPI) formulation.
Amorphous APIs are thermodynamically unstable and prone to recrystallization over time or upon exposure to humidity, which can significantly affect the efficacy of a product. For formulations containing amorphous APIs, ICH guidelines dictate that acceptance criteria must be determined for the polymorph content of the API. While it is relatively straightforward to identify the crystalline content of an API in isolation using XRD, it is challenging when the API is in a formulation with other excipients.
In this study, a model DPI formulation was developed containing a low dose of an amorphous API that is known to recrystallize under certain conditions. To quantify the degree of crystalline API, spiked samples containing mixtures of amorphous and crystalline API in different ratios were prepared. During the method development, different sample sizes and analysis times were evaluated. XRD analysis was performed using a Panalytical X’Pert Pro instrument, with a copper radiation source and X-Celerator detector. Data analysis was performed using the HighScore software.
The data generated in this study demonstrated that a relatively simple XRD method for the detection and quantification of very low levels of recrystallized API can be developed and validated. In the future, this will be a useful tool to support the development of low-dose DPI formulations and characterize the physical form of the API.
Poster authors
1. Martin Wing-King, Jason Gray, Yuncheng Yan, Jose Ruiz, and Bildad Nyambura
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