Formulation analyses of high-volume prescription drugs

Abstract

A collection of 65 formulated tablets and capsules were analyzed for phase composition by full pattern matching powder diffraction methods. The collection contained 32 of the top 200 prescription drugs sold in 2016 as well as many high-volume prescriptions and over the counter drugs from prior years. The study was used to evaluate new methods of analysis as well as the efficacy of programs designed to collect references on high volume excipients and pharmaceuticals for inclusion in the Powder Diffraction File™. The use of full pattern matching methods as well as reference pattern additions of many common excipients enabled major phase excipient identification in all formulations. This included identification of crystalline, nanocrystalline, and amorphous ingredients because full pattern matching involved the use of characteristic coherent and incoherent scatter. Oftentimes identification of the major excipients significantly aided the clean identification of the active pharmaceutical ingredients (APIs) and their polymorphic form, even at low concentrations (1–10 wt. %). Overall 93% of the APIs were identified, most through a PDF®material reference, but also through patent cross-referencing and similarity analysis comparisons.

A practical guide to pharmaceutical analyses using X-ray powder diffraction

“…This combined with the increased amount of publicly available patent literature and targeted acquisition programs have resulted in very high success rates for commercial products. In the 2017–18 formulation study, we identified the API in 57 out of 60 formulations (Fawcett et al , 2019). The APIs that were identified by specific patents were provided to the ICDD editorial staff, so that these patents can be extracted for their reference data.…”

Best references for the QPA of Portland cement

“…The three methods were (1) whole pattern reference intensity ratio method (RIR), (2) Rietveld refinement, and (3) restricted parameter and block refined Rietveld refinement. The whole pattern RIR method (Fawcett et al, 2015(Fawcett et al, , 2019(Fawcett et al, , 2020 is software embedded in the PDF-4 database product line. PDF-4+ Release 2022 was used for the analysis.…”

Total pattern analyses for non-crystalline materials

“…The analysis of the weakly scattering API was made possible through the identification of the major excipients and then comparing the appropriate references to a difference pattern. This is an effective identification strategy for many pharmaceutical formulations (Fawcett et al ., 2019b). Independent of the means of identifying the amorphous material, graphic comparison can be made using the drop-down menu, shown in Figure 2.…”