An approach for predicting the true density of powders based on in-die compression data

• Published in: International journal of pharmaceutics Vol. 637; p. 122875
• Main Authors: Elsergany, Ramy N., Vreeman, Gerrit, Sun, Changquan Calvin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.04.2023
• Subjects: Helium; Helium pycnometry; In-die Py; Powders; Pressure; Stress transmission coefficient; Tablets - chemistry; True density; Water-containing materials; In-die Py; True density; Helium pycnometry; Water-containing materials; Stress transmission coefficient
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2023.122875

[Display omitted] Helium pycnometry, a commonly used technique for measuring the true density of powders, is sensitive to the release of volatiles during measurement. This can lead to over-estimated true density, and as such, an accurate method for determining the true density of powders containing volatile components is needed. Here, a method based on in-die compression data obtained with a compaction simulator was assessed. Specifically, the stress transmission coefficient (STC), measured using an instrumented die, was used to predict the in-die Heckel mean yield pressure (Py). A true density was derived by repeatedly performing a Heckel analysis using iteratively estimated true density values until the predicted Py value from the measured STC value is obtained from in-die density - pressure data. This novel method was validated using a set of water-free powders. Using crystalline hydrates, we further showed that the calculated true densities were closer to values calculated from crystal structure than those from helium pycnometry. Hence, this method may be used for determining the true density of powders from their STC values.