Predicting capsule fill weight from in-situ powder density measurements using terahertz reflection technology

Sandra Stranzinger, Eva Faulhammer, Jingyi Li, Runqiao Dong, J. Axel Zeitler, Stefano Biserni, Vittorio Calzolari, Johannes G. Khinast, Daniel Markl

Research output: Contribution to journalArticle

Abstract

The manufacturing of the majority of solid oral dosage forms is based on the densification of powder. A good understanding of the powder behavior is therefore essential to assure high quality drug products. This is particularly relevant for the capsule filling process, where the powder bulk density plays an important role in controlling the fill weight and weight variability of the final product. In this study we present a novel approach to quantitatively measure bulk density variations in a rotating container by means of terahertz reflection technology. The terahertz reflection probe was used to measure the powder density using an experimental setup that mimics a lab-scale capsule filling machine including a static sampling tool. Three different grades of α-lactose monohydrate excipients specially designed for inhalation application were systematically investigated at five compression stages. Relative densities predicted from terahertz reflection measurements were correlated to off-line weight measurements of the collected filled capsules. The predictions and the measured weights of the powder in the capsules were in excellent agreement, where the relative density measurements of Lactohale 200 showed the strongest correlation with the respective fill weight (R 2 =0.995). We also studied how the density uniformity of the powder bed was impacted by the dosing process and the subsequent filling of the holes (with excipient powder), which were introduced in the powder bed after the dosing step. Even though the holes seemed to be filled with new powder (by visual inspection), the relative density in these specific segments were found to clearly differ from the undisturbed powder bed state prior to dosing. The results demonstrate that it is feasible to analyze powder density variations in a rotating container by means of terahertz reflection measurements and to predict the fill weight of collected capsules.

LanguageEnglish
Article number100004
Number of pages8
JournalInternational Journal of Pharmaceutics: X
Volume1
Early online date4 Jan 2019
DOIs
Publication statusE-pub ahead of print - 4 Jan 2019

Fingerprint

Powders
Capsules
Technology
Weights and Measures
Specific Gravity
Excipients
Dosage Forms
Lactose
Inhalation

Keywords

  • capsule filling process
  • PAT
  • powder bulk density
  • terahertz technology

Cite this

Stranzinger, Sandra ; Faulhammer, Eva ; Li, Jingyi ; Dong, Runqiao ; Zeitler, J. Axel ; Biserni, Stefano ; Calzolari, Vittorio ; Khinast, Johannes G. ; Markl, Daniel. / Predicting capsule fill weight from in-situ powder density measurements using terahertz reflection technology. In: International Journal of Pharmaceutics: X. 2019 ; Vol. 1.
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Predicting capsule fill weight from in-situ powder density measurements using terahertz reflection technology. / Stranzinger, Sandra; Faulhammer, Eva; Li, Jingyi; Dong, Runqiao; Zeitler, J. Axel; Biserni, Stefano; Calzolari, Vittorio; Khinast, Johannes G.; Markl, Daniel.

In: International Journal of Pharmaceutics: X, Vol. 1, 100004, 31.12.2019.

Research output: Contribution to journalArticle

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AU - Faulhammer, Eva

AU - Li, Jingyi

AU - Dong, Runqiao

AU - Zeitler, J. Axel

AU - Biserni, Stefano

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AU - Markl, Daniel

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