3PC-034 Development of a density measurement protocol for injectable sterile drugs: application to amsacrine in a hospital pharmacy
Year: 2025
Type: conference-paper
Abstract: Background and Importance Gravimetric Control (GC) is an in-and post-process control technique used for monitoring the preparation of sterile injectable drugs. However, it requires precise data on the density of molecules, which are not always available in the summary of product characteristics or from pharmaceutical laboratories. Aim and Objectives Hospital pharmacies may need to perform these density measurements themselves. This study aims to develop an accurate, and reproducible density measurement protocol, suitable for use in hospital pharmacies, using amsacrine as an example. Material and Methods The measurement method using a pycnometer (PYC) (monograph 2.2.5 ‘density measurement’, Ph. Eur., 11th ed.) was chosen. A PYC (Megal) and a precision balance (QUINTIX) were used. The density (ρ = m/V) was determined by weighing a 25 mL sample. The relative density (da) of the samples was obtained using the formula da = ρa/ρWFI, after measuring the density of water for injectable preparations (WFI). Measurements performed on amsacrine solutions (Amsalyo 75 mg, 1.5 mg/mL) were compared to five standard solutions (0.9% NaCl, 5% and 30% Dextrose (Dex), Methanol (MeOH), Dichloromethane (DCM)) and repeated 3 times at fixed temperature. Results The protocol implemented produced results consistent with expected values (calculated mean density vs theoretical density) for the standard solutions (0.9% NaCl : 1.006 vs 1.005; 5% Dex: 1.019 vs 1.020; 30% Dex: 1.113 vs 1.112; MeOH: 0.796 vs 0.790; DCM : 1.332 vs 1.330), thus validating our method. Measurements performed on amsacrine solutions determined a density of 1.001. This result is consistent with the excipient composition of Amsalyo (lactic acid and WFI). Density measurement using a PYC is a simple technique, but it requires a significant volume of solution, considerable execution time (5 min/sample), and adequate protection against the risk of chemical contamination (CC). In comparison, the hydrometer method presents similar drawbacks, requiring a larger volume and offering lower precision. Using an electronic densimeter would allow for faster, serial measurements, with less risk of CC, but it comes with a high cost (€3,000 vs €35 for a PYC). Conclusion and Relevance Our study, conducted in the context of GC within a sterile drug production unit, allowed the establishment of a simple and reliable protocol suitable for occasional measurements. References and/or Acknowledgements Conflict of Interest Corporate sponsored research or other substantive relationships: Lucane Pharma
Authors: M Wang, M Sangnier, A Berroneau, G Bougueon
Institution: Centre Hospitalier Universitaire de Bordeaux
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
OpenAlex ID: W4408376013