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Dynamic compatibility testing of DMP 840, an experimental antitumor agent
J T Rubino1, R Nellore, B Parmar
1DuPont Merck Pharmaceutical Company, Wilmington, DE, USA.
Summary
DMP 840, an experimental antitumor agent, can precipitate in saline and buffers. Dilution below 2 mg/mL or slow injection, and albumin presence, prevented precipitation in protein-phosphate buffer and human plasma.
Area of Science:
- Pharmaceutical Science
- Drug Formulation
- Oncology
Background:
- DMP 840 is a novel experimental antitumor agent.
- Understanding drug precipitation is crucial for safe and effective administration.
Purpose of the Study:
- To evaluate the precipitation potential of DMP 840 during injection and dilution.
- To investigate the influence of predilution and buffering on DMP 840 compatibility.
- To examine DMP 840 compatibility with normal saline, phosphate buffers, and human plasma.
Main Methods:
- In vitro compatibility studies of DMP 840 with normal saline, pH 7.4 phosphate buffers, and human plasma.
- Evaluation under static and dynamic flow conditions.
- Investigation of predilution, buffering (acetate buffer), and varying injection rates.
Main Results:
- DMP 840 formed an insoluble dihydrochloride salt in normal saline.
- Precipitation in protein-phosphate buffer (PPB) was concentration and administration rate-dependent.
- Dilution below 2 mg/mL or slow injection prevented precipitation.
- Acetate buffering improved miscibility, suggesting free base formation.
- Albumin in PPB and human plasma prevented solid phase formation.
Conclusions:
- DMP 840 precipitation is influenced by vehicle composition, concentration, and administration rate.
- Dilution and controlled injection are key to preventing precipitation.
- Protein presence, like albumin, enhances DMP 840 miscibility in biological fluids.