Polymeric Amorphous Solid Dispersions of Dasatinib: Formulation and Ecotoxicological Assessment

Area of Science:

• Pharmaceutical Sciences
• Environmental Toxicology
• Materials Science

Background:

• Dasatinib (DAS), an anticancer drug, faces challenges including poor oral bioavailability and significant first-pass metabolism.
• Limited metabolism and unchanged excretion of DAS raise concerns about its environmental accumulation and ecotoxicological effects.
• Developing advanced drug delivery systems is crucial for improving therapeutic efficacy and mitigating environmental risks.

Purpose of the Study:

• To enhance the oral bioavailability and release profile of dasatinib (DAS) through formulation.
• To investigate the ecotoxicological impact of the native form of DAS on various environmental organisms.
• To assess the combined benefits of improved drug delivery and reduced environmental burden.

Main Methods:

• Amorphous solid dispersions (ASDs) of DAS were prepared using solvent-free co-grinding with polyvinylpyrrolidone (PVP) in a planetary ball mill.
• The release rate of DAS from ASD capsules was compared to capsules containing the native drug.
• Ecotoxicological effects of native DAS were evaluated using bacteria (Vibrio fischeri, Pseudomonas putida), microalgae (Chlorella sp.), and duckweed (Lemna minor).

Main Results:

• Mechanochemical activation via co-grinding successfully produced DAS-PVP amorphous solid dispersions.
• ASD capsules demonstrated a significantly enhanced release rate of DAS compared to native DAS capsules.
• Vibrio fischeri showed the highest sensitivity to native DAS, while other tested organisms exhibited negligible effects.

Conclusions:

• Amorphous solid dispersions of DAS with PVP effectively improve its release characteristics, potentially enhancing oral absorption.
• The formulation strategy offers a dual benefit of improved therapeutic delivery and reduced environmental release of the active pharmaceutical ingredient.
• Understanding and addressing the ecotoxicological profile of drugs like DAS is essential for sustainable pharmaceutical development.