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Updated: Jun 5, 2026

Preclinical Drug Testing in Scalable 3D Engineered Muscle Tissues
Published on: April 7, 2023
Effect of particle size of parenteral suspensions on in vitro muscle damage
Gayle Brazeau1, Shauna L Sauberan, Larry Gatlin
1Department of Pharmaceutical Sciences, University at Buffalo, Amherst, New York, USA.
Objective:
Suspension particle size plays a key role in the release and stability of drugs for oral and parenteral formulations. However, the role of particle size in suspension formulations on tissue damage (myotoxicity) following intramuscular (IM) injection has not been systematically investigated.
Materials And Methods:
Myotoxicity was assessed by the release of cumulative creatine kinase (CCK) from the isolated extensor digitorium longus (EDL) and soleus (SOL) rat muscles for selected suspensions of phenytoin, bupivicane and diazepam. Particle size effects on myotoxicity, independent of any specific drug, were also investigated using characterized non-dissolving polystyrene beads.
Results:
Myotoxicity was quantitated by the cumulative release of creatine kinase (CCK) from these isolated muscles over 90 or 120 min. The relationship between particle size and myotoxicity was dependent upon the drug in these suspensions. Diazepam and phenytoin suspensions were found to be less myotoxic than bupivicaine. Using unmodified and carboxy modified polystyrene beads, an optimal particle size for reduced myotoxicity following IM injection ranges from approx. 500 nm to 1 µM.
Conclusions:
The relationship between myotoxicity of IM suspensions and particle size is dependent upon the particular drug and suspension particle size.
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