title: Effect of particle size of parenteral suspensions on in vitro muscle damage.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, Amherst, New York, USA.
authors.forename: Gayle
authors.initials: G
authors.lastname: Brazeau
authors.forename: Shauna L
authors.initials: SL
authors.lastname: Sauberan
authors.forename: Larry
authors.initials: L
authors.lastname: Gatlin
authors.forename: Peter
authors.initials: P
authors.lastname: Wisniecki
authors.forename: Jaymin
authors.initials: J
authors.lastname: Shah
mesh_terms: D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000633:toxicity*; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000008:administration & dosage / Q000633:toxicity*; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D053758:Nanoparticles; D010316:Particle Size; D010672:Phenytoin / Q000008:administration & dosage / Q000633:toxicity*; D011137:Polystyrenes / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013535:Suspensions; D013997:Time Factors
chemical_list: D011137:Polystyrenes; D013535:Suspensions; D010672:Phenytoin; D003402:Creatine Kinase; D003975:Diazepam; D002045:Bupivacaine