A formulation comparison, using a solution and different nanosuspensions of a poorly soluble compound.
The pharmacokinetic parameters of AZ68 administered as a solution have been compared with those from an amorphous and a crystalline nanosuspension using rats as in vivo specie. All formulations were administered intravenously (i.v.) and orally. The purpose of the study was to find out if the three different formulations were comparable and safe to administer. The results indicate that AZ68 is absorbed at a lower rate for crystalline nanosuspensions compared to amorphous nanosuspensions and solutions. However, the absorbed extent of the compound is similar. The results are a consequence of the lower solubility and the slower dissolution rate for crystalline material compared to amorphous substance in the gastrointestinal tract. The dissolution process is excluded for a solution, resulting in the fastest absorption rate. No significant difference was found between pharmacokinetic parameters when comparison was made between the formulations after i.v. administration. There were no adverse events observed after i.v. administration of the nanosuspensions.
Sigfridsson
Kalle
K
Pharmaceutical and Analytical R&D, AstraZeneca R&D Mölndal, Mölndal, Sweden. carl-gustav.sigfridsson@astrazeneca.com
Forssén
Sara
S
Holländer
Paula
P
Skantze
Urban
U
de Verdier
Jennie
J
D000818:Animals; D001391:Azo Compounds / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013696:Temperature; D014867:Water / Q000737:chemistry
D001391:Azo Compounds; D014867:Water