Drug solubilization behavior during in vitro digestion of suspension formulations of poorly water-soluble drugs in triglyceride lipids.

PURPOSE

The purpose of this study was to characterize the solubilization and precipitation characteristics of a range of poorly water-soluble drugs during the in vitro digestion of long-chain or medium-chain triglyceride (TG) lipid suspension formulations.

METHODS

TG suspensions of model drugs (present at double their equilibrium solubilities in the respective lipid) were digested in vitro and the drug solubilization and precipitation pattern in the resulting digests analyzed.

RESULTS

For griseofulvin, diazepam, and danazol, solubilization of the small mass of drug originally presented in the TG lipid was efficient with only a small proportion of the dose precipitating and being recovered in the pellet phase after digestion of the TG lipid. For the more lipophilic and lipid-soluble drugs (cinnarizine, halofantrine), in which higher drug loadings were possible, significant enhancement in drug solubilization in the postdigestion aqueous phase was not apparent compared with simple TG lipid solutions.

CONCLUSIONS

Suspensions of drugs, which are poorly soluble in water and TG lipid, may prove beneficial as the relatively high solubilizing capacity of the colloidal phases produced on TG digestion will likely exceed the mass of drug that could have been administered as a simple lipid solution. However, for more lipid-soluble drugs, suspension formulations may offer little benefit as sufficiently high drug loadings can otherwise be achieved with simple solution formulations that still provide for adequate solubilization after TG digestion.