Effect of formulation on the rheology of theophylline compound suspensions in Gelucires

The theophylline derivatives, etofylline, diprophylline and proxyphylline, which exhibit increasing aqueous solubility, were used to prepare suspensions in seven saturated polyglycolyzed glycerides (Gelucires) characterized by their rising hydrophilic-lipophilic balance (HLB). Drug concentration was set at 25% w/w and the production temperature was set at the Gelucire melting point plus 30 degrees C in order to obtain suitable suspensions. Various formulation factors were studied. Ostwald flow indices revealed that the suspensions had a thixotropic shear-thinning behaviour and a relative viscosity which increased as drug aqueous solubility rose and Gelucire HLB decreased. These rheological properties could be explained by the chemical composition of Gelucires and drugs used. A microstructure was proposed for the liquid suspension such that colloidal particles and aggregates formed in these suspensions directly influenced the observed rheological properties. Observation of solidified suspensions by scanning electron microscopy confirmed this hypothesis. Moreover, a correlation between the relative viscosity of drug suspensions on the one hand and drug concentration, drug solubility and Gelucire HLB on the other allowed for the calculation of the required concentration of each theophylline derivative in each Gelucire to obtain a given viscosity.