EFFECT OF FORMULATION ON THE RHEOLOGY OF THEOPHYLLINE COMPOUND SUSPENSIONS IN GELUCIRES

The theophylline derivatives, etofylline, diprophylline and proxyphyll ine, which exhibit increasing aqueous solubitity, were used to prepare suspensions in seven saturated polyglycolysed glycerides (Gelucires) characterized by their rising hydrophilic-lipophilic balance (HLB). Dr ug 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 obtai n suitable suspensions. Various formulation factors were studied. Ostw ald flow indices revealed that the suspensions had a thixotropic shear -thinning behaviour and a relative viscosity which increased as drug a queous solubility rose and Gelucire HLB decreased. These rheological p roperties could be explained by the chemical composition of Gelucires and drugs used. A microstructure was proposed for the liquid suspensio n such that colloidal particles and aggregates formed in these suspens ions directly influenced the observed rheological properties, Observat ion of solidified suspensions by scanning electron microscopy confirme d this hypothesis. Moreover, a correlation between the relative viscos ity of drug suspensions on the one hand and drug concentration, drug s olubility and Gelucire HLB on the other allowed for the calculation of the required concentration of each theophylline derivative in each Ge lucire to obtain a given viscosity.