V. Ratsimbazafy et al., EFFECT OF FORMULATION ON THE RHEOLOGY OF THEOPHYLLINE COMPOUND SUSPENSIONS IN GELUCIRES, Journal of Pharmacy and Pharmacology, 49(9), 1997, pp. 852-857
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.