MODELING OF THEOPHYLLINE COMPOUND RELEASE FROM HARD GELATIN CAPSULES CONTAINING GELUCIRE MATRIX GRANULES

Hard shell capsules containing four theophylline compounds of different solubilities (theophylline, etofylline, diprophylline and proxyphylline) were prepared with saturated polyglycolysed glycerides (Gelucires) of melting point above 45-degrees-C and HLB value below 10. A polyvalent formulation was obtained after granulation by melting and congealing and use of glyceryl behenate (Compritol) as a lubricant of the solidified suspensions. The best yields of granulation were obtained with Gelucires 64/02, 54/02 and 50/02. The influence of three parameters was studied: melting point and HLB of the Gelucires, as well as drug solubility. Drug release was found to increase as the melting point decreased and as HLB and drug solubility rose. Theophylline showed abnormal behaviour because the length of its needle-like crystals reduced its capacity for inclusion in the fatty matrix. Multiple linear regression was used to evaluate the influence of the three formulation parameters and thus confirmed the validity of the mathematical model initially formulated for tablets made with the same granules.