Development of a 100 mg theophylline sustained release formulation using POVIAC polymer for infants

Resumen

The goal of the present work is the development of an oral pharmaceutical formulation of theophylline in tablets and with a 100 mg dosis of active principle, suitable for preventive use in the treatment of infants who suffer from asthma. A polyvinylacetate polymer (POVIAC 0) with a very high purity and an appropriate molecular mass is used as the unique component of the release regulating matrix. The in-vitro theophylline release kinetics of different formulations were followed. The tablets were prepared in accordance with a 23 experimental design using mixtures of two granulates with different composition of theophylline and in POVIAC 0. The independent variables of the design were X1 (polymer content of the granulate with lower polymer content), X2 (polymer content of the granulate with higher polymer content), X3 (fraction of the total mass of the formulation that corresponds to the polymer lower content granulate. The release kinetics of two prestigious pharmaceutical sustained release commercial formulations (Theo-Dur from Key Pharmaceuticals and Slo-Bid from Rhone Poulenc) were also followed for comparison. Two formulations were also prepared by using only one granulate in their composition. Each of these two granulates presented a polymer content equal to the polymer average content of the two formulations of the mentioned design with the closest similar release kinetics to the Slo-Bid formulation. One of these formulations showed a very good release kinetics. Single and multiple dosis in vivo experiments on Beagle dogs (n = 8) and human volunteers (n = 8) were performed. The results, although should be considered as preliminary on account of the relative reduced number of subjects studied, have shown themselves as highly satisfactory.