Rc. Diluccio et al., SUSTAINED-RELEASE ORAL DELIVERY OF THEOPHYLLINE BY USE OF POLYVINYL-ALCOHOL AND POLYVINYL ALCOHOL-METHYL ACRYLATE POLYMERS, Journal of pharmaceutical sciences, 83(1), 1994, pp. 104-106
Crystalline polyvinyl alcohol (PVA) polymer and low-crystallinity poly
vinyl alcohol-methyl acrylate copolymer (PVA-MA) were examined as sust
ained-release tablet excipients with theophylline as a model drug. By
blending of different proportions of the crystalline polymer and the l
ow-crystallinity copolymer, it was possible to affect the release char
acteristics of the tablets. Tablets made with crystalline PVA provided
instant release of theophylline in vitro. Tablets made with a larger
proportion of PVA-MA relative to PVA provided a very prolonged release
profile in vitro. A formulation containing PVA-MA:PVA:theophylline in
a ratio of 1:9:10 provided sustained-release profiles in vitro and in
vivo in dogs. The dissolution release profile of this PVA-blend table
t formulation in vitro agreed extremely well with the percentage of bi
oavailable dose absorbed over time in vivo. The formulation provided a
plateau of levels in plasma over 16 h. The oral bioavailability of th
eophylline from this formulation in dogs was similar to 80 % and was e
quivalent to that obtained after administration of Theo-Dur, a markete
d extended-release theophylline tablet from Key Pharmaceuticals.