Sustained-release oral delivery of theophylline by use of polyvinyl alcohol and polyvinyl alcohol—methyl acrylate polymers

✍ Scribed by Robert C. Diluccio; Munir A. Hussain; David Coffin-Beach; George Torosian; Eli Shefter; Arthur R. Hurwitz

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 292 KB
• Volume: 83
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600830124

✦ Synopsis

Crystalline polyvinyl alcohol (PVA) polymer and low-crystallinity polyvinyl alcohol-methyl acrylate copolymer (PVA-MA) were examined as sustained-release tablet excipients with theophylline as a model drug. By blending of different proportions of the crystalline polymer and the low-crystallinity copolymer, it was possible to affect the release characteristics 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 tablet formulation in vitro agreed extremely well with the percentage of bioavailable dose absorbed over time in vivo. The formulation provided a plateau of levels in plasma over 16 h. The oral bioavailability of theophylline from this formulation in dogs was approximately 80% and was equivalent to that obtained after administration of Theo-Dur, a marketed extended-release theophylline tablet from Key Pharmaceuticals.