Sustained-release oral delivery of theophylline by use of polyvinyl alcohol and polyvinyl alcohol-methyl acrylate polymers.
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.
DiLuccio
R C
RC
Experimental Station, DuPont Merck Pharmaceutical Co., Wilmington, DE 19880-0400.
Hussain
M A
MA
Coffin-Beach
D
D
Torosian
G
G
Shefter
E
E
Hurwitz
A R
AR
D000042:Absorption; D000179:Acrylates; D000284:Administration, Oral; D000818:Animals; D003460:Crystallization; D003692:Delayed-Action Preparations; D004285:Dogs; D005260:Female; D011142:Polyvinyl Alcohol; D013806:Theophylline / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000179:Acrylates; D003692:Delayed-Action Preparations; D011142:Polyvinyl Alcohol; D013806:Theophylline; C035956:methyl acrylate