The pH-dependent biphasic release of azidothymidine from a layered composite of PVA disks and P(MMA/MAA) spheres.
A composite device was developed to provide a biphasic drug release using poly(vinyl alcohol) (PVA) and poly(methylmethacrylate-co-methacrylic acid) (P(MMA/MAA)) spheres. Azidothymidine (AZT), an anti-HIV agent with a short biological half-life, was used as the model drug. Dynamic and equilibrium swelling of the polymers, and kinetics of AZT release from these polymers were determined in pH 1.2 and 6.8 buffer solutions. The swelling of PVA and release of AZT from PVA disks were fast and nearly pH-independent, whereas the swelling behavior and drug release kinetics of P(MMA/MAA) spheres were strongly pH-dependent. A swelling interface number for the spheres at pH 6.8 was determined to be Sw&z.Lt;1 and time dependent. Nevertheless, Fickian diffusion might also contribute to the drug release in this system. The composite disks consisting of PVA matrix and P(MMA/MAA) spheres provided prolonged (over 20 h) and more steady release profiles, differing profoundly from individual components. Such release profiles resulted from the second phase release at pH 6.8 and the presence of PVA layer. The relative drug loading in the matrix could be tailored to produce release profiles varying from a distinct bimodal release to a pseudo zero-order release with an initial burst.
Huang
J
J
Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.
Kao
H
H
Wu
X Y
XY
D000042:Absorption; D000465:Algorithms; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000737:chemistry*; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008863:Microspheres; D010316:Particle Size; D011109:Polymethacrylic Acids; D011142:Polyvinyl Alcohol; D012995:Solubility; D015215:Zidovudine / Q000008:administration & dosage* / Q000737:chemistry*
D019380:Anti-HIV Agents; D005079:Excipients; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D015215:Zidovudine; D011142:Polyvinyl Alcohol