Pharmaceutical Technology: Controlled Drug Release, Volume 2

14
In vitro-in vivo comparison of timolol maleate release from
buffered and unbuffered matrices of monoisopropyl ester of
poly(vinyl methyl ether-maleic anhydride)
U.Finne, V.Väisänen and A. Urtti
Department of Pharmaceutical Technology, University of Kuopio, PO Box 6, 70211
Kuopio, Finland
SUMMARY
Alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) are bioerodible acidic
polymers that are used to control drug release. In biological fluids with poor buffering capacity,
drug release from the polymers and their dissolution are slowed owing to the lower pH on the
polymer surface. We studied whether the release of timolol from matrices of monoisopropyl ester
of PVM-MA in vitro and in vivo in rabbits’ eyes could be affected by disodium phosphate in the
matrices. Addition of disodium phosphate to the matrices doubled the release rate of timolol in
vitro, but it did not affect the bulk pH of the dissolution medium. On the basis of the timolol
concentrations in the tear fluid and in systemic circulation, disodium phosphate seems to
accelerate drug release in vivo also. Disodium phosphate probably affects the rate of drug release
by increasing the microenvironmental pH on the polymer surface.
INTRODUCTION
Bioerodible alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) (Fig. 1)
can be used to control drug release. Being acidic, ionizable polymers the pH of the disolution
medium affects the rate of polymer dissolution [1].
During polymer dissolution, the pH on the polymer surface decreases. This decreases the rate of
polymer dissolution. When buffer is added to dissolution medium, hydrogen ions are neutralized
by the buffer on the surface of the polymer. The buffer concentration thus affects the rates of
polymer dissolution and erosion-controlled drug release [1]. In biological fluids with poor