Controlled drug delivery devices for experimental ocular studies with timolol 1. In vitro release studies

Abstract

Controlled drug delivery devices which can be easily tailored and conveniently prepared to release ocular drugs at specified controlled rates can be useful in studies of ocular drug delivery and drug response. The devices were fabricated by injecting 6.0, 9.0 or 12.5 μl of aqueous borate buffered solutions of timolol (2.5–20.0 mg ml ) into end-plugged pieces of silicone tubing and the release of timolol was studied in vitro. An initial lag in timolol release was avoided by storing the devices for an appropriate time (3–9 h) after filling the devices. The appropriate storage time was dependent on the steady-state flux of timolol, indicating that timolol was binding to the silica filler in the silicone tubing. Timolol was released at a constant rate (0.7–7.2 μg h ) for 8 h from the devices when the initial core pH was 8.64 and when the devices were stored for an appropriate time before an experiment. The steady-state release rate of timolol was increased 2.4-fold when the pH inside the device was increased from 8.34 to 9.24, As expected, the observed release rate increased with increased drug concentration in the device core and with increased length of the device. The permeability of timolol in the silicone membrane walls was 2.48−6.03 × 10 −9 cm 2 s −1 depending on the composition of the inner core solution. Thickness of the end-plugs (0.5 or 3.5 mm) did not affect timolol release from the devices, when the volume of timolol solution in the devices was 12.5 μl.