KINETICS OF PROTEIN DIFFUSION FROM A POLY(D,L-LACTIDE) RESERVOIR SYSTEM

The release kinetics of albumin diffusion from a poly(D, L‐lactide) reservoir system was investigated with the long‐term aim of developing a multidose pulsatile delivery system. Albumin pellets were coated with polylactide of varying viscosity‐average molecular weight, M̄v and concentration, and incubated in aqueous solution. The albumin release profile was approximated by zero‐order release kinetics, with release rates ranging from 3 to 1800 mg/day. The permeability of the poly(D, L‐lactide) membranes to albumin diffusion ranged from 1 × 10−9 to 100 × 10−9 cm2/s, and was found to decrease with increasing membrane thickness (18 to 1400 μm) and density (300 to 3000 mg/cm3). The initiation of albumin release from the pellets could be delayed from a few hours to more than one month by increasing the M̄v of the polylactide from 6.2 × 103 to 140 × 103 and raising the concentration of the polymer coating solution from 50 to 100 mg/mL. The diversity in delayed‐release effect and the variations in membrane permeabilities were attributed to changes in membrane porosity and polymer morphology. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company