BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Typical Release Profiles Surface eroding bulk eroding Fig. 2. Kinetics of hydrocortisone telease from a half esterified copolymer of meth Tme(days) ether and maleic anhydride from disks placed in the lower conjunctival cul-d k abstance fr(▲▲ PL-LAca,(■PLA rabbits. Devices removed at periodie intervals and residual hydrocortisone deter microspheres with a L-LA/XO molar ratio of 9o10 Garcia et al. Corresponding RATES: ON BOARD Surface eroding bulk eroding Release Cent) Toxic dose dc(t) dc(t) PARADOX: zero-order release best obtained from surface-erodiing devices, but polymers with surface erosion mode typically also degrade very quickly-often too fast for the timescales of most interest Factors Controlling Release 1. Erosion mechanism i. PH/hydrophobic contacts can cause protein degradation, aggregation, and denaturation 2. Device microstructure i. Burst effect often seen- controversy as to whether this is near-surface entrapped drug or surface adsorbed drug Lecture 5- Controlled Release Devices 7 of 14BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Typical Release Profiles: Surface eroding bulk eroding (Garcia et al.6 ) • Corresponding RATES: ON BOARD: Surface eroding: bulk eroding: Release Release rate rate dc(t) dc(t) ceff(t) dt dt Toxic dose t t t • PARADOX: zero-order release best obtained from surface-erodiing devices, but polymers with surface erosion mode typically also degrade very quickly- often too fast for the timescales of most interest Factors Controlling Release: 1. Erosion mechanism i. PH/hydrophobic contacts can cause protein degradation, aggregation, and denaturation 2. Device Microstructure i. Burst effect often seen- controversy as to whether this is near-surface entrapped drug or surface￾adsorbed drug7 Lecture 5 – Controlled Release Devices 7 of 14