Critical Variables Associated with Nonbiodegradable Osmotically Controlled Implants

Abstract

Osmotically controlled implants yield precise zero-order drug delivery kinetics and are utilized in a number of applications. The implants deliver drugs for extended periods (weeks to years) and exhibit good in vivo/in vitro correlation. This paper reviews critical variables associated with these implants, with a focus on release rate testing. The extended-duration kinetics can be problematic when attempting to test for >70% cumulative delivery. An innovative scheme based on the scientific principles of operation of the system is described to ensure > 70% delivery at the target rate and duration for the DUROS Viadur (leuprolide acetate) implant.

Long-term delivery of protein therapeutics

“…Osmotically controlled, mechanical devices, “nonbiodegradable” implants have been designed for extended delivery at a constant rate. These systems have been shown to be biocompatible and effective to provide constant therapeutic concentrations in a number of animal and human trials 115-120 . Some of the osmotically-driven implants include Duros® (DURECT), ALZET® (veterinary medicine, research application) and Viadur® (leuprolide acetate, marketed formulation) 120 .…”

“…These systems have been shown to be biocompatible and effective to provide constant therapeutic concentrations in a number of animal and human trials 115-120 . Some of the osmotically-driven implants include Duros® (DURECT), ALZET® (veterinary medicine, research application) and Viadur® (leuprolide acetate, marketed formulation) 120 . Precise control over drug release for extended duration (months to year) is achieved by osmotic pressure.…”

Future of Sustained Protein Delivery

“…Non-biodegradable silicon-based polymer implants and osmotically driven implants have shown considerable promise in achieving sustained release at constant rates for several proteins and peptides [16, 17]. Although these implants are bio-compatible, a major limitation is the need for surgery to administer and remove the implants.…”

In-vitro dissolution methods for controlled release parenterals and their applicability to drug-eluting stent testing

“…An interesting alternative to accelerated dissolution testing for batch release studies of an extended release implant has been reported by Wright [43] for the Viadur implant. The osmotically‐driven device releases leuprolide acetate for the treatment of prostate cancer over a time span of approximately one year.…”