Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 573

Flow modulator
Drug-releasing pathway
Removable cap
Impermeable
reservoir wall
Saturated solution of
osmotic agent
Semipermeable
membrane
Flow moderator
Drug reservoir
Water entering
Figure 11.13 Schematic representation of osmotic pump, consisting of osmotic agent, drug
reservoir, semipermeable membrane, impermeable reservoir wall, and drug-releasing orifice.
Arrows indicate water inlet pathways.
the pump, enough care should be taken to avoid air inclusion. Such pumps along with a
computerized timing device have been used to deliver LHRH in a pulsatile fashion for the
treatment of infertility, and successful induction of pregnancy in patients with severe hypo-
thalamic amenorrhea has been reported [383] . Zyklomat, Siemens promedos, Sandia, and
the Medtronic systems are other examples of the peristaltic pump.
4. The Alza (now marketed by Durect Corp., Cupertino, CA) osmotic minipump (Alzet ® )
can also be implanted subcutaneously and has been widely used in research investigations
in animal models for the delivery of P/P. This pump (Figs. 11.13 and 11.14) delivers drug
under a gradient of osmotic pressure. It is a targeted drug delivery catheterized system. The
lymph nodes, tumors, ovary, eyes, kidneys, and liver are some organs which have been tar-
geted using Alzet for various drugs like LHRH, insulin, GHs, interleukins, gonadotropins,
and so on. The pump consists of a flexible impermeable diaphragm, surrounded by a sealed
layer containing an osmotic agent (e.g., salt), which is enclosed within a cellulose ester semi-
permeable membrane. The rate-determining process is the influx of water through the rigid,
external semipermeable membrane. The incoming water empties the drug-containing reser-
voir (solution or dispersion), which is surrounded by the flexible impermeable membrane.
The release rate depends upon the characteristics of this semipermeable membrane
and on the osmotic pressure difference over this membrane. Zero order kinetics exists as