Alzet osmotic pumps

1. ALZET osmotic pumps
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ALZET osmotic pumps
The ALZET pumps are miniature, implantable infusion devices which are intended to continuously
deliver a solution over a given duration at a constant rate.
They offer a simple, convenient and reliable alternative to repetitive injections, which require
frequent animal handling.
Itisthesmall,infusionpumpsforcontinuousdosingofunrestrainedlaboratoryanimals.
➢ Alzet® osmotic pump, as indicated by its name, was a system developed by Alza
Corporation for experimental research.
➢ The osmotic delivery device is based on Higuchi–Theeuwes pump design.
➢ It became available for investigational use in the mid-1970s, and researchers used it
routinely in the screening of active agents, animal toxicology and pharmacology, and
initial clinical testing, creating new therapeutic options.
Design:
Fig. Cross-section of ALZET osmotic pump showing the principle of the functioning.

2. ALZET osmotic pumps
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Empty reservoir within the core of the pump is filled with the drug or hormone solution to be
delivered and is surrounded by salt chamber with impermeable layer between them. It is self
powered by osmotic displacement, there is no batteries, no electronics and moving parts.
The internal reservoir is filled with the solution to be delivered. The external chamber has a high
salt concentration and pulls water through the outer, semipermeable surface, pushing the drug
solution out through the exit port.
Mechanism of drug release:
They are composed of a drug core (reservoir), the osmotic agent, and the semipermeable
membrane (rate controller). In addition, a flow moderator is inserted into the body of the osmotic
pump after filling. It is a type of implantable or insertable system in which the active agent is a
solution or suspension contained in a cylindrical reservoir formed from a synthetic, collapsible,
impermeable elastomer wall (e.g., polyester) that is open to the external environment via a single
orifice.
When the osmotic pump is subcutaneously implanted at the desired site of the body, the water
content in the tissue fluid will penetrate through the semipermeable membrane at a controlled
rate and dissolve the osmotically active agent. Osmotic pressure (compression of flexible
reservoir) is produced in the narrow spacing between the flexible reservoir wall and the rigid
semipermeable compartment. The reservoir is gradually reduced in volume and the solution of
the active agent is forced to exit through the flow moderator and deliver the drug at a controlled
rate.
Flow rate regulation:
➢ The first step in formulating a test solution to be administered is to decide on the dose or
hourly mass flow of test material we wish to deliver.
➢ To cut the mass flow rate in half, use half the concentration;
➢ to double the mass flow rate, use twice the concentration, etc.
➢ The highest mass flow of test material that the pump can deliver is set by the maximum
solubility of the test agent in its vehicle (saturated solution) at the temperature of loading
(usually room temperature, or about 23º C).

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➢ The amount of agent (µg/hr) that a pump delivers can be adjusted by altering the
concentration of agent in the test solution.
➢ agents, enzyme inhibitors, and gastrointestinal modulators).
Vehicle selection:
When planning the administration of a given compound, it is important to select the optimum
vehicle. This choice of solvent should include the following considerations:
• Solubility of the agent to be delivered.
• Compatibility with the interior reservoir of the pump.
• Compatibility with tissues or fluids at the site of administration.
• Stability of the compound/vehicle solution for the duration of the experiment (if possible, vehicle
control studies are recommended).
• Sterility.
Commonly used solvents known to be compatible with ALZET pumps:
• Acids, with pH greater than 1.8
• Bases, with pH less than 14
• Cremophor EL, up to 25% in water
• Culture media (1% benzyl alcohol as bacteriostatic)
• Cyclodextrins
• Dextrose, up to 5%, in water or NaCl
• N,N-Dimethyl formamide (DMF), up to 25% in water
• DMSO, up to 50% in water or polyethylene glycol
• DMSO, up to 50% in ethanol (< or =15%) and water
• Ethanol, up to 15% in water
• Glycerol
• 1-Methyl-2-Pyrrolidone, up to 12.5% in water
• Phosphate buffer
• Polyethylene glycol 300 or 400, neat or in water

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• Propylene glycol, neat or in water
• Ringer’s solution (with or without lactate)
• Saline, 0.9% (or other aqueous salt solution)
• Serum (rat, mouse, etc.)
• Solutol, up to 30% in water
• Triacetin, up to 5% in water
• Tween 80, up to 2%
• Water, distilled.
The Flow Moderator
The flow moderator is not a flow regulator and it has no role in determining the pumping rate of
an ALZET Osmotic Pump.
The flow moderator has several important roles:
• After the pump is filled, the insertion of the flow moderator helps to displace any air trapped
within the pump reservoir. This is essential because all air must be evacuated in order for the
pump to function correctly.
• More importantly, the flow moderator restricts diffusion of the agent from the exit portal, thereby
assuring osmotic control of delivery.
• The flow moderator also acts as an internal splint (support) around which the drug reservoir can
be compressed without obstructing outflow.
Advantages:
• Ensure around – the –clock exposure to test agents at predictable levels.
• Permit continuous administration of short half life proteins and peptides.
• Convenient method for chronic dosing of laboratory animals.
• Minimize unwanted experimental variables and ensure reproducible, consistent results.
• Eliminate the need for night time or week end dosing.
• Reduce handling and stress to laboratory animals.
• Small enough for use in mice or very young rats.
• Allow for targeted delivery of agents to virtually any tissue.

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• Cost effective research tool.
• Convenient, reliable, and cost-effective alternative to chronic injections.
• Continuous delivery ensures constant compound levels in plasma or tissues for
maximized therapeutic efficacy and reduced adverse effects.
• No external connections or researcher intervention required during infusion.
• Save time by eliminating the need for frequent animal handling and repetitive injection
schedules.
• ALZET mini pumps are available in small sizes for use in mice and young rats (bigger
sizes available for rats and larger animals).
Different types, reservoir capacities, and delivery rates of ALZET® osmotic pumps:
They have capsular shape and are available in a variety of sizes, and it is possible to relate
the delivery rates with the reservoir capacities.
Type Capacity Delivery rate (μl/h) Period of delivery
1003D 100 μl 1.0 3 days
1007D 100 μl 0.5 1 week
1002 100 μl 0.25 2 weeks
1004 100 μl 0.11 4 weeks
2001 200 μl 1.0 1 week
2001D 200 μl 8.0 1 day

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2002 200 μl 0.5 2 weeks
2004 200 μl 0.25 4 weeks
2006 200 μl 0.15 6 weeks
2ML1 2 ml 10 1 week
2ML2 2 ml 5.0 2 weeks
2ML4 2 ml 2.5 4 weeks
Application:
➢ To deliver drugs, hormones and other test agents continuously at controlled rates from
one day to six weeks.
➢ Many active agents have been delivered by the Alzet® system (e.g., amino
acids, anesthetics, antibiotics, antibodies, anticancer agents, anticoagulants, anti-
epileptics, antigens, antihypertensives, anti-parasitic agents, anti-Parkinson agents, ascitic
fluid, catecholamines, chelators, cholinergics, central nervous system acting
agents, enzyme inhibitors, and gastrointestinal modulators.
DUROS INFUSION IMPLANT