Journal of Medical Engineering & Technology

ISSN: 0309-1902 (Print) 1464-522X (Online) Journal homepage: http://www.tandfonline.com/loi/ijmt20

Design and performance of the implantable osmotic minipump R. Capozza, B. Eckenhoff & S. I. Yum To cite this article: R. Capozza, B. Eckenhoff & S. I. Yum (1977) Design and performance of the implantable osmotic minipump, Journal of Medical Engineering & Technology, 1:5, 281-283, DOI: 10.3109/03091907709162196 To link to this article: http://dx.doi.org/10.3109/03091907709162196

Published online: 09 Jul 2009.

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These results need to be approachecl with some caution ;ince the accuracy of any extrapolation from rats to iumans is by no means certain. These results also assume hat a chance contact of only a few square millimetres is htained and maintained for sufficient time for the burn o occur. However, bearing in mind these reservations t appears that “isolated” output equipment could give -ise to a greater burns hazard under normal conditions han the conventional diathermy, even though the risks Nith a broken plate lead would be greatly reduced. The ‘isolated” output accidental currents are proportional to ‘requency and therefore can be reduced by dropping the ’requency of operation as far as possible. A limit is set 2t about 300 kHz since below this frequency neural stimulation can occur. Even then it appears that an solated output machine whilst giving a considerably -educed risk of serious burns, can give an increased risk 3f small burns. REFERENCE

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1. Dobbie, A . K. (1969). The electrical aspects of surgical diathermy. Bio-Mediral Eljgi/weri/jg, 4 , 5 . 206-21 6 .

saturated with 5-fluorouracil’ and implanted in mice have achieved sustained delivery effects. In other studies, drugs contained within a Silastic tube or in the form of a solid pellet were implanted in animals. Monolithic polymer-drug mixtures also have been described as implant delivery systems? These drug delivery systems have several drawbacks : (1) it is difficult to predict accurately the pumping rate and amount of agent delivered; (2) the systems have a utility limited to a small number of drugs; (3) reproducibility of results with identical systems is low; and (4) the route of administration is limited for a given system. The advent of Alzet* osmotic minipumps has greatly reduced most of the above problems and limitation^.^-^ Minipumps are programmed to deliver small amounts of biologically active agents constantly and continuously over periods ranging from several hours to weeks. The device makes it possible to predict the amount of active agent delivered and the pumping rate at any given time of actual use. By means of minor surgical procedures, the filled device can be placed in the peritoneal cavity or subcutaneous sites in mice or larger experimental animals; with use of a catheter, drugs can be delivered to specific target tissues, for example ventricles, veins, eye or uterus. Osmosis offers several attractive features as a pumping principle. Unlike electro-mechanical and mechanical energy, utilisation of osmotic energy does not require any transduction, and is controllable by membrane water permeation. Thus, chemical energy lends itself to the designing of a portable delivery system that has 3 relatively small mass and volume in relation to deliverable volume. -,

‘Alzet is a registered trademark o f A l z a Corporation, Polo Alto. Califnriiia 94304. USA.

Design and performance of the implantable osmotic minipump R. Capozza, B. Eckenhoff and S. I. Yum Alza Corporatiori, 950 Page Mill Road, Palo Alto, C A 94304, USA.

When it is necessary to administer small doses of an active agent to laboratory animals over a prolonged period, it is generally more efficacious and convenient to administer the agent continuously instead of intermittently. Several methods used to achieve prolonged delivery of various agents have been described.1-4 For instance, Hydron films

Scheniatic Representation of the Osmotic Pump

flow m o d e r a t o r

Fig. 1. Schematic representaiiori o / the osniotic p u m p . September, 1977

filling tube

Fig. 2. Compotienis o f the osmotic minipump.

28 I

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Osmotic pumps of different designs have been described i n the literature.R Most consist of a semipermeable memOsmotic Minipump in Use brane for selective transport of water, an osmotic agent, a drug reservoir, a deformable or movable partition between the osmotic agent and the drug reservoir, and a delivery orifice (Figure I ) . The flux of water into the osmotic agent compartment is controlled by the membrane; pressure is exerted on the partition, and the con:cn:s of the drug reservcir zre de!ivered through the orifice. Theoretically, the drug reservoir contents are pumped out at a rate equivalent to water permeation across the semipermeable membrane. If osmotic activity and temperature of the environment where the device is placed remain constant, the pumping rate of the system will be constant. The pumping rate is dependent primarily on the water permeation coefficient and surface area of the membrane, and the osmotic pressure of the osmotic agent . The osmotic minipump consists of a reservoir made from a synthetic elastomer, an osmotic energy source, which is an inorganic salt, and a rate-controlling membrane, which is a cellulosic material. The flow moderator and the filling tube materials are stainless steel 316. The minipump's external dimensions are 2.5 cm length and 0.6 cm diameter; the reservoir volume is 170 p1 and the nominal pumping rate is 1.0 pl/hr in isotonic saline at 37°C (Figure 2). Nominal internal dimensions of the drug reservoir are 0.36 cm diameter and 1.70 cm depth. The dimensions and performance specifications were derived from: (1) the available size of subcutaneous and intraperitoneal spaces of small mice; and (2) the average Fig. 4. The nsmnric miriipump in USC. duration of animal investigations, for example, in cancer research, and amount of various drugs administered during Other design considerations included ease of filling the the period. Thickness of the membrane is about 0.04 cm. pumps, and chemical compatibility of structural material: with aqueous drug vehicles and formulations. During the Eompatibility study, the minipump materials were immersed in solutions for several weeks and the concentration of key constituents determined before and after the immersion. Changes in physicochemical properties of the structural materials were also determined after immersion. Osmotic Pump Materials must also be tissue compatible; that is, their Filled and Assembled implantation in laboratory animals for several weeks either subcutaneously or intraperitoneally should produce no un. toward histopathologic phenomena nor any significanl :hanges in the properties of the materials. The materials used for the fabrication of the device nave passed the above compatibility tests. This was demon. strated by implanting in the dorsal region of rats a mini?ump, and a Silastic rod used as a positive control, Fourteen days after implant, no tissue irritation or en:apsulation was noted with either the minipump or the Silastic rod. Furthermore, minipumps implanted for Deriods up to 16 weeks caused no detectable tissue re. ictions. The osmotic minipumps described in 'this communica:ion are designed to be filled with drug solution by the Jser, with a filling tube and syringe. The filling tube has I blunt tip to prevent accidental puncture of the reservoir walls. The pump is ready for use as soon as the drug .eservoir is completely filled and the flow moderator inserted into the system (Figure 3). The flow moderator ninimises diffusional loss of active agent from the pump md minimises any interruption in pumping rate due to mtrapped air inadvertently introduced during filling. When i filled and assembled minipump is exposed to an aqueous mvironment or placed in biological tissue, the osmotic tgent beneath the semipermeable membrane imbibes water k t a rate that is controlled by the membrane. The imbibed water generates hydrostatic pressure, which is exerted on :he reservoir, thereby displacing drug solution through the lelivery portal as shown in Figure 4. The minipump is a I Fig. 3 . The filled arid assembled osmotic minipump. me-time-use device. 282

Journal of Medical Engineering and Technology

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Design and performance of the implantable osmotic minipump.

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