Abstract:
An osmotic pump system includes a capsule having at least one delivery port, a membrane plug retained at an open end of the capsule remote from the delivery port, the membrane plug providing a fluid-permeable barrier between an interior and an exterior of the capsule, and a removable imbibition rate reducer attachable to the capsule. The imbibition rate reducer comprises one or more flow controllers selected from the group consisting of an orifice having a selected size smaller than a surface area of the membrane plug and a membrane having a selected thickness, surface area, radial compression, and permeability. The imbibition rate reducer allows customizable delivery of medicaments.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS  
       [0001]     This application claims the benefit of U.S. Provisional Application No. 60/518,111, filed Nov. 6, 2003. 
     
    
     BACKGROUND OF THE INVENTION  
       [0002]     The invention relates generally to implantable osmotic pumps for delivering beneficial agents. More specifically, the invention relates to an implantable osmotic pump having a semipermeable membrane for controlling the delivery rate of a beneficial agent.  
         [0003]     Implantable osmotic pumps for delivering beneficial agents within the body of a patient are known in the art. For illustration purposes,  FIG. 1  shows a cross-section of a typical implantable osmotic pump  100  having an implantable capsule  102 . A delivery port  104  is formed at a closed end  106  of the capsule  102 , and a semipermeable membrane plug  108  is received in an open end  110  of the capsule  102 . The semipermeable membrane plug  108  forms a fluid-permeable barrier between the exterior and the interior of the capsule  102 . A piston  112  is disposed in the capsule  102 , forming two chambers  114 ,  116  within the capsule  102 . The chamber  114  contains an osmotic agent  118 , and the chamber  116  contains a beneficial agent  120 . When the osmotic pump  100  is implanted in a patient, fluid from the body of the patient enters the chamber  114  through the semipermeable membrane plug  108 , permeating the osmotic agent  118  and causing the osmotic agent  118  to swell. The swollen osmotic agent  118  pushes the piston  112  in a direction away from the semipermeable membrane plug  108 , reducing the volume of the chamber  116  and forcing an amount of the beneficial agent  120  out of the capsule  102 , through the delivery port  104 , into the body of the patient.  
         [0004]     The rate at which the osmotic pump  100  delivers the beneficial agent to the patient depends on the rate at which fluid is imbibed through the semipermeable membrane plug  108 . The rate at which fluid is imbibed depends on the permeability, thickness, exposed surface area, and radial compression of the semipermeable membrane plug  108 . Thus, once the osmotic pump  100  is assembled, the rate at which the beneficial agent  120  will be delivered to the patient is already established. This limits use of the osmotic pump in applications such as personalized care, where a caregiver requires the flexibility of administrating dosages to patients using non-standard dosing regimens. For these applications, the ability to adjust the delivery rate of the osmotic pump post-manufacture and pre-implantation could be beneficial. Preferably, the adjustment means does not have an adverse effect on the ability of the osmotic pump to deliver the beneficial agent.  
       BRIEF SUMMARY OF THE INVENTION  
       [0005]     In one aspect, the invention relates to an osmotic pump system which comprises a capsule having at least one delivery port, a membrane plug retained at an open end of the capsule remote from the delivery port, the membrane plug providing a fluid-permeable barrier between an interior and an exterior of the capsule, and a removable imbibition rate reducer attachable to the capsule. The imbibition rate reducer comprises one or more flow controllers selected from the group consisting of an orifice having a selected size smaller than a surface area of the membrane plug and a membrane having a selected thickness, surface area, radial compression, and permeability.  
         [0006]     In another aspect, the invention relates to an osmotic pump system which comprises an implantable osmotic pump having a membrane plug at a first end and a delivery port at a second end remote from the first end. The membrane plug forms a fluid-permeable barrier between an interior and an exterior of the osmotic pump. The osmotic pump system further includes a removable imbibition rate reducer that is attachable to the osmotic pump. The imbibition rate reducer is selected from the group consisting of an orifice module having an orifice with a selected size, a membrane module having a membrane with a selected thickness, surface area, radial compression, and permeability, and combinations thereof. The orifice and membrane are configured to decrease an imbibition rate of the osmotic pump.  
         [0007]     In another aspect, the invention relates to a method of adjusting a predefined delivery rate of an osmotic pump having a membrane plug forming a fluid-permeable barrier between an exterior and an interior of the osmotic pump. The method comprises reducing an imbibition rate of the osmotic pump by attaching an imbibition rate reducer to the osmotic pump so that fluid enters the membrane plug by passing through the imbibition rate reducer. The imbibition rate reducer comprises one or more flow controllers selected from the group consisting of an orifice having a selected size and a membrane having a selected thickness, surface area, radial compression, and permeability. The orifice is configured to reduce an effective surface area of the membrane plug, and the membrane is configured to increase an effective flow path length of the membrane plug.  
         [0008]     In yet another aspect, the invention relates to an osmotic pump kit which comprises an implantable osmotic pump including a semipermeable membrane plug forming a fluid-permeable barrier between an interior and an exterior of the osmotic pump, a membrane module for increasing an effective flow path length of the membrane plug, and an orifice module for decreasing an effective surface area of the membrane plug, wherein the membrane module and orifice module are separately and independently attachable to or detachable from the osmotic pump.  
         [0009]     Other features and advantages of the invention will be apparent from the following description. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]      FIG. 1  is a cross-section of a prior-art osmotic pump.  
         [0011]      FIG. 2  is a cross-section of an orifice module for reducing imbibition rate of an osmotic pump according to one embodiment of the invention.  
         [0012]      FIG. 3A  shows a membrane module for reducing imbibition rate of an osmotic pump according to one embodiment of the invention.  
         [0013]      FIG. 3B  shows two membrane modules coupled together to form a membrane module stack according to another embodiment of the invention.  
         [0014]      FIGS. 3C-3E  show examples of possible modifications to the membrane module of  FIG. 3A .  
         [0015]      FIG. 3F  shows an orifice module coupled to a membrane module for reduction of imbibition rate of an osmotic pump according to another embodiment of the invention.  
         [0016]      FIG. 4A  shows an osmotic pump system including a modular imbibition rate reducer installed on an osmotic pump in accordance with one embodiment of the invention.  
         [0017]      FIG. 4B  shows an osmotic pump system including a modular imbibition rate reducer installed on an osmotic pump in accordance with another embodiment of the invention. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0018]     The invention will now be described in detail with reference to a few preferred embodiments, as illustrated in accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the invention. However, it will be apparent to one skilled in the art that the invention may be practiced without some or all of these specific details. In other instances, well-known features and/or process steps have not been described in detail in order to not unnecessarily obscure the invention. The features and advantages of the invention may be better understood with reference to the drawings and discussions that follow.  
         [0019]     An imbibition rate reducer according to embodiments of the invention may be attached to or detached from an osmotic pump post-manufacture. When the imbibition rate reducer is attached to the osmotic pump, it functions to reduce the imbibition rate of the osmotic pump. In accordance with embodiments of the invention, the imbibition rate reducer includes an orifice to reduce the exposed surface area of a semipermeable membrane plug, which forms a fluid-permeable barrier between the exterior and interior of the osmotic pump, and/or one or more membranes to increase the effective flow path length of the membrane plug. The imbibition rate reducer allows the delivery rate of the osmotic pump to be reduced by an amount corresponding to the reduction in the imbibition rate of the osmotic pump. In one practical application, a caregiver could start with an osmotic pump designed to deliver a larger amount of medicament than what may be required for a particular patient. Based on the actual delivery rate desired by the caregiver, a reduction in exposed surface area and/or an increase in effective flow path length that would give the required imbibition rate can be determined and used to configure the imbibition rate reducer.  
         [0020]     The imbibition rate reducer can be configured post-manufacture and pre-implantation using an orifice module and/or one or more membrane modules. For illustration purposes,  FIG. 2  shows a cross-section of an orifice module  200  in accordance with one embodiment of the invention. The orifice module  200  includes a housing  202  having a capped end  204  and an open end  206 . The open end  206  is sized to fit over an end portion of an osmotic pump (not shown). The capped end  204  is provided with an orifice  208  through which fluid can flow into the interior  210  of the housing  202 . When the orifice module  200  is attached to the osmotic pump, the orifice  208  precedes the semipermeable membrane plug (not shown) of the osmotic pump. In this way, fluid from the exterior of the osmotic pump flows into the interior of the osmotic pump through the orifice  208  and the semipermeable membrane plug. The orifice  208  is sized such that it effectively reduces the exposed surface area of the semipermeable membrane plug, and hence the imbibition rate of the osmotic pump.  
         [0021]     It should be noted that the invention is not limited to use of the single orifice  208  to control flow into the semipermeable membrane plug. For example, a cluster of holes can replace the single orifice  208 , the combined flow area of the holes being selected to achieve the desired reduction in imbibition rate. Reduction in imbibition rate through the use of the orifice module  200  produces a corresponding reduction in the rate at which a beneficial agent is delivered by the osmotic pump.  
         [0022]     The housing  202  is constructed so that it can be attached to an end portion of the osmotic pump including the semipermeable membrane plug. Preferably, the housing  202  can be snap-fitted to the osmotic pump. In one embodiment, an annular lip  212  is provided on an inner surface  214  of the housing  202 . The annular lip  212  can engage with an annular groove (not shown) provided on an outer surface of the osmotic pump. Alternatively, the annular lip can be provided on the osmotic pump and the annular groove for engagement with the annular lip can be provided on the housing  202 . Basically, any means of coupling tubular members, such as a threaded connection, can be used to affix the housing  202  to the osmotic pump. To maintain the osmotic pump in a sterile condition, the housing  202  should be attached to the osmotic pump using aseptic technique. In general, the cross-section of the housing  202  should be selected such that it can fit on or over an end portion of the osmotic pump. In general, any configuration such that a biofluidic path cannot be formed between the junction of the housing  202  and the end portion of the osmotic pump can be used. For example, if the end portion of the osmotic pump containing the semipermeable membrane plug has a circular cross-section, the housing  202  should preferably have a circular cross-section.  
         [0023]     The housing  202  is formed from an inert and, preferably, biocompatible material. The material is “inert” in the sense that it will not react with the materials it will come in contact with during use. Exemplary inert, biocompatible materials include, but are not limited to, metals such as titanium, stainless steel, platinum and their alloys, and cobalt-chromium alloys and the like. Other compatible materials include polymers such as polyethylene, polypropylene, polycarbonate, polymethylmethacrylate (PMMA), and the like.  
         [0024]      FIGS. 3A-3F  show various embodiments of a membrane module. In  FIG. 3A , a membrane module  300  includes a sleeve  302  and a membrane  304  inserted in the sleeve  302 . The thickness of the membrane  304  is selected to increase the effective flow path length from the exterior of the osmotic pump (not shown), through the semipermeable membrane plug (not shown) at an end of the osmotic pump, to the interior of the osmotic pump. An increase in the effective flow path length produces a decrease in imbibition rate and a corresponding decrease in the delivery rate of the osmotic pump. The material used in making the membrane  304  may be the same as or may be different from the material used in making the semipermeable membrane plug of the osmotic pump. The material used in making the membrane  304  is preferably semipermeable and preferably can conform to the inner shape of the sleeve  302  upon wetting and adhere to the inner surface of the sleeve  302 . Suitable semipermeable materials are typically polymeric materials, including, but not limited to, plasticized cellulosic materials, enhanced PMMAs such as hydroxyethylmethacrylate (HEMA), and elastomeric materials such as polyurethanes and polyamides, polyether-polyamind copolymers, thermoplastic copolyesters, and the like.  
         [0025]     The exposed surface area of the membrane  304  may be the same as or may be different from the exposed surface area of the semipermeable membrane plug of the osmotic pump. That is, fluid imbibition can be controlled not just by the thickness of the membrane  304  but also by the exposed surface area of the membrane  304 . The sleeve  302  radially constrains the membrane  304 , exerting an amount of radial compression on the membrane  304 . This radial compression along with the thickness, permeability, and exposed surface area of the membrane  304  can be selected to achieve a desired reduction in imbibition rate of the osmotic pump.  
         [0026]     The membrane module  300  is constructed so that it can be attached to the osmotic pump post-manufacture and pre-implantation. Preferably, the membrane module  300  can be snap-fitted to the osmotic pump. In one embodiment, this could be accomplished by providing an annular lip  306  on an inner surface  308  of the sleeve  304  that can engage with an annular groove (not shown) on an end portion of the osmotic pump containing the semipermeable membrane plug. Alternatively, the annular lip could be provided on the osmotic pump and an annular groove that can engage with the annular lip can be provided on the sleeve  304 . However, the invention is not limited to use of annular lip/annular groove to couple the membrane module  300  to the osmotic pump. In general, any means of coupling tubular members, such as a threaded connection, can be used to affix the membrane module  300  to the osmotic pump. Preferably, any coupling configuration used is such that a biofluidic path cannot be formed between the junction of the sleeve  302  and the end portion of the osmotic pump. The membrane module  300  should be attached to the osmotic pump using aseptic technique.  
         [0027]     The membrane module  300  is also constructed so that a plurality of the membrane modules can be coupled together to form a membrane stack. In  FIG. 3B , for example, a membrane stack  312  is formed by connecting the membrane modules  300 ,  300   a . Note that the characteristics of the membrane modules in the stack, such as the thickness, permeability, exposed surface area, and radial compression of the membranes in the modules, can be the same or different. Returning to  FIG. 3A , in one embodiment, an annular groove  314  is provided on the outer surface  310  of the membrane module  300  for engagement with an annular lip (similar to annular lip  306 ) on the inner surface of another membrane module, thereby allowing multiple membrane modules to be stacked to provide a desired flow path length. Other means of connecting tubular members, such as threaded connections, may also be employed to couple multiple membrane modules together. Preferably, any coupling configuration used is such that a biofluidic path cannot be formed between the junctions of multiple sleeves  302 . The outer diameter of the sleeve  302  can be selected such that the outer surface  310  of the sleeve  302  is flush with the outer surface of the osmotic pump when the membrane module  300  is fitted to the osmotic pump.  
         [0028]     The sleeve  302  is formed from an inert and, preferably, biocompatible material. Exemplary inert, biocompatible materials include, but are not limited to, metals such as titanium, stainless steel, platinum and their alloys, and cobalt-chromium alloys and the like. Other examples of compatible materials include polymers such as polyethylene, polypropylene, polycarbonate, polymethylmethacrylate (PMMA), and the like.  
         [0029]     The membrane module  300  can be modified in various ways. For example, as shown in  FIG. 3C , the outer surface of the membrane  304  could include ribs  316  (or threads, ridges, and the like) which form a seal between the membrane  304  and the sleeve  302 . In  FIG. 3D , the sleeve  302  includes holes  318  through which fluid can flow into the sleeve  302  or pressure can be vented out of the sleeve  302 . The holes  318  can also double up as retention means for the membrane  304 , as taught by Rupal Ayer in U.S. Pat. No. 6,270,787. In  FIG. 3E , the sleeve  302  includes a mating surface, such as an annular groove  320 , for engagement with a corresponding mating surface, such as the annular lip ( 212  in  FIG. 2 ), on the orifice module ( 200  in  FIG. 2 ). As shown in  FIG. 3F , the annular lip  212  on the housing  202  of the orifice module  200  is fitted into the annular groove  320  on the sleeve  302  of the membrane module  300 . When this structure is installed on an osmotic pump, the imbibition rate of the osmotic pump can be reduced by both the orifice  208  in the orifice module  200  and the membrane  304  in the membrane module  300 .  
         [0030]     In practice, an imbibition rate reducer can be constructed using any of the modular structures described in  FIGS. 2 and 3 A- 3 F. As described above, the orifice module and membrane module are designed such that they can be separately and independently attached to the osmotic pump. Additionally, a stack of membrane modules can be formed and attached to the osmotic pump. Also, the orifice module can be coupled to a membrane module, which can then be attached to the osmotic pump. The imbibition rate reducer can be installed on the osmotic pump post-manufacture and pre-implantation to reduce the imbibition rate of the osmotic pump by a selected amount, where a reduction in imbibition rate produces a corresponding reduction in the delivery rate of the osmotic pump.  
         [0031]     For illustration purposes,  FIG. 4A  shows an osmotic pump system  400  having an imbibition rate reducer, e.g., the orifice module  200 , installed on an osmotic pump  402  according to an embodiment of the invention. The internal structure of the osmotic pump  402  is presented for illustration purposes only and is not to be construed as limiting the present invention. The present invention is generally applicable to all osmotic pumps having any number of shapes, and to all such pumps administered in implantable osmotic delivery techniques.  
         [0032]     The osmotic pump  402 , as illustrated in  FIG. 4A , includes an elongated cylindrical capsule  404 . The capsule  404  may be sized such that it can be implanted within a body. In  FIG. 4A , one end  406  of the capsule  404  is closed and the other end  408  of the capsule  404  is open. The closed end  406  includes a delivery port  410 . In an alternative embodiment, the closed end  406  may be modified to include a flow modulator (not shown), such as taught by Peterson et al. in U.S. Pat. No. 6,524,305. A semipermeable membrane plug  412  is received in the open end  408  of the capsule  404 . The semipermeable membrane plug  412  may be inserted partially or fully into the open end  408 . In the former case, the semipermeable membrane plug  412  may include an enlarged end portion that acts as a stop member engaging an end of the capsule  404 . The outer surface of the semipermeable membrane plug  412  may have ribs, threads, ridges and the like which form a seal between the membrane  412  and the inner surface of the capsule  404 , as taught by Chen et al. in U.S. Pat. No. 6,113,938.  
         [0033]     The semipermeable membrane plug  412  is made of a semipermeable material that allows water to pass from an exterior of the capsule  404  into the interior of the capsule  404  while preventing compositions within the capsule from passing out of the capsule. Semipermeable materials suitable for use in the invention are well known in the art. Semipermeable materials for the membrane plug are those that can conform to the shape of the capsule upon wetting and that can adhere to the inner surface of the capsule. Typically, these materials are polymeric materials, which can be selected based on the pumping rates and system configuration requirements, and include, but are not limited to, plasticized cellulosic materials, enhanced PMMAs such as hydroxyethylmethacrylate (HEMA), and elastomeric materials such as polyurethanes and polyamides, polyether-polyamind copolymers, thermoplastic copolyesters, and the like.  
         [0034]     Two chambers  414 ,  416  are defined inside the capsule  404 . The chambers  414 ,  416  are separated by a partition  418 , such as a slidable piston or flexible diaphragm, which is configured to fit within the capsule  404  in a sealing manner and to move longitudinally within the capsule. Preferably, the partition  418  is formed from an impermeable resilient material. As an example, the partition  418  may be a slidable piston made of an impermeable resilient material and including annular ring shape protrusions that form a seal with the inner surface of the capsule  404 . An osmotic agent  420  is disposed in the chamber  414  adjacent the semipermeable membrane plug  412 , and a beneficial agent  422  to be delivered to a body is disposed in the chamber  416  adjacent the delivery port  410 . The partition  418  isolates the beneficial agent  422  from the environmental liquids that are permitted to enter the capsule  404  through the semipermeable membrane plug  412  such that in use, at steady-state flow, the beneficial agent  422  is expelled through the delivery port  410  at a rate corresponding to the rate at which liquid from the environment of use flows into the osmotic agent  420  through the orifice module  200  and semipermeable membrane plug  412 .  
         [0035]     The osmotic agent  420  may be in the form of tablets as shown or may have other shape, texture, density, and consistency. For example, the osmotic agent  420  may be in powder or granular form. The osmotic agent may be, for example, a nonvolatile water soluble osmagent, an osmopolymer which swells on contact with water, or a mixture of the two.  
         [0036]     In general, the present invention applies to the administration of beneficial agents, which include any physiologically or pharmacologically active substance. The beneficial agent  422  may be any of the agents which are known to be delivered to the body of a human or an animal such as medicaments, vitamins, nutrients, or the like. Drug agents which may be delivered by the present invention include drugs which act on the peripheral nerves, adrenergic receptors, cholinergic receptors, the skeletal muscles, the cardiovascular system, smooth muscles, the blood circulatory system, synoptic sites, neuroeffector junctional sites, endocrine and hormone systems, the immunological system, the reproductive system, the skeletal system, autacoid systems, the alimentary and excretory systems, the histamine system and the central nervous system. Suitable agents may be selected from, for example, proteins, enzymes, hormones, polynucleotides, nucleoproteins, polysaccharides, glycoproteins, lipoproteins, polypeptides, steroids, analgesics, local anesthetics, antibiotic agents, anti-inflammatory corticosteroids, ocular drugs and synthetic analogs of these species. An exemplary list of drugs that may be delivered using the osmotic pump system  400  is disclosed in U.S. Pat. No. 6,270,787. The list is incorporated herein by reference.  
         [0037]     The beneficial agent  422  can be present in a wide variety of chemical and physical forms, such as solids, liquids and slurries. On the molecular level, the various forms may include uncharged molecules, molecular complexes, and pharmaceutically acceptable acid addition and base addition salts such as hydrochlorides, hydrobromides, sulfate, laurylate, oleate, and salicylate. For acidic compounds, salts of metals, amines or organic cations may be used. Derivatives such as esters, ethers and amides can also be used. A beneficial agent can be used alone or mixed with other beneficial agents. The beneficial agent may optionally include pharmaceutically acceptable carriers and/or additional ingredients such as antioxidants, stabilizing agents, permeation enhancers, etc.  
         [0038]     Materials which may be used for the capsule  404  must be sufficiently rigid to withstand expansion of the osmotic agent  420  without changing its size or shape. Further, the materials should ensure that the capsule  404  will not leak, crack, break, or distort under stress to which it could be subjected during implantation or under stresses due to the pressures generated during operation. The capsule  404  may be formed of chemically inert biocompatible, natural or synthetic materials which are known in the art. The capsule material is preferably a non-bioerodible material which remains in the patient after use, such as titanium. However, the material of the capsule may alternatively be a bioerodible material which bioerodes in the environment after dispensing of the beneficial agent. Generally, preferred materials for the capsule  404  are those acceptable for human implantation.  
         [0039]     In general, typical materials of construction suitable for the capsule  404  according to the present invention include non-reactive polymers or biocompatible metals or alloys. The polymers include acrylonitrile polymers such as acrylonitrile-butadiene-styrene terpolymer, and the like; halogenated polymers such as polytetraflouroethylene, polychlorotrifluoroethylene, copolymer tetrafluoroethylene and hexafluoropropylene; polyimide; polysulfone; polycarbonate; polyethylene; polypropylene; polyvinylchloride-acrylic copolymer; polycarbonate-acrylonitrile-butadiene-styrene; polystyrene; and the like. Metallic materials useful for the capsule  404  include stainless steel, titanium, platinum, tantalum, gold, and their alloys, as well as gold-plated ferrous alloys, platinum-plated ferrous alloys, cobalt-chromium alloys and titanium nitride coated stainless steel.  
         [0040]     A capsule  404  made from the titanium or a titanium alloy having greater than 60%, often greater than 85% titanium, is particularly preferred for the most size-critical applications, for high payload capability and for long duration applications, and for those applications where the formulation is sensitive to body chemistry at the implantation site or where the body is sensitive to the formulation. In certain embodiments, and for applications other than the fluid-imbibing devices specifically described, where unstable beneficial agent formulations are in the capsule  404 , particularly protein and/or peptide formulations, the metallic components to which the formulation is exposed must be formed of titanium or its alloys as described above.  
         [0041]     The orifice module  200  is installed by, for example, snapping the annular lip  212  on the housing  202  into an annular groove  424  on the outer surface of the capsule  404 . As previously mentioned, other means of installing the orifice module  200  may be used, such as a threaded connection. An optional porous substrate  426 , such as a screen or mesh, may be inserted between the orifice  208  and the semipermeable membrane plug  412  to prevent deformation of the membrane  412 . That is, the semipermeable membrane plug  412  can bulge out because of pressure inside the capsule  404 . The semipermeable membrane plug  412  may extend into the orifice  208  if the bulging is not controlled. If desired, the housing  202  may be sized such that a chamber (not shown) is formed between the semipermeable membrane plug  412  and the capped end  204  of the housing  202  that allows for a degree of movement of the semipermeable  412  into the housing  202  as a result of pressure in the interior of the capsule  404 . The capped end  204  can act as a stopper to prevent the semipermeable membrane plug  412  from being separated from the osmotic pump  402 .  
         [0042]      FIG. 4B  shows the membrane module  300  installed on the osmotic pump  402 . As previously mentioned, any of the disclosed orifice module ( 200  in  FIG. 2 ) and membrane modules ( 300  in  FIGS. 3A-3D ) and other variations may be installed on an osmotic pump to reduce the imbibition rate of the osmotic pump by a selected amount.  
         [0043]     The invention typically provides the following advantages. The invention provides a means of adjusting the delivery rate of an osmotic pump post-manufacture. A variety of delivery profiles can be achieved without adversely affecting the operation of the osmotic pump. This gives caregivers flexibility in treatment options.  
         [0044]     While the invention has been described with respect to a limited number of embodiments, those skilled in the art, having benefit of this disclosure, will appreciate that other embodiments can be devised which do not depart from the scope of the invention as disclosed herein.