Drug delivery systems and related methods

Abstract

The intra-orifice drug delivery system and method of formation includes a housing defining an inner chamber extending along a longitudinal axis, the chamber walls defining one or more openings therethrough. A retainer extends from the housing and is adapted to removably retain the housing within a body orifice defined by the orifice walls. The osmotic delivery device is disposed within the chamber and includes an osmogenic portion and a drug-containing portion disposed within a semipermeable membrane. The osmogenic portion expands in response to absorption of liquid from within the body orifice that permeates the semipermeable membrane, exerting pressure on the drug-containing portion. The drug-containing portion is arranged to release drug in response to pressure exerted by the expanded osmogenic portion, the drug exiting through a membrane orifice defined by the semipermeable membrane and then exiting the housing through the one or more openings such that the drug is delivered into the body orifice.

Description

[Technical Field]

[0001] The present disclosure relates to drug delivery systems and methods, and more particularly to drug delivery systems and methods for making and using drugs, the drug delivery system having an osmotic delivery device or erodible body engaged with a retaining device for removably retaining the osmotic delivery device or erodible body within a body orifice for delivery of a drug thereto. [Background technology]

[0002] Some medications for animals need to be delivered over an extended period of time, as opposed to individual doses. Traditionally, such medications can be delivered to animals through a bodily orifice, such as the vaginal opening. For example, vaginal delivery of medications may function to control the reproductive cycle of an animal, which may be, for example, a pig, cow, and / or sheep. Some prior art intravaginal drug delivery devices implement a physical framework having a drug-releasing portion that engages with and surrounds a portion of the physical framework such that the drug-releasing portion is exposed to the exterior. The drug-releasing portion may be configured to gradually release, for example, a contraceptive. Limitations associated with such prior art intravaginal drug delivery devices include a lack of flexibility in the drug-releasing form, passive diffusion, reduced drug loading, and drug residue after initial use that allows for indiscriminate reuse.

[0003] Therefore, there is a need for an improved drug delivery system for delivering drugs into the body orifices of animals. Summary of the Invention

[0004] These and other needs are met by aspects of the present disclosure, including, but not limited to, the following exemplary embodiments. In one particular aspect, an intra-orifice drug delivery system is provided, the system including: a housing having a chamber wall defining an interior chamber extending along a longitudinal axis, the chamber wall further defining one or more openings extending from the chamber and through the chamber wall; a retainer adapted to engage with the housing, extend from the housing, and removably retain the housing within a body orifice defined by the orifice wall; an osmotic delivery device disposed within the chamber and including an osmogen portion and a drug-containing portion disposed within a semipermeable membrane; the osmogen portion is configured to expand in response to absorption of fluid from within the body orifice through the semipermeable membrane and apply pressure to the drug-containing portion; the drug-containing portion is configured to release the drug in response to the pressure applied by the expanded osmogen portion, the drug exiting through a membrane orifice defined by the semipermeable membrane and then exiting the housing through the one or more openings so that the drug is delivered into the body orifice.

[0005] Another aspect of the present disclosure provides a method of forming an intra-orifice drug delivery system, the method including: forming a housing having chamber walls defining an interior chamber extending along a longitudinal axis, the chamber walls defining one or more openings extending from the chamber and through the chamber wall; engaging a retention device with the housing, the retention device extending from the housing and adapted to removably retain the housing within a body orifice defined by the orifice wall; and disposing an osmotic delivery device including an osmogen portion and a drug-containing portion disposed within a semipermeable membrane within the chamber, the osmogen portion configured to expand and apply pressure to the drug-containing portion in response to absorption of fluid from within the body orifice through the semipermeable membrane, the drug-containing portion configured to release the drug in response to the pressure applied by the expanded osmogen portion, and the drug exiting through the membrane orifice defined by the semipermeable membrane and thereafter exiting the housing through the one or more openings for delivery into the body orifice.

[0006] Yet another aspect of the present disclosure provides an intra-orifice drug delivery system including a housing having a chamber wall defining an internal chamber extending along a longitudinal axis, the chamber wall further defining one or more openings extending from the chamber and therethrough. A retention device engages with the housing, extends from the housing, and is adapted to removably retain the housing within a body orifice defined by the orifice wall. An erodible body is disposed within the chamber and includes a drug component. The erodible body is configured to dissolve in response to interaction with fluid from within the body orifice, thereby releasing the drug component out of the housing through the one or more openings so that the drug component is delivered into the body orifice.

[0007] Yet another aspect of the present disclosure provides a method of forming an intra-orifice drug delivery system, the method including: forming a housing having a chamber wall defining an internal chamber extending along a longitudinal axis, the chamber wall defining one or more openings extending from the chamber and through the chamber wall; engaging a retention device with the housing, the retention device extending from the housing and adapted to removably retain the housing within a body orifice defined by the orifice wall; and disposing an erodible body including a drug component within the chamber, the erodible body being arranged to dissolve in response to interaction with fluid from within the body orifice, thereby releasing the drug component to exit the housing through the one or more openings for delivery into the body orifice.

[0008] Accordingly, the present disclosure includes, but is not limited to, the following exemplary embodiments.

[0009] 10. An intra-orifice drug delivery system comprising: a housing having a chamber wall defining an inner chamber extending along a longitudinal axis, the chamber wall further defining one or more openings extending from the chamber and through the chamber wall; a retention device engaging with and extending from the housing, the retention device adapted to removably retain the housing within a body orifice defined by the orifice wall; and an osmotic delivery device disposed within the chamber and including an osmogenic portion and a drug-containing portion disposed within a semipermeable membrane, the osmogenic portion being configured to expand in response to absorption of fluid from within the body orifice through the semipermeable membrane and apply pressure to the drug-containing portion, the drug-containing portion being configured to release the drug in response to the pressure applied by the expanded osmogenic portion, the drug exiting through a membrane orifice defined by the semipermeable membrane and thereafter exiting the housing through the one or more openings for delivery into the body orifice.

[0010] Exemplary embodiment 2: A system according to any one of the preceding exemplary embodiments, or combinations thereof, comprising a housing removal device that engages with the housing or retention device and is adapted to facilitate removal of the housing from the body orifice.

[0011] Exemplary embodiment 3: A system according to any one of the preceding exemplary embodiments or combinations thereof, wherein the housing removal device engages with the housing via a stem disposed between the housing and the stem, the stem extending along the longitudinal axis.

[0012] Exemplary Embodiment 4: The system of any one of the preceding exemplary embodiments or combinations thereof, wherein the housing removal device comprises a ring member.

[0013] Exemplary embodiment 5: A system of any one of the preceding exemplary embodiments, or combinations thereof, wherein the housing removal device further comprises an elongated handle having a distal end including a hook member arranged to engage with the ring member to facilitate removal of the housing from the body orifice.

[0014] Exemplary Embodiment 6: The system of any one of the preceding exemplary embodiments or combinations thereof, wherein the retention device engages in-line between the housing removal device and the housing.

[0015] Exemplary embodiment 7: A system according to any one of the preceding exemplary embodiments or combinations thereof, wherein the retaining device engages with a first end of the housing and the housing removal device engages with a second end of the housing.

[0016] Exemplary Embodiment 8: The system of any one of the preceding exemplary embodiments or combinations thereof, wherein the retention device engages the stem between the housing removal device and the housing.

[0017] Exemplary embodiment 9: A system of any one of the preceding exemplary embodiments or combinations thereof, wherein the retention device includes one or more retention members that engage with and extend away from the housing or stem so as to be biased toward and positioned in engagement with the orifice wall to retain the housing within the body orifice.

[0018] Exemplary Embodiment 10: The system of any one of the preceding exemplary embodiments or combinations thereof, wherein the one or more retaining members are cantilevered relative to the housing or stem.

[0019] Exemplary embodiment 11: A system according to any one of the preceding exemplary embodiments or combinations thereof, wherein one or more retention members are flexible or the engagement between one or more retention members and the housing or stem is flexible, and the flexibility associated with the one or more retention members urges the one or more retention members into interaction with the orifice wall to retain the housing within the body orifice, or facilitates disengagement of the one or more retention members from the orifice wall to remove the housing from the body orifice.

[0020] Exemplary embodiment 12: A system according to any one of the preceding exemplary embodiments or combinations thereof, wherein the distal end of one or more retention members is rounded or includes a rounded member that engages with the distal end to prevent the distal end from perforating the orifice wall or to facilitate removal of the housing from the body orifice.

[0021] Exemplary embodiment 13: A system according to any one of the preceding exemplary embodiments or combinations thereof, wherein the housing defines a maximum diameter perpendicular to the longitudinal axis, and the distal ends of the one or more retention members, or rounded members engaging therewith, are larger than the maximum diameter of the housing and extend outward from the stem.

[0022] Exemplary Embodiment 14: A system according to any one of the preceding exemplary embodiments, or combinations thereof, wherein the membrane around the drug-containing portion defines one or more pores, and the drug released by the drug-containing portion exits the membrane through the one or more pores.

[0023] Exemplary embodiment 15: A system according to any one of the preceding exemplary embodiments, or a combination thereof, wherein the membrane, drug-containing portion, or osmogenic portion is configured to cause the drug-containing portion to release the drug at a predetermined rate.

[0024] Exemplary Embodiment 16: A system according to any one of the preceding exemplary embodiments, or combinations thereof, wherein one or more openings defined by the chamber wall and extending from the chamber through the chamber wall define a relatively large opening area around an outer surface of the chamber wall and a relatively small opening area around an inner surface of the chamber wall for funneling liquid from the body orifice into the chamber.

[0025] Exemplary embodiment 17: A system of any one of the preceding exemplary embodiments, or combinations thereof, including one or more protrusions extending from the chamber wall into the chamber, the one or more protrusions facilitating spacing of the osmotic delivery device away from the chamber wall to facilitate circulation of liquid around the osmotic delivery device.

[0026] Exemplary Embodiment 18: A system according to any one of the preceding exemplary embodiments or combinations thereof, wherein the chamber wall is generally cylindrical and has opposing first and second ends, the housing includes end walls engaging each of the opposing ends, one of the end walls defining one or more openings.

[0027] Exemplary embodiment 19: A system according to any one of the preceding exemplary embodiments, or combinations thereof, wherein the drug-containing portion of the osmotic delivery device is disposed adjacent to one of the end walls defining the one or more openings.

[0028] Exemplary embodiment 20: A system according to any one of the preceding exemplary embodiments, or combinations thereof, comprising a biasing device engaged between the chamber wall and the osmotic delivery device, the biasing device being arranged to bias the osmotic delivery device against one of the end walls to facilitate release of the drug from the drug-containing portion through one or more openings defined by one of the end walls.

[0029] Exemplary embodiment 21: A system according to any one of the preceding exemplary embodiments, or a combination thereof, wherein the osmogenic portion is disposed in contact with the drug-containing portion, and the semipermeable membrane comprises a coating disposed around the osmogenic portion and the drug-containing portion.

[0030] Exemplary embodiment 22: A system according to any one of the preceding exemplary embodiments, or a combination thereof, wherein the housing comprises two interlocking portions that, when engaged therebetween, contain an osmotic delivery device within a chamber defined thereby.

[0031] Exemplary Embodiment 23: The system of any one of the preceding exemplary embodiments, or combinations thereof, wherein the drug-containing moiety comprises a steroid, a hormone, a cytokine signaling molecule, a pain management drug, a cardiovascular drug, an immunomodulatory agent, a protein, a peptide, a glycoprotein, or a combination thereof.

[0032] Exemplary Embodiment 24: The system of any one of the preceding exemplary embodiments, or a combination thereof, wherein the osmogenic moiety comprises magnesium stearate.

[0033] Exemplary embodiment 25: A method of forming an intra-orifice drug delivery system, the method comprising: forming a housing having chamber walls defining an inner chamber extending along a longitudinal axis, the chamber walls defining one or more openings extending from the chamber through the chamber wall; engaging a retaining device with the housing, the retaining device extending from the housing and adapted to removably retain the housing within a body orifice defined by the orifice wall; disposing an osmotic delivery device including an osmogenic portion and a drug-containing portion disposed within a semipermeable membrane within the chamber, the osmogenic portion being configured to expand and apply pressure to the drug-containing portion in response to absorption of fluid from within the body orifice through the semipermeable membrane, the drug-containing portion being configured to release the drug in response to the pressure applied by the expanded osmogenic portion, and the drug exiting through the membrane orifice defined by the semipermeable membrane and thereafter exiting the housing through the one or more openings and being delivered into the body orifice.

[0034] Exemplary embodiment 26: A method according to any one of the preceding exemplary embodiments, or combinations thereof, comprising engaging a housing removal device with the housing or retention device, wherein the housing removal device is adapted to facilitate removal of the housing from the body orifice.

[0035] Exemplary embodiment 27: The method of any one of the preceding exemplary embodiments or combinations thereof, wherein engaging the housing removal device includes engaging the housing removal device with the housing via a stem disposed between the housing and extending along the longitudinal axis.

[0036] Exemplary Embodiment 28: The method of any one of the preceding exemplary embodiments, or combinations thereof, wherein engaging the housing removal device includes engaging a ring member of the housing removal device with the housing or the retaining device.

[0037] Exemplary embodiment 29: A method according to any one of the preceding exemplary embodiments, or combinations thereof, comprising engaging a ring member of the housing removal device with a distal end of the elongated handle, the distal end including a hook member arranged to engage with the ring member to facilitate removal of the housing from the body orifice.

[0038] Exemplary Embodiment 30: The method of any one of the preceding exemplary embodiments or combinations thereof, wherein engaging the retention device includes engaging the retention device in series between the housing removal device and the housing.

[0039] Exemplary embodiment 31: The method of any one of the preceding exemplary embodiments or combinations thereof, wherein engaging the retaining device includes engaging the retaining device with a first end of the housing and engaging a housing removal device with a second end of the housing.

[0040] Exemplary embodiment 32: The method of any one of the preceding exemplary embodiments or combinations thereof, wherein engaging the retaining device includes engaging the retaining device with the stem between the housing removal device and the housing.

[0041] Exemplary embodiment 33: The method of any one of the preceding exemplary embodiments or combinations thereof, wherein engaging the retention device includes engaging one or more retention members with the housing or stem and extending away from the housing or stem such that the one or more retention members are biased toward and positioned in engagement with the orifice wall to retain the housing within the body orifice.

[0042] Exemplary Embodiment 34: The method of any one of the preceding exemplary embodiments or combinations thereof, comprising disposing one or more retention members in a cantilevered manner relative to the housing or stem.

[0043] Exemplary embodiment 35: The method of any one of the preceding exemplary embodiments or combinations thereof, including rounding the distal ends of one or more retention members or engaging a rounded member with each of the distal ends to prevent perforation of the orifice wall by the distal ends or to facilitate removal of the housing from the body orifice.

[0044] Exemplary Embodiment 36: The method of any one of the preceding exemplary embodiments, or combinations thereof, wherein the housing defines a maximum diameter perpendicular to the longitudinal axis, and wherein rounding the distal end or engaging a rounded member includes rounding the distal end or engaging a rounded member with each of the distal ends of the one or more retention members such that the distal end, or the rounded member engaging therewith, is larger than the maximum diameter of the housing and extends outward from the stem.

[0045] Exemplary Embodiment 37: The method of any one of the preceding exemplary embodiments, or combinations thereof, comprising forming a membrane around the drug-containing portion, the membrane defining one or more pores, such that drug released by the drug-containing portion exits the membrane through the one or more pores.

[0046] Exemplary Embodiment 38: The method of any one of the preceding exemplary embodiments, or combinations thereof, comprising disposing the membrane, drug-containing portion, or osmogenic portion to cause the drug-containing portion to release the drug at a predetermined rate.

[0047] Exemplary Embodiment 39: The method of any one of the preceding exemplary embodiments, or combinations thereof, comprising forming one or more openings defined by a chamber wall, the one or more openings defining a relatively large opening area around an outer surface of the chamber wall and a relatively small opening area around an inner surface of the chamber wall.

[0048] Exemplary embodiment 40: The method of any one of the preceding exemplary embodiments, or combinations thereof, comprising forming one or more protrusions extending from the chamber wall into the chamber, wherein the one or more protrusions facilitate spacing of the osmotic delivery device away from the chamber wall to facilitate circulation of liquid around the osmotic delivery device.

[0049] Exemplary Embodiment 41: The method of any one of the preceding exemplary embodiments or combinations thereof, wherein forming the housing includes forming the housing such that the chamber wall is generally cylindrical and has opposing first and second ends, and engaging end walls with each opposing end, one of the end walls defining one or more openings.

[0050] Exemplary embodiment 42: The method of any one of the preceding exemplary embodiments, or combinations thereof, wherein disposing the osmotic delivery device includes disposing the osmotic delivery device within the chamber such that a drug-containing portion of the osmotic delivery device is disposed adjacent to one of the end walls defining the one or more openings.

[0051] Exemplary Embodiment 43: The method of any one of the preceding exemplary embodiments, or combinations thereof, comprising engaging a biasing device between the chamber wall and the osmotic delivery device, the biasing device being positioned to bias the osmotic delivery device against one of the end walls to facilitate release of the agent from the agent-containing portion through one or more openings defined by one of the end walls.

[0052] Exemplary embodiment 44: A method of any one of the preceding exemplary embodiments, or combinations thereof, wherein disposing the osmotic delivery device comprises disposing the osmotic delivery device within a first portion of a housing and engaging a second portion of the housing with the first portion, such that the two portions interlock to contain the osmotic delivery device within a chamber defined thereby upon engagement therebetween.

[0053] These and other features, aspects, and advantages of the present disclosure will become apparent from a reading of the following detailed description in conjunction with the accompanying drawings, which are briefly described below. The present disclosure includes any combination of two, three, four, or more features or elements described herein, whether such features or elements are explicitly combined in the description of a particular embodiment herein or otherwise described. The present disclosure is intended to be read as a whole such that any separable features or elements of the disclosure are to be considered contemplated, i.e., combinable, in any of its aspects and embodiments, unless the context clearly dictates otherwise.

[0054] It will be understood that the Abstract of this specification is provided merely for the purpose of summarizing some exemplary aspects to provide a basic understanding of the present disclosure. Accordingly, it will be understood that the exemplary aspects described above are merely examples and should not be construed to narrow the scope or spirit of the present disclosure in any way. It will be understood that the scope of the present disclosure encompasses many potential aspects in addition to those summarized herein, some of which are further described below. Furthermore, other aspects and advantages of such aspects disclosed herein will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the described aspects. [Brief explanation of the drawings]

[0055] Having described the present disclosure in general terms, therefore, reference will now be made to the accompanying drawings, which are not necessarily drawn to scale.

[0056] [Figure 1A] 1A and 1B illustrate schematically a drug delivery system according to an exemplary embodiment of the present disclosure. [Figure 1B] 1A-1C schematically illustrate osmotic delivery devices usable in drug delivery systems according to various aspects of the present disclosure. [Figure 2A] 1B and 1C schematically illustrate a perspective view, a top view, and a side view, respectively, of a drug delivery system according to the exemplary embodiment shown in FIG. 1A. [Figure 2B] 1B and 1C schematically illustrate a perspective view, a top view, and a side view, respectively, of a drug delivery system according to the exemplary embodiment shown in FIG. 1A. [Figure 2C] 1B and 1C schematically illustrate a perspective view, a top view, and a side view, respectively, of a drug delivery system according to the exemplary embodiment shown in FIG. 1A. [Figure 3A] 10A-10C schematically illustrate perspective, top, and side views, respectively, of a drug delivery system having a different housing removal device according to another exemplary aspect of the present disclosure. [Figure 3B] 10A-10C schematically illustrate perspective, top, and side views, respectively, of a drug delivery system having a different housing removal device according to another exemplary aspect of the present disclosure. [Figure 3C] 10A-10C schematically illustrate perspective, top, and side views, respectively, of a drug delivery system having a different housing removal device according to another exemplary aspect of the present disclosure. [Figure 4A] 10A-10C schematically illustrate a perspective view, a top view, and a side view, respectively, of a medication delivery system having another different housing removal device, according to a further exemplary aspect of the present disclosure; [Figure 4B] 10A-10C schematically illustrate a perspective view, a top view, and a side view, respectively, of a medication delivery system having another different housing removal device, according to a further exemplary aspect of the present disclosure; [Figure 4C]10A-10C schematically illustrate a perspective view, a top view, and a side view, respectively, of a medication delivery system having another different housing removal device, according to a further exemplary aspect of the present disclosure; [Figure 5A] 10A-10D schematically illustrate perspective views of drug delivery systems having different retention devices according to other exemplary aspects of the present disclosure; [Figure 5B] 10A-10D schematically illustrate perspective views of drug delivery systems having different retention devices according to other exemplary aspects of the present disclosure; [Figure 6] 10A and 10B schematically illustrate an exemplary alternative embodiment of a medication delivery system according to the present disclosure having a housing with two interlocking portions and a cantilevered serpentine retention member. [Figure 7] 10A and 10B schematically illustrate an exemplary alternative embodiment of a medication delivery system according to the present disclosure having a housing with two interlocking portions and a cantilevered serpentine retention member. [Figure 8] 10A and 10B schematically illustrate an exemplary alternative embodiment of a medication delivery system according to the present disclosure having a housing with two interlocking portions and a cantilevered serpentine retention member. [Figure 9] 10A and 10B schematically illustrate an exemplary alternative embodiment of a medication delivery system according to the present disclosure having a housing with two interlocking portions and a retaining member including an oval ring. [Figure 10] 10A and 10B schematically illustrate an exemplary alternative embodiment of a medication delivery system according to the present disclosure having a housing with two interlocking portions and a retaining member including an oval ring. [Figure 11] 10A and 10B schematically illustrate an exemplary alternative embodiment of a medication delivery system according to the present disclosure having a housing with two interlocking portions and a retaining member including an oval ring. [Figure 12] 10A and 10B schematically illustrate an elongated handle having a hook member that engages a distal end of the handle for engaging a housing removal device of a medication delivery system to remove the housing from a body orifice, according to one aspect of the present disclosure. [Figure 13A]1A and 1B schematically illustrate a removable end cap of a housing of a drug delivery system according to one aspect of the present disclosure. [Figure 13B] 10A-10C schematically illustrate a removable end cap of a housing of a drug delivery system according to one aspect of the present disclosure, the end cap having an elongated tether that engages with the end cap as part of a housing removal device for removing the drug delivery system from a body orifice. [Figure 14] 10A-10C schematically illustrate an alternative removable end cap for a housing of a medication delivery system according to one aspect of the present disclosure. [Figure 15] 1A and 1B schematically illustrate a medication delivery system having a retention device including opposing retention members extending from a distal end of a stem extending from a housing, according to one aspect of the present disclosure. [Figure 16] 1A and 1B schematically illustrate a medication delivery system having a retention device including opposing retention members extending from a distal end of a stem extending from a housing, according to one aspect of the present disclosure. [Figure 17] 10A and 10B schematically illustrate a medication delivery system having a retention device including opposing retention members extending from a distal end of a stem extending from a housing, according to an alternative aspect of the present disclosure; [Figure 18] 10A and 10B schematically illustrate a medication delivery system having a retention device including opposing retention members extending from a distal end of a stem extending from a housing, according to an alternative aspect of the present disclosure; DETAILED DESCRIPTION OF THE INVENTION

[0057] The present disclosure will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all, aspects of the present disclosure are shown. Indeed, this disclosure may be embodied in many different forms and should not be construed as limited to the aspects set forth herein; rather, these aspects are provided so that this disclosure will satisfy applicable legal requirements. Like numbers refer to like elements throughout.

[0058] 1A schematically illustrates an intra-orifice drug delivery system, generally designated by the numeral 100, according to one embodiment of the present disclosure. In such embodiment, system 100 includes a housing 110 having a chamber wall 112 defining an interior chamber 113 extending along a longitudinal axis D from a first end 115 to a second end 116. Chamber wall 112 further defines one or more openings 114 extending from chamber 113 through chamber wall 112. In certain embodiments, osmotic delivery device 120 (see also FIG. 1B ) is disposed within chamber 113 and includes an osmogen portion 122 and a drug-containing portion 124 disposed within a semipermeable membrane 125.

[0059] 1A, an elongated stem 126 extends from a first end 115 of the housing 110 along a longitudinal axis D, and the retainer 135 includes one or more retaining members 140 extending from the stem 126. In some embodiments, each retaining member 140 includes a body 141 having a proximal end that engages the stem 126 and extends to a distal end. In some examples, a terminal member 142 engages the distal end of the body 141.

[0060] In one exemplary embodiment, system 100, including housing 110 and retainer 135, is particularly adapted for insertion into a bodily orifice of an animal (e.g., a female mammal such as a pig), the bodily orifice (e.g., the vaginal opening) being defined by an orifice wall. Upon insertion into the orifice, system 100 is configured to deliver a drug from chamber 113 (e.g., from drug-containing portion 124 of osmotic delivery device 120), through opening 114, and into the bodily orifice, such that the drug is absorbed into the animal's body through the orifice wall. Thus, in certain aspects of the present disclosure, system 100 is further configured such that retainer 135 is adapted to removably retain housing 110 within the orifice defined by the orifice wall.

[0061] To facilitate removability of the system 100 from the orifice, some embodiments of the present disclosure further include a housing removal device 150 that engages with the housing 110 or the retaining device 135, where the housing removal device 150 is adapted to facilitate removal of the housing 110 from the orifice. In the exemplary embodiment shown in FIG. 1A , the housing removal device 150 engages with the housing 110 via the stem 126. That is, the housing removal device 150 engages with the distal end of the stem 126 opposite the engagement of the proximal end of the stem 126 with the first end 115 of the housing 110. The retaining device 135 can be engaged in-line between the housing removal device 150 and the housing 110, or, as shown in FIG. 1A , the retaining device 135 engages with the stem 126 between the housing removal device 150 and the housing 110. In the particular embodiment shown in FIG. 1A , the housing removal device 150 includes a ring member 155.

[0062] In some embodiments, system 100 can be positioned such that, when inserted into a body orifice, housing 110 and retention device 135 are disposed within the orifice, while housing removal device 150 is disposed outside the orifice. However, in other examples, housing removal device 150 can also be disposed within the orifice upon insertion of system 100. In some examples, instead of directly engaging housing removal device 150 to remove system 100 from the orifice (e.g., after delivery of a sufficient dose of the agent to the orifice), housing removal device 150 can further include a removal member (see, e.g., element 660 in FIG. 6 , element 960 in FIG. 9 , or element 1260 in FIG. 12 ). More specifically, the removal member can include an elongated handle having a distal end including a hook member positioned to engage ring member 155 to facilitate removal of housing 110 from the orifice.

[0063] 1A , the retention device 135 includes one or more retention members 140 (e.g., a body 141 thereof) that engage with the housing 110 or stem 126 and extend away from the housing 110 or stem 126 such that the one or more retention members 140 are positioned to be biased toward and into engagement with the orifice wall to retain the housing 110 within the orifice. For example, the one or more retention members 140 may be cantilevered relative to the housing 110 or stem 126. In such an arrangement, the one or more retention members 140 are flexible, or the engagement between the one or more retention members 140 and the housing 110 or stem 126 is flexible. Thus, the flexibility associated with the one or more retention members 140 biases at least a distal end of the one or more retention members 140 into interaction with the orifice wall to retain the housing within the body orifice. In some embodiments, the housing 110 defines a maximum diameter perpendicular to the longitudinal axis D, and the distal ends of the one or more retention members 140, or rounded members (e.g., terminal members 142) engaging therewith, extend outwardly from the housing 110 or stem 126 greater than the maximum diameter of the housing 110. The greater extension of the one or more retention members 140 outside the diameter of the housing 110 facilitates and secures engagement between the distal ends of the one or more retention members 140 and the orifice wall.

[0064] This same flexibility associated with the one or more retention members 140 further facilitates and enables the distal end of the one or more retention members 140 to disengage from the orifice wall (e.g., in response to an outward longitudinal force applied by the housing removal device 150) to remove the housing 110 from the body orifice. That is, in response to an outward longitudinal force applied by the housing removal device 150, the flexible one or more retention members 140 are pushed toward the housing 110 / stem 126, thereby allowing the housing 110 to be removed through the body orifice. In some embodiments, the distal end of the one or more retention members 140 is rounded or includes a rounded member (e.g., terminal member 142) that engages the distal end to facilitate removal of the housing 110 from the body orifice and / or to prevent perforation of the orifice wall by the distal end of the one or more retention members 140.

[0065] 1B , osmogenic portion 122 is disposed in contact with drug-containing portion 124, and semipermeable membrane 125 comprises a coating collectively disposed around osmogenic portion 122 and drug-containing portion 124. That is, no portion of membrane 125 or a different membrane is present between osmogenic portion 122 and drug-containing portion 124, although such a portion of membrane or a different membrane may be included between osmogenic portion 122 and drug-containing portion 124 as needed or desired. In any example, osmogenic portion 122 of osmotic delivery device 120 is configured to expand and apply pressure to drug-containing portion 124 in response to absorption by osmogenic portion 122 of fluid from within a body orifice that enters housing 110 through one or more openings 114 and permeates membrane 125. Drug-containing portion 124 is further configured to release drug in response to the pressure applied by expanded osmogenic portion 122. That is, osmotic delivery device 120 is arranged to function as a pump to expel, for example, a drug into chamber 113 and from housing 110 into a body orifice. Upon expulsion by drug-containing portion 124, the drug exits housing 110 through one or more openings 114 such that the drug is delivered into the body orifice.

[0066] To facilitate transport of liquid from the orifice or drug from drug-containing portion 124 across membrane 125, membrane 125 may be composed of a semipermeable material, such as a coating composition including, for example, cellulose acetate (CA), cellulose acetate butyrate (CAB), and polyethylene glycol (PEG). According to some embodiments, the semipermeable material is selected to allow the inflow of bodily fluids (e.g., water) while preventing or limiting the outflow of drug. Thus, in some embodiments, one or more membrane orifices 127 ( FIG. 1B ) may be formed in membrane 125 around drug-containing portion 124 (e.g., by drilling) to facilitate drug release through membrane 125. In certain embodiments, such formed membrane orifices 127 in membrane 125 are formed at longitudinal ends of membrane 125 that extend above drug-releasing portion 124. Thus, drug release from osmotic delivery device 120 occurs through physically formed holes in membrane 125 instead of via a permeation mechanism through intact membrane 125.

[0067] In some embodiments, membrane 125, drug-containing portion 124, and / or osmogen portion 122 are configured to cause drug-containing portion 124 to release the drug at a predetermined rate. For example, osmogen portion 122 can be composed of, for example, magnesium stearate, which absorbs liquid at a known or controllable rate. In another example, drug-containing portion 124 includes a drug, including, for example, a steroid, hormone, cytokine signaling molecule, pain management drug, vaccine antigen, eicosanoid, immunomodulator, protein, peptide, glycoprotein, or combination thereof, associated with or absorbed within a carrier matrix, and pressure applied to the carrier matrix causes the drug to be released at a predetermined or controllable rate.

[0068] In some embodiments, the chamber wall 112 is generally cylindrical and has opposing first and second ends 115 and 116, and the housing 110 includes end walls engaging each opposing end (see, e.g., elements 1360 and 1402 in FIGS. 13A, 13B, and 14). In such cases, one or both of the end walls 1360, 1402 define one or more openings (see, e.g., element 1361 in FIG. 13A or 13B). In some such embodiments, the drug-containing portion 124 of the osmotic delivery device 120 is disposed adjacent to one of the end walls 1360, 1402 that defines one or more openings 1361 (or see, e.g., element 114 in FIG. 1A) such that at least a portion of the drug can be released from the housing 110 through the one or more openings 114, 1361. 1A , the housing 110 includes two interlocking portions, such as a body portion 1101 and a cap portion 1102, which cooperate to define a chamber 113 for containing the osmotic delivery device 120 upon engagement therebetween. That is, the end caps 1360, 1402 engaging with the chamber walls 112, or the body portion 1101 engaging with the cap portion 1102, facilitates insertion of the osmotic delivery device 120 into the chamber 113. Furthermore, at least the exterior shape, contour, or configuration of the housing 110 is rounded (e.g., free of sharp edges or corners) to facilitate insertion / removal of the housing 110 (and / or the end caps and / or the first and second interlocking portions) from the orifice and / or to prevent or reduce the risk of puncturing or other damage to the orifice walls.

[0069] In some embodiments, osmotic delivery device 120 is cylindrical, corresponding to chamber 113, which is also cylindrical. In such embodiments, chamber wall 112 can include, for example, one or more protrusions (see, e.g., element 775 in FIG. 7 ) extending from chamber wall 112 into chamber 113. Thus, osmotic delivery device 120 housed in chamber 113 is supported by one or more protrusions 775 spaced from chamber wall 112. In this manner, fluid / liquid from the orifice entering chamber 113 through opening 114 is more evenly distributed around osmotic delivery device 120, for example, to allow osmogenic portion 122 to more evenly and uniformly absorb the fluid / liquid for the disclosed pumping function or to provide pressure to drug-containing portion 124 for releasing the drug. Furthermore, in additional aspects, the opening 114 defined by the housing 110 may be angled (e.g., a larger opening on the outer surface of the chamber wall 112 tapering to a smaller opening on the inner surface of the chamber wall 112 (see, e.g., element 175 in Figures 2A-2C, 3A-3C, 4A-4C, and 5A-5B)), shaped (e.g., as a venturi), or otherwise configured (e.g., as a one-way valve) to provide for increased drawing or withdrawal of fluid / liquid from the orifice into the chamber 113.

[0070] In yet another embodiment, as shown in FIG. 1A , for example, the osmogenic portion 122 of the osmotic delivery system 120 is disposed toward the first end 115 of the housing 110, while the drug-containing portion 124 is disposed toward the second end 116. In such a case, the second end 116 also includes one or more holes (e.g., element 114 in FIG. 1A ), while one or more membrane orifices 127 formed in the membrane 125 around the drug-containing portion 124 of the osmotic delivery device 120 (e.g., by drilling) correspond to the holes. In such an embodiment, the drug released through the membrane orifices 127 in the membrane 125 around the longitudinal ends of the drug-containing portion 124 is intended to be released from the housing through one or more holes in the second end 116 of the housing 110. However, if drug-containing portion 124 does not tightly engage chamber wall 112 around second end 116 of housing 110, drug released by drug-containing portion 124 may tend to migrate within chamber 113, between chamber wall 112 and around osmotic delivery device 120, toward osmogenic portion 122. Thus, in some embodiments, drug-containing portion 124 may be configured to fit with close tolerances to chamber wall 112 toward second end 116, or a biasing member (not shown) may be positioned to bias osmotic delivery device 120 toward the end wall of chamber 113 toward second end 116, such that membrane 125 engages the end wall of chamber 113. In such a case, the released drug is pushed through opening 114 and out of chamber 113, avoiding remaining within chamber 113.

[0071] According to some embodiments of the present disclosure, an erodible body may be used in place of or in combination with the osmotic delivery device 120. In some examples, the erodible body is in the form of a tablet. The erodible body may include a drug component capable of releasing a pharmaceutically active ingredient at a predictable release rate, such as for at least seven days. The erodible body may be either a physical blend or a chemical mixture of the active ingredient with a slowly dissolving (erodible) or swellable polymer and other inactive ingredients. The release rate of the active ingredient from the erodible body may be a function of the composition of each component and their physicochemical properties. Generally, release rate control from the erodible body may be achieved by controlling the inflow of fluid (e.g., water) into the retention device 135. Dissolution rate control may or may not be combined with solubility enhancement technology to achieve a desired rate or duration of drug release. In some examples, the erodible body may include one or more active ingredients and excipients, and disintegrate / dissolve (erode) upon complete release of the drug payload, thereby making the retention device 135 reusable or easy to dispose of. Drug ingredients may include drugs including, for example, steroids, hormones, cytokine signaling molecules, pain management drugs, vaccine antigens, eicosanoids, immunomodulators, proteins, peptides, glycoproteins, or combinations thereof. The drug ingredients may be associated with or absorbed into a carrier matrix.

[0072] In various embodiments, system 100, including housing 110, stem 126, one or more retention members 140, and housing removal device 150, is constructed from a polymeric material, such as, for example, nylon 6 / 6, and formed, for example, in an injection molding process. However, one skilled in the art will appreciate that system 100 can be constructed from many different materials, whether polymeric or non-polymeric, or combinations thereof, as needed or desired.

[0073] 1A and 2A-2C schematically illustrate an embodiment in which terminal member 142 of retaining member 140 is a ring that engages the distal end of body 141. Housing removal tool 150 also engages the distal end of stem 126 and includes ring member 155. In addition, housing 110 is configured to include an interlocking body portion 1101 and a cap portion 1102.

[0074] 3A-3C schematically illustrate an embodiment of a drug delivery system 300 similar to the embodiment shown in FIGS. 1A and 2A-2C, the system including a housing removal device 150 configured to include a textured gripping portion 350 for facilitating gripping by a user for insertion / removal of the system 300 from an orifice.

[0075] 4A-4C schematically illustrate an embodiment of a drug delivery system 400 similar to the embodiment shown in FIGS. 3A-3C, in which the textured gripping portion 450 of the housing removal device 150 is tapered and reduced in size.

[0076] 5A-5B schematically illustrate two embodiments of drug delivery systems 500A, 500B similar to the embodiments shown in Figures 1A and 2A-2C, including a reduced cross-section gripping portion 550 of ring member 155 of housing removal device 150. Additionally, the terminal member of the retaining member may be a spherical terminal member 542A (Figure 5A) as opposed to ring member 542B (Figure 5B).

[0077] FIG. 6 schematically illustrates an embodiment of a drug delivery system 600 including a body portion 6101 and an interlocking cap portion 6102, similar to the embodiment shown in FIGS. 1A and 2A-2C. Additionally, the resilient retention member 640 includes a serpentine body 641 extending from the stem 626 to a distal end, the distal end having a rounded (arcuate or convex) terminal member 642 engaging therewith. In addition to the flexibility of the material comprising the serpentine body 641, the serpentine body 641 provides a resilient or biasing force that urges the rounded terminal member into engagement with the orifice wall. Additionally, the removal member 660 includes an elongated handle having a distal end with a hook member positioned to engage with the ring member 655 to facilitate removal from the orifice of the housing 610. The dimensions shown in FIG. 6 are exemplary only and are non-limiting.

[0078] Figures 7 and 8 schematically illustrate alternative embodiments of drug delivery systems 700, 800, similar to the embodiment shown in Figure 6, in which rounded terminal members 742, 842 include overmolded outer layers 7401, 8401. Also shown are reduced cross-section gripping portions 750, 850 of ring members 755, 855 of housing removal devices 750, 850. The dimensions shown in Figures 7 and 8 are for illustrative purposes only and are not limiting.

[0079] Similar to the embodiment shown in FIGS. 6-8, FIGS. 9-11 schematically illustrate alternative embodiments of drug delivery systems 900, 1000, and 1100, in which the bodies 941, 1041, and 1141 of the resilient retention members 940, 1040, and 1140 are configured as elliptical rings. However, those skilled in the art will understand that the elliptical rings can be replaced with circular rings, if necessary or desired. In addition to the flexibility of the material comprising the elliptical ring bodies 941, 1041, and 1141, the elliptical ring bodies 941, 1041, and 1141 provide a resilient or biasing force that urges the rounded terminal members into engagement with the orifice wall. Additionally, the removal member 960 of FIG. 9 includes an elongated handle having a distal end with a hook member positioned to engage the ring member to facilitate removal from the housing orifice. The dimensions shown in FIGS. 9-11 are exemplary only and are not limiting.

[0080] Figure 12 schematically illustrates an embodiment of a removal member 1260 similar to those shown in Figures 6 and 9, including an elongated handle having a distal end with a hook member positioned to engage a ring member of a housing removal device of a drug delivery system to facilitate removal from the housing orifice. The dimensions shown in Figure 12 are exemplary only and are non-limiting.

[0081] 13A-13B and 14 schematically illustrate end cap portions 1360, 1402 of a drug delivery system that implement cylindrical chamber walls configured to interlockingly accommodate the end cap portions 1360, 1402 shown. Dimensions shown in FIGS. 13A and 14 are exemplary only and are non-limiting. In the embodiment shown in FIGS. 13A-13B, the end cap portion 1360 defines an opening 1361 through which drug released by the osmotic delivery device is dispensed. In some examples, the end cap portion can define a further opening 1362 for receiving and engaging a removal member 1363 (see, e.g., FIG. 13B) configured to facilitate removal from the orifice of the drug delivery system.

[0082] 15-18 schematically illustrate alternative embodiments of a drug delivery system according to further aspects of the present disclosure, in which a laterally outwardly extending retention member forms a "T"-shaped configuration of the retention device. In this manner, the retention device is configured to engage a housing having either one or both of the end cap portions shown in FIGS. 13A, 13B, or 14. In this embodiment, end cap portion 1360 having removal member 1363 (see, e.g., FIG. 13B) engages one longitudinal end of the housing, while the retention member / retention device engages the opposite longitudinal end of the housing. Thus configured, the retention device is disposed on the opposite side of the housing from the housing removal device, and thus guides the housing as it is inserted into the orifice along longitudinal axis D.

[0083] Many modifications and other embodiments of the inventions described herein will suggest themselves to one skilled in the art to which these disclosed embodiments pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. It is therefore to be understood that embodiments of the invention are not limited to the particular embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the present invention. Furthermore, while the foregoing description and the associated drawings describe exemplary embodiments in the context of particular example combinations of elements and / or functions, it is to be understood that different combinations of elements and / or functions may be provided by alternative embodiments without departing from the scope of the present disclosure. In this regard, for example, different combinations of elements and / or functions than those explicitly described above are also contemplated within the scope of the present disclosure. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0084] Terms such as first, second, etc. may be used herein to describe various steps or calculations, but it should be understood that these steps or calculations should not be limited by these terms. These terms are used only to distinguish one operation or calculation from another. For example, a first calculation may be referred to as a second calculation, and similarly, a second step may be referred to as a first step, without departing from the scope of the present invention. As used herein, the term "and / or" and the symbol " / " include any and all combinations of one or more of the associated listed items.

[0085] As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly dictates otherwise. It will be further understood that the terms "comprises," "comprising," "includes," and / or "including," as used herein, specify the presence of stated features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or groups thereof. Accordingly, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

Claims

1. 1. An intra-orifice drug delivery system comprising: a housing having a chamber wall defining an inner chamber extending along a longitudinal axis, the chamber wall further defining one or more openings extending from the inner chamber through the chamber wall; a retention device engaging and extending from the housing, the retention device adapted to removably retain the housing within a body orifice defined by an orifice wall; and an osmotic delivery device disposed within the inner chamber, the osmogenic portion being disposed within a semipermeable membrane, the osmogenic portion being configured to expand in response to absorption of fluid from within the body orifice through the semipermeable membrane and apply pressure to the drug-containing portion, the drug-containing portion being configured to release drug in response to the pressure applied by the expanded osmogenic portion, the drug exiting through a membrane orifice defined by the semipermeable membrane and thereafter exiting the housing through the one or more openings so that the drug is delivered into the body orifice.

2. The system of claim 1 , comprising a housing removal device adapted to engage the housing or the retention device and to facilitate removal of the housing from the body orifice.

3. The system of claim 2 , wherein the housing removal device engages the housing via a stem disposed therebetween, the stem extending along the longitudinal axis.

4. The system of claim 2 , wherein the housing removal device comprises a ring member.

5. 5. The system of claim 4, wherein the housing removal device further comprises an elongated handle having a distal end including a hook member positioned to engage the ring member to facilitate removal of the housing from the body orifice.

6. The system of claim 2 , wherein the retaining device engages inline between the housing removal device and the housing.

7. The system of claim 2 , wherein the retaining device engages a first end of the housing and the housing removal device engages a second end of the housing.

8. The system of claim 3 , wherein the retaining device engages the stem between the housing removal device and the housing.

9. 4. The system of claim 3, wherein the retention device includes one or more retention members that engage with the housing or the stem and extend away from the housing or the stem so as to be biased toward and positioned in engagement with the orifice wall to retain the housing within the body orifice.

10. The system of claim 9 , wherein the one or more retaining members are cantilevered relative to the housing or the stem.

11. 10. The system of claim 9, wherein the one or more retaining members are flexible or the engagement between the one or more retaining members and the housing or the stem is flexible, and the flexibility associated with the one or more retaining members urges the one or more retaining members into interaction with the orifice wall to retain the housing within the body orifice or facilitates disengagement of the one or more retaining members from the orifice wall to remove the housing from the body orifice.

12. 10. The system of claim 9, wherein the distal end of the one or more retention members is rounded or includes a rounded member that engages with the distal end to prevent the distal end from perforating the orifice wall or to facilitate removal of the housing from the body orifice.

13. 13. The system of claim 12, wherein the housing defines a maximum diameter perpendicular to the longitudinal axis, and the distal ends of the one or more retention members, or the rounded members engaging therewith, extend outwardly from the stem greater than the maximum diameter of the housing.

14. The system of claim 1 , wherein the semipermeable membrane, the drug-containing portion, or the osmogen portion is configured to cause the drug-containing portion to release the drug at a predetermined rate.

15. 2. The system of claim 1, wherein the one or more openings defined by the chamber wall and extending from the inner chamber through the chamber wall define a relatively large open area around an outer surface of the chamber wall and a relatively small open area around an inner surface of the chamber wall for funneling liquid from the body orifice into the inner chamber.

16. 10. The system of claim 1, further comprising one or more protrusions extending from the chamber wall into the inner chamber, the one or more protrusions facilitating spacing of the osmotic delivery device away from the chamber wall to facilitate circulation of liquid around the osmotic delivery device.

17. 2. The system of claim 1, wherein the chamber wall is generally cylindrical and has opposing first and second ends, the housing including end walls engaging each of the opposing ends, one of the end walls defining one or more openings.

18. 20. The system of claim 17, wherein the drug-containing portion of the osmotic delivery device is disposed adjacent to the one of the end walls that define the one or more openings.

19. 20. The system of claim 18, comprising a biasing device engaged between the chamber wall and the osmotic delivery device, the biasing device being positioned to bias the osmotic delivery device against the one of the end walls to facilitate release of the agent from the agent-containing portion through the one or more openings defined by the one of the end walls.

20. The system of claim 1 , wherein the osmogen portion is disposed in contact with the drug-containing portion, and the semipermeable membrane comprises a coating disposed around the osmogen portion and the drug-containing portion.

21. 10. The system of claim 1, wherein the housing comprises two interlocking portions that, when engaged therebetween, contain the osmotic delivery device within the internal chamber defined thereby.

22. 1. A method of forming an intra-orifice drug delivery system, comprising: forming a housing having a chamber wall defining an interior chamber extending along a longitudinal axis, the chamber wall defining one or more openings extending from the interior chamber through the chamber wall; engaging a retention device with the housing, the retention device extending from the housing and adapted to removably retain the housing within a body orifice defined by an orifice wall; disposing an osmotic delivery device in the internal chamber, the osmogenic portion including an osmogen portion and a drug-containing portion disposed within a semipermeable membrane, such that the osmogenic portion is configured to expand in response to absorption of fluid from within the body orifice through the semipermeable membrane and apply pressure to the drug-containing portion, the drug-containing portion is configured to release drug in response to the pressure applied by the expanded osmogenic portion, and the drug exits through a membrane orifice defined by the semipermeable membrane and thereafter exits the housing through the one or more openings and is delivered into the body orifice.

23. 23. The method of claim 22, comprising engaging a housing removal device with the housing or the retention device, the housing removal device adapted to facilitate removal of the housing from the body orifice.

24. 24. The method of claim 23, wherein engaging the housing removal device comprises engaging the housing removal device with the housing via a stem disposed between the housing and extending along the longitudinal axis.

25. 24. The method of claim 23, wherein engaging the housing removal device includes engaging a ring member of the housing removal device with the housing or the retaining device.

26. 26. The method of claim 25, comprising engaging the ring member of the housing removal device with a distal end of an elongated handle, the distal end including a hook member positioned to engage the ring member to facilitate removal of the housing from the body orifice.

27. 24. The method of claim 23, wherein engaging the retaining device comprises engaging the retaining device in-line between the housing removal device and the housing.

28. 24. The method of claim 23, wherein engaging the retaining device comprises engaging the retaining device with a first end of the housing and engaging the housing removal device with a second end of the housing.

29. 25. The method of claim 24, wherein engaging the retainer comprises engaging the retainer with the stem between the housing removal tool and the housing.

30. 25. The method of claim 24, wherein engaging the retention device includes engaging one or more retention members with the housing or the stem and extending away from the housing or the stem such that the one or more retention members are biased toward and positioned in engagement with the orifice wall to retain the housing within the body orifice.

31. The one or more retaining members are arranged in a cantilevered manner relative to the housing or the stem.

31. The method of claim 30, comprising:

32. The method of claim 30, comprising rounding the distal ends of the one or more retaining members or engaging a rounded member with each of the distal ends to prevent perforation of the orifice wall by the distal ends of the one or more retaining members or to facilitate removal of the housing from the body orifice.

33. 33. The method of claim 32, wherein the housing defines a maximum diameter perpendicular to the longitudinal axis, and wherein rounding the distal end or engaging the rounded member comprises rounding the distal end or engaging the rounded member with each of the distal ends of the one or more retention members such that the distal end, or the rounded member engaging therewith, is larger than the maximum diameter of the housing and extends outward from the stem.

34. 23. The method of claim 22, comprising positioning the semipermeable membrane, the drug-containing portion, or the osmogen portion to cause the drug-containing portion to release the drug at a predetermined rate.

35. 23. The method of claim 22, comprising forming the one or more openings defined by the chamber wall such that the one or more openings define a relatively large open area around an outer surface of the chamber wall and a relatively small open area around an inner surface of the chamber wall.

36. 23. The method of claim 22, comprising forming one or more protrusions extending from the chamber wall into the inner chamber, the one or more protrusions facilitating spacing of the osmotic delivery device away from the chamber wall to facilitate circulation of liquid around the osmotic delivery device.

37. 23. The method of claim 22, wherein forming the housing comprises forming the housing so that the chamber wall is generally cylindrical and has opposite first and second ends, and engaging an end wall with each opposite end, one of the end walls defining one or more openings.

38. 38. The method of claim 37, wherein disposing the osmotic delivery device comprises disposing the osmotic delivery device within the inner chamber such that the drug-containing portion of the osmotic delivery device is disposed adjacent to the one of the end walls defining the one or more openings.

39. 39. The method of claim 38, comprising engaging a biasing device between the chamber wall and the osmotic delivery device, the biasing device being positioned to bias the osmotic delivery device against the one of the end walls to facilitate expulsion of the agent from the agent-containing portion through the one or more openings defined by the one of the end walls.

40. 23. The method of claim 22, wherein disposing the osmotic delivery device comprises disposing the osmotic delivery device within a first portion of the housing and engaging a second portion of the housing with the first portion such that the two portions interlock to contain the osmotic delivery device within the internal chamber defined thereby upon engagement therebetween.

Images