Agent delivery systems and devices which use an expansion means can deliver a beneficial agent to an environment of use over a period of hours, days, or months. The expansion means absorbs liquid, expands, and acts to drive out beneficial agent formulation from the interior of the device in a controlled manner.
Agent delivery devices which use an expansion means can be designed to deliver agent over a relatively short term, i.e., 20-25 days or less. Such devices generally comprise a highly permeable semipermeable membrane, together with a beneficial agent in a carrier s which is liquid, relatively non-viscous, and easily extruded by the action of the expansion means. The agent delivery profile of such a short-term device is shown, for example, in FIG. 12 of U.S. Pat. No. 4,595,583, the disclosure of which is hereby incorporated by reference. As shown in U.S. Pat. No. 4,643,731, the disclosure of which is hereby incorporated by reference, instantaneous concentration of beneficial agent obtained from short-term devices can be achieved by providing a loading dose, i.e., an initial, immediate, short-term dose of beneficial agent, prior to the onset of the continuous delivery provided by the osmotic pump device.
Agent delivery devices can alternatively be designed to deliver agent over a longer term, i.e., 25-30 days or greater, and especially 60-120 days or greater. Such devices generally comprise a slowly permeable semipermeable membrane, together with a beneficial agent in a carrier which is viscous or paste-like and extruded by the action of the expansion means over relatively longer times than shown by the short-term devices. The startup time of the device, that is, the time during which the device does not deliver beneficial agent, depends upon the rate at which the semipermeable membrane allows hydration of the system and the rate at which the expansion means becomes hydrated sufficiently to begin extrusion of the beneficial formulation. The agent delivery curve of a device designed to deliver a given dosage for 120 days is shown, for example, in FIG. 21 of U.S. Pat. No. 4,729,793.
The teachings of the prior art pertaining to loading doses of beneficial agent regarding short-term delivery devices do not provide a solution to the problem of the startup delay in long-term devices. Due to the kinetics of the release of loading doses for short-term devices, the loading doses are active for only a short time and do not sustain the concentration of beneficial agent during the startup period demonstrated by long-term devices. Those loading doses provided within the coating of a short-term device are not appropriate for use with long-term devices having a semipermeable membrane, as such coatings can interfere with the permeability of the semipermeable membrane, and thus interfere with the operation of the device.
Ruminant animals, including cattle, sheep, goats, deer, bison, camels and giraffes, and especially domestic animals such as cattle, sheep and goats, comprise an important group of animals that require periodic administration of medicines and nutrients. The medicines and nutrients are administered for the treatment and alleviation of various conditions and for improved health. Ruminants have a complex stomach generally having three or four compartments. The largest of the stomach compartments is the rumen, which acts as an important location for receiving and passing medicines and nutrients into other compartments, including the abomasum and the intestine.
One method of treating ruminants requires the repeated administration of medicines and nutrients at frequent time intervals. This form of treatment is inconvenient and expensive and does not lend itself to reliable therapy.
Prior art devices which have been designed to maintain continuous dosages of a beneficial agent for extended periods of time have the disadvantage of exhibiting a significant startup time between administration to the subject animal or human and the onset of agent delivery. Provision of effective dosages upon administration of the device has been obtained by prehydration (i.e., soaking) of the device prior to administration. For example, a prior art device which exhibits a three-week delay prior to onset of effective delivery of the desired agent can be soaked for three weeks at 40.degree. C. or two months at room temperature prior to administration to the subject. Effective delivery of the desired agent thus begins upon administration.
Prehydration of a long-term device has several significant disadvantages. The soaking of a single device for a period of at least three weeks requires a processing step which is undesirable but which is likely to be manageable. The soaking of sufficient individual devices with which to supply an entire herd of animals can require a container the size of a swimming pool or a small lake. The active agent which is being delivered by the device is distributed into the water in which the device is soaked, and can require special treatment of the water before it can be released into ground or sewage waters. Additionally, if the device has limited stability (i.e., decomposition of the semipermeable membrane, density means, or other component of the device takes place over time), the time during which the device is prehydrated may limit the effective use in the subject animal. Or, prehydration of the device may require a special package, increasing the cost of the final, packaged device.
To overcome the limitations associated with the prior art delivery devices, a delivery device has been developed and is described and claimed in copending, commonly-assigned patent application U.S. Ser. No. 07/463,109, filed Jan. 10, 1990, now U.S. Pat. No. 5,045,082, to Ayer et al. for Long-Term Delivery Device Including Loading Dose. This delivery device comprises a semipermeable wall and a reservoir containing a beneficial agent formulation, an expansion means and, optionally, a density means. Additionally, it comprises another beneficial agent formulation in a loading dose that is at the surface of or within the device.
Although the device of U.S. Pat. No. 5,045,082 functions well when the beneficial agent is present in the loading dose in relatively large concentrations, when the agent is present in the loading dose in a relatively small concentration the device demonstrated an undesirably fast and unacceptably high release of the agent from the loading dose, thus providing an unacceptable release rate curve.
USPTO Backgrounds
USPTO Backgrounds