« PreviousContinue »
United States Patent [w]
Dong et al.
US005902605A [ii] Patent Number: 5,902,605  Date of Patent: May 11,1999
 DRUG DELIVERY DEVICE WITH MINIMAL RESIDUAL DRUG RETENTION
 Inventors: Liang C. Dong, Sunnyvale; Patrick S.-L. Wong, Palo Alto; Si-Hong Yum, Dale City; Crystal Pollock, Mountain View, all of Calif.
 Assignee: Alza Corporation, Palo Alto, Calif.
 Appl. No.: 08/851,525  Filed: Apr. 18, 1997
Related U.S. Application Data
[ 60] Provisional application No. 60/015,567, Apr. 18, 1996.
 Int. CI. A61K 9/22
 U.S. CI 424/453; 424/451; 424/463;
424/473; 424/438; 424/462
 Field of Search 424/451, 463,
424/473, 438, 453, 462; 604/892.1, 890.1
 References Cited
U.S. PATENT DOCUMENTS
3,845,770 11/1974 Theeuwes et al 128/260
3,865,108 2/1975 Hartop 128/260
3,995,631 12/1976 Higuchi 128/260
4,002,173 1/1977 Manning et al 128/296
4,034,756 7/1977 Higuchi et al 128/260
4,111,202 9/1978 Theeuwes 128/260
4,207,893 6/1980 Michaels 128/260
4,265,874 5/1981 Bonsen et al 424/15
4,320,759 3/1982 Theeuwes 128/260
4,327,725 5/1982 Cortese et al 128/260
4,449,983 5/1984 Cortese et al 604/892
4,595,583 6/1986 Eckenhoff et al 424/15
4,612,008 9/1986 Wong et al 604/892
4,874,388 10/1989 Wong et al 604/891.1
5,198,229 3/1993 Wong et al 424/473
5,312,388 5/1994 Wong et al 604/892.1
5,312,390 5/1994 Wong 604/892.1
5,358,502 10/1994 Herbig et al 604/892.1
5,443,459 8/1995 Wong et al. .
5,498,255 3/1996 Wong .
5,630,808 5/1997 Magruder et al. .
5,714,160 2/1998 Magruder et al. .
5,728,088 3/1998 Magruder et al. .
5,750,143 5/1998 Rashid et al. .
FOREIGN PATENT DOCUMENTS
0384642 8/1990 European Pat. Off A61K 9/22
Primary Examiner—Thurman K. Page
Assistant Examiner—Brian K. Seidleck
Attorney, Agent, or Firm—-John A. Dhuey; Steven F. Stone;
Michael J. Rafa
The present invention is directed to a fluid-imbibing drug delivery device which is useful for the initial delayed delivery of an active agent formulation to a fluid environment of use, the initial delay period to startup or activation of the device being of a predetermined length of time. The delivery of the agent formulation from the dispensing device is continued until essentially all of the active agent formulation is delivered as a result of the fluid inhibition into a fluid flow path in the housing of the device and the expansion of an expansion agent in the active agent delivery chamber.
17 Claims, 2 Drawing Sheets
DRUG DELIVERY DEVICE WITH MINIMAL
RESIDUAL DRUG RETENTION
This application claims priority of U.S. Provisional application No. 60/015,567, filed Apr. 18, 1996. 5
FIELD OF THE INVENTION
The present invention is related to the delayed delivery of an active agent to a fluid environment of use, where the active agent is minimally retained in the delivery device, Jo More particularly, the invention is an active agent delivery device that allows for water infiltration into the device to ensure release of the active agent from the device.
BACKGROUND OF THE INVENTION
Oral delivery of therapeutically active agents is a convenient and cost effective method of delivery. The active agent can be released in the mouth or anywhere in the alimentary canal. The delivery can be in a bolus, it can be intermittent, or it can be continuous. 2Q
Osmotic dispensing devices for delivery of therapeutically active agents are well known in the art. Such devices use an expansion means to deliver an agent to an environment of use over a period of hours, days or months. The expansion means absorbs liquid, expands, and acts to drive 25 out the beneficial agent formulation from the interior of the device in a controlled, usually constant manner. The osmotic expansion means is used to controllably, usually relatively slowly, and over a period of time, deliver the agent.
Osmotic devices have also been described for prolonged 30 and controlled delivery of one or more active agents where an initial delay of delivery is desired. U.S. Pat. No. 5,198, 229, which is incorporated herein by reference, is directed to an osmotic device for delivery of an active agent to the upper gastrointestinal tract. The dispensing device comprises con- 35 centric housings that are in slidably telescoping arrangement with each other. A first expansion means imbibes fluid when placed in the stomach environment. This expansion means expands and pushes against a partition layer that in turn pushes against an active agent formulation. The active agent 40 is delivered to the stomach environment through a small exit port in a controlled and continuous manner. After all the active agent has been delivered, the housings separate, the buoyancy chamber is exposed to the stomach environment, the density of the device increases, and the device sinks and 45 exits out of the stomach.
U.S. Pat. No. 5,312,388, which is incorporated herein by reference, describes the use of slidably telescopic concentric housings in an osmotic device where delivery of more than one active agent is desired or where separate dosings of one 50 active agent is desired. In a particular embodiment, initial rapid delivery of a particular active agent is followed by delayed delivery of the active agent. A loading dose of the active agent is dispensed as soon as the device enters the environment of use. Prolonged delivery is accomplished as 55 a result of an expansion means that imbibes fluid and expands to separate the concentric housings. Upon separation, the active agent contained within the housings is dispensed.
U.S. Pat. No. 5,312,390, which is incorporated herein by 60 reference, describes an osmotic device useful for the initially delayed delivery of an active agent. Slidably telescoping concentric housings separate following absorption of fluid through the housing. A fluid passage means is exposed to the fluid environment and the active agent is expelled in a 65 controlled and continuous manner through an exit port at the end of the housing opposite the fluid passage means.
U.S. Pat. No. 5,358,502, which is incorporated herein by reference, describes an osmotic device with a semipermeable membrane with an agent that is pH sensitive and thus will dissolve at a given pH, thereby releasing the contents of the device.
Bolus delivery of an active agent is described in U.S. patent application Ser. No. 08/459,387, which is incorporated herein by reference. The patent application describes a fluid-imbibing drug delivery device that is useful for the delayed delivery of drug. A first and second housing are in reversibly sliding telescoping arrangement. The first housing contains an active agent and a first expansion agent. The second housing contains a second expansion agent. The second expansion agent imbibes fluid and pushes apart the housings. The drug is delivered and the first expansion agent imbibes fluid and expands to push any remaining drug out of the device.
As can be observed in the above-referenced patents and patent applications, osmotic devices have been described that provide for an initial pulse of an active agent, that provide for prolonged delivery of an active agent, and that provide for delivery of more than one active agent. However, there remains a continuing need for improved methods and systems for delivering one or more active agents in a reliable and reproducible manner.
SUMMARY OF THE INVENTION
We have observed that devices such as those described above will open in a predictable manner but that the agent contained in the device may not always be completely released to the environment of use following the desired delay period. Accordingly, the present invention is directed to a fluid-imbibing dispensing device and a method for the essentially complete delivery of an active agent to a fluid environment of use following an initially delayed period of delivery of the agent.
In one aspect, the invention is directed to a fluid-imbibing delivery device formed of a housing and a closure for the housing. The housing contains an active agent formulation and a first expansion agent. The active agent formulation comprises at least one active agent. The housing is configured to provide a flow path between the interior of the housing and the active agent formulation. The closure comprises a second expansion agent.
The invention is further directed to a device for dispensing an active agent formulation to an environment of use following an initial period of delay, that comprises a housing with a closed end and an open end. The housing contains an active agent formulation that comprises at least one active agent. The housing further contains an expansion agent. The device further comprises a plug sealing the open end of the housing. The improvement of the invention comprises a fluid flow path between the interior of the housing and the active agent formulation.
The invention is also directed to a device for dispensing an active agent formulation to an environment of use following an initial period of delay, that comprises a first impermeable housing and a second semipermeable housing. The first and second housings are in reversibly sliding telescoping arrangement with each other. The first housing contains an active agent formulation that comprises at least one active agent. The first housing further contains a first expansion agent. The second housing contains a second expansion agent. The improvement of the invention comprises a fluid flow path between the interior of the first housing and the active agent formulation.