Claims
- 1. An improvement in a device for delivering a beneficial agent composition to a fluid environment of use, wherein the device comprises:
- (a) a wall comprising a composition that is permeable to the passage of fluid and is substantially impermeable to the passage of agent, which wall surrounds and forms;
- (b) a compartment, and wherein the improvement comprises;
- (c) a beneficial agent composition comprising a beneficial agent and 10% to 90% of an osmopolymer in the compartment, which beneficial agent composition is delivered substantially as a ribbon, at a rate expressed by ##EQU41## is the does of beneficial agent delivered in unit time, ##EQU42## is the total volume of the agent composition delivered in unit time, and C.sub.D is the amount of beneficial agent mixed with the osmopolymer composition delivered from the device;
- (d) a push composition in contact with the beneficial agent composition in the compartment, which push composition, in the presence of fluid that enters the device, increases in dimension and pushes the beneficial agent composition from the device; and,
- (e) exit means in the wall for delivering the beneficial agent composition from the device, at a controlled rate over time.
- 2. An improvement i a device for delivering a beneficial agent to a fluid environment of use, wherein the device comprises:
- (a) a wall comprising a composition that is permeable to the passage of fluid and is substantially impermeable to the passage of agent, which wall surrounds and defines;
- (b) a compartment, and wherein the improvement comprises;
- (c) a beneficial agent composition in the compartment comprising 10% to 90% of an osmopolymer and an osmagent that exhibit fluid influx, which beneficial agent composition is delivered substantially as a ribbon, and when the device is in operation in a fluid environment, a fluid influx ##EQU43## wherein dV is the volume influxed in unit time dt; (d) a push composition in contact with the beneficial agent composition in the compartment, said push composition exhibiting, when the device is in operation, a fluid influx ##EQU44## wherein dV is the volume influxed in unit time dt; and, (e) at least one exit orifice in the wall for delivering the beneficial agent by the cooperating operation of beneficial agent composition and the push composition acting together for delivering the beneficial agent through said orifice.
- 3. An improvement in a device for delivering a beneficial agent to a fluid environment of use, wherein the device comprises:
- (a) a wall comprising a composition that is permeable to the passage of fluid and is substantially impermeable to the passage of agent, which wall surrounds;
- (b) a compartment, and wherein the improvement comprises:
- (c) a beneficial agent composition in the compartment that is delivered substantially as a ribbon, which composition comprises 10% to 90% of means for absorbing fluid that enters the compartment at a rate ##EQU45## for providing at least a fraction of the composition comprising fluid in unit time dt;
- (d) a push composition in contact with the beneficial agent composition in the compartment, which push composition absorbs fluid that enters the compartment at a rate ##EQU46## for providing at least in part a fraction of the push needed for pushing the beneficial agent compoition from the device at a rate comprising ##EQU47## wherein F.sub.D is the fraction of beneficial agent in the agent composition and .rho..sub.dc is the density of the beneficial agent composition; and,
- (e) at least one exit pore passageway in the wall for delivering the beneficial agent composition from the device, at a rate governed by the wall, the beneficial agent composition and the push composition interacting to deliver the beneficial agent through the orifice.
BACKGROUND OF THE INVENTION
This patent application is a continuation-in-part of U.S. Pat. Appln. Ser. No. 07/212,552, filed on June 28, 1988 which patent application is a continuation-in-part of U.S. Pat. Appln. Ser. No. 06/912,712, filed on Sept. 29, 1986, now U.S. Pat. No. 4,783,337 issued on Nov. 8, 1988, which Appln. Ser. No. 06/912,712 is a continuation-in-part of U.S. Pat. Appln. Ser. No. 06/685,687 filed on Dec. 24, 1984 (now abandoned), which Appln. Ser. No. 06/685,687 is a continuation-in-part of U.S. Pat. Appln. Ser. No. 06/493,760 filed May 11, 1983 (now abandoned), which applications are incorporated herein by reference and benefits are claimed of their filing dates. These patent applications are assigned to the ALZA Corp., of Palo Alto, Calif.
This invention pertains to both a novel and unique delivery system. More particularly, the invention relates to a delivery device comprising a wall that surrounds a compartment comprising: (1) a first composition comprising a beneficial agent, an osmopolymer and optionally an osmagent, said first composition in arrangement with (2) a second composition comprising a constant pushing means for pushing the first composition from the device. The device comprises at least one passageway through the wall that connects the exterior of the device with the compartment for delivering the first composition comprising the beneficial agent from the device. The device in one presently preferred embodiment is useful for delivering (3) beneficial agents that because of their solubilities are difficult to deliver in a known amount at a controlled rate from a delivery device, and for delivering (4) beneficial agents that are therapeutically very active and are dispensed in small amounts, that is in minidoses, at a controlled rate from the dispensing system.
Since the beginning of antiquity, both pharmacy and medicine have sought a delivery system for administering a beneficial drug. The first written reference to a delivery system is in the Eber Papyrus, written about 1552 B.C. The Eber Papyrus mentions delivery systems such as anal suppositories, vaginal pessaries, ointments, oral pill formulations, and other delivery systems. About 2500 years passed without any advance in dosage form development, when the Arab physician Rhazes, 865-925 A.D., invented the coated pill. About a century later the Persian Avicenna, 980-1037 A.D., coated pills with gold or silver for increasing patient acceptability and for enhancing the effectiveness of the drug. Also around this time, the first tablet was described in Arabian manuscripts written by al-Zahrawi, 936-1009 A.D. The manuscripts described a tablet formed from the hollow impressions in two facing tablet molds. Pharmacy and medicine waited about 800 years for the next innovation in delivery systems when, in 1883, Mothes invented the capsule for administering drug. The next quantum leap in dosage forms came in 1972 with the invention of the osmotic delivery system by inventors Theeuwes and Higuchi as disclosed in U.S. Pat. Nos. 3,845,770 and 3,916,889.
The osmotic systems disclosed in U.S. Pat. Nos. 3,845,770 and 3,916,889 comprise in at least part a semipermeable wall that surrounds a compartment containing a beneficial agent. The semipermeable wall is permeable to the passage of an external fluid, and it is substantially impermeable to the passage of a beneficial agent. There is at least one passageway through the wall for delivering the beneficial agent from the osmotic system. These systems release a beneficial agent by fluid being imbibed through the semipermeable wall into the compartment at a rate determined by the thickness and permeability of the semipermeable wall and the osmotic pressure gradient across the semipermeable wall to produce an aqueous solution containing a beneficial agent that is dispensed through a passageway from the system. These systems are extraordinarily effective for delivering a beneficial agent that is soluble in the fluid and exhibits an osmotic pressure gradient across the semipermeable wall against the external fluid.
A pioneer advancement in osmotic delivery systems, manufactured in the form of an osmotic device, was presented to the dispensing arts by inventor Felix Theeuwes in U.S. Pat. No. 4,111,202. In this patent, the delivery kinetics of the osmotic device is enhanced for delivering beneficial agents, including drugs, that are insoluble to very soluble in the fluid, by manufacturing the osmotic device with a beneficial agent compartment and an osmagent compartment separated by an internal film. The internal film is movable from a rested to an expanded state. The osmotic device delivers the beneficial agent by fluid being imbibed through the semipermeable wall into the osmagent compartment producing a solution that causes the compartment to increase in volume and act as a driving force that is applied against the film. This force urges the film to expand in the device against the beneficial agent compartment and, correspondingly, diminish the volume of the beneficial agent compartment, whereby beneficial agent is dispensed through the passageway from the osmotic device. While this device operates successfully for its intended use, and while it can deliver numerous useful agents of varying solubilities, its use can be limited because of the manufacturing steps and costs needed for fabricating and placing the movable film in the compartment of the osmotic device.
In the U.S. Pat. No. 4,327,725 patentees Richard Cortese and Felix Theeuwes provided an osmotic dispensing device for delivering beneficial agents that, because of their solubilities in aqueous and biological fluids, are difficult to deliver in meaningful amounts at controlled rates over time. The osmotic devices of this patent comprise a semipermeable wall surrounding a compartment containing a beneficial agent that is insoluble to very soluble in aqueous and biological fluids, and an expandable hydrogel. In operation the hydrogel expands in the presence of external fluid that is imbibed into the device thereby dispensing the beneficial agent through the passageway from the device. This device operates successfully for its intended use, and it delivers many difficult to deliver beneficial agents for their intended purpose.
Now it has been observed that the value of the prior art system described immediately above can be enhanced unexpectedly by the present invention providing an unobvious composition comprising the beneficial agent and a pharmaceutically acceptable carrier gel, which composition cooperates with a separate expanding hydrogel for pushing the beneficial agent from the device, thereby leading to improved administration and to improved therapy. It will be appreciated by those versed in the art, that if such an osmotic device can be provided that exhibits a high level of delivery activity, such an osmotic device would have a positive value and represent an advancement in the dispensing art. Likewise, it will be immediately appreciated by those versed in the dispensing art that if an osmotic device is made available possessing dual thermodynamic osmotic activity for delivering increased amounts of a beneficial agent accompanied by a pharmaceutically acceptable carrier at a controlled rate, said osmotic device would find practical application in the fields of pharmacy and medicine.
Accordingly, in view of the above presentation, it is an immediate object of this invention to provide a delivery system that can be manufactured by standard manufacturing techniques into osmotic devices of various sizes, shapes and forms that represent a further improvement and advancement in the dispensing art.
Another object of the invention is to provide a delivery system manufactured in the form of an osmotic device for delivering in vivo a beneficial agent including drug that is difficult to delivery and now can be delivered by the device provided by this invention in therapeutically effective amounts over time.
Another object of the invention is to provide a delivery system possessing dual osmotic activity that operates as an integrated unit, which system comprises a compartment containing a first osmotic composition comprising a beneficial agent such as a drug, and an osmopolymer carrier for the agent or drug and optionally an osmagent, and a second osmotic composition comprising an osmopolymer, an optional osmagent and free of agent or drug, with the compositions acting in concert for delivering the drug through a passageway of controlled dimensions from the osmotic device.
Yet another object of the invention is to provide a delivery device having means for high loading of a water insoluble or a slightly water soluble beneficial agent such as a drug and means for delivering the beneficial agent in either instance at a controlled rate and continuously over time to a drug recipient.
Yet another object of the invention is to provide an osmotic device that can deliver a pH dependent beneficial agent by providing a neutral medium for delivering the beneficial agent in a finely dispersed form for increasing its surface area and for maximizing and dissolution rate of the beneficial agent.
Still yet another object of the invention is to provide an osmotic device for delivering a drug having a very low dissolution rate that is the rate limiting step for delivering the drug from the device, but now can be delivered by using an osmotic composition that functions in situ as a carrier that is delivered with the drug, thereby enhancing the drug's delivery from the osmotic device.
Another object of the invention is to provide an osmotic device comprising means for maintaining a high level of osmotic activity of a polymer which polymer is used for delivering a beneficial agent from the osmotic device.
Still a further object of the invention is to provide an osmotic, therapeutic device that can administer a complete pharmaceutical dosage regimen comprising poorly soluble to very soluble agents, at a controlled rate and continuously for a particular time period, the use of which requires intervention only for the initiation and possible termination of the regimen.
Still another object of this invention is to provide an osmotic device, which device can house a small amount of a therapeutic agent and dispense small doses, that is minidoses, of the therapeutic agent at a controlled rate to the gastrointestinal tract throughout the length of the gastrointestinal tract.
Still another object of the invention is to provide an improvement in an osmotic device manufactured with a compartment housing a first drug polymer means and a second drug free polymer means in spaced arrangement that simultaneously maintain their original identity and function as an integrated layered unit for delivering the beneficial drug accompanied by the first drug polymer means in paste or gel ribbon-like form from the osmotic device.
Still a further object of this invention is to provide a delivery device that possesses the ability to deliver drugs over a broad range of drug delivery rates, and can deliver the drugs according to a predetermined drug release rate pattern to a biological recipient over time.
A still further object of the invention is to provide a delivery system that avoids patient compliance problems and uses less drug, minimizes side effects and thereby provides efficiency in treatment for better health.
Other objects, features, aspects and advantages of the invention will be more apparent to those versed in the dispensing art from the following detailed specification taken in conjunction with the figures and the accompanying claims.
US Referenced Citations (21)
Continuation in Parts (4)
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Number |
Date |
Country |
| Parent |
212552 |
Jun 1988 |
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| Parent |
912712 |
Sep 1986 |
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| Parent |
685687 |
Dec 1984 |
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| Parent |
493760 |
May 1983 |
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Patent Grant
5082668
