HK1015671B - Oral delivery of discrete units - Google Patents

Description

Oral active agent delivery system

Technical Field

The present invention relates to oral delivery of active agents. In particular, a method and apparatus for orally delivering an active agent formulation in the form of a discrete unit for mixing with a fluid is accomplished by introducing the discrete unit into a hollow active agent formulation chamber. A retainer at the first end of the chamber prevents the dispensing unit from being released from that end, but allows fluid flow when aspirating at the second end of the chamber. The dispersion unit can be easily swallowed in a mixture with the fluid inhaled through the chamber.

Background

For oral delivery of active agents are tablets, capsules, caplets and many other types of devices. These dosage forms are relatively easy to manufacture and convenient to use in a hospital or other public place or at home. Many different types of active agents have been incorporated into such dosage forms-from analgesics to antibiotics to hormones.

Some patients have difficulty swallowing solid oral dosage forms due to age or physical weakness. According to Kikendall et al,digestive diseases and science28: 2(1983), 221 cases of esophageal injuries caused by tablets and capsules were reported in 1970-1982. The most common related drugs are tetracycline (108 cases), emethylammonium bromide (36 cases), potassium chloride (16 cases) and ferrous salts (12 cases).

It can thus be seen that there is a need for oral dosage forms that are easy to use and manufacture, without swallowing large solid systems.

U.S. patent No.2,436,505 to DuRall describes a pill dispenser (pill doser) for administering a drug in liquid form or as a pill or tablet. At the top end of the device there is a circular well containing the drug and a hose which can be immersed in the liquid contained in the drinking glass. The liquid and any pills or tablets present in the well may be administered by inhalation of the liquid.

U.S. patent No.2,867,536 to Mead et al describes an improved drinking straw having an inner tube and an outer tube defining an annular space therebetween containing a soluble flavoring agent. The inner tube has an aperture for drawing in liquid. In use, the upper and lower covers are removed and the flavoring agent and flavored liquid flowing into the liquid are passed through the intake opening of the inner tube.

U.S. patent No.3,610,483 to Visconti describes a straw-shaped dispensing device for liquid medicaments. A predetermined amount of liquid medicament is loaded into the straw and then capped at both ends until the medicament is dispersed when the patient removes the caps and inhales air into the device.

EP- ｃA-0383503 discloses ｃA tubular system for delivering ｃA therapeutic agent in free-flowing form to ｃA patient. The therapeutic agent is placed in the tube or in a loop formed in the tube by a fixed, liquid permeable mesh. As the patient draws fluid through the tube, the fluid transports and diffuses the therapeutic agent from the stationary mesh or ring to the patient.

Many other oral delivery systems have been described, including: medicated pacifiers (U.S. patent No.5,123,915 to Miller et al) and lollipop-type devices for solid medications (U.S. patent No.5,223,259 to Lackney). None of these or the aforementioned devices allow delivery of solid medicaments as a bolus into the oral cavity while avoiding the swallowing difficulties inherent in solid systems such as tablets or capsules or shelf life problems encountered when the medicament is dissolved or dispersed in a fluid, preferably an aqueous liquid.

Summary of The Invention

Accordingly, one aspect of the present invention relates to an oral delivery system for delivering discrete units of an active agent formulation mixed with a fluid. The system comprises a hollow active agent formulation chamber. The chamber has a first end and a second end and contains an active agent formulation in the form of discrete units. The active agent formulation comprises an active agent. The system further comprises a fluid-permeable active agent formulation retainer at the first end of the chamber. The retainer prevents the dispensing unit from being released from the first end but allows fluid to enter the chamber.

In one embodiment, the dispersion unit contained in the chamber is in the form of microparticles.

In another embodiment, the discrete units contained in the chambers are in the form of multiple active agent dosage forms.

Another aspect of the invention relates to a method of orally delivering discrete units of an active agent formulation mixed with a fluid. The method involves placing discrete units of an active agent formulation into a hollow drug delivery chamber of a drug delivery device. The chamber has a first end and a second end. The first end of the chamber has an active agent formulation retainer through which fluid can pass. The drug delivery device has first and second ends. The first end of the drug delivery device is inserted into the fluid and the second end is placed into the patient's mouth, and the patient inhales on the second end of the device to cause the discrete units of fluid and active agent formulation to be delivered into the patient's mouth.

Drawings

The drawings are not intended to limit the scope of the invention, but are merely intended to illustrate various embodiments of the invention. The relevant numbers refer to the relevant structures.

FIG. 1A is a cross-sectional view of one embodiment of the transfer device of the present invention in a ready form prior to placement in a liquid medium. FIG. 1B is an enlarged cross-sectional view of the first end of the device of FIG. 1A.

Figure 2A shows the device of figure 1A placed in a liquid medium and delivering a portion of the active agent formulation. Fig. 2B is an enlarged cross-sectional view of a mid-section of the apparatus of fig. 2A.

Figure 3A shows the device of figure 1A after the active agent formulation has been completely delivered. Fig. 3B is an enlarged cross-sectional view of the second end of the device of fig. 3A.

Fig. 4 is a cross-sectional view of another embodiment of the delivery apparatus of the present invention in a ready form.

Fig. 5A is a cross-sectional view of a preparatory form of a third embodiment of the conveying apparatus of the present invention, fig. 5B is a bottom view, and fig. 5C and 5D are top views.

Fig. 6-9 are cross-sectional views of alternate embodiments of the delivery apparatus of the present invention in a ready form.

Detailed Description

The present invention provides a device for oral delivery of an active agent formulation in discrete units, which is easy to manufacture and use, and which can deliver a predetermined amount of active agent. The invention also provides a method of orally delivering a dispersion unit mixed with a fluid.

Definition of

The term "active agent formulation" refers to any active agent or drug in combination with a pharmaceutically acceptable carrier and other inert ingredients.

The term "discrete unit" refers to a formulation of an active agent in solid or particulate form.

As used herein, "oral dosage form" refers to an active agent formulation that maintains its physical structure and chemical integrity when placed in discrete units placed in a delivery device.

The term "therapeutically effective amount" or "therapeutically effective rate" as used herein refers to the amount or rate of active agent required to produce the desired pharmacological, often beneficial, result.

The term "active agent formulation retainer" refers to a valve, plug or anti-flow coil or similar device that prevents the passage of active agent formulation from the device. By "fluid-passing active agent formulation retainer" is meant a valve, plug or choke or similar device that allows fluid to pass but does not allow passage of other ingredients such as the active agent formulation contained in the delivery device.

The diffusion device of the present invention may be used when it is inconvenient or unsafe to use a solid oral dosage form such as a capsule or tablet. The device is particularly suitable for elderly or pediatric patients, but it is also useful for people who have difficulty swallowing capsules or tablets. A single delivery device or multiple devices may be used to administer drugs to a patient during treatment.

FIG. 1A shows a cross-sectional view of one embodiment of a transfer apparatus according to the present invention. The device is in a ready configuration prior to being placed in a fluid. The dispensing apparatus 1 shown in fig. 1A comprises a hollow active agent formulation chamber 10 having a first end 16 and a second end 18. Chamber 10 contains an active agent formulation 12 and a fluid-pervious active agent formulation retainer 14. The fluid-passing active agent formulation retainer 14 includes an anti-flow coil 24 and a one-way plug 28. The opening 20 is smaller in diameter than the plug 28. In the embodiment shown in fig. 1A, the end 16 of the chamber 10 is bent to form a choke. The second end 18 of the chamber 10 has an active agent formulation retainer 26 that prevents release of the plug 28. In the embodiment shown in fig. 1A, retainer 26 is formed by bending end 18 of chamber 10. The active agent formulation 12 may be drug particles, coated drug particles or "fine timing pills" that are placed into the chamber 10 alone or with another carrier. The cap 34 is placed over the second end 18 of the chamber 10 prior to use to prevent release of the active agent formulation 12. Fig. 1B is an enlarged view of plug 28, showing plug 28 substantially sealing first end 16 of chamber 10 in the ready configuration, thereby preventing the loss of active agent formulation 12 from first end 16.

Fig. 2A shows the transfer device 1 in operation after having been placed in the fluid 30. The first end 16 of the delivery device 1 is placed in the fluid 30 and the second end 18 of the device is placed in the mouth of the patient. The patient sips at the second end 18 of the device and the mixture of fluid 30 and active agent formulation 12 is transferred through the opening 22 and into the patient's mouth. As shown in fig. 2B, the plug 28 acts as a one-way valve. When air is drawn through the tubular portion 10, the plug 28 deforms, thereby allowing fluid to flow around the plug 28, as indicated by arrows 32. When the inhalation stops, the stopper 28 relaxes and automatically closes the chamber 10 (see fig. 3B). The plug 28, having a density less than 1, moves radially of the tubular portion, thereby assisting in the delivery of the active agent formulation 12. The position of the plug 28 in the chamber 10 may serve as an approximate indicator of the amount of active agent formulation 12 that has been delivered.

Figure 3A shows the delivery device 1 after the active agent formulation has been substantially completely delivered. The plug 28 is adjacent the opening 22 but does not exit the chamber 10 because the opening is smaller in diameter than the plug 28 (see fig. 3B). The location of the plug 28 adjacent the opening 22 may serve as an indicator that the active agent formulation 12 has been completely delivered.

Fig. 4 shows a cross-sectional view of a second embodiment of the transfer device according to the invention. The device is in a ready configuration prior to being placed in a fluid. The dispensing device 40 shown in fig. 4 contains an active agent formulation chamber 42. The chamber 42 contains a plurality of oral dosage forms 44. The first end 46 of the chamber 42 has a fluid-permeable active agent formulation retainer 54 formed by bending the chamber 42 so that the opening 48 has a smaller diameter than the dosage form 44. In this manner, dosage form 44 will not exit chamber 42. The second end 50 contains an active agent formulation retainer 56 in the form of a removable sealing plug 52. In operation, the first end 46 of the chamber 42 is inserted into the fluid, the removable sealing plug 52 is removed and the second end 50 is placed into the patient's mouth. The patient then sips at tip 50 so that the fluid/dosage form mixture is delivered into the oral cavity and can be easily swallowed. Depending on the intended mode of administration, dosage form 44 may be immediate release, delayed release, continuous release, or controlled release.

Fig. 5A is a cross-sectional view of another embodiment of the apparatus of the present invention in a ready configuration prior to placement in a fluid. In this embodiment, the diameter of the active agent formulation chamber 60 of the delivery device 62 is substantially uniform throughout its length. In its ready form, the fluid-passing active agent formulation retainer 80 comprises a stopper 28 and a bottom cap 64. The cap 66 is positioned over the second end 72 of the chamber 60 and forms an active agent formulation retainer 82. Bottom cap 64 at first end 68 of chamber 60 serves to allow fluid to pass freely therethrough but prevents one-way plug 28 from exiting first end 68 of chamber 60. As shown in FIG. 5B, the bottom cap 64 may have a cross-shaped internal member, however, any commonly used shape internal member that allows fluid to pass therethrough but does not allow the one-way plug 28 to exit may be used. The cap 66, which is disposed at the second end 72 of the chamber 60, serves to allow free passage of fluid when the patient inhales, but provides a means for closing that end of the device prior to use. Thus, a rotary valve 74 is disposed on the cap 66. Fig. 5C shows a top view of the cap 66 and the rotary valve 74. This configuration allows fluid to freely pass when the open portions 76 are aligned with each other, and prevents fluid flow when the open portions 76 are aligned with the closed portions 78. Fig. 5D is a top view of the fig. 5A device with the opening portion 76 of the valve 74 aligned with the closing portion 78 of the cap 66.

FIG. 6 is a cross-sectional view of another embodiment of the apparatus of the present invention in a ready configuration prior to placement in a fluid. In this embodiment, the active agent formulation chamber 90 is located at the top end of the elongated tubular portion 92 and is separated by an active agent formulation retainer 94 that is fluid-permeable, in this case a porous plug. When the first end 96 of the device 100 is placed in the fluid 30 and the active agent formulation retainer 102 in the form of a removable plug is removed from the second end 104 of the device, the fluid may be drawn through the elongated tubular portion 92 and through the chamber 90, thereby forming a mixture of the fluid 30 and the active agent formulation 12 contained in the active agent formulation chamber 90 prior to delivery of the medicament into the oral cavity.

FIG. 7 is a cross-sectional view of another embodiment of the apparatus of the present invention. This embodiment is similar to that shown in fig. 6, except that the active agent formulation chamber 110 is located at the first end 112 of the device 114, rather than at the second end 116. The delivery process of the active agent is described in figure 6.

Fig. 8 is a cross-sectional view of an embodiment similar to that shown in fig. 1, except that the second end 120 of the active agent formulation chamber 122 is not bent, but rather has an active agent formulation retainer 124, in this case a pull-out tab, the post-retention projection 126 preventing the plug 28 from being removed as the active agent formulation 12 is delivered.

Fig. 9 is a cross-sectional view of an embodiment similar to that shown in fig. 4, except that the removable plug is absent and the second end 130 is sealed with a fitting 134 that is completely removed before the device is placed in the fluid 30 and the oral dosage form 44 is delivered.

The active agent may be in liquid, solid or semi-solid form. Active agent formulations containing the active agent may also contain other materials such as binders, coating materials or stabilizers to form the formulation into one or more discrete units. The discrete units may be designed in a number of ways to provide a particular drug delivery profile. One embodiment comprises the formulation in particulate form. These particles typically have a diameter of about 50-2000 μm, typically about 100-500. mu.m. When the taste of the particles is not good, the taste of the particles can be masked by methods well known in the art. The microparticles may be designed to deliver the active agent immediately, they may be coated to provide prolonged or delayed pulsatile release of the active agent, or they may be designed to provide a combination of immediate, pulsatile and/or prolonged delivery of the active agent. The microparticles may also be coated with an enteric coating to provide targeted release of the active agent. In addition, there are active agent preparations containing more than one active agent.

In other embodiments, the active agent may be in liquid form and contained in a soft gelatin capsule or a solid oral dosage form. These dosage forms may include matrix or other types of tablets, dragees and elongated tablets having a high to diameter ratio exceeding 1, capsules, primary osmotic pumps such as those disclosed in U.S. Pat. No.3,845,770, fine osmotic pumps such as those disclosed in U.S. Pat. Nos. 3,995,631, 4,034,756 and 4,111,202, and multilayer osmotic systems known as push-pull and push-dissolve osmotic pumps such as those disclosed in U.S. Pat. Nos. 4,320,759, 4,327,725, 4,449,983 and 4,765,989, all of which are incorporated herein by reference.

The method of determining the release profile of an active agent from a solid dosage form can be calculated as follows:

n＝x+y+z

n being the total number of dispersing units in the apparatus

x is an immediate release discrete unit

y is a constant release discrete unit

A dispersed unit with z-delayed release will release constantly when x-z-0; two pulse releases when y is 0; when z is 0, it will be a constant release with an initial pulse. When none of x, y or z equals 0, it will be pulsed/constant release/pulsed release. Such a system provides the possibility of dosing once a day for high capacity devices.

The term "active agent" refers to an agent, drug, compound, composition, or mixture thereof that provides some pharmacological, often beneficial, effect. This includes foods, food additives, nutritional agents, drugs, vitamins and other beneficial agents. The term as used herein further includes any physiologically or pharmacologically active substance that produces a local or systemic effect in a patient. Active agents that can be delivered include antibiotics, antivirals, anepileptics, analgesics, anti-inflammatory agents, and bronchodilators, as well as inorganic and organic compounds, including but not limited to, agents that act on the peripheral nerves, adrenergic receptors, cholinergic receptors, skeletal muscles, the cardiovascular system, smooth muscles, the blood circulatory system, sites of involvement [ synoptic sites ], sites of neuroeffector junctions, endocrine and hormonal systems, the immune system, reproductive system, skeletal system, autologous active substance systems, digestive and excretory systems, histamine systems, and central nervous systems. Suitable formulations may be selected, for example, from: polysaccharides, steroids, hypnotics and sedatives, psychostimulants, tranquilizers, anticonvulsants, muscle relaxants, antiparkinsonian agents, analgesics, anti-inflammatories, muscle contractants, antimicrobials, antimalarials, hormonal agents including contraceptives, sympathomimetics, polypeptides and proteins capable of eliciting physiological responses, diuretics, lipid regulators, antiandrogens, antiparasitics, neoplasms, anti-neoplasms, hypoglycemic agents, nutritional agents and additives, growth supplements, fats, ophthalmic agents, anti-inflammatory agents, electrolytes and diagnostic agents.

Examples of active agents useful in the present invention include: mepiquat chloride edisylate, ferrous sulfate, glycine, mecamylamine hydrochloride, procaine hydrochloride, amphetamine sulfate, methamphetamine hydrochloride, benzphetamine hydrochloride, isoproterenol sulfate, phenmetrazine hydrochloride, clobecholine, methacholine chloride, pilocarpine hydrochloride, atropine sulfate, scopolamine bromide, iodonium iodide, tricyclo-ammonium chloride, phenformin hydrochloride, methylphenidate hydrochloride, choline theophylline, cephalexin hydrochloride, difenidol, meclizine hydrochloride, mepiquat maleate, chlorphenamine, phenoxybenzamine, thiethylperazine maleate, anisindione, benzindene, dilantine, isoflurophosphate, acetazolamide, methazolamide, benzflumethiazide, chlorpropamide, tolazamide, chlormadinone, finadiol, allopurinol, allopurin, aspirin, methotrexate, sulfasalazine, hydrocortisone acetate, cortisone acetate, dexamethasone and derivatives thereof such as betamethasone, triamcinolone, methyltestosterone, 17-b-estradiol, ethinylestradiol 3-methyl ether, prednisolone, 17-b-hydroxyprogesterone acetate, 19-norprogesterone, norethindrone, norethiederone, progesterone, norgestrel, norethindrone, aspirin, acetaminophen, indomethacin, naproxen, phenoxyphenylpropionic acid, sulindac, indoprofen, nitroglycerin, isosorbide dinitrate, propranolol, timolol, atenolol, alprenol, cimetidine, clonidine, mepramine, levodopa, chlorpromazine, methyldopa, levodopa, calcium gluconate, ketoprofen, ibuprofen, cephalexin, erythromycin, haloperidol, zomepirac, ferrous lactate, vincamine, phenoxybenzamine, diltiazem, milrinone, captopril, cefaclor, quanbenz, hydrochlorothiazide, ranitidine, flurbiprofen, fenbufen, fluprofen, tolmetin, alclofenac, mefenacin, flufenacin, difurninal, nimodipine, nitrendipine, nisoldipine, nicardipine, felodipine, ridozine, tiapamil, galopamid, amlodipine, mifeprazine, lisinopril, enalapril, carpprodelil, ramipril, enalaprilat, famotidine, nizatidine, sucralfate, statintidine, tetratoll, minoxidil, chlordiazepoxide, diazepam, amitriptyline, and mipramine. Other examples are: proteins and peptides, which include, but are not limited to, insulin, colchicine, glucagon, thyroid stimulating hormone, parathyroid and pituitary hormones, bovine growth hormone, porcine growth hormone, oxytocin, vasopressin, prolactin, growth hormone, lypressin, pancreatin and luteinizing hormone.

It will be understood that more than one active agent may be incorporated in the active agent formulation in the device of the invention and that the use of the term "agent" does not exclude the use of two or more such agents.

The agent may be in various forms, such as soluble and insoluble charged or uncharged molecules, components of molecular complexes, or nonirritating, pharmaceutically acceptable salts.

The amount of active agent used in the delivery device will be that amount necessary to deliver a therapeutically effective amount of the agent to achieve the desired effect. In fact, the amount used will vary widely depending upon the particular agent, the severity of the condition, and the desired therapeutic effect. However, the device is typically used for active agents that must be delivered in relatively large doses of about 100mg to 5000mg, typically about 250mg to about 2500 mg. However, since the device can also be used for pediatric patients, doses of 25-250mg can also be used.

Representative materials for forming the device, including the active agent formulation chamber, elongated tubular portion, end caps and fittings include, but are not limited to: paper, plastics such as propylene/styrene copolymer, polypropylene, high density polyethylene, low density polyethylene, and the like. Typically the apparatus has an internal diameter of about 3 to about 8mm, a wall thickness of about 0.1 to 0.4mm and a length of about 10 to 30 cm.

The fluid-permeable active agent formulation retainer allows the liquid medium to flow freely, but prevents the passage of the active agent formulation from the device prior to delivery. The retainer contains a one-way plug or valve that will seal the straw at atmospheric pressure. Upon inhalation, fluid will flow around the plug and into the active agent formulation chamber. In addition, the plug has a density of less than 1 so that it rises to the top when the active agent formulation is delivered into the mouth. When inhalation is no longer taking place, the plug will remain in the highest position it has reached during inhalation. This plug may also be made of closed cell polyethylene foam such as EthaFoam. Other forms of one-way stopper may be a bulb of elastomeric material, a one-way mechanical ball valve, or the like.

The fluid for suspending the active agent formulation which is inhaled through the active agent formulation chamber is preferably any palatable liquid including, but not limited to, water, juice, milk, soda, coffee, tea, and the like. Care must be taken to ensure that the fluid is miscible with the active agent formulation.

The following examples are intended to illustrate the invention and they have no limiting effect on the scope of the invention. Variations and modifications to these embodiments will be readily apparent to those skilled in the art, having reference to the present specification, drawings and claims.

Examples

Example 1

The transfer device according to the present invention was prepared as follows. One end of a large-sized straw having an inner diameter of 0.21 inch and a length of 8 inches was heat-sealed. A partial seal is cut away so that the "one-way" stopper does not leak out. The partially fused ends were enclosed by half of a size 1 hard gelatin capsule. 600mg of coated potassium chloride particles Micro-K extenscap  (a.h. robins) having a particle size of about 0.5mm were placed into the open end of the pipette. A "one-way" stopper made of closed cell polyethylene foam, Microfoam (DuPont), was trimmed to fit into the pipette and then placed into the pipette so that it was on top of the Micro-K particles.

During operation, the end of the straw with the stopper is placed in a glass of water and the protective gelatin capsule at the top end of the straw is removed. By slowly inhaling through the partially fused end of the straw, 600mg of Micro-K particles were inhaled into the mouth and easily swallowed.

Example 2

The device was prepared as in example 1 except that, instead of Micro-K, the contents of the contin  12 hour capsule (SmithKline Beechem), a sustained-action nasal decongestant/antihistamine containing 25mg phenylpropanolamine and 12mg chlorpheniramine maleate, were placed in a straw without prescription (as is available). The particles are about 0.5-1.0 mm. These particles were sucked into the mouth as described in example 1.

Example 3

The transfer device according to the present invention was prepared as follows. One end of a large-sized straw having an inner diameter of 0.21 inch and a length of 6 inches was heat-sealed. The partial seal is cut off so that the diameter of the small hole is less than 5 mm.

A small primary osmotic pump of calcium ascorbate was prepared as follows. The core portion was formed with 50mg calcium ascorbate, 2.7mg polyvinylpyrrolidone and 0.6mg magnesium stearate. The ingredients were mixed thoroughly and compressed using a Manesty press with an 3/16 inch perforator using a 11/2 ton punch head. 80% cellulose acetate with an acetyl content of 39.0%, 10% sorbitol and 5% polyethylene glycol 400 were mixed to form a 5mg semipermeable wall. A solution made of a solvent consisting of 714ml of acetone and 186ml of water was sprayed onto the core in an air suspension machine. The coated osmotic tablets were dried at 50 ℃ for 72 hours. A 0.2mm hole was drilled in the wall by hand.

20 mini-osmotic systems of total dose 1000mg of calcium ascorbate were placed into the straw from the open end. The partially fused end of the straw was placed in a cup of water. The 20 small osmotic dosage forms were easily sipped into the mouth with little suction to provide long-term release of vitamin C.

The above description is only for easier understanding of the present invention. No unnecessary limitations are to be understood therefrom, as modifications will be obvious to those skilled in the art.

Claims (15)

1. An oral active agent delivery system for delivering discrete units of an active agent formulation for mixing with a fluid, the system comprising:

a hollow active agent formulation chamber (10) having a first end and a second end and containing an active agent formulation (12) in the form of discrete units, said ends being adapted for the passage of fluid during delivery of the active agent formulation; and a fluid-pervious active agent formulation retainer in said active agent formulation chamber (10) for preventing release of the dispensing unit from the first end (16) of the chamber but allowing fluid to enter the chamber;

the transfer system is characterized in that: the retainer is movable toward the second end (18) with fluid entering the system.

2. An oral active agent delivery system for delivering discrete units of an active agent formulation for mixing with a fluid, the system comprising:

a hollow active agent formulation chamber (10) having a first end (16) and a second end (18) and containing a plurality of active agent formulations in discrete units, said ends being adapted for passage of fluid during delivery of the active agent formulations; and

a fluid-passing active agent retainer having an anti-flow coil in cross-section at said first end of said chamber for preventing release of the dispersing unit from the first end (16) of the chamber but allowing fluid to enter the chamber;

wherein each of the discrete elements has a diameter larger than the choke coil.

3. The delivery system according to claim 1 or 2, further comprising an active agent formulation retainer (14) at a second end (18) of the active agent formulation chamber (10) which prevents release of said active agent formulation from said second end (18) prior to use.

4. A delivery system according to claim 1 or 2, wherein the dispersal units are selected from the group consisting of: microparticles, oral dosage forms and combinations thereof.

5. The delivery system according to claim 4, wherein said dispensing unit allows for prolonged delivery of the active agent in said formulation.

6. The delivery system according to claim 4 wherein said dispensing unit allows immediate delivery of the active agent in said formulation.

7. The delivery system according to claim 4, wherein said dispensing unit delays pulsed delivery of said active agent in said formulation.

8. The delivery system according to claim 4 wherein said discrete units comprise an oral dosage form comprising an osmotic layer and an active agent layer.

9. A delivery system according to claim 1 or 2, wherein said active agent formulation retainer comprises a one-way plug.

10. The delivery system according to claim 9, wherein the position of the plug (28) is an indicator of the extent of delivery of the active agent.

11. A delivery system according to claim 1 or 2, further comprising a cover concentrically surrounding the first end (16) of the chamber.

12. A delivery system according to claim 3, wherein said active agent formulation retainer (14) at the second end (18) of the chamber comprises a rotary valve.

13. The delivery system according to claim 3 wherein said active agent formulation retainer (14) at the second end (18) of the chamber comprises a slit at the second end of the second end (18) of the chamber.

14. The delivery system according to claim 3 wherein said active agent formulation retainer (14) at said chamber second end (18) comprises a removable cap (66).

15. The delivery system according to claim 1 or 2, wherein said active agent formulation comprises an active agent selected from the group consisting of: antibiotics, antivirals, antiepileptics, analgesics, anti-inflammatories, and bronchodilators.