RELATED APPLICATION

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application Number 61/405,490 titled ORAL DOSING DEVICE FOR

ADMINISTRATION OF MEDICATION" filed on October 21, 2010, the contents of which are incorporated in this application by reference.

TECHNICAL FIELD

[0002] The present invention relates generally to devices used for administering medications to patients. More particularly, the disclosed invention relates to a device for administration of medication to patients wherein the device allows the medication to be stored within it for a significant period of time with the medication particles suspended in a liquid, and administered orally to the patient using the device with improved patient compliance.

BACKGROUND OF THE INVENTION

[0003] The proper dosing of medication for patients is an important concern within the medical field. For infants or smaller children in particular, the administration of medications and dosing methods often present substantial issues. Many devices have been developed to address the issues presented during the administration of fluidic material, for example liquid medicine, to infant, aged, or incapacitated persons and to small animals and pets (which often require the same degree of care as infants). Thus, as used in this document, the term "patients" is intended to cover infants, aged or incapacitated persons, small animals (whether wild or receiving care from

veterinarians or zoos), and domestic pets (e.g., fish, birds, reptiles, and other species). As is well known in the art, medications are provided in many forms (e.g., liquid, solid, and combinations of solids in liquids) and are delivered to patients in many ways (e.g., orally, via injection, and transdermally). [0004] Oral administration of liquids especially to children can be extremely difficult at times, such as when a measured amount of a medicine is to be given. The usual method is simply to use a spoon. The spoon may be specific to a certain measure or just an ordinary household spoon, but if the child does not want to accept the medicine it is extremely difficult to coax the child to take the medicine without some loss. Alternatively, too much medicine may be administered if more is given to compensate for that lost in the previous attempt. This effect is heightened considerably if the medicine is distasteful.

[0005] A dropper can be used for oral administration. Such a device comprises a bulb head, usually made of rubber, and is attached to one end of a tube. The other end of the tube has an opening through which liquid can enter. A certain amount of liquid is drawn into the tube if pressure is first applied to the bulb, the open end of the tube is placed in a liquid, and the pressure then released. Therefore, a dropper provides some measure of directional control as the liquid can only leave the tube by way of the opening at the tube end. Because continual pressure must be administered to the bulb in order to retain the liquid within the tube, however, only one hand is left free to correctly position the dropper in the mouth of the child. Great care is also required to ensure that the correct number of drops are administered.

[0006] Many other devices have been developed to facilitate the oral administration of liquid medications. U.S. Patent No. 5,431,680 issued to Jones discloses, for example, a device having a manually operable plunger slidably mounted within a container for orally administering liquid. The plunger operates to administer the liquid through an outlet, which is at least partially surrounded by a radially extending shield. U.S. Patent No. 6,981,962 issued to Lenkersdorf discloses a liquid-dispensing device for the selective oral administration of a liquid medicine simultaneously with a liquid beverage.

[0007] U.S. Patent No. 7,399,295 issued to Waldenburg discloses a medical syringe having a capsule containing multiple doses of liquid medication (particularly insulin) within a sealed storage chamber formed between concentric inner and outer walls. The inner wall forms a cavity including a delivery chamber from which a single dose of medication is ejected. The syringe includes an ejection port, an axial moveable plunger extending into the cavity and delivery chamber, and a body with a compartment that holds the capsule. With the plunger in a first position, the capsule is closed. With the plunger in a second position, the delivery chamber is filled with a single dose of medication. With the plunger in a third position, the single dose of medication is ejected from the delivery chamber though the injection port.

[0008] Often, syringes are used to inject medication though a needle used to pierce the skin of the patient. Such syringes face the problem of assuring accurate dosage of the medication injected by syringe, especially when the medication is self- administered or administered by other members of the household. In many cases the amount of the dosage for each injection is critical and, although such syringes are marked with gradations to indicate the amount of the dosage, it is relatively easy for users to misread the syringe and therefore inject either an inadequate dose or an excessive dose of medication. The misreading of the syringe gradations could occur for any number of reasons including obscured indicia on the syringe, poor lighting, simple carelessness, inexperience, or impaired eyesight on the part of the user or the person administering the injection. U.S. Patent No. 3,965,945 issued to Ross and U.S. Patent No. 7,470,259 issued to Hoyle, Jr. address problems with syringes used to inject medication through needles. The present invention does not use a needle, does not inject medication through the skin, and does not rely on gradations and, therefore, avoids these problems.

[0009] U.S. Patent No. 4,784,641 issued to White discloses another example of a syringe and method for the oral administration of fluidic material to a patient. The syringe includes a cannula at its dispensing end. The cannula is of sufficient size and shape to approximate a nipple so as to provide a feeding surface which encourages normal sucking by a patient. The cannula is provided with a restricted metering aperture at its downstream end to limit the flow rate of fluidic material from the syringe in order to prevent gagging of the patient and to allow the patient to safely draw fluidic material from the syringe in a controlled manner. [0010] Caps are often used in combination with syringes to sealingly close the opening in a syringe body. Such caps help to ensure the sterility of the syringe and the medication contained within the syringe. U.S. Patent No. 4,286,591 issued to Raines and U.S. Patent No. 7,648,481 issued to Geiger, et al. disclose examples of such caps. Raines teaches a syringe cap used to close a filled syringe in preparation for storage. A needle is attached to the syringe before injection of the fluid. The cap can be used without risking the sterility of the syringe. Geiger, et al. teach a syringe tip cap for closing the distal opening of a syringe body where the syringe tip cap has a fastening ring or luer lock adapter for fastening the syringe tip cap to the distal end of the syringe body.

[0011] U.S. Patent No. 5,125,415 issued to Bell teaches a syringe tip cap containing a hydrophilic self-sealing filter used to prevent the backflow of air into the syringe. The filter provides for accurate arterial blood gas samples because the flow of air into the syringe is blocked. After a blood sample has been taken, the needle is unscrewed from the syringe, and the syringe cap is then screwed onto the luer adapter of the syringe. The male luer adapter of the syringe fastens to the female luer connector of the syringe tip cap. While the syringe is held so that the needle end is pointing up to allow the air to rise to the luer end, the plunger of the syringe is advanced to expel air from the syringe body into the syringe tip cap. After the air passes through the filter, the front edge of the blood sample meets the filter, causing the filter to expand due to its hydrophilic character. The expansion thus creates a seal against the flow of air back into the blood sample.

[0012] U.S. Patent No. 4, 137,917 issued to Cohen teaches a syringe filter unit used to prevent contamination during the method of filling a syringe with fluid and injecting the fluid into a patient. The filter unit is attached to the hub of a syringe, the hub being the portion of the syringe closest to the point where the needle is attached to the syringe. The filter unit comprises three individual filters, each used separately during the three parts of the injection method. The user pushes the appropriate filter unit inwardly toward the syringe hub for a respective part of the method. The filters completely filter first the air going into the solution. The solution being drawn into the syringe is filtered next. Finally, the solution in the syringe is doubly filtered in that it passes through a third filter on its way into the patient.

[0013] Occasionally, particulate medication is sprinkled over a small amount of a favorite food (e.g., applesauce) and fed to the patient with a spoon. Where such medications are administered orally for infants and children, however, the use of a syringe device has often been viewed as the best way to deliver the medication to the patient. With such syringe devices, the placement of the particulate medication in the syringe along with the liquid used to administer the medication can be problematic. Such problems with preparation of a syringe often make it difficult to determine accurate dosage.

[0014] U.S. Patent No. 7,658,918 issued to Ortenzi et al. and is owned by Aptalis Pharma. The '918 patent explains that certain particulate medications, administered orally, are designed to pass through the stomach of the patient and thereafter to release within the intestines. The administration of a proper dosage of such particulate medications to infants and children should be as accurate as possible. The typical method of putting particulate medication into a syringe requires, however, placing a closed cap on the end of the syringe so that the liquid and medication added to the syringe do not run through the syringe. Once the liquid and medication are added to the syringe, it is very difficult to then place the syringe plunger back into the syringe body without ejecting a portion of the liquid, the particulate medication, or both. In addition, when liquid and medication are present in the syringe, it is difficult to reinsert the plunger without ejecting the closed cap and spilling the contents of the syringe.

[0015] A commercial product marketed by GlaxoSmithKline pic (a company with headquarters in the United Kingdom and with operations based in the United States) avoids the use of syringes. As illustrated in Figs. 1A, IB, 1C, ID, and IE, particulate medication can be readied for delivery to a patient using the product in six steps. Fig. 1 A depicts the first step, in which a caregiver or user 10 twists the top 12 on a vial 14 containing liquid 16 in the direction of the arrow "A" (e.g., counter-clockwise) to remove the tamper-evident ring. Fig. IB depicts the second step, in which the user twists the top 12 on the vial 14 in the direction of the arrow "B" (e.g., clockwise) to make the particulate medication drop into the liquid 16 within the vial 14.

[0016] Fig. 1C depicts the third step, in which the user 10 shakes the vial 14 vigorously, in the direction of arrows "C," to mix the particulate medication 20 in the liquid 16 and create a suspension. Fig. ID depicts the fourth step, in which the user 10 again twists the top 12 on the vial 14 in the direction of the arrow "A" to open the vial 14. As shown in Fig. E, the top 12 is completely removed from the vial 14.

[0017] The known product includes a large number of separate components. The product also requires the user to execute a large number of steps when preparing the product to deliver medication to the patient. In addition, the opening of the vial 14 is less than optimal for delivery of the suspension to infants, finicky youngsters, or other uncooperative patients.

[0018] Therefore, there remains a need in the art for an improved apparatus that overcomes the shortcomings of conventional solutions. More specifically, there is a need in the medical field for an inexpensive technique and assembly for delivering uncontaminated medicinal particles orally to a patient. This need exists

notwithstanding numerous syringe and cap designs which have been proposed or adopted, such as the devices disclosed in the patents mentioned above, and various commercially available products. To overcome the shortcomings of the current solutions, a new device for and method of administering medicines including a liquid mixture containing particles or particles of medication suspended in a liquid are provided.

[0019] A primary object of the present invention is to provide an improved oral dosing device for use with patients which allows medication to be dispensed safely and carefully. Another object of the present invention is to provide an oral dosing device of such size and shape as to dispense medication to even the smallest, youngest, and most uncooperative of patients. A related object is to provide an improved oral dosing device that ensures a desired flow of medication from the device without gagging the patient. [0020] Another object of the present invention is to provide an oral dosing device that is easy to assemble and is made of conventional materials and manufacturing technology. A related object is to provide an oral dosing device that is easy to use, economical, and disposable. It is another object of the present invention to minimize the number of steps required for the user to administer a particulate medication, a combination comprising particles of medication and a liquid, or both.

[0021] Yet another object of the present invention is to provide an improved oral dosing device that avoids spillage of liquid or particulate medication. Additional objects of the present invention are to (1) assure safe and relatively long-term storing of a medicinal product; (2) provide an administration vehicle; (3) suspend particles of medication in a liquid; and (4) improve patient compliance. Related objects are to form the device of materials which are compatible with the medicinal product;

separate the solid medicinal product from the liquid vehicle until the precise time for administration; and ensure suitable shelf life. Additional related objects are to provide a simple and extemporaneous procedure easily implemented without (or with little) prior preparation or practice by the user, while preserving the quality and efficacy of the drug. A further related object is to avoid direct manipulation or contamination of, or damage to, the medicine. Still further related objects are to avoid the need for extraneous tools and to provide a device that is portable, handy, and discrete.

[0022] The present invention also has as an object the provision of an improved method for administering an accurate dosage of particulate medication to a diverse group of patients, including the pediatric population. By avoiding the aforementioned disadvantages regarding measurement of medication, a more accurate dosage of medication can be administered. In particular, the inventive oral dosing device provides for the accurate dosage of particulate medications in small children and infants. An additional object is to permit a user to administer medication alone.

[0023] In particular, the inventive oral dosing device provides an improved way to administer particulate medication in patients with cystic fibrosis. Exocrine pancreatic insufficiency is marked by the inability of the digestive tract to absorb fats, proteins, and to a lesser extent, carbohydrates. Exocrine pancreatic insufficiency in cystic fibrosis results in limited pancreatic digestive enzymes due to impaired fluid secretion and obstruction of pancreatic ducts. The use of the inventive oral dosing device provides for improved administration of particulate medications for treatment of exocrine pancreatic insufficiency.

[0024] In view of all of the foregoing, it is a main object of the present invention to provide an efficient, effective, and inexpensive technique and apparatus for delivering medicine to a patient.

BRIEF SUMMARY OF THE INVENTION

[0025] To achieve these and other objects, and to meet these and other needs, and in view of its purposes, the present invention provides a device adapted to orally administer particles of medication suspended in a liquid to a patient. In a first embodiment, the device has a medicine chamber and a liquid chamber. The medicine chamber includes (a) a body enclosing the particles and a foot with an opening, and (b) a membrane releasably sealing the opening. The liquid chamber includes (a) an enclosure retaining the liquid and having a nipple-like head with an aperture, and (b) a closure sealing the aperture. A structure is adapted to engage a sealing mechanism that forms a seal between the medicine chamber and the liquid chamber.

[0026] In a second embodiment, the device has a package and an ampoule. The package includes (a) a body enclosing the liquid, and (b) a lid sealing the body and having a membrane connected to a projection, the membrane defining a space enclosing the particles. The ampoule includes a casing having a nipple-like head with an aperture on one end and an element on the opposite end, the element adapted to attach the ampoule to the body in a liquid-tight manner.

[0027] The present invention also provides a method for orally administering a combination of particles of medication suspended in a liquid to a patient. In using the device according to the first embodiment, the method comprises the steps of: (a) removing the closure from the aperture of the enclosure; (b) forming a liquid-tight seal between the medicine chamber and the liquid chamber; (c) depositing the particles of medication from the medicine chamber into the liquid within the liquid chamber, thereby suspending the particles in the liquid, by releasing the membrane to unseal the opening and permit the particles to exit the body and enter the liquid; (d) removing the medicine chamber to expose the aperture; and (e) administering the particulated liquid combination to the patient.

[0028] In using the device according to the second embodiment, the method comprises even fewer steps. The first step is to release the particles of medication from the space defined by the membrane into the liquid within the body by opening the membrane. The second step is to replace the lid with the ampoule on the body. And the final step is to administer the liquid combination comprising the suspended particles to the patient.

[0029] It is to be understood that both the foregoing general description and the following detailed description are exemplary, but are not restrictive, of the invention.

BRIEF DESCRIPTION OF THE DRAWING

[0030] The invention is best understood from the following detailed description when read in connection with the accompanying drawing. It is emphasized that, according to common practice, the various features of the drawing are not to scale. On the contrary, the dimensions of the various features are arbitrarily expanded or reduced for clarity. Moreover, although the particles of medication may be shown floating on the surface of a liquid or on the bottom of a container, some or a portion of the particles may be dispersed or suspended in the liquid. Included in the drawing are the following figures:

[0031] Fig. 1A illustrates the first step of a five-step method by which a

commercially available product is readied to deliver particulate medication to a patient; [0032] Fig. IB illustrates the second step of the five-step method by which a commercially available product is readied to deliver particulate medication to a patient;

[0033] Fig. 1C illustrates the third step of the five-step method by which a commercially available product is readied to deliver particulate medication to a patient;

[0034] Fig. ID illustrates the fourth step of the five-step method by which a commercially available product is readied to deliver particulate medication to a patient;

[0035] Fig. IE illustrates the fifth step of the five-step method by which a commercially available product is readied to deliver particulate medication to a patient;

[0036] Fig. 2 is a schematic representation of a first embodiment of the device according to the present invention, including a medicine chamber and a liquid chamber;

[0037] Fig. 3A illustrates the first step of a method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 2;

[0038] Fig. 3B illustrates the second step of the method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 2;

[0039] Fig. 3C illustrates the third (and optional) step of the method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 2;

[0040] Fig. 3D illustrates the fourth step of the method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 2;

[0041] Fig. 3E illustrates the final step of the method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 2;

[0042] Fig. 4 A illustrates a first embodiment of the head of the device shaped like a nipple according to the present invention; [0043] Fig. 4B illustrates a second embodiment of the head of the device shaped like an alternative nipple according to the present invention;

[0044] Fig. 5 is a schematic representation of a second embodiment of the device according to the present invention, including a package and an ampoule;

[0045] Fig. 6A illustrates the first step of a method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 5;

[0046] Fig. 6B illustrates the second step of the method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 5; and

[0047] Fig. 6C illustrates the final step of the method by which particulate medication is readied for delivery to a patient using the device shown in Fig. 5.

DETAILED DESCRIPTION OF THE INVENTION

[0048] As described in detail below, the device of the present invention

encompasses two main device components. The two components may be collected and provided as a kit. In a first embodiment of the present invention, one component is a medicine chamber that stores a particulate medication and provides an easy way to add the particulate medication to the second component, namely a liquid chamber. In a second embodiment of the present invention, one component is a package that stores (separately) both the particulate medication and a liquid. The package provides an easy way to add a particulate medication suspended in a liquid to the second component, namely an ampoule, for delivery to the patient. The device avoids the typical problems of measuring proper dosage and the difficulties of preparing a syringe with such medications. The present invention also encompasses the method of using the components to administer medicine to a patient. The method is easy to implement and does not require the use of any complex equipment. Also disclosed are example medications that can be administered using the device and method of the present invention. A. First Embodiment Device Components and Method of Administration

[0049] Two embodiments of the device 30 are illustrated and described for purposes of example only. Referring now to the drawing, in which like reference numbers refer to like elements throughout the various figures that comprise the drawing, Fig. 2 is a schematic representation of a first embodiment of the device 30 including a medicine chamber 40 and a liquid chamber 60. The medicine chamber 40 contains particles 100 of medication. Example particulate medications are described below. The liquid chamber 60 contains a liquid 98.

[0050] The liquid 98 may be any suitable liquid as is commonly used to dispense medication. The liquid 98 is formulated (amount, viscosity, density, surface tension, and the like) to suspend the particles 100 and properly administer the full product dose through the device 30. The liquid 98 must avoid agglomeration of the particles 100 during the preparation. Preferably, the liquid 98 will be desirable in some way (e.g., taste good) to the patient, to facilitate the patient's receptiveness to taking the medication along with the liquid 98. The liquid 98 also must be able to carry or transport the particles 100 of medication. Suitable liquids 98 include milk, formula, flavored syrup or water, and juice (e.g., apple, grape, or other fruit juice), among others, as well as liquid compositions specifically designed to ensure a full recovery of a predetermined medication dose.

[0051] Turning to the medicine chamber 40, the medicine chamber 40 has a body 42 enclosing the particles 100. In preferred embodiments, the body 42 has a foot 54 with an opening 56. A membrane 58 seals the opening 56 and prevents the particles 100 from exiting the body 42. Although various materials of construction are possible, the membrane 58 is preferably made of a relatively thin aluminum that can be easily ruptured, torn, or peeled to unseal the opening 56 and permit the particles 100 to exit the body 42. The membrane 58 protects the particles 100 from the environment and separates the particles 100 from the liquid 98 upon engagement of the medicine chamber 40 and the liquid chamber 60. [0052] As shown in Fig. 2, the medicine chamber 40 also has a housing 50. The housing 50 includes a mechanism (for example, internal threads 52) which engages a corresponding structure on the liquid chamber 60 to seal the medicine chamber 40 and the liquid chamber 60 together as one unit. The housing 50 defines an orifice 46 at its lower end.

[0053] The body 42 of the medicine chamber 40 preferably has a substantially circular and cylindrical shape. The body 42 and the housing 50 preferably have a unitary, integral construction. By "integral" is meant a single piece or a single unitary part that is complete by itself without additional pieces, i.e., the part is of one monolithic piece formed as a unit with another part.

[0054] The liquid chamber 60 has an enclosure 62 that retains the liquid 98. The enclosure 62 has a base 64 and a nipple-like head 44 disposed opposite the base 64. The nipple-like head 44 of the enclosure 62 has at least one aperture 66. A closure 48 seals the aperture 66 and prevents the liquid 98 from exiting the enclosure 62. The aperture 66 of the nipple-like head 44 has a pre-determined cross-sectional area such that medication placed in the enclosure 62 will be dispensed from the aperture 66 during use of the device 30. By "predetermined" is meant determined beforehand, so that the predetermined characteristic must be determined, i.e., chosen or at least known, in advance of some event.

[0055] A suitable diameter for the aperture 66 falls within a range of about 2-15 mm and, preferably, 4-10 mm. It is also important that the cross-sectional area of the aperture 66 and the geometry of the nipple-like head 44 be such as to allow administration of the total dose of medication. The enclosure 62 also has a structure (for example, external threads 72) which engages the corresponding mechanism on the medicine chamber 40 to seal the medicine chamber 40 and the liquid chamber 60 together as one unit. Alternative or in addition to threads, the medicine chamber 40 can be snap-fit on the liquid chamber 60 or affixed to the liquid chamber 60 via an interference fit.

[0056] Volumes of the medicine chamber 40 should be in the same range as conventional hard gelatin capsules: from size 3 (0.3 ml) to size 00 (0.95 ml). Although for capsule administration the size 00 is considered a physiological limit, in terms of patient compliance, larger volumes are within the scope of the present invention. Thus, the device 30 can be used to administer up to 3-5 grams of product, corresponding to volumes of the liquid chamber 60 in the range of 3-20 ml, or even more in the case of a teen or adult population.

[0057] The present invention also provides a method of treating or preventing a disorder. The method permits the ready and precise preparation of medication dosage within the device 30. More specifically, the device 30 described above can be used to administer medicine through a fluidic material into the mouth of an infant, aged, or incapacitated person or other patient. The typical steps included in the first exemplary embodiment of the method of the present invention are illustrated in Figs. 3A-3E.

[0058] As illustrated in Figs. 3 A, 3B, 3C, 3D, and 3E, particles 100 of medication can be readied for delivery to a patient using the device 30 in relatively few steps. Fig. 3 A depicts the first step, in which a user 10 twists the closure 48 on the enclosure 62 containing the liquid 98 in the direction of the arrow "A" (e.g., counter-clockwise) to open the enclosure 62 and give the user 10 access to the liquid 98 through the aperture 66. Alternatively, the user 10 can peel the closure 48 in the direction of arrow "D" to remove the closure 48 from the enclosure 62.

[0059] Fig. 3B depicts the second step, in which the user 10 seals the medicine chamber 40 and the liquid chamber 60 together as one unit. Typically, the user 10 moves the medicine chamber 40 in the direction of the arrow "E" toward the liquid chamber 60 (of course, the user 10 might move the liquid chamber 60 toward the medicine chamber 40 in the direction opposite arrow "E" or might move both chambers 40, 60 toward each other simultaneously). Depending upon the mechanism on the medicine chamber 40 and the structure on the liquid chamber 60, the user 10 forms the sealed unit by, as illustrated, rotating the chambers 40, 60 relative to each other in the direction of the arrow "A" so that their respective threads engage.

Alternatively, the user 10 can snap-fit the medicine chamber 40 onto the liquid chamber 60 or can slide the medicine chamber 40 onto the liquid chamber 60 to create a friction or interference fit. The user 10 can also take the appropriate actions to engage any other mechanism and structure combination—as would be known to an artisan. Whatever mechanism and structure are adopted, it is important that an efficient seal result from their combination.

[0060] Fig. 3C depicts the third step, in which the user 10 deposits the particles 100 of medication from the medicine chamber 40 into the liquid 98 within the liquid chamber 60. This third step can be completed automatically, as part of the second step, which would avoid the need for the user 10 to implement a separate third step; if so, the total number of steps required to ready the medication for delivery to a patient using the device 30 would be reduced. As illustrated in the embodiment shown in Fig. 3C, however, the user 10 deposits the particles 100 of medication into the liquid 98 by pushing downward on the body 42 of the medicine chamber 40 in the direction of the arrow "E" (alternatively, the user 10 might twist the medicine chamber 40). Regardless of the action taken, the result is to rupture, tear, peel, or otherwise open or release the membrane 58 to unseal the opening 56 and permit the particles 100 to exit the body 42 and enter the liquid 98.

[0061] The user 10 can facilitate the method of forming a suspension by shaking the device 30, especially when the particles 100 are non-homogeneously distributed within the liquid 98. For example, the particles 100 may be floating primarily on the surface of the liquid 98 or they may be distributed primarily in the upper part of the liquid 98 before shaking. Thus, the step of depositing the particles 100 of medication may be followed by shaking the device 30 to better distribute the particles 100 within the liquid 98.

[0062] Fig. 3D depicts the fourth step, in which the user 10 twists the medicine chamber 40 in the direction of the arrow "A" to remove the medicine chamber 40, expose the aperture 66, and open the device 30. As shown in Fig. 3D, the medicine chamber 40 is completely removed.

[0063] Finally, as shown in Fig. 3E, the user 10 can orient the liquid chamber 60 (for example, as shown, invert the liquid chamber 60) so that the combination of particles 100 and liquid 98 flows in a direction "F." This orientation allows the user 10 to deliver or administer the particulated suspension to the patient: the particles 100 and the liquid 98 exit the liquid chamber 60 through the aperture 66. Delivery is accomplished by inserting the nipple-like head 44 into the mouth of the patient and gently squeezing the enclosure 62 of the liquid chamber 60.

[0064] The nipple-like head 44 may be placed between the gums or teeth of the patient, to facilitate the patient's sucking on the nipple-like head 44. The user 10 may optionally squeeze the enclosure 62 of the liquid chamber 60 to force or inject the suspended particles into the mouth of the patient concurrently with (or alternative to) the patient sucking on the nipple-like head 44. Delivery is continued until all of the particles 100 have been transferred from the liquid chamber 60 to the patient, at which time the liquid chamber 60 is removed from the mouth of the patient.

[0065] In summary, a first embodiment of the inventive method of using the device 30 comprises the steps of (a) removing the closure 48 from the enclosure 62 containing the liquid 98 to open the enclosure 62 and give the user 10 access to the liquid 98 through the aperture 66; (b) forming a seal between the medicine chamber 40 and the liquid chamber 60; (c) depositing the particles 100 of medication from the medicine chamber 40 into the liquid 98 within the liquid chamber 60 by opening or releasing the membrane 58 to unseal the opening 56 and permit the particles 100 to exit the body 42 and enter the liquid 98; (d) removing the empty medicine chamber 40 to expose the aperture 66; and (e) administering the medication dosage to the patient.

[0066] The method of the present invention eases the administration of medication. In the specific example provided above, the present invention eases administering pancreatic enzymes. The need for manual skills is reduced by the method of the present invention, as is the amount of time required to administer the medication. The caretaker uses familiar tools and does not need help from a second person.

Administration is substantially mess-free. In addition, the patient readily accepts the medication being administered and is less likely to reject or spit out the medication, chew or keep the medication in its mouth without swallowing, or exhibit signs of distress such as crying.

[0067] As illustrated in Fig. 2, the nipple-like head 44 has the shape of a right circular cylinder. The nipple-like head 44 may also have a funnel shape. The nipple- like head 44 may also be constructed and arranged to be of such size and shape that it approximates a nipple, in order to provide a feeding surface for patients to suck on, allowing them to draw particles 100 of medication, liquid 98, and the like from the device 30.

[0068] The nipple-like head 44 may approximate a nipple, as stated above and as illustrated in Fig. 2. Rather than approximate a nipple, however, the nipple-like head 44 may be constructed just like a nipple (or, alternatively, a separate nipple may be inserted onto the nipple-like head 44). Fig. 4A illustrates a first embodiment of the nipple-like head 44 shaped like a nipple; Fig. 4B illustrates a second embodiment of the nipple-like head 44 shaped like an alternative nipple. The nipple-like head 44 has at least one aperture 66, and preferably a plurality of apertures 66, which are large enough to permit both the liquid 98 and the particles 100 of medication to pass from the liquid chamber 60 to the patient. Each aperture 66 is a metered dispensing aperture that prevents the flow of particles 100 or liquid 98 from the liquid chamber 60 at a rate high enough to cause gagging of the patient.

B. Second Embodiment Device Components and Method of Administration

[0069] Fig. 5 is a schematic representation of a second embodiment of the device 30 including a package 80 and an ampoule 90. The package 80 has a body 82 enclosing the liquid 98. The package 80 further has a lid 84 that engages and seals the body 82 to enclose the liquid 98 within the body 82. The package 80 still further has a tamper- evident seam 86 that is broken when the user 10 removes the lid 84 from the body 82. Typically, although not necessarily, the body 82 and the lid 84 have corresponding threads and, if so, the user 10 removes the lid 84 from the body 82 by rotating (i.e., unscrewing) the lid 84.

[0070] The lid 84 has a membrane 58 connected to a projection 88. The membrane 58 defines a space within the lid 84 enclosing the particles 100. The membrane 58 protects the particles 100 from the environment and separates the particles 100 from the liquid 98. [0071] The ampoule 90 has a casing 92 with a nipple-like head 44 on one end and an element on the opposite end. Typically, although not necessarily, the element includes threads 94 that correspond to the threads on the body 82 of the package 80. The threads 94 permit the user 10 to attach the ampoule 90 to the body 82 in a liquid- tight manner. A shoulder 96 forms the transition between the casing 92 and the nipple-like head 44. The nipple-like head 44 has an aperture 66 with a predetermined cross-sectional area such that medication will be dispensed from the aperture 66 during use of the device 30.

[0072] The shoulder 96 provides a convenient abutment which prevents the patient from drawing the casing 92 of the ampoule 90 into the patient's mouth and causing consequent gagging or choking. In addition, the shoulder 96 serves as a convenient guide to the caretaker dispensing the medication, letting the caretaker know when the nipple-like head 44 has been inserted to a proper depth into the mouth of the patient. Because the shoulder 96 is rounded, there are no sharp transition edges that might injure the patient. Another advantage of the shoulder 96 is that when the nipple-like head 44 is suitably positioned in the mouth of a patient, the ampoule 90 does not abut the nose of the patient.

[0073] The casing 92 of the ampoule 90 preferably has a substantially circular and cylindrical shape. The casing 92, the nipple-like head 44, and the threads 94 preferably have a unitary, integral construction. The integral construction achieves a number of functions: enhancing safety by preventing the nipple-like head 44 from being injected into the mouth of the patient and choking or gagging the patient, preventing leakage of fluids, and providing a smooth and uninterrupted surface to a patient.

[0074] The ampoule 90 is preferably made from a flexible material. The ampoule 90 has dimensions proportional to the volume of the liquid 98 to be administered and to the age of the patient. Typical volumes range from 3-5 ml (small volumes suitable for infants or toddlers) to 20 ml or more (larger volumes, up to 50 ml, may be suitable for the adult population). [0075] As illustrated in Figs. 6A, 6B, and 6C, particles 100 of medication can be readied for delivery to a patient using the device 30 shown in Fig. 5 in relatively few steps. Fig. 6 A depicts the first step, in which the user 10 releases the particles 100 of medication from the space defined by the membrane 58 into the liquid 98 within the body 82. The user 10 releases the particles 100 of medication into the liquid 98 by pushing downward on the projection 88 of the lid 84 in the direction of the arrow "E" (alternatively, the user 10 might rotate the lid 84 in the direction of arrow "A"). Regardless of the action taken, the result is to rupture, tear, peel, or otherwise open the membrane 58 and permit the particles 100 to enter the liquid 98. Optionally, the user 10 may shake the package 80 at this point in the method to facilitate formation of the suspension.

[0076] Fig. 6B depicts the second step, in which the user 10 rotates the lid 84 to remove the lid 84 completely from the body 82, expose the suspension of the particles 100 and the liquid 98 in the body 82, and open the body 82. The tamper-evident seal 86 is broken in this step, providing information that the lid 84 has been removed and the body 82 has been opened. Immediately thereafter, the user 10 places the ampoule 90 into engagement with the body 82. Typically, such engagement is achieved by rotating the ampoule 90 relative to the body 82 so that the corresponding threads on the two components engage. Fig. 6B illustrates the device 30 with the ampoule 90 in position on the body 82. Note that the device 30 now resembles a conventional baby bottle. In essence, upon completion of the second step as described above, the lid 84 has been replaced with the ampoule 90 on the body 82.

[0077] Finally, as shown in Fig. 6C, the user 10 can orient the device 30 (for example, as shown, invert the device 30) so that the particles 100 and the liquid 98 flow downwardly with the assistance of gravity. This orientation allows the user 10 to deliver or administer the medicament to the patient: the particles 100 and the liquid 98 exit the device 30 through the nipple-like head 44. The patient's mouth may engage the nipple-like head 44 to facilitate reception. To facilitate delivery of the particles 100 suspended in the liquid 98, the user 10 can gently squeeze the casing 92 of the ampoule 90 in the direction of arrows "G," thereby forcing the suspension out of the casing 92 and into the patient. This action may be necessary if the patient is uncooperative or incapable of sucking.

[0078] In summary, a second embodiment of the inventive method of using the device 30 comprises the steps of (a) releasing the particles 100 of medication from the space defined by the membrane 58 into the liquid 98 within the body 82 by opening or releasing the membrane 58; (b) removing the lid 84 completely from the body 82, to expose the particles 100 and the liquid 98 in the body 82 and to open the body 82, and placing the ampoule 90 into engagement with the body 82— thereby replacing the lid 84 with the ampoule 90 on the body 82; and (c) administering the medication to the patient. The method according to the second embodiment enjoys many of the benefits and advantages that are characteristic of the first embodiment.

C. Example Medications Administered

[0079] The device 30 described above can be used to administer a variety of medications. Aptalis Pharma markets at least some of those medications. For example, Aptalis Pharma markets delayed-release capsules for the treatment of exocrine pancreatic insufficiency (EPI) in patients under the designation EUR-1008 and the registered trademark Zenpep ^® .

[0080] The U.S. Food and Drug Administration (FDA) estimates that more than 200,000 Americans suffer from EPI. EPI is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. Loss of digestive enzymes leads to maldigestion and malabsorption of nutrients. This is a common disorder for those suffering from cystic fibrosis (CF) and other conditions compromising the exocrine function of the pancreas, such as pancreatic cancer, gastrointestinal surgery, and chronic pancreatitis. EPI results in malnutrition and, especially in CF patients, impaired growth in children, compromised immune response, and shortened life expectancy.

[0081] The Aptalis Pharma pharmaceutical preparations replace missing enzymes, improve digestion and absorption, and meet the standards of the United States Pharmacopeia. Each Zenpep ^® and EUR-1008 capsule contains small enteric-coated beads of porcine enzyme concentrate comprising pancrelipase, which is

predominantly a mixture of the main pancreatic enzymes lipase, protease, and amylase. Inactive ingredients of the Zenpep ^® and EUR- 1008 products include croscarmellose sodium, hydrogenated castor oil, colloidal silicon dioxide, microcrystalline cellulose, magnesium stearate, hypromellose phthalate, talc, and triethyl citrate. More detailed information about the Aptalis Pharma pharmaceutical preparations is available from U.S. Patent No. 7,658,918, which is incorporated by reference into this document in its entirety.

[0082] Every dose of the Aptalis Pharma pharmaceutical preparations provides patients and physicians with a consistent amount of digestive enzymes, that is the main pancreatic enzymes lipase, protease, and amylase in a highly stable formulation. Capsules can be opened and the contents split to individually titrate the dose. These features allow health-care professionals to fine tune treatment regimens to achieve optimal symptom control with improved dosing precision. In addition, the pill burden of the patient is potentially reduced.

[0083] The device 30 of the present invention can be used with any suitable composition of digestive enzymes. The invention can be used with compositions comprising digestive enzymes containing particles 100 of medication. Preferably, the particles 100 are coated.

[0084] The particles 100 can have any suitable particle size or shape. The term "particles" may include tablets, spheres, pellets, beads, minitablets, microtablets, microparticles, microspheres, microcapsules, and micropellets. The term "particles" as used in this document includes fine powders having particle diameters in the range of about 1 μπι up to pellets having a diameter of about 5 mm. For example, the particles 100 can have a particle size range of about 50 μηι to about 5,000 μηι or of about 50 μιη to about 2,000 μηι, they can have a nominal (e.g., mean) particle diameter in the range of about 2 to about 5 mm, or of less than about 2 mm (for example, of about 0.5 to about 2 mm). Beads may have a diameter, for example, of about 0.7 to about 1.6 mm or of about 0.7 to about 1.25 mm. "Minimicrospheres" having a smallest median particle size of about 1.15 mm or "microtablets" having a highest median particle size of about 2.63 mm are also suitable. The beads can have an average particle size of less than about 800 μηι, preferably less than about 500 μηι, and most preferably of about 400 μηι to about 600 μηι or of about 250 μηι to about 500 μ ι. These beads may have a volume diameter d(v, 0.1) (defined as the diameter where 10% of the volume distribution is below this value and 90% is above this value) of not less than 400 μιη and a volume diameter d(v, 0.9) (defined as the diameter where 90% of the volume distribution is below this value and 10% is above this value) of not more than 900 μπι.

[0085] The digestive enzyme particles 100 used in the device 30 of the invention are preferably formed into particles having a coating. The coating can be predetermined to direct the medication to the site within the patient where the medication will be most effective. The coating might be predetermined before the medication is administered, for example, to dissolve in the blood, stomach, intestines, or any other suitable site. In the example highlighted, the medication is coated with an enteric (of or within the intestine) polymer. The phrase "enteric polymer" means a polymer that protects the digestive enzymes from gastric contents, for example a polymer that is stable at acidic pH, but can break down rapidly at higher pH or a polymer whose rate of hydration or erosion is slow enough to ensure that contact of gastric contents with the digestive enzymes is relatively minor while it is in the stomach, as opposed to the remainder of the gastro-intestinal tract.

[0086] Therefore, the enteric coating of the particles 100 used in the device 30 of the present invention acts as a barrier protecting the medication from the acidic environment of the stomach and substantially prevents the release of the medication before it reaches the small intestine. The individual particles 100 can each have the same coating composition, or can include mixtures of particles 100, some of which have a different coating composition. Any suitable combination of coating compositions can be used to provide the desired type of release or therapeutic effect.

[0087] To avoid irritation of the oral mucosa or inactivation of enzymes, Zenpep® particles 100 should not be chewed or retained in the mouth. [0088] Lipase activities of the compositions used in the device 30 of the present invention can range from about 650 to about 45,000 USP units, from about 675 to about 825 USP units, from about 2,700 to about 3,300 USP units, from about 4,500 to about 5,500 USP units, from about 9,000 to about 1 1,000 USP units, from about 13,500 to about 16,500 USP units, from about 18,000 to about 22,000 USP units, from about 22,500 to about 27,500 USP units, from about 36,000 to about 44,000 USP units, and all ranges and sub-ranges there between. The enzymatic assays of the compositions expressed with USP units are performed according to USP protocols. The "USP" unit is used in the United States to measure the potency of a drug, that is, its expected biological effects. "USP" is a registered trademark of the United States Pharmacopeial Convention, Inc., a private standards organization that establishes standards for the pharmaceutical industry.

[0089] Amylase activities in the compositions used in the device 30 of the present invention can range from about 1,600 to about 6,575 USP units, from about 6,000 to about 225,000 USP units (for example, from about 6,400 to about 26,300 USP units), from about 10,700 to about 43,800 USP units, from about 21,500 to about 87,500 USP units, from about 32,100 to about 131,300 USP units, from about 42,900 to about 175,000 USP units, from about 53,600 to about 218,700 USP units, and all ranges and sub-ranges there between. Protease activities in the compositions used in the device of the present invention can range from about 1,250 to about 3,850 USP units, from about 5,000 to about 130,000 USP units (for example, from about 5,000 to about 15,400 USP units), from about 8,400 to about 25,700 USP units, from about 16,800 to about 51,300 USP units, from about 25,000 to about 77,000 USP units, from about 33,500 to about 102,800 USP units, from about 41,800 USP units to about 128,300 USP units, and all ranges and sub-ranges there between.

[0090] The lipase activity can range from about 675 to about 825 USP units, the amylase activity from about 1,600 to about 6,575 USP units, and the protease activity from about 1,250 to about 3,850 USP units. The lipase activity can range from about 2,700 to about 3,300 USP units, the amylase activity from about 6,400 to about 26,300 USP units, and the protease activity from about 5,000 to about 15,400 USP units. Or the lipase activity can range from about 4,500 to about 5,500 USP units, the amylase activity from about 10,700 to about 43,800 USP units, and the protease activity from about 8,400 to about 25,700 USP units. Or the lipase activity can range from about 9,000 to about 1 1,000 USP units, the amylase activity from about 21,500 to about 87,500 USP units, and the protease activity from about 16,800 to about 51,300 USP units. Or the lipase activity can range from about 13,500 to about 16,500 USP units, the amylase activity from about 32,100 to about 131,300 USP units, and the protease activity from about 25,000 to about 77,000 USP units. The lipase activity can range from about 18,000 to about 22,000 USP units, the amylase activity from about 42,900 to about 175,000 USP units, and the protease activity from about 33,500 to about 102,600 USP units. The lipase activity can range from about 22,000 to about 27,500 USP units, the amylase activity from about 53,600 to about 218,700 USP units, and the protease activity from about 41,800 USP units to about 128,300 USP units.

[0091] Lipase activities in the compositions used in the device 30 of the present invention can range from about 5,000 PhEur lipase units to about 30,000 PhEur lipase units; they may be about 5,000, or about 10,000, or about 15,000, or about 20,000, or about 30,000 or about 40,000 PhEur lipase units. (The European Pharmacopoeia (PhEur) of the Council of Europe is a pharmacopoeia, listing a wide range of active substances and excipients used to prepare pharmaceutical products in Europe.) The digestive enzymes of the compositions used in the device 30 of the invention can include one or more lipases (i.e., one lipase, or two or more lipases), one or more amylases (i.e., one amylase, or two or more amylases), one or more proteases (i.e., one protease, or two or more proteases), and mixtures of these enzymes in different combinations and ratios. The ratio of amylase: lipase in the compositions used in the device 30 can range from about 1 to about 10, such as from about 2.38 to about 8.75 (e.g., determined by enzymatic assays performed according to USP protocols). In yet another embodiment, the ratio of protease:lipase can range from about 1 to about 8, such as from about 1.86 to about 5.13 (e.g., determined by enzymatic assays performed according to USP protocols). In still other embodiments, the ratio of amylase: lipase activities is about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10.

D. An Example Kit

[0092] The components of the device 30 described above may be combined and made available to users 10 as a kit. More specifically, in the first embodiment, the medicine chamber 40 and the liquid chamber 60 may be made available together. In the second embodiment, the package 80 and the ampoule 90 may be made available together. The kit may also include one or more example medications as described above. The compositions (e.g., the particles 100) of the present invention are stored, depending on the embodiment, in either the medicine chamber 40 or in the package 80.

[0093] Although other materials would be suitable, and various components of the device 30 could be glass, rubber, or the like, the device 30 is preferably formed of a smooth, rigid, non-toxic, synthetic, plastic material. A wide variety of standard plastic materials can be used to manufacture the components of the device 30, providing they are chemically compatible with the product. Polyethylene

terephthalate (PET) is a thermoplastic polymer resin of the polyester family and is used in liquid containers. Polypropylene (PP) is a thermoplastic polymer made by the chemical industry and used in a wide variety of applications, including packaging. High-density polyethylene (HDPE) is a polyethylene thermoplastic made from petroleum; low-density polyethylene (LDPE) is a thermoplastic made from petroleum. Polyethylene (PE) is the most widely used plastic, with an annual production of approximately 80 million metric tons; its primary use is within packaging. PET, PE, and PP are the materials most useful to manufacture the components of the device 30. Hard plastic material (PET, PP, and HDPE) are especially preferred to manufacture the package 80. The plastic material of the ampoule 90 should be flexible and soft, characteristics achieved by using certain grades of PP and LDPE.

[0094] Preferably, the body 42 of the medicine chamber 40 and the ampoule 90 are transparent, allowing the user 10 to view their contents. The body 42 and the ampoule 90 also might be colored or have other indicia providing information to the user 10, such as identification of the medicine contained in the device 30, the day of the week when the medication should be administered, or the like. Regardless of the material of construction, the device 30 does not need to be calibrated.

[0095] The components of the device 30 can be presented and sold as a unit dosage form in "blister packs." To improve stability of the compositions, the device 30 should be stored in a sealed, moisture-proof blister pack. The phrase "moisture- proof refers to a pack which has a permeability to water of less than about 0.5 mg of water per cubic centimeter (cm ³ ) of container volume per year. The blister pack containing the compositions of the present invention can also contain a desiccant (i.e., a substance which absorbs, reacts with, or adsorbs water) capable of reducing the humidity inside the blister pack, for example a desiccant capsule capable of

"scavenging" moisture from the atmosphere sealed inside the blister pack.

[0096] From the foregoing description, it can be seen that the present invention provides several important advantages. The invention provides an improved oral dosing device 30 for use with infant, aged, or incapacitated persons and other patients which allows medication to be dispensed safely and carefully. The nipple-like head 44 is of such a size and shape as to provide a feeding surface for patients to suck on and draw medicine from the device 30 without having the spillage and trauma that accompanies the conventional force feeding of medication to such patients.

Moreover, the metered aperture 66 at the dispensing end of the nipple-like head 44 ensures that the flow rate of medication from the device 30 will be insufficient to cause gagging of the patient.

[0097] Additional functional advantages of the device 30 include (1) safe and relatively long-term storing (e.g., 2-3 years at room temperature) of a medicinal product; (2) providing an administration vehicle; (3) suspending particles of medication in a liquid; (4) orally administering to a pediatric population; and (5) improving patient compliance. The storage function is achieved by, among other characteristics, forming the device 30 of materials which are compatible with the medicinal product; separating the solid medicinal product from the liquid vehicle until the precise time for administration; and ensuring suitable shelf life (which requires physio-chemical stability and can be difficult because many medicines are sensitive, for example, to temperature and humidity). The function of suspending particles of medication in the liquid is achieved by, among other characteristics, a simple and extemporaneous procedure easily implemented without (or with little) prior preparation or practice by the user 10, while preserving the quality and efficacy of the drug. Such preservation is achieved by avoiding direct manipulation or contamination of, or damage to, the drug.

[0098] The oral administration function is achieved by, among other characteristics, direct and easy administration. The device 30 mimics the conventional infant or baby feeding bottle, including its nipple shape. Hopefully, the familiarity of the infant with the texture and shape of the device 30 will facilitate both patient receptiveness and administration of the entire requisite dose.

[0099] The function of improved patient compliance is achieved by, among other characteristics, avoiding the need for extraneous tools such as spoons, measuring utensils, syringes, or the like. The device 30 is also portable and handy. Finally, the device 30 is discrete. These characteristics render the device 30 ideal for teenagers as well as for other patients.

[00100] Although illustrated and described above with reference to certain specific embodiments and examples, the present invention is nevertheless not intended to be limited to the details shown. Rather, various modifications may be made in the details within the scope and range of equivalents of the claims and without departing from the spirit of the invention. It is expressly intended, for example, that all ranges broadly recited in this document include within their scope all narrower ranges which fall within the broader ranges.