WO2004006825A2

WO2004006825A2 - Ampules for delivery of small liquid volumes

Info

Publication number: WO2004006825A2
Application number: PCT/US2003/022169
Authority: WO
Inventors: Robert E. Coifman
Original assignee: Coifman Robert E
Priority date: 2002-07-15
Filing date: 2003-07-15
Publication date: 2004-01-22
Also published as: AU2003256560A8; WO2004006825A3; AU2003256560A1

Abstract

Ampules for quantitative delivery of a small volume of liquid and mixing vials for preparation of diluted mixtures containing the small volume of liquid in these ampules are provided. The ampules are particularly useful for storage of sterile, concentrated drug solutions for single dose administration upon dilution in a pharmaceutically acceptable diluent. This invention solves the problem of loss of content from incomplete emptying of ampules and allows quantitative delivery from fill volumes as low as or possibly lower than 0.02 ml.

Description

Ampules for Quantitative Delivery of Small Volumes of Liquid

Introduction

This patent application claims the benefit of priority from U.S. Provisional patent application 60/397,593, filed July 19, 2002 and U.S. Provisional patent application 60/396,395, filed July 15, 2002, the contents of which are herein incorporated by reference in their entireties.

Field of the Invention

The present invention relates to ampules which quantitatively deliver a volume of liquid too small to be quantitatively expelled by pouring or squeezing. The ampules of the present invention are particularly useful in dispensing small volumes of sterile, concentrated drug- containing liquids to a mixing vial for dilution in a pharmaceutically acceptable diluent. A mixing vial for use with the ampules of the present invention is also provided.

Background of the Invention Pharmaceutical substances such as drugs are typically stored in sealed vials or other containers for later use. Such pharmaceuticals may be in a dry or powdered form to increase the shelf life of the substance and reduce inventory space. Such dry or powdered substances are generally stored in a sealed vial and reconstituted in liquid form for administration to a patient by adding diluent or solvent. Alternatively, the substance may in a liquid or even a gaseous form.

Often liquids comprise concentrated substance in a vehicle in which the substance is stable, but which may be unsuitable for administration to a subject. Such concentrated liquids require dilution in a vehicle which is pharmaceutically acceptable for administration to a subject.

Conventional vials for storing pharmaceutical substances generally comprise an open end, a radial rim portion surrounding the open end and a reduced diameter neck portion adjacent to the rim portion. Such vials are generally sealed with an elastomeric stopper comprising a tubular portion or an annular rim which fits into the neck of the vial and a planar rim portion which overlies the vial rim. The elastomeric stopper is typically secured to the vial using a thin malleable metal cap, such as aluminum. The metal cap comprises a tubular portion which surrounds the rim portion of the stopper and vial, an inwardly projecting annular rim portion which overlies the rim portion of the stopper and a free end portion which is crimped or deformed radially into the vial neck beneath the vial rim portion.

Often, liquid medicines are provided in such vials or glass bottles with a rubber sheet diaphragm across the spout of the bottle sealed with a metal rim and removable seal. The liquid medicines can be accessed by hypodermic needle, for example, piercing through the rubber diaphragm and withdrawing liquid medicine into a hypodermic needle.

However, multiple dosing via this method compromises sterility of the liquid medicine.

Accordingly, vials are also provided in measured concentrated doses, often referred to as unit doses, by the drug manufacturer so that sterile diluted solutions containing the full contents of a single vial can be prepared.

Prior to the discovery and development of polymeric materials, pharmaceutical liquids were supplied to pharmacies, health care providers and hospitals exclusively in glass vials. However, glass vials have multiple disadvantages including, but not limited to, high production costs, excessive weight in shipping, fragility in storage and difficulty in disposal.

Accordingly, multiple attempts have been made in the prior art to provide flexible, sterile containers in the forms of bags and bottles for the containment and delivery of parenteral solutions, such as diagnostic contrast media, and nutritional and drug formulations. Such containers typically comprise: a flexible plastic sheet formed into a pouch, bag or bottle shape filled with a sterile solution; and one or more ports to fill and/or access the solution. One of the requirements to be satisfied in such flexible containers for storage and delivery of pharmaceutical solutions to patients is that by their construction and design they deliver their total contents without retaining liquid drops on their walls . For parenteral solutions delivered directly to a patient, for example via I.V. the prior art has addressed this requirement, as shown for example in U.S. Patent 4,892,537, which discloses a bag having substantially parallel major sides or edges and converging minor sides which meet at a point forming an obtuse angle of at least 110 degrees. The converging edges are designed to guide the filled bag contents in a substantially unobstructed manner in a funnel-like fashion to an exit port.

U.S. Patent 4,088,166 also addresses the problem of incomplete and non-uniform collapse of parenteral solution containers by incorporating gusset portions into the body portion of the container adjacent the shoulder portion. The gusset portions include lines of flexing weakness to facilitate the collapse of the container adjacent the shoulder portion as the contents thereof are withdrawn. The gussets facilitate both the lateral and longitudinal collapse of the container as it is emptied.

Another problem observed with flexible containers is referred to by medical practitioners as fluid "hold up", i.e., when drops of parenteral solutions tend to remain on the internal walls of the flexible container as the solution is being delivered to the site of administration. Moderate suction pressure exerted on the walls of a container is insufficient to overcome the force existing between the drops of liquid and the walls of the container. Often, as the container is being drained, the emptied portion of the parallel walls adhere to each other further trapping drops of the liquid. As a consequence, the prescribed amount of parenteral solution is not delivered to the patient. Such delivery, especially in traumatic circumstances where a precise amount of a drug must be delivered into the patient, can make the difference between life and death of the patient.

U.S. Patent 5,779,693 discloses a flexible plastic container for the containment and delivery of diagnostic contrast media and parenteral drug formulations. This flexible medical fluid container comprises a first and second flexible plastic sheet sealed together at their periphery to form a pouch defining an interior. The bottom portion of the container terminates in a first angle and a second angle of from 5 degrees to 45 degrees to facilitate the flow of medical fluid towards an access port. Portions of the interior of the pouch are embossed in a V-shaped configuration to direct flow of fluid towards the access port.

U.S. Patent 4,872,872 discloses a medicament container/dispenser assembly which includes a substantially non-collapsible main body defining a chamber for containing the medicament in liquid form. The main body has an upper and lower portion, an opening formed in the upper portion, a liquid impervious, gas permeable membrane secured to the upper portion of the main body in sealing relation to the opening, and a rupturable exit port formed in the lower portion of the main body. The assembly can also include a second opening formed in the upper portion of the main body in spaced relation to the first-mentioned opening and an elastomeric, puncturable, sealing material secured to the upper portion of the main body in sealing relation to the second opening. In a further embodiment, a conduit may be positioned adjacent the membrane at the upper section of the main body, and may contain a blower for supplying forced air to the membrane through the conduit. A sensing device for sensing flow of the liquid medicament from the exit port and for controlling the blower in response thereto may be associated with the blower, in order to selectively activate the blower to maintain a substantially constant flow of medicament from the exit port.

U.S. Patent 6,247,617 discloses a single use container for accurately dispensing separately housed sterile compositions with minimal contact to non-sterile surfaces of the container. Embodiments include a container having a first and second chamber within the container for housing a first and second sterile composition. Each chamber has an angled channel which defines an axis for directing the sterile composition from their respective chambers. The angled channels are directed towards each other and are so angled as to minimize contact of the escaping sterile compositions with a non-sterile surface of the container, e.g. the tip. A plurality of tear-off closures seal the angled channels to prevent the sterile compositions from escaping from their respective chambers and a tab portion is provided joining the plurality of closures . Removing the tab portion causes all of the solid closures to be removed in a single action .

However, there is a need for vials or ampules capable of quantitatively delivering the entire contents of liquid medicament, particularly when in small volume, to a diluent while maintaining sterility.

Summary of the Invention

An object of the present invention is to provide ampules for quantitative delivery of a small volume of liquid. The ampules of the present invention prevent loss of delivered drug by incomplete emptying of small volume ampules, preferably for nebulizer dosing, by cleanly or sterilely cutting off or tearing open the parts of the ampule to which drug may adhere so that they fall into a mixing vial or other container in which they may be washed off and into the diluent by the diluent itself. In one embodiment, the ampule comprises: a chamber for housing a small volume of liquid, said chamber having an inside and outside and a top portion and bottom portion, said bottom portion and top portion of the chamber being separated by a cut line on the outside of the chamber; a holding tab extending from the top portion of the chamber; and a stop tab extending perpendicularly from the holding tab. In this embodiment, the ampule is held by the holding tab and gently shaken in a manner which propels the full content into the bottom portion of the chamber which is dropped into a diluent with its contents upon cutting of the ampule along its cut line.

In a preferred embodiment, after gently shaking the ampule to propel the full content of the ampule into the bottom portion of the chamber, the ampule is positioned in a cutting guide the top of a mixing vial of the present invention via its holding tab and stop tab and the ampule is cleanly cut along the cut line of the chamber so that the bottom portion of the chamber and its full liquid contents are released into the mixing vial.

In another embodiment, the ampule comprises: a chamber for housing a small volume of liquid, said chamber having a top and bottom; a holding tab attached to the top of said chamber; a stop tab extending perpendicularly from the holding tab; and one or more pull tabs, each attached to a cutting string or wire which extends from the pull tab down to the bottom of the chamber wherein a portion of the cutting wire or string is molded into the chamber and extends from the bottom of the chamber to the top of the chamber. In this embodiment, when each pull tab is pulled, the cutting wire or string to which the pull tab is attached tears the chamber completely open from bottom to top thereby releasing the small volume of liquid in the chamber. Thus, the pull tab serves as a gripping means for the tough, sharp cutting string or wire that extends from the pull tab and is molded into the chamber. In this embodiment, it is preferred that the pull tab(s) and cutting wire(s) or string (s), after being pulled to open the chamber, become completely detached from the ampule. It is also preferred that the stop tab be only temporarily secured to the holding tab and/or chamber, for example, by a thin plastic webbing, for additional strength during storage of the sealed ampule. However, after opening of the ampule, the stop tab can be torn, thereby releasing the open chamber of the ampule or parts thereof from its other components into the mixing vial.

Another object of the present invention is to provide mixing vials for use with these ampules. These mixing vials comprise: a cylindrical container having a closed bottom, an inside and outside, and open top; a closing means which fits onto the open top of the cylindrical container for liquid-tight closure of the mixing vial; and a slotted lip positioned in the closure means at the top of the cylindrical container or on the inside of the cylindrical container which holds the ampule and/or prevents pieces of the ampules from being poured out of the cylindrical container. In a preferred embodiment, for use with ampules wherein the top and bottom portion of the chamber are separated by a cut line on the outside of the chamber, the mixing vial comprises a closing means with a top and side which fits onto the top of the cylindrical container and contains a guide in the side of the closing means for insertion of a cutting device and a slot in the top of the closing means for insertion of an ampule. In this embodiment, the slot is preferably sized so that the stop tab of the ampule prevents the ampule from falling into the cylindrical container of the mixing vial.

Brief Description of the Drawings

Figure 1 is a diagram of one embodiment of an ampule having a chamber for housing a small volume of liquid with a top portion and bottom portion separated by a cut line on the outside of the chamber and a holding tab and stop tab at the top of the chamber for holding and positioning of the ampule for cutting.

Figure 2 is a diagram of another embodiment of this ampule wherein the holding tab and stop tab extend at an angle from the chamber.

Figures 3a, 3b and 3c are diagrams for the components of first closing a preferred mixing vial of the present invention including a cylindrical container with a slotted lip (3a) , a first closing means for liquid-tight closure of the mixing vial (3b) ; and a second closing means with a top and side which fits onto the top of the cylindrical container and contains a guide in the side of the second closing means for insertion of a cutting device and a slot in the top of the second closing means for insertion of an ampule (3c) .

Figure 4 provides a diagram of exemplary steps involved in using an ampule and mixing vial of the present invention to produce a sterile diluted drug containing solution for administration via nebulizer. In step 1, diluent is placed in the bottom of the cylindrical container; the ampule is positioned in the top of the second closing means (Figure 3C) ; a cutting device is inserted into the guide in the side of the second closing means (Figure 30) ; and the bottom portion of the ampule chamber is cut and released into the bottom of the cylindrical container. In step 2 the first closing means for liquid-tight closure (Figure 3B) is placed on the cylindrical container and the mixing vial is shaken to release the full dose of medication in the bottom portion of the ampule into the diluent. In step 3, the first closing means for liquid-tight closure is removed or re- positioned for pouring. In step 4, the bottom portion of the ampule is trapped by the slotted lip in the cylindrical container as the solution is poured into a second cylindrical container. Step 5 may be required when more than one ampule of medicament is added. In this step, after disposing of the empty ampule chamber from the first cylindrical container, the solution in the second cylindrical is returned to the first cylindrical container. In step 6, a nebulizer unit is slid into the cylindrical container containing the solution for use with a nebulizer unit. Step 7 shows the components of a preferred mixing vial of the present invention in storage configuration after cleaning and drying. Detailed Description of the Invention

Various drugs, many of which can be delivered by nebulizer, lose their potency and/or deteriorate or undergo physical changes which alter their nebulization properties when stored in pharmaceutically acceptable diluents. Many such drugs have superior storage properties in small volumes of solvents, which themselves are not pharmaceutically acceptable for nebulizer administration, but which become acceptable if sufficiently small volumes are mixed with acceptable diluents prior to nebulization. It is thus desirable to sterilely store therapeutic doses of such drugs in sufficiently small volumes of solvent that are not themselves pharmaceutically acceptable for nebulizer administration, for clean, quantitative delivery into nebulizable volumes of diluents such that the resulting mixtures contain quantitatively accurate doses of drug in mixtures that are pharmaceutically acceptable for administration, particularly nebulizer administration.

The same technology can reduce the cost of shipment and storage of drugs that are stable in nebulizable volumes of diluent, by enabling smaller, lighter weight packaging of various drugs and doses, each of which can be diluted with the same, standard diluent prior to administration .

However, it is impossible to quantitatively deliver volumes of liquid of less than 0.5 ml from standard ampules requiring pouring or squeezing to expel the liquid because of incomplete emptying.

In the present invention, ampules are provided for quantitative delivery of a small volume of liquid. For purposes of the present invention, by Asmall volumeδ it is meant a liquid volume of less than 0.5 ml, preferably as low or lower than 0.02 ml up to 0.5 ml. In one embodiment, as depicted in Figure 1, the ampule 1 comprises a chamber 2 for housing a small volume of liquid. The chamber 2 has an inside 3 and outside 4, as well as a top portion 5 and bottom portion 6. The top portion 5 and bottom portion 6 are separated by a cut line 7 on the outside 4 of the chamber 2. A holding tab 8 extends from the top portion 5 of the chamber 2. In some embodiments, as depicted in Figure 1, the holding tab 8 extends directly perpendicular at a 90° angle with the chamber 2. Alternatively, as depicted in Figure 2, the holding tab 8 may extend at an angle of less than 90°, for example 45°, from the chamber 2. As shown in Figures 1 and 2, the ampule further comprises a stop tab 9 located above the chamber 2 and extending perpendicularly on both sides with respect to the holding tab 8.

In the ampule embodiment depicted in Figures 1 and 2, liquid in the ampule is propelled into the bottom portion of the chamber, for^' example by holding the ampule by its holding tab and gently shaking the ampule in similar fashion to a fever thermometer to force the liquid into the bottom portion of the chamber. Liquid is then released into a mixing vial positioned beneath the ampule by cutting the chamber along the cut line so that the bottom portion of the chamber containing the liquid falls into the vial. The bottom portion of the chamber may be cut using a small pair of clean scissors provided with the ampules, with a cutting device incorporated into the closing means of the mixing vial, or with alternate cutting means. In a preferred embodiment, the bottom portion of the chamber is thicker as compared to the top portion to prevent collapsing under inward pressure as the chamber is cut. In another embodiment, instead of a cut line, the ampule may comprise one or more pull tabs, each attached to a cutting string or wire which extends from the pull tab down to the bottom of the chamber wherein a portion of the cutting wire or string is molded into the chamber and extends from the bottom of the chamber to the top of the chamber. When each pull tab is pulled, the cutting wire or string to which the pull tab is attached tears the chamber completely open from bottom to top thereby releasing the small volume of liquid in the chamber. Thus, the pull tab serves as a gripping means for the tough, sharp cutting string or wire that extends from the tab and is molded into the chamber. In this embodiment, the portion (s) of cutting wire(s) or string (s) which is molded into the chamber is positioned to enable complete peeling or opening of the bottom and sides of the chamber upon pulling of the pull tab. As will be understood by one of skill in the art upon reading this application, a portion of the cutting string or wire may be molded into the chamber in various configurations to facilitate opening of the chamber. In a preferred embodiment, the ampule comprises more than one pull tab and cutting wire or string. In this embodiment, the portions of cutting strings or wires molded into the chamber may overlap in the chamber and the pull tabs may be labeled for pulling in a specified sequence or order to avoid tangling. In this embodiment, ■ it is preferred that the stop tab be only temporarily secured to the holding tab and/or chamber, for example, by a thin plastic webbing, for additional strength during storage of the sealed ampule. However, after opening of the ampule, the stop tab can be torn, thereby releasing the open chamber of the ampule or parts thereof from its other components so that portions of the ampule containing the liquid are released into the mixing vial or other container.

The ampules of the present invention are designed for securing in a mixing vial via insertion into a slotted lip of a cylindrical container or liquid-tight closing means or an open slot in a closing means which fits onto a cylindrical container of the mixing vial. The slotted lip or open slot is preferably sized so that the stop tab of the ampule prevent the ampule from falling into the mixing vial .

For example, for the ampule of Figure 1, the slotted lip preferably fits between the top portion of the chamber and the stop tab of the ampule so that when the ampule is opened, its contents are expelled into the mixing vial.

In a preferred embodiment, the ampule is secured in the slotted lip of the mixing vial in a fashion which allows for tilting of the ampule for efficient tearing or opening of the chamber of the ampule. For example, in one embodiment the ampule is placed in the slotted lip at a 30 to 45 degree angle from vertical so the force of pulling a first pull tab and cutting string or wire properly tears the ampule along one side of the chamber from bottom to top. The ampule is then preferably repositioned to be tilted at a 30 to 45 degree angle in the opposite direction for pulling a second pull tab and cutting string or wire on the opposite side of the chamber. In this embodiment, it may be preferred to label the chamber of the ampule with terms such as "front" and "back" to identify which face of the chamber should be facing forward for optimal tearing and emptying.

In this embodiment, it is also preferred that the cutting strings or wires be positioned so that upon proper angling of the ampule in the slotted lip of the mixing vial, the bottom and sides of the chamber completely peel open by pulling of the pull tabs and cutting strings or wires. The ampule can then be repositioned vertically in the slotted lip and the stop tab of the ampule can be broken by twisting or tearing so that the open chamber or pieces of the chamber attached thereto fall to the bottom of the mixing vial where any remaining droplets of its contents can be swirled into the resulting mixture after diluent is added. In this embodiment, the cutting strings or wires pull completely out of the top of the chamber of the ampule after tearing or peeling open the bottom and sides of the rim of the chamber, so that they do not get in the way of adding diluent, swirling and cleanly pouring the resulting mixture into a delivery device such as a nebulizer . Variations in thickness and geometry of different portions of the ampule chamber may facilitate effective tearing or cutting over a wider range of ampule positions, making proper opening and mixing of the contents less dependent on the position in which the ampule is held when the cutting strings or wires are pulled or the ampule is cut to open the ampule. Such variations will render quantitative release from the ampule more reliable by reducing demand for rigorous user technique.

In a preferred embodiment, ampules of either embodiment of the present invention comprise a plastic not wettable by the liquid solvent held in the chamber.

Also provided in the present invention is a mixing vial 20. Preferred components of the mixing vial are depicted in Figure 3. The mixing vial 20 comprises a cylindrical container 21. In a preferred embodiment, the container 21 has a closed conical-shaped or rounded bottom 22, an inside 23 and outside 24, and an open top 25.

In one embodiment, a slotted lip 26 is located on the inside 23 of the container 21. Alternatively, a slotted lip can be incorporated into a liquid-tight closing means 27 which fits onto the top of the cylindrical container.

The slotted lip 26 of the mixing vial can perform two functions. First, the slotted lip can hold an ampule of the present invention in place while it is emptied and then dropped without hand contamination into the cylindrical container. Second, the slotted lip prevents the opened ampule or portion of opened ampule from falling into the delivery device such as a nebulizer to which solution from the cylindrical container is transferred. The size of the lip depends on the type of ampule being used and its function. If the ampules are to be torn open by pulling cutting wires or strings, the lip must be large enough and sturdy enough to hold the ampules in place for this purpose. For example, upon positioning of an ampule with one or more cutting wires or strings in the slotted lip on the inside of a cylindrical container of a mixing vial, the pull tab of the ampule can be pulled thereby opening the ampule via the cutting wire(s) or string (s) and releasing the small volume of liquid in the ampule into the bottom of the container. In embodiments comprising more than one pull tab and cutting wire or string, the pull tabs are preferably pulled in a sequential order. In this embodiment, the slotted lip preferably keeps the ampule properly aligned should the user need to tilt the ampule to a 30 to 45 degree angle in the vertical plane of the slot. The pull tabs most effectively tear open the bottom of the chamber if they are continuously pulled in a backward direction slightly away from and parallel to the bottom at the point from which they are being pulled. Accordingly, the slotted lip preferably allows for continuous repositioning by the user of the ampule as the tabs are pulled. Repositioning of the ampule as the pull tabs are pulled is preferably performed with hand contact only via the stop tab and/or holding tab. In embodiments wherein the pull tabs are completely removed after opening and the chamber is completely torn open, the chamber or pieces thereof may be dropped into the mixing vial after opening by tearing of the stop tab until it breaks away from the portion of the ampule below the stop tab.

If the ampules are to be cut, the lip must be small enough and sufficiently out of the way not to keep the cut ampule chamber and its contents from falling into the cylindrical container, yet large enough to keep pieces of ampule from being poured out with the solution, as the slot or slots in an ice water pitcher are designed to hold back ice cubes when water is poured. The mixing vial further comprises a first closing means 27 for liquid-tight closure of the cylindrical container which fits on the outside top of the container so that a diluent can be added to the cylindrical container and swirled in the cylindrical container after capping to physically remove any small droplets that may remain adhered to the portions of the chamber of the ampule in the mixing vial. The first closing means may be removed after mixing in order to pour the solution into another container. In this embodiment, it is preferred that the cylindrical container comprise a slotted lip to keep ampule pieces from being poured from the cylindrical container with the solution. Alternatively, and preferably in embodiments wherein the slotted lip is in the first closing means, the first closing means is designed to have a closed position sealing the cylindrical container and an open position wherein the solution can be poured from the cylindrical container while the slotted lip of the first closing means prevents the ampule pieces from being poured out with the solution. In a preferred embodiment, for use with ampules comprising a cutting line, the first closing means of the mixing vial further contains a guide 28 in the side for insertion of a cutting device and a slot 29 in the top for insertion of an ampule. This embodiment of a closing means thus contains and provides all of the following functions: a device which quickly and accurately positions the ampule for cutting; a device which cleanly cuts the ampule at the cut line; a device which provides for adequate closure to prevent spilling when the mixing vial is swirled to wash off any droplets of ampule content that might have adhered to the walls of the ampule chamber; and a device with a pouring lip or slot to keep fragments of ampule from being transferred into the delivery device with the solution. Mixing vials of the present invention may comprise a single closing means providing all of these functions. Alternatively, as shown in Figure 4, the mixing vial may comprise two closing means, a first closing means which functions to seal the cylindrical container during mixing and a second closing means which provides an ampule cutting guide and a slot for insertion of the ampule.

Figure 4 provides a step-by-step diagram for preparation of a diluted solution using a mixing vial and an ampule comprising a small volume of liquid of the present invention. In this example, the solution is prepared for nebulizer administration. However, as will be understood by those skilled in the art upon reading this disclosure, there are multiple appreciation for the solutions prepared in this manner. In the present invention, it is preferred that the ampule be provided in a sterile outer pack. The mixing vial and any cutting means, like the device into which the mixture will be poured, must be clean and dry before each use but need not be sterile depending upon the application. The open ampule, or portion thereof, can then be allowed to fall with its remaining contents to the bottom of the mixing vial with no hand contact contamination .

In a preferred embodiment, the liquid in the ampule comprises a sterile, concentrated drug solution, which upon dilution in the mixing vial, can be transferred to a device such as nebulizer for administration of the diluted drug mixture to a subject in need thereof. When preparing nebulizer formulations, liquids are preferably kept sterile and hygroscopic solids are preferably kept protected from moisture. However, dry, non-hygroscopic surfaces need only be kept clean prior to nebulization. Further, the liquid mixture prepared for nebulization requires maintenance of cleanliness, not of sterility, during the nebulation process which typically encompasses time spans of up to 30 to 40 minutes from time of mixing through administration. The ampules and mixing vials of the present invention are particularly useful in the preparation of such nebulizer formulations.

Claims

What is Claimed is :

1. An ampule for quantitative delivery of a small volume of liquid to a diluent comprising a chamber which is cleanly or sterilely cut off or torn open so that a portion of the ampule containing the liquid falls into a mixing vial or other container so that it can be washed quantitatively into the diluent by mixing with the diluent.

2. The ampule of claim 1 comprising: a chamber for housing a small volume of liquid, said chamber having an inside and outside and a top portion and bottom portion, said bottom portion and top portion of the chamber being separated by a cut line on the outside of the chamber; a holding tab extending from the top portion of the chamber; and a stop tab extending perpendicularly from the holding tab.

3. The ampule of claim 1 comprising: a chamber for housing a small volume of liquid, said chamber having a top and bottom; a holding tab attached to the top of said chamber; a stop tab extending perpendicularly from the holding tab; and one or more pull tabs, each attached to a cutting string or wire which extends from the pull tab down to the bottom of the chamber wherein a portion of the cutting wire or string is molded into the chamber and extends from the bottom of the chamber to the top of the chamber.

4. A mixing vial comprising: a cylindrical container having a closed bottom, an inside and outside, and an open top; a first liquid tight closing means at the top of the cylindrical container; and a slotted lip on the inside of said cylindrical container or in the first liquid tight closing means for preventing an opened ampule of claim 1 through 3 from falling into a delivery device to which liquid from the mixing vial is transferred.

5. The mixing vial of claim 4 wherein the first liquid tight closing means further comprises an ampule cutting guide for insertion of a cutting device.

6. The mixing vial of claim 4 wherein the first liquid tight closing means further comprises' an open slot for insertion of an ampule.

7. The mixing vial of claim 4 further comprising a second closing means containing an ampule cutting guide and an open slot for insertion of an ampule.