Contamination-resistant dispensing and metering drop forming device

We claim:

1. A device for dispensing liquids in drop form of substantially uniform size which comprises a container having a dropper tip including a passageway for ingress of air to and egress of liquid from said device, said passageway communicating between the container and an orifice in the dropper tip; means for temporarily reducing the volume of the container; and disposed within the dropper tip, across the passageway, a microporous composite membrane with pores of a size to resist passage of contaminants, said membrane having a liquophilic component permitting delivery of drops of a liquid to a desired location outside the container and a liquophobic component adapted to resist the passage of such liquid but to permit the passage therethrough of air, the surface area and pore size of said liquophilic component being so selected as to meter liquid being dispensed in drop form and avoid a stream of liquid from emerging from the dropper tip during normal use, said passageway being intersected by said membrane and communicating with both the liquophilic and liquophobic components.

2. A device according to claim 1 wherein and the pore size of the liquophoilic component of the membrane is from about 0.04 to about 0.65 .mu.m.

3. A device according to claim 1 wherein the pore size of the liquophobic component of the membrane is from about 0.01 to about 0.45 .mu.m.

4. A device according to claim 1 wherein the liquophilic component comprises from about 50 to about 70% of the surface area of the membrane.

5. A device according to claim 1 wherein the volume between the composite membrane and the dropper tip orifice is from about 0.001 to about 0.15 cm.sup.3.

6. A device according to claim 1 adapted to dispense an aqueous solution wherein the liquophobic component has a critical wetting surface tension of less than 35 dynes/cm.

7. A device according to claim 6 wherein the liquophilic component of the composite membrane has a critical wetting surface tension of at least 72 dynes/cm.

8. A device according to claim 6 wherein said aqueous solution includes a medicine.

9. A device according to claim 1 wherein the liquophilic component is made from a surface-modified microporous nylon polymer membrane.

10. A device according to claim 1 wherein the liquophobic component is made from a surface-modified microporous polyvinylidene fluoride membrane.

11. A device according to claim 1 wherein the container has elastically deformable sides.

12. A device according to claim 1 wherein the porosity of the composite microporous membrane is suitable for resisting the passage of bacterial contamination and the liquophilic component has a surface area of from about 20 mm.sup.2 to about 90 mm.sup.2.

13. A device according to claim 1 wherein said liquophilic component comprises a surface-modified microporous nylon membrane and said liquophobic component comprises a surface-modified microporous polyvinylidene fluoride membrane.

14. A device according to claim 1 wherein said liquophilic component comprises a surface-modified polyamide membrane having a CWST of at least about 50 dynes/cm and said liquophobic component comprises a surface-modified polyamide having a CWST of less than about 35 dynes/cm.

15. A device according to claim 14 wherein the CWST of said liquophilic component is at least about 72 dynes/cm and said liquophobic component is less than about 29 dynes/cm.

16. A device according to claim 1 wherein said orifice comprises a single orifice.

17. A device according to claim 1 wherein said liquophilic and liquophobic components are arranged in juxtaposed relationship.

18. A device according to claim 1 wherein the liquophilic component comprises a surface treated polyvinylidene fluoride membrane.

19. A device according to claim wherein each of the liquophilic and liquiphobic components comprise polyvinylidene fluoride membranes.

20. A device according to claim 1 wherein said liquophilic component comprises a surface-treated polyvinylidene fluoride membrane having a CWST of at least 50 dynes/cm and said liquophobic component comprises a polyvinylidene fluoride membrane having a CWST of less than about 75 dynes/cm.

21. A device for dispensing liquids in drop form of substantially uniform size which comprises an elastically deformable container having a dropper tip with a passageway therethrough for ingress of air to and egress of liquid from said device, said passageway terminating in an orifice and, disposed within the dropper tip and across the passageway, a composite microporous membrane with pore sizes less than 0.45 .mu.m, said membrane comprising a hydrophilic component and a hydrophobic component, said hydrophilic component providing from about 60 to about 70% of the surface area of the composite membrane, said hydrophilic component having a surface area so selected as to meter liquid being dispensed in drop form and avoid a stream of liquid from emerging from the dropper tip during normal use, and said passageway being intersected by said membrane and communicating with both of said hydrophilic and hydrophobic components.

22. A device according to claim 21 wherein a composite microporous membrane has first and second components bonded together in side-by-side relationship, the first component having a surface area of from about 40 mm.sup.2 to about 50 mm.sup.2, an average pore size of from about 0.15 to about 0.25 .mu.m, and a CWST of at least about 72 dynes/cm and being made from a surface-modified polyamide; and the second component being made from a polyamide that has been surface-modified to produce a CWST of less than about 35 dynes/cm and having an average pore size of from about 0.1 to about 0.2 .mu.m.

23. A device according to claim 22 wherein the volume between the orifice of the dropper and the surface of the composite membrane closest to the tip is from about 0.05 to about 0.1 cm.sup.3.

24. A device for dispensing liquids in drop form of substantially uniform size which comprises a container having a dropper tip including a passageway for ingress of air to and egress of liquid from said device, said passageway communicating between the container and an orifice in the dropper tip and, disposed within the dropper tip across the passageway, a microporous membrane with pores of a size to resist passage of contaminants, said membrane having a liquophilic component permitting delivery of drops of a liquid to a desired location outside the container, and a liquophobic component adapted to resist the passage of such liquid but to permit the passage therethrough of air, said passageway being intersected by said membrane and communicating with both of said liquophilic and liquophobic components, the surface area and pore size of the liquophilic component being selected so as to meter the liquid being dispensed in drop form and avoid a stream of liquid from emerging from the dropper tip during normal use.

25. A device according to claim 24 wherein the porosity of the microporous membrane is selected so as to resist the passage of bacterial contaminants and the surface area of the hydrophilic component is from about 20 mm.sup.2 to about 90 mm.sup.2.

Description Submit all comments and votes

TECHNICAL FIELD

This invention relates to a liquid dispensing and metering device that is especially useful in, for example, the dispensing of optical drugs that typically need to be dispensed in drop form. The present invention provides such a device that also protects the solution from contamination while retained in the device.

BACKGROUND OF THE INVENTION

This invention has wide application in situations where a liquid is required to be dispensed in metered amounts at regular intervals from a container and in which it is critical that contamination from outside, whether particulate or bacterial in nature, be excluded. This is most frequently encountered in the context of the dispensing of medicines such as ophthalmic medicines but the utility of the invention extends to the protection of any liquid against particulate contamination. For ease of understanding, however, the invention will be described primarily in the context of the application that, as is presently anticipated, will be the most commercially attractive.

Many drugs, particularly those used in treatment of various eye disorders, are administered in drop form. The drops are intended to free-fall onto the eye surface, where they distribute across the exposed eye. Dosage of these ophthalmic drugs is often crucial: lower than prescribed levels can result in failure of the treatment and consequent progression of the disease, higher levels can result in untoward side effects that can also interfere with successful resolution.

Complicating the administration of these drugs is the fact that they are often required several times a day and thus, to be practical, must be applied by the patients themselves and not by medical personnel who are formally trained in drug delivery. Patient administration of such drugs has resulted in two serious problems which must be solved for these medications to be successfully used: container contamination and flow rate.

CONTAINER CONTAMINATION

The possibility that bacterial contamination may enter the drug container and proliferate there is an ever-present problem that can destroy the utility of the medicine. This can be the result of dropper contact with a non-sterile surface, such as a body part, or by some other mechanism.

The problem can be most readily understood in the context of the administration of drops of an ophthalmic medicine. Ideally, the pendant drop formed at the tip of the conventional dropper container when the container is squeezed should be allowed to free-fall to the surface of the eye. In addition, the distance between the dropper tip and the surface of the eye should be kept reasonably close. This is important so that the momentum acquired by the free-falling drop will not be so great as to encourage the drop to splatter on impact with the eye surface and thus be substantially lost to the outer surface of the lids and face. Where administration is by a trained professional, it is relatively easy to ensure that the free-falling drop is discharged close to the eye surface. It is substantially more difficult to do this when the drug is self-administered. Gauging such short distances is physiologically difficult due to the inability to focus, and in addition the anticipation of the impacting drop often causes a blink and subsequent loss of portions of the drop. As a result, the user may inadvertently permit the dropper tip to contact the eye surface.

In any event, small amounts of eye liquids can thus be inadvertently permitted to commingle with the liquid of the drop to be delivered. Thus, when the pressure on the delivery container forcing the drop out is relieved, a small amount of the mixed liquids may be drawn back into the container. With time the bacteria originally present in the eye, both normal and pathological, will be permitted access to a medium which may cause them to proliferate. Thus, subsequent drops of medication may reintroduce to the eye either excessive levels of typically present bacteria, or large numbers of pathogens. Neither situation is acceptable.

To cope with the problems of contamination, drug manufacturers often introduce an anti-bacterial agent to the drug container. In most cases, this agent or preservative can be very effective at suppressing the growth of bacterial contaminants within the container. Unfortunately, there exists a significant population of patients for whom these preservatives represent ocular irritants, or in more severe cases, cause allergic reactions. Such untoward ocular reactions prevent such patients from using the drug in this kind of packaging. For these patients, single-use, non-preserved drug packaging is a partial answer, but at significantly increased cost and inconvenience.

Of course, similar problems are encountered with other drop-administered medicines, for example, for the ear or nose.

Container contamination can also be the result of particulate matter being drawn back into the container with the liquid in the dropper tip that has not been delivered as a drop. Over several drop deliveries in, for example, dusty conditions, a significant accumulation of dust in the container is possible. If the liquid to be delivered needs to be ultrapure as, for example, in certain microelectronic applications, such accumulation could raise a serious problem.

FLOW RATE

Dosage of drugs administered as drops is regulated on the basis of the number of drops to be applied. Formation of the drops is directly related to flow rate of the liquid from the container. The drops themselves fall from the dropper tip when the weight of the pendant drop exceeds the surface tension forces holding the drop to the dropper tip. In the ideal case, each drop should be identical to the previous one. In practice, however, other factors intervene to cause significant variation in drop size. One of the most significant factors is the rate of drop formation. If the drop is formed rapidly, more liquid can be "injected" into the body of the drop as it is beginning to break free. These drops will be larger, and thus will carry more drug, than if the container is squeezed very slowly. In extreme circumstances, drug may be ejected in a steady stream.

While this is a minimal problem when the drugs are delivered by a trained professional, it becomes significant when the drugs are delivered by the patients themselves. The flow rate, which is directly related to the finger pressure while squeezing, cannot be easily controlled. The visual clue, that is, the growth of the drop itself, cannot be readily observed if the eye is about to receive the same drop or if the dropper is not positioned in the line of sight in use.

The problem of delivery control is not restricted to ophthalmic drugs, of course, and there is a clear need for controllable addition devices in a wide range of, for example, pharmaceutical dispensing applications.

DESCRIPTION OF THE INVENTION

In the metering device defined in the present invention there is an inherently greater resistance to liquid flow than in a metering device of the prior art. For this reason, it becomes most difficult to produce a continuous stream of liquid by squeezing the container. This resistance to liquid flow also tends to damp out the natural variations in squeezing force that occur from moment to moment during use of a metering device of this type. As a result, the sequential drops metered from such a device tend to have a much more uniform size.

It is therefore an object of this invention to provide a flow metering device in which the problems of contamination and uncontrolled flow rate are substantially reduced.

It is a further object of this invention to provide a dropper for ocular medicines that is protected from inadvertent bacterial contamination and thus permit a significant reduction or the complete elimination of preservatives in the medicine.

It is another object of the invention to provide a liquid metering and dispensing device in which a liquid, such as a medicine, is dispensed as substantially uniform drops.

The above objects are provided by a device for dispensing a liquid in drop form which comprises a container having a dropper tip comprising a passage-way for ingress of air to and egress of liquid from the device, the passageway communicating between the body of the container and an orifice, means for temporarily reducing the volume of the container and, disposed within the dropper tip, across the passageway and adjacent the orifice, a composite microporous membrane with pores of a size to resist the passage of undesired contamination, the membrane having a liquophilic portion permitting delivery of metered drops of a liquid to a desired location outside the container, and a liquophobic portion adapted to resist the passage of such liquid but to permit the passage therethrough of air being intersected by the membrane and portions. The surface area of the liquophilic portion is so selected as to provide an appropriate drop dispensing rate and avoid a stream of liquid from emerging from the dropper tip.

The membrane is sealed to the inside surface of the dropper within the tip region so as to prevent the passage of liquid around, as opposed to through, the membrane.

The membrane comprises two components in side-by-side or juxtaposed relationship. One component has a liquophobic character, that is, it resists the passage of liquids. The other component has a liquophilic character, that is, liquids pass through it readily. Thus, liquids exiting the container through the porous membrane will pass exclusively through the liquophilic component and will be rejected by the liquophobic component. Liquids being sucked back into the container will pass exclusively through the liquophilic component. However, air will flow into the container to replace the expelled liquid through the liquophobic side.

THE CONTAINER

In use, the container functions as a reservoir for the liquid to be dispensed. It is provided with means to temporarily to reduce its volume, typically by providing that at least part of the container is elastically deformable. Thus, pressure on a deformable portion of the container will reduce the effective volume and force the liquid contained therein out of the container when it is appropriately oriented.

After a desired number of drops have been expelled from the container and the deforming pressure is removed, the liquid below the membrane in the tip is drawn back into the container. It is preferred that this occurs as a continuous column, that is, no droplets should break away and be left behind in the tip area. Such droplets could be a hospitable environment for bacterial growth and as such should be avoided so far as possible. Making the volume of the tip area very small helps to minimize this problem. It is, therefore, particularly preferred that the volume between the orifice of the dropper and the surface of the composite membrane be as small as possible. Volumes of the order of from about 0.001 to about 0.15 cm.sup.3 are suitable and most preferred are volumes of from about 0.05 to about 0.1 cm.sup.3.

The tip area of the dropper can be designed to provide membrane support by various means including, for example, a series of ribs on the inside surface of the dropper tip and/or an interior beading providing a seating surface to which the membrane can be bonded. Care should, however, be exercised to ensure that such support devices do not impede or distort the flow of metered drops from the device. Support could also be provided by the provision of a transverse septum or bar that would help resist any tendency of the membrane to deform under pressure.

WETTING OF POROUS MEDIA

The wettability or liquophilicity of a porous structure, e.g., a membrane, is a function of that structure's critical wetting surface tension (CWST) (discussed below) and the surface tension of the applied liquid. If the CWST is at least as high as the surface tension of the liquid, the liquid will spontaneously wet the porous structure, which may be termed "liquophilic" with respect to that liquid. Conversely, if the CWST is lower than the surface tension of the liquid then it will not be wet and will be liquophobic with respect to that liquid.

When a liquid is brought into contact with the upstream surface of a porous medium and a small pressure differential is applied, flow into and through the porous medium may or may not occur. A condition in which no flow occurs is that in which the liquid does not wet the material of which the porous structure is made.

A series of liquids can be prepared, each with a surface tension about 3 dynes/cm higher compared with the one preceding. A drop of each may then be placed on a porous surface and observed to determine whether it is absorbed quickly, or remains on the surface. For example, applying this technique to a 0.2 .mu.m porous polytetrafluoroethylene (PTFE) membrane, instant wetting is observed for a liquid with a surface tension of about 26 dynes/cm. However, the structure remains unwetted when a liquid with a surface tension of about 29 dynes/cm is applied.

Similar behavior is observed for porous media made using other synthetic resins, with the wet/unwet values dependent principally on the surface characteristics of the material from which the porous medium is made and, secondarily, on the pore size characteristics of the porous medium. For example, fibrous polyester, specifically polybutylene terephthalate (hereinafter "PBT") sheets which have pore diameters less than about 20 .mu.m will be wetted by a liquid with a surface tension of about 50 dynes/cm, but will not be wetted by a liquid with a surface tension of about 54 dynes/cm.

In order to characterize this behavior of a porous membrane, the term "critical wetting surface tension" (CWST) is defined as follows. The CWST of a porous medium may be determined by individually applying to its surface a series of liquids with surface tensions varying by about 2 to about 4 dynes/cm, and observing the absorption or non-absorption of each liquid. The CWST of a porous medium, in units of dynes/cm, is defined as the mean value of the surface tension of the liquid which is absorbed and that of a liquid of neighboring surface tension which is not absorbed. Thus, in the examples of the two preceding paragraphs, the CWST's are