GB1579282A - Unit dose - Google Patents

Description

(54) UNIT DOSE (71) We, WARNER-LAMBERT COMPANY, of 201 Tabor Road, Morris Plains, New Jersey, United States of America, a Corporation organised under the laws of the State of Delaware, United States of America, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement: This invention relates to a single use unit dose pharmaceutical delivery system.

The aim of bronchodilation therapy is to reduce abnormally high airway resistance which is most often accomplished by the administration of adrenergic drugs among which are isoproterenol, phenylephrine, racemic epinephrine, and ephedrine. Generally, these drugs are given as aerosols in powered nebulizers or intermittent positive pressure breathing apparatus (IPPB). The usual dose is 0.5-1.0 ml of 1:200 isoperterenol or 2.25% racemic epinephrine is diluted in enough saline or water (2-5 ml) to assure aerosol therapy for 5-10 minutes.

Most hospitals utilize a multi-does method of IPPB therapy in which multi-dose vials of sterile saline or water are carried by the technician to the administration site. A prescribed amount of liquid is then withdrawn from the multi-dose vial by use of a presterilized disposable syringe. In theory, a new syringe and needle are used for each patient. The liquid is withdrawn from the container into the syringe and then expressed into the nebulizer reservoir. The active ingredient, such as isoproternol, Bronkosoltm, is added to the reservoir by means of a measuring dropper supplied with the drug bottle or drawn up from the drug bottle by a single sterile syringe. In any case, the same bottles are taken from hospital room enhancing the possibility of cross contamination and loss of sterility.

It is an object of the present invention to overcome the possibility of contamination of aerosol solutions.

Another object of the present invention is to afford a drug delivery system wherein the parts of the system are arranged in a novel and expeditious manner to allow a bronchial dilator solution easily to be administered to the nebulizer reservoir of an IPPB apparatus.

Another object of the present invention is to afford a novel drug delivery system which is practical and efficient in construction and operation and which may be readily and economically produced.

With the foregoing and other objects in view the present invention consists in a single use, unit dose pharmaceutical delivery system, comprising a hollow cylindrical tube adapted to contain a unit dose of a pharmaceutically active material and having sealing means at each end of the tube, and a single use liquid container made of a pharmaceutically inert material which is deformable upon squeezing by the user and which is adapted to contain a pharmaceutically acceptable diluent, and wherein the container has a hollow neck through which the diluent is expressed and has a rupturable closure means whereby the container is antiseptically sealed from its environment, the outside diameter of the neck in relation to the inside diameter of the cylindrical tube is such as to provide a friction fit liquid seal when the neck after rupturing the closure means, is inserted into either end of the tube after removing the sealing means at the end, the thus assembled container and tube being ready for dispensing the unit does of the active material mixed with the diluent by removing the remaining sealing means of the tube and squeezing the container to express the diluent through the hollow neck into the tube and to discharge the diluted active material therefrom.

Reference is also made to co-pending Application 7934492, (Serial No. 1 579 283) the subject of which has been divided from this application and in which there is described and claimed a single use liquid container for antiseptic application of a pharmaceutically accepted liquid, the container comprising a moulded deformable translucent bottle generally oval in cross section and having a flat closed bottom portion and a closed top portion, said top portion having a hollow neck extending upwardly therefrom and offset from the centre of the top portion whereby the hollow portion of said neck communicates with the hollow interior of said bottle, said neck having closure means whereby the container may be antiseptically sealed from its environment, and wherein the closure means is a disc of greater diameter than the hollow neck and which is attached to the opened end of said neck along a weakened portion at the junction of said neck and disc, said disc further having an integral lever arm parallel to said bottom portion and extending along a plane passing through the long axis of the generally oval cross section, said container further having a tab extending downwardly from the bottom portion and extending completely across the bottom portion along the long axis of the generally oval cross section.

Reference is further made to co-pending Application 7934493, (Serial No. 1 579 284) the subject of which has been divided from this application and in which there is described and claimed an open ended pharmaceutical unit dose package comprising a hollow cylindrical tube containing a unit dose of a bronchodilator selected from the group consisting of isoproternol, phenylephrine, racemic epinephrine, and ephedrine within a cavity and having sealing means at each end of the tube, both sealing means being removable to enable flushing of the tube contents by flowing a liquid diluent through the tube, both sealing means having portions not contained within the tube, for enabling gripping of the sealing means for removal thereof from the tube, at least one of the two sealing means having a portion extending into the tube a predetermined distance so that the two sealing means form with the tube into a cavity of a predetermined volume equal to the desired unit dose of the bronchodilator to the exclusion of an air space and wherein the said one sealing means is in intimate frictional contact between the interior of the tube and the entire portion of the said one sealing means extending into the tube, said contact comprising an airtight seal, the other sealing means being of similar construction to the said one sealing means, or being in the form of a cap in airtight sealing contact with the outside of the tube.

In order that the invention may be more readily understood, reference is made to the accompanying drawings which illustrate diagrammatically and by way of example an embodiment thereof and in which:- Figure 1 is a front view of a liquid diluent container; Figure 2 is a side view of the container of Figure 1; Figure 3A is a perspective view of a drug containing tube; Figure 3B is a modification of the tube shown in Figure 3A; and Figure 4 is a perspective view of the tube of Figure 3A or 3B attached to the neck of the container of Figure 1.

More particularly the container 10 is moulded from pharmaceutically inert plastics or other deformable material in the form of a bottle of generally oval cross-sectional shape and carries a downwardly extending tab 11 on which a control number, expiration date, or other information may be embossed. The container or bottle also carries graduations 18 by which to measure the volume of the fluid expressed through the capillary opening of an offset neck 15 at the top of the bottle.

The bottle opening is sealed by a closure seal 13 which comprises a lever arm 14 and an integral flat disc or cover 19 attached to the neck 15 by a weakened portion at the junction.

The neck is offset the central axis of the bottle in such a manner that one shoulder of the bottle is longer than the other and this longer shoulder defines a downwardly tapered shoulder 12. The taper increases the spacing between the bottle and the lever arm so that when the bottle is grasped in one hand, the users thumb may be inserted in this space and by positioning the lever arm in the direction of the arrow, the closure may be broken at the weakened portion and the arm 14 and disc 19 discarded. The seal-neck junction is so molded that once the seal is removed, a secondary sealing ring 36 is exposed.

The bottle neck is molded to comprise a number of ribs 16 which strengthen the neck and aid in guiding the dose capsule 30 over the bottle neck. The midportion of the neck comprises an outwardly extending shoulder sealing system 17 which is suitable for large inner diameter dose capsules. The cylindrical portion 15 immediately adjacent the bottle is adapted to frictionally contact the inner surface of the capsule to form a primary seal 37.

The dose capsule is a hollow cylindrical capillary tube 31 having closure means 32 sealing both ends of the tube. These closures may extend into the tube as shown in Figure 3A to form a central cavity 34 of a predetermined volume equal to the desired amount of the active ingredient. Alternatively, the capsule may be prepared as shown in Figure 3B wherein the cavity 35 is under a vacuum and asceptically sealed by the closure means 32 at one end and a resilient cap 33 at the other. The cap 33 has a surface 33A intended to be punctured by a hypodermic needle to fill the capsule. In this embodiment, the technician may prepare an active ingredient other than those listed and inject the ingredient into the cavity 34 and store the preparation in the capsule until it is needed. Withdrawal of the hypodermic needle causes the cap 33 aseptically to close itself.

In use, the bottle containing the premeasured amount of diluent, such as water or saltine, is grasped by the technician in one hand, the technician's thumb is inserted between the tapered shoulder 12 and the lever arm 14 and the closure top is positioned away, removed, and discarded. The liquid remains within the bottle since the internal diameter of the neck forms a capillary and requires the bottle to be squeezed in order to express the diluent.

The technician next removes one of the sealing means 32 on the capsule and positions the open end of the tube 31 over the bottle neck to form a friction fit. A primary seal 37 and a secondary seal 36 formed by the friction contact of the neck and capsule prevent liquid loss. By merely removing the remaining sealing means from the capsule, the unit can be inverted, the bottle squeezed and the contents of the capsule flushed into the IPPB nebulizer by the diluent in the bottle.

WHAT WE CLAIM IS: 1. A single use, unit dose pharmaceutical delivery system, comprising a hollow cylindrical tube adapted to contain a unit dose of a pharmaceutically active material and having sealing means at each end of the tube, and a single use liquid container made of a pharmaceutically inert material which is deformable upon squeezing by the user and which is adapted to contain a pharmaceutically acceptable diluent, and wherein the container has a hollow neck through which the diluent is expressed and has a rupturable closure means whereby the container is antiseptically sealed from its environment, the outside diameter of the neck in relation to the inside diameter of the cylindrical tube is such as to provide a friction fit liquid seal when the neck, after rupturing the closure means, is inserted into either end of the tube after removing the sealing means at that end, the thus assembled container and tube being ready for dispensing the unit dose of the active material mixed with the diluent by removing the remaining sealing means of the tube and squeezing the container to express the diluent through the hollow neck into the tube and to discharge the diluted active material therefrom.

2. A system as claimed in claim 1, wherein each sealing means has a portion extending into said tube a predetermined distance so that the two sealing means when positioned in each end of the tube form a cavity for the active material, and wherein each sealing means is an intimate frictional contact between the interior of said tube and the entire portion of the sealing means extending into said tube.

3. A system as claimed in claim 2, wherein the active material completely fills the cavity to the exclusion of an air space, and wherein the sealing means is air tight.

4. A system as claimed in claim 1, wherein the container comprises a moulded deformable translucent bottle generally oval in cross section and having a flat closed bottom portion and a closed top portion, said top portion having said hollow neck extending upwardly therefrom and offset from the centre of the top portion, said container further having a tab extending downwardly from the bottom portion and extending completely across the bottom portion along the major axis of the generally oval cross section.

5. A system as claimed in claim 4, wherein the exterior of said bottle contains raised portions extending parallel to said bottom portion and aligned longitudinally along said exterior, said raised portions functioning to represent graduations whereby the volume of any material within the container can be ascertained.

6. A system as claimed in claim 4 or 5, wherein the closure means is a disc of greater diameter than the hollow neck and which is attached to the end of said neck along a weakened portion at the junction of said neck and disc, said disc further having an integral lever arm parallel to said bottom portion and extending along a plane passing through the major axis of the generally oval cross section.

7. A system as claimed in claim 6, wherein the lever arm is of a length equal to the width of the bottle taken along the major axis of the generally oval cross section.

8. A system as claimed in any of the preceding claims, wherein the active material is a unit dose selected from the group consisting of isoproternol, phenylephrine, racemic epinephrine, and ephedrine.

9. A single use, unit dose pharmaceutical delivery system substantially as hereindescribed with reference to and as shown in Figures 1, 2, 3A and 4 or Figures 1,2, 3B and 4 of the accompanying drawings.

**WARNING** end of DESC field may overlap start of CLMS **.

Claims (9)

**WARNING** start of CLMS field may overlap end of DESC **. tapered shoulder 12 and the lever arm 14 and the closure top is positioned away, removed, and discarded. The liquid remains within the bottle since the internal diameter of the neck forms a capillary and requires the bottle to be squeezed in order to express the diluent. The technician next removes one of the sealing means 32 on the capsule and positions the open end of the tube 31 over the bottle neck to form a friction fit. A primary seal 37 and a secondary seal 36 formed by the friction contact of the neck and capsule prevent liquid loss. By merely removing the remaining sealing means from the capsule, the unit can be inverted, the bottle squeezed and the contents of the capsule flushed into the IPPB nebulizer by the diluent in the bottle. WHAT WE CLAIM IS:

1. A single use, unit dose pharmaceutical delivery system, comprising a hollow cylindrical tube adapted to contain a unit dose of a pharmaceutically active material and having sealing means at each end of the tube, and a single use liquid container made of a pharmaceutically inert material which is deformable upon squeezing by the user and which is adapted to contain a pharmaceutically acceptable diluent, and wherein the container has a hollow neck through which the diluent is expressed and has a rupturable closure means whereby the container is antiseptically sealed from its environment, the outside diameter of the neck in relation to the inside diameter of the cylindrical tube is such as to provide a friction fit liquid seal when the neck, after rupturing the closure means, is inserted into either end of the tube after removing the sealing means at that end, the thus assembled container and tube being ready for dispensing the unit dose of the active material mixed with the diluent by removing the remaining sealing means of the tube and squeezing the container to express the diluent through the hollow neck into the tube and to discharge the diluted active material therefrom.

2. A system as claimed in claim 1, wherein each sealing means has a portion extending into said tube a predetermined distance so that the two sealing means when positioned in each end of the tube form a cavity for the active material, and wherein each sealing means is an intimate frictional contact between the interior of said tube and the entire portion of the sealing means extending into said tube.

3. A system as claimed in claim 2, wherein the active material completely fills the cavity to the exclusion of an air space, and wherein the sealing means is air tight.

4. A system as claimed in claim 1, wherein the container comprises a moulded deformable translucent bottle generally oval in cross section and having a flat closed bottom portion and a closed top portion, said top portion having said hollow neck extending upwardly therefrom and offset from the centre of the top portion, said container further having a tab extending downwardly from the bottom portion and extending completely across the bottom portion along the major axis of the generally oval cross section.

5. A system as claimed in claim 4, wherein the exterior of said bottle contains raised portions extending parallel to said bottom portion and aligned longitudinally along said exterior, said raised portions functioning to represent graduations whereby the volume of any material within the container can be ascertained.

6. A system as claimed in claim 4 or 5, wherein the closure means is a disc of greater diameter than the hollow neck and which is attached to the end of said neck along a weakened portion at the junction of said neck and disc, said disc further having an integral lever arm parallel to said bottom portion and extending along a plane passing through the major axis of the generally oval cross section.

7. A system as claimed in claim 6, wherein the lever arm is of a length equal to the width of the bottle taken along the major axis of the generally oval cross section.

8. A system as claimed in any of the preceding claims, wherein the active material is a unit dose selected from the group consisting of isoproternol, phenylephrine, racemic epinephrine, and ephedrine.

9. A single use, unit dose pharmaceutical delivery system substantially as hereindescribed with reference to and as shown in Figures 1, 2, 3A and 4 or Figures 1,2, 3B and 4 of the accompanying drawings.