CA1283014C

CA1283014C - Bandage for transdermal delivery of systemically-active drug

Info

Publication number: CA1283014C
Application number: CA000556400A
Authority: CA
Inventors: Eric L. Nelson; Rajaram Vaidyanathan
Original assignee: Whitby Research Inc
Current assignee: Whitby Research Inc
Priority date: 1987-01-14
Filing date: 1988-01-13
Publication date: 1991-04-16
Anticipated expiration: 2008-04-16
Also published as: KR890700374A; AU1491588A; WO1988005293A1

Abstract

ABSTRACT
A transdermal delivery bandage and system is provided which includes a supply of topically and/or systemically-active drug, an adhesive for releasably securing the bandage to a dermal surface and control means which are separate from the supply of topical and/or systemically-active drug for adjustably controlling surface contact area between the topical and/or systemically-active drug and the dermal surface.
The control means are manually operable by a user of the bandage for adjustably controlling the dose of drug to be administered. Alternatively, the maximum available dose from a given bandage may be preselected by a dispensing pharmacist.

Description

~2~30~4 1391 BANDAGE ~OR TRANSDERMAL DELIVERY OF
SYSTEMICA~LY-ACTIVE DRUG
-The present inventlon is generally directed to a device for the adminlstration of a drug and, more particularly, directed to a medical bandage and system ior controlled transdermal delivery o~ a topical and/or systemically-active drug or agent.
In the treatment o~ many diseases andlor body conditions, metered, or controlled, medication is most desirable. Unfortunately, intravenouæ and oral adminis-tration o~ drugs typically results in a non-uniiorm introduction of the drug into the body's system as a function o~ time. To overcome this dis-advantage, transdermal drug delivery systems have been developed, such as bandages, or the like, which include topically active or systemically-active drugs.
In these systems, the drug is absorbed into the body via its dermal surface in a more uni~orm manner, the drug released by the transdermal system being regulated by both the structure o~ the system and the area o~ dermal surface contacted.
Topically active drugs include one or more agents which cause a pharmacolog~cal or physiological response at or near the site o~ the application on a dermal suriace. The term "dermal sur~ace", as it is used throughout this specification, is meant to be any skin or mucosa surface.
Systemically-active drugs, on the other hand, include one or more agents which are absorbed through the body via a dermal surface and thereafter dis-tributed throughout the patient's circulatory or ~283014 lymphatic system to cause a pharmacologic or physiologic response in the patient. A topical and/or systemically-active drug may also include a penetration enhancer if the topical or systemically-active agent does not penetrate the dermal sur~ace in eifective ; quantities. As the name implies, the penetration enhancer acts in concert with the topical or systemically-active agent to racilitate the passage thereof through the dermal surface.
Transdermal systems that have been developed for the delivery of drugs generally may be classified as either a matrix system or a membrane system.
In a matrix system, the drug is suspended in a permeable microporous substrate to iorm a monolithic body which, when held ~gainst a dermal sur~ace by an adhesive, enables di~fusion of the drug out oi' the substrate and into the dermal surfaceO In this system, the release rate and the amount of drug released is dependent upon the permeability o~ the microporous structure. In a membrane system, the drug, in a liquid or semi-solid ~orm, is disposed on one side of a membrane which is held to a dermal surface by an adhesive. The membrane ~unctions to regulate, or meter, the drug into the dermal surface.
In each of these systems, the amount of surface area exposed to the dermal surface controls the amount of migration of the drug into the patient's body;
that is, each system has a delivery rate over time which is dependent upon the amount of surface contact 3~ area between either the monolithic body or the membrane and the dermal surface.

3.

Heretofore, the adhesive in each o~ these bandage systems has usually been disposed uni~ormly on the contact sur~ace area so that the drug being administered passes therethrough. While this may be satisiactory with some drugs, those containing a penetration enhancer may also e~fect an undesired transfer o~ some component of the adhesive through the d,ermal ~ur~ace and into the patient's body.
~ach o~ the transdermal delivery systems herein-above-described are ~ingle dose systems in which the drug dose is determined by the contact area between the drug supporting structure on the dermal sur~ace.
Hence, a di~erent size 6ystem must be provided for each prescribed drug dose.
Consequently, in order to dispense the bandage system in accordance with a physician's prescribed dose, it is necessary to manu~acture and stock an array o~ bandage systems to supply the needs o~
patients requiring dif~ering doses of medication.
This, o~ course, gives rise to i~creased manufacturing, dispensing and storage costs associated with the treatment of any disease or body condition utilizing a transdermal system.
The present invention provides ~or a bandage for a transdermal delivery o~ a topical and/or sys-temically-active drug which enables a pharmacist or end user of the bandage to control the amount of drug being dispensed, thereby adjustably controlling the surface contact area between the topical and/or sys-temically~active drug and the dermal sur~ace. Thisieature enables the bandage in accordance with the present invention to provide a varying number o~
;

.

~33~14 doses of particular drug as may be prescribed by a physician without the neceæsity ior manuiacturing an array o~ bandages having di~erent doses and the concomitant storage and dispensing costs.
SUMMARY OF ~HE INVENTION
In accordance with the present invention, a bandage ~or a transdermal delivery o~ a topical and/or systemically-active agent includes a supply o~ topical and/or systemically-active agent and adhesive means ~or releasably securing the bandage to a dermal sur~ace. Control means are provided which are separate ~rom the supply of topical and/or systemically-active agent for adjustably controlling sur~ace contact area between the topical and/or systemically-active agent and the dermal sur~ace when the bandage is held thereagainst. By controlling the surface contact area, the control means effectively controls the amount of migration o~ the toplcal and/or systemically-active agent into the dermal sur~ace.
~ore specifically, the control means includes manual means, operable by a user o~ the bandage ~or adjustably controlling the surface contact area between the topical and/or systemically-active agent and the dermal sur~ace. The manual means may include at least one selectably removable cover segment disposed adjacent the supply o~ topical and/or sys-temically-active agents. Pre~erably, the manual means includes a plurality of selectably removable cover segments which together ~orm a cover sheet. The cover sheet pre~erably completely covers the supply o~

':

:., .
~L2~33~
5.

topical and/or systemically-active agent, with the selectably removable cover segments being deiined by per~orations in the cover sheet. In this manner, the periorations enable manual ~eparation o~ one or more o~ the removable cover æegments ~rom the cover sheet by tearing along the per~orations.
This ~eature o~ the present invention enableæ
the user to select a dose to be delivered ~rom any given bandage. Be~ause the dose may be selected at the point o~ use, storage and dispensing costs can be signi~icantly reduced. Such cost savings result ~rom the elimination o~ the manu~acture o~ a plurality o~ bandages, each having a di~erent dispensing dose.
As hereinaiter summarized in greater detail, selection o~ the dose may be by the user or by a pharmacist dispensing the bandage.
In accordance with the present invention, the supply of topical and/or systemically-active agent may comprise a microporous material containing a topical and/or systemically-active agent which is permeable to the passage thereof. In this instance, the supply of topical and/or systemically-active agent may be considered a matrix system.
Alternatively, the supply o~ topical and/or systemically-active agents may comprise a liquid or a gel containing the agent which is separated ~rom the cover sheet by a membrane permeable to the passage o~ the agent. In this instance, the source oi topical and/or systemically-active agent may be considered a membrane~type source.

~. ..... .

~2830~
6.

Preferably, the bandage in accordance with the present invention ~urther comprises a backing sheet with the supply o~ topical and/or systemically-active agent and adhesive means being disposed on one side of the backing sheet. In instances where the supply o~ topical and/or systemically-active agents includes a penetration e1lhancer, lt is pre-~erred that the adhesive means :Ls disposed on the backing sheet in a spaced-apart relationship with the supply o~ topical andtor systemically-active agents.
In this manner, the control means can adjustably control, or meter, migration o~ the topical and/or systemically-active agent into the dermal sur~ace without contact with the adhesive means, thereby eliminating or substantially reducing the possibility of the penetration enhancer causing unwanted migration of components o~ the adhesive through the dermal surface.
To ~acilitate use by a patient, the bandage in accordance ~ith the present invention may also include indicia means which are associated with each covered segment ior displaying the dosage o~ topical and/or systemically-active agent delivered into the dermal surface when the bandage is secured in an operational position on the dermal sur~ace with a preselected color segment removed. Pre~erably, the plurality o~
selectably removable color segments comprises a set of elongate strips disposed in a parallel relation-ship with one another over the supply o~ topical and/or systemically-active agent, with each strip having tab means thereon ~or manually separating each strip :.
`

~2~330~
7.

~rom the cover sheet.
As hereinbefore noted, the bandage in accordance with the present invention may include means ior enabling preselective limiting of the operation o~ the control means to providing a preselected maximum surface contact between the topical and/or sys-temically-active agent and the clermal surface. In this instance, the tabs on the ~;et of elongate strips are severable, and each tab has a length su~ficient to extend beyond a periphery of the bandage to enable preselecting severing thereo~.
When the adhesive means of the present invention is disposed along the periphery of the backing sheet and the tab means extend thereover, the adhesive means operates ~or preventing separation of a tab ~rom the backing sheet and corresponding cover segment from the cover sheet when an end portion means thereon is severed; that is, the adhesive means securely grips the remaining portion of the tab, thereby preventing in-advertent removal of a cover segment. The remainingend portions and tabs are easily gripped in comparison thereto thereby facilitating the removal of cover segments appropriate ~or the dose described.
As earlier and briefly mentioned, the present invention includes a bandage system for providing multiple doses of a topical and/or systemically-active agent in selectively equal or differing amounts. In this instance, the system comprises a plurality of individual bandage means ~or transdermal delivery of the topical and/or systemically-active agent, with each of the individual bandage means comprising elements hereinbefore recited.

.

83~
8.

This system has the advantage o~ enabling the production oi' a plurality o~ ~andages, each having a selectable medica$ion dose which eliminates the need ~or manu~acturing, storing and dispensing o~ an array of bandages having diii'ering doses which otherwi~e would be necessary.
BRIEF DESCRIPTION OF THE DRAWINGS
The advantages and ~eatures oi the present in-vention will appear ~rom the ~ollowing descriptionconsidered in con~unction with the accompanying drawings in which:
Figure 1 is a perspective view showing a bandage in accordance with the present invention having a supply o~ topical and/or systemically-active agent, adhesive means, control means, as well as a backing sheet and a releasable liner;
Figure 2 is a perspective view o~ the bandage shown in Figure 1 showing the releasable llner partially removed and a plurality o~ tabs, inter-connected with cover segments, with end portions thereof extending beyond a periphery o~ the bandage;
Figure 3 is a perspective view o~ the bandage shown in Figures 1 and 2 showing the release liner removed and a cover segment partially removed;
Figure 4 is a cross-sectional view of the present invention;
Figure 5 is an enlarged cross-sectional view o~
the present invention generally showing the supply o~
topical and/or systemically-active agent incorporating a matrix-type delivery system; and ' , .

~ZB~Ol~
9.

Figure 6 is an enlarged cross-sectional view of an alternative embodiment o~ the present invention showing the supply o~ topical and/or systemically-active agent incorporating a membrane-type delivery system.
DETAILED DESCRIPTION OF THE INVhNTION
Turning now to Figures 1, 2 and 3, there is shown a bandage, or drug delivery system, 10 in accordance with the present invention which, taken alone, provides ~or delivery oY a topical and/or systemically-active agent, and taken in combination with identical bandages encompasses a system for providing multiple doses o~
topical and/or systemically-active agent in selectively equal or dif~ering amounts to a dermal surface. (Not shown).
Generally, the bandage 10 includes a backing sheet 12, a supply 16 oi topical and/or ~ystemically-active agent, an adhesive 18 disposed on the backing sheet 12, a release sheet 22 and a periorated cover sheet 26 which provides means, separate from the supply 16 o~ topical and/or systemically-active agent, for adjustably controlling the suriace contact area between the supply 16 of topical and/or systemically-active agent and a dermal suriace.
It is to be appreciated that it is not necessaryto utilize the adhesive 18 ~or releasably securing the bandage 10 to a dermal surface. For example, a separate elastic band or cloth (not shown) may be utilized to hold the bandage 10 against a person's arm or leg. An adhesive is preferred, however, so that the bandage can be more easily applied to any dermal surface on a person's body.

, `\
330~

10 .

The backing sheet 12 may be ~ormed of any suitable ~lexible material, such as mylar or the like. Simi-larly, the release ~heet 22 may be ~ormed of any suitable material and may have a silicone-type coating thereon, not shown, ~or ensuring adequate release ~rom the adhesive 18, when it ls ~eparated there~ore to prepare the bandage 10 ~or application to a dermal ~ur~ace.

Typlcal systemically_active agents ~hich may be suitable ~or use in the present invention are thera-peutic agents which are suf~iciently potent such that they can be delivered through the skin or other membrane to the bloodstream in su~icient quantities to produce the desired therapeutic ei~ect. In general, this includes therapeutic agents in all o~ the major therapeutic areas including, but not limited to, anti-in~ectives, such as antibiotice and antiviral agents, analgesics a~d analgesic combinations, anorexics, anthelmintics, antiarthritics, antiasthma agents, anticonvulsants, antidepressants, antidiabetic agents, antidiarrheals, antihistamines, anti-in~lammatory agents, antimigraine preparations, antimotion sickness, antinauseants, antineoplastics, antiparkinsonism drugs, antipruritics, antipsychotics, antipyretics, anti-spasmodics, including gastrointestinal and urinary;anticholinergics, sympathomimetics, xanthine deriva-tives, cardiovascular preparations including calcium channel blockers, beta-blockers, antiarrhythmics, antihypertensives, diuretics, vasodilators including general, coronary, peripheral and cerebral; central nervous system stimulants, cough and cold preparations, decongestants, diagnostics, hormones, hypnotics, im-munosuppressives, muscle relaxants, parasympatholytics, ... .

-o~

parasympathomimetics, psychostimulants, sedatlves and tranquilizers.
The active ingredients o~ systemically-active agents may include, but are not limited to:
Isosorbide Dinitrate, Nitroglycerin, ~stradiol, Clonidine, Propranolol, Indomethacine, Ni~edipine, Nicardipine, Dicloro~enac, ~etaproterenol.
Alternatively, a combination oi a suitable agent and a penetration enhancer, such as Azone, may be used. When an enhancer is utilized, it is pre ~erred that the adhesive 18 be disposed on the backing sheet 12 along a periphery 34 thereoi while the supply 16 is disposed in a center portion 36 thereo~ to establish a ~paced-apart relationshlp between the adhesive 18 and the supply 16 in order to ensure that the penetration agent does not act to conduct components of the adhesive through the dermal æurPace, which may be undesirable.
The supply 16 may be o~ the matrix-type, shown in Figures 4 and 5, or membrane-type, shown ln Figure 6.
As shown in Figures 4 and 5, the supply 16 includes any suitable matrix 42 permeable to the agent disposed ln microporous 46 o~ the matrix. The matrix 42 may be disposed on the backing sheet 12 dlrectly, or on a separate layer 50 attached to the backing sheet by any suitable means. A ~ront sheet 54 may also be provided ~or supporting the matrix 42 which has an aperture 56 therein to expose the matrix to a dermal surface when the release sheet 22 is removed and the cover sheet 26 partially removed as hereina~ter described. The layer 50 and ~ront sheet 54 may be ~Z830~

formed ~rom any suitable material, such as mylar or the like Alternately, as shown in F:igure 6, the supply of 16 may include a liquid or gel 64 o~ agent disposed between an i~pervious layer 68, such asMylar*, and a membrane 70, the impervious layer 68 being attached to the backing sheet 12 in any conventional manner.
The membrane acts in a conventional manner to limit the migration o~ the agent therethrough and out an aperture 72 formed in a front sheet 74 when the release sheet 22 is removed and the per~orated cover sheet removed, all or in part, as hereinafter described.
- Turning now to Figures 2 and 3, operation of the bandage ls shown in conjunction with the description of the perforated cover sheet 26.
The perforated cover sheet 26 may comprise a set of spaced-apart patterns, each defining cover segments 80a, 80b, 80c, 80d, and it is preferable that the cover segments are ~ormed into elongated strips disposed in a parallel relationship over the supply 16, with each strip 80a, 80b, 80c, 80d, having a tab 84a, 84b, 84c, 84d, thereon, which provides means for manually separating each strip 80a, 80b, 80c, 80d, ~rom the cover sheet 26.
While any number o~ elongated strips 80a, 80b, 80c, 80d having tabs 84a, 84b, 84c, 84d, interconnected therewith, may be provlded, only ~our are shown in the Figures 1, 2 and 3 ~or the sake o~ clarity of presentation. Each o~ the tabs 84a, 84b, 84c, 84d has an end portion 88a, 88b, 88c, 88d, thereon to ~acilitate manual pulling thereof by the fingers of a user to separate the corresponding tab 84a, 84b, 84c, 84d, from the adhesive 18 and tear the corre-*Mylax trademark .. . . .... . .... .

1~3301~

13.

sponding segment 80a, 80b, 80c, 80d ~rom the per-forated cover sheet 26, leaving the remaining elongated strips in place.
A removed strip 80a (Figure 33 then exposes a preselected contact area which occurs between the supply 16 and a dermal sur~ace (not shown) when the bandage 10 is disposed in an operational relationship with the dermal surface by the adhesive 18. It should be appreciated that the cover segments 80a, 80b, 80c, 80d, may be o~ varying widths as shown in Figure 3 to enable a wider selection o~ doses available ~rom a single bandage 10.
It can be seen irom Figures 1, 2 and 3 that the tabs 84a, 84b, 84c, 84d, with end portions 88a, 88b, 88c, 88d provide means for enabling preselective limiting o~ the operation of the control means. Each of the tab means has a su~iicient length to allow the end portion 88a, 8~b, 88c, 88d to extend beyond the periphery 34 oi the backing sheet. Hence, before the release sheet 22 is removed, one or more o~ the end portions, ior example, 88c, 88d, may be clipped flush with the periphery 34 (~ee Figures 2 and 3) to limit the number o~ end portions 88a, 88b, which may be pulled by a patient. In this manner, the tabs 84c, 84d remaining are secured to the backing sheet 12 by the adhesive 18 thereon and not easily separated there-from. This limits the dose which the patient may select by pulling the tabs 88a, 88b, and removing the cover segments 80a, 80b. This feature of the invention ; 30 may have particular importance in the administration o~ speci~ic drugs in which it is important to ensure that the patient does not inadvertently select a greater dose than tha- prescribed by the physician.

~2133(~1~

The severing or cutting of the end portions 80a, 80b, 80c, 80d, may be done on a one-by-one basis, or a jig, not shown, may be provided so that a pharmacist may stack a plurality oi the bandages on one another and cut all selected tabs, ~or c~xample, BOc, 80d, with one operation.
Each of the end portions 88a, 88b, 88c, 88d, as well as the elongated segments 80a, 80b, 80c, 80d, may have various colors (as indicated by di~ferent cross hatching in Figure 3) to provide indicia means ior displaying the dosage of topical and/or sys-temically-active agent deli~ered to the dermal sur~ace when the bandage is secured in operation position on the dermal sur~ace, with preselected cover segments 80a, 80b removed.
It is to be appreciated that any number o~ bandages and/or systems may be constructed in accordance with the method oi the present invention and, although there has been described hereinabove a number of speci~ic bandage embodiments in accordance with the present in~ention, ior the purpose of illustrating the manner in ~hich the invention may be used to advantage, it should be appreciated that the ~nvention is not limited thereto.
Accordingly, any and all modi~ications, variations or equivalent arrangements which may occur to those skilled in the art, should be considered to be within the scope o~ the invention as defined in the appended claims.

Claims

1. A bandage for transdermal delivery of an active agent, said bandage comprising:
a fixed supply of an active agent; and control means, separate from said fixed supply of active agent, for adjustably and incrementally controlling surface contact area between the fixed supply of active agent and the dermal surface when the bandage is held thereagainst in order to select one of a plurality of available doses greater than zero that can be delivered by the bandage without altering the fixed supply of active agent.

2. The bandage, in accordance with claim 1 wherein said control means includes manual means operable by a user of said bandage for adjustably controlling surface contact area between the fixed supply of active agent and the dermal surface.

3. The bandage in accordance with Claim 2 wherein said manual means includes at least two selectably removable cover segments disposed over said supply of active agent.

4. A bandage for transdermal delivery of an active agent, said bandage comprising:
a supply of active agent; and control means, separate from said supply of active agent, for adjustably controlling surface contact area between the active agent and the dermal surface when the bandage is held there-against, said control means including manual means comprising a plurality of selectably removable cover segments, said plurality of selectably removable cover segments together forming a cover sheet, said cover sheet completely covering said supply of active agent, said selectably removable cover segments being defined by perforations in said cover sheet, said perforations enabling manual separation of one or more of the removable cover segments from the cover sheet to control surface contact area between the active agent and the dermal surface.

5. The bandage, in accordance with Claim 4 wherein the supply of active agent comprises a microporous material containing said active agent, said microporous material being permeable to the passage of said active agent.

6. The bandage, in accordance with Claim 4 wherein the supply of active agent comprises a liquid or gel containing the active agent separated from said cover sheet by a membrane permeable to the passage of the active agent.

7. The bandage, in accordance with Claim 4 wherein said perforations define a set of cover segments having differing sizes.

8. The bandage, in accordance with Claim 4 wherein said plurality of selectably removable cover segments comprise a set of elongated strips disposed in a parallel relationship over said supply of active agent, each strip having tab means thereon for manually separating each strip from the cover sheet and the fixed supply of active agent.

9. The bandage, in accordance with Claim 8, further comprising indicia means, associated within each cover segment, for displaying the dosage of active agent delivered into the dermal surface when the bandage is secured in an operational position on the dermal surface with a preselected cover segment removed.

10. The bandage in accordance with claim 9 wherein the indicia means comprises a plurality of distinguishable colors, each tab means having a different color.

11. A bandage for transdermal delivery of an active agent, said bandage comprising:
a fixed supply of active agent;
adhesive means for releasably securing the bandage to a dermal surface; and control means, separate from said fixed supply of active agent, for adjustably and incrementally controlling the amount of migration of the active agent into the dermal surface to provide one of a plurality of available doses greater than zero without altering the fixed supply of active agent, said control means including means for controlling surface contact area between the fixed supply of active agent and the dermal surface.

12. The bandage, in accordance with claim 11, further comprising a backing sheet and said fixed supply of active agent and said adhesive means is disposed on one side of said backing sheet.

13. The bandage, in accordance with claim 12, wherein said adhesive means is disposed on said backing sheet in a spaced-apart relationship with said fixed supply of active agent for securing the bandage to a dermal surface in an operational relationship permitting the control means to adjustably control migration of the active agent into the dermal surface without contact with the adhesive means.

14. A bandage for transdermal delivery of an active agent, said bandage comprising:
a fixed supply of active agent;
adhesive means for releasably securing the bandage to a dermal surface;
control means, separate from said fixed supply of active agent, for adjustably controlling surface contact between the fixed supply of active agent and the dermal surface in multiple increments greater than zero; and means for enabling preselective limiting of the operation of the control means to pro-viding a preselected maximum surface contact between the fixed supply of active agent and the dermal surface.

15. The bandage, in accordance with claim 14, wherein said control means includes means, operable by a user of said bandage, for controlling surface contact area between the fixed supply of active agent.

16. The bandage, in accordance with claim 15, wherein said manual means includes at least two selectably removable cover segments disposed over said fixed supply of active agent.

17. A bandage for transdermal delivery of an active agent, said bandage comprising: manual means comprising a plurality of selectably removable cover segments, said cover segments together forming a cover sheet, said cover sheet completely covering said supply of active agent, said selectably removable cover segments being of the removable cover segments from the cover sheet to control surface contact area between the active agent and the dermal surface.

18. The bandage, in accordance with claim 17 wherein said plurality of selectably removable cover segment comprises a set of elongated strips disposed in a parallel relationship over said supply of active agent.

19. The bandage, in accordance with claim 18 , further comprising a backing sheet having the supply of active agent disposed along a central portion thereof and the adhesive means disposed along the periphery of the backing sheet and a releasable protection sheet disposed over said adhesive means.

20. The bandage in accordance with claim 19 wherein each of said severable tabs comprises end portion means, extending beyond the backing sheet, for enabling manual grasping thereof for separating each corresponding tab from the backing sheet and corresponding cover segment from the cover sheet along the perforations therein, said adhesive means including tab adhesive means disposed under each tab, for preventing separation of a severable tab from the backing sheet, and corresponding cover segment from the cover sheet, when the end portion means is removed from the severable tab.

21 21. A bandage system for providing multiple doses of an active agent in selectively equal or differing amounts, said bandage system comprising:
a plurality of individual bandage means of trans-dermal delivery of the active agent, each said individual bandage means comprising an active agent adhesive means for releasably securing the individual bandage means to a dermal surface and control means, separate from said supply of active agent, for adjustably and incrementally controlling surface contact area between the active agent and the dermal surface when the individual bandage is secured in an operational position on the dermal surface in order to provide one of a plurality of available doses greater than zero.

22. The bandage system, in accordance with claim 21, wherein said control means of each in-dividual bandage includes manual means operable by a user of said individual bandage for adjustably controlling surface contact area between the active agent and the dermal surface.

23. A bandage system for providing multiple doses of an active agent in selectively equal or different amounts, said bandage system comprising:
a plurality of individual bandage means for transdermal delivery of the active agent, each said individual bandage means comprising a supply of the active drug, adhesive means for releasably securing the individual bandage means to a dermal surface and control means, separate from said supply of active agent, for adjustably controlling surface contact between the active agent and the dermal surface when the individual bandage is secured in an operational position on the dermal surface, said control means of each bandage means including manual means, operable by a use of said individual bandage, for adjustably controlling surface contact area between the active agent and the dermal surface, each said manual means including a plurality of selectably removable cover segments disposed over said supply of active agent on each individual bandage means.

24. The bandage system in accordance with claim 23 wherein said plurality of selectably removable cover segments on each individual bandage together forms an associated cover sheet on each individual bandage, each said associated cover sheet completely covering said supply of active agent on each individual bandage, said selectably removable cover segment being defined by perforations in each said associated cover sheet, said perforations enabling manual separation of one or more of the removable cover segments from the associated cover sheet to control surface contact area between the active agent and the dermal surface when each individual bandage is placed in an operational relationship with the dermal surface.

25. The bandage system in accordance with claim 21 further comprising indicia means associated with each cover segment on each individual bandage for displaying the dosage of active agent delivered into the dermal surface when each bandage is secured in an operational position on the dermal surface with a preselected cover segment removed.

26. A bandage for transdermal delivery of an active agent, said bandage comprising:
a supply of an active agent; and control means, separate from said supply of active agent for adjustably controlling surface contact area between the active agent and the dermal surface when the bandage is held thereagainst, said control means including manual means comprising selectably removable cover segments, a plurality of said selectably removable cover segments forming a cover sheet, said cover sheet completely covering said supply of active agent.