WO1986000536A1 - Bandage for sustained delivery of drugs - Google Patents

Bandage for sustained delivery of drugs Download PDF

Info

Publication number
WO1986000536A1
WO1986000536A1 PCT/US1985/001295 US8501295W WO8600536A1 WO 1986000536 A1 WO1986000536 A1 WO 1986000536A1 US 8501295 W US8501295 W US 8501295W WO 8600536 A1 WO8600536 A1 WO 8600536A1
Authority
WO
WIPO (PCT)
Prior art keywords
bandage
adhesive
drug
styrene
pellet
Prior art date
Application number
PCT/US1985/001295
Other languages
French (fr)
Inventor
Nelda M. Marecki
Gary A. Avalon
Original Assignee
Avery International Corporation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Avery International Corporation filed Critical Avery International Corporation
Publication of WO1986000536A1 publication Critical patent/WO1986000536A1/en
Priority to DK100586A priority Critical patent/DK100586D0/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/02Adhesive plasters or dressings
    • A61F13/023Adhesive plasters or dressings wound covering film layers without a fluid handling layer
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/02Adhesive plasters or dressings
    • A61F13/023Adhesive plasters or dressings wound covering film layers without a fluid handling layer
    • A61F13/0243Adhesive plasters or dressings wound covering film layers without a fluid handling layer characterised by the properties of the skin contacting layer, e.g. air-vapor permeability
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00Bandages or dressings; Absorbent pads
    • A61F13/02Adhesive plasters or dressings
    • A61F13/0246Adhesive plasters or dressings characterised by the skin adhering layer
    • A61F13/0253Adhesive plasters or dressings characterised by the skin adhering layer characterized by the adhesive material
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

Definitions

  • This invention relates to bandages and systems for controlled release of transderrnally or topically administered drugs and, more particularly, to an improved bandage in which the patient's normal skin moisture effects dissolution and delivery of the drug.
  • the word "drugs" is intended in its broadest sense to apply to all medicaments of any type, wnether topical or systemic, applied for therapeutic purposes.
  • bandages designed for delivery of drugs to the skin or mucosa of the wearer.
  • One group of such prior bandages is represented by U. S. Patent Nos.
  • U. S. Patent No. 4,286,592 teaches another laminate bandage in which the drug is dispersed in a dissolution carrier matrix, and discusses the use of an adhesive to control the rate of dissolution and administration of the drug.
  • the bandage was complex and costly and required specific manufacturing parameters.
  • the present invention grows out of the discovery that sustained, substantially constant rate of release over long periods of time can be obtained using drugs in solid form.
  • the bandage of the invention comprises only a liquid-impermeable backing, a solid drug, preferably in pellet form, and a moisture-permeable skin contact adhesive. Controlled rate dissolution of the solid drug results from contact therewith of water or water vapor emanating from the skin of the wearer.
  • the solid drug may be used in its pure form and no added excipients, matrices, or dissolution carriers are required.
  • the salutary results achieved derive from the correlation between the body moisture and the solubility of the drug therein and the fact that such moisture can pass through the adhesive up to the drug and the dissolved drug is able to pass back through the adhesive to the skin of the patient.
  • the rate of dissolution can be obtained in a number of ways.
  • One method is by varying the composition of the adhesive and/or its thickness.
  • Another method is to incorporate into the adhesive a vehicle in which the drug is soluble, but more or less soluble than in the body moisture of the patient.
  • the bandage may also include a carrier web for the adhesive.
  • the carrier web material can also be selected so that it may have an effect on the rate of dissolution.
  • the inventive bandage is simple, efficient, inexpensive to make, and eliminates the objectionable features of the prior art devices, such as, drug reservoirs, matrices, microencapsulation, diffusion membranes, and the like.
  • FIG. 1 is a perspective view of a bandage embodying the principles of the invention with portions of the adhesive layer being broken away to reveal internal structure;
  • FIG. 2 is an enlarged vertical sectional view taken on the plane of line 2-2 in FIG. 1;
  • FIG. 3 is a similar view of a modified form of the bandage
  • FIG. 4 is a similar view of another modified form of the bandage; and FIG. 5 is a graph of the dissolution of two representative drugs plotted against time, the drug for the bandages of Examples 1, 2, and 3 being ti olol, and the drug for the bandage of Example 4 being phenylephrine hydrochloride.
  • FIGS. 1 and 2 there is illustrated in FIGS. 1 and 2 the basic bandage structure of the invention indicated generally by the numeral 10.
  • Bandage 10 comprises a flexible liquid-impermeable backing layer or sheet 12.
  • the backing sheet 12 is chosen to prevent migration of the drug therethrough and insure one-way diffusion of the drug when applied.
  • the backing sheet may be gas-impermeable as well as liquid-impermeable, it being necessary only that the same be impermeable to the drug in its dissolved or vaporized state.
  • backing sheet 12 is thin and flexible, having a thickness in the range of 6 to 50 microns.
  • the solid drug pellet 14 may be substantially circular in form and have an inner face 16 of substantially larger dimensions than the pellet's thickness.
  • the pellet 14 may range between 0.5 and 10 cm in diameter, 5 and 1,000 microns in thickness, and have a mass between 1 and 1,000 g. The significance of the relatively large surface area 16 will become apparent as the description proceeds.
  • a layer of skin contact adhesive 18 covers the pellet 14 and retains the same on the backing sheet 12.
  • the layer 18 may comprise any of the conventional pressure sensitive adhesives, such as, acrylic copolymer, styrene-butadiene-styrene, styrene-isoprene-styrene and silicone polymer, and may also contain tackifying resins.
  • the acrylic adhesives may be selected from a variety of pressure-sensitive adhesive copolymers as are well known in the art.
  • the useful pressure-sensitive adhesives include the copolymers of acrylic and/or methacrylic acids, alkyl acrylate and methacrylate esters containing 1 to 10 carbon atoms, such as, methyl methacrylate and 2-ethyl-hexyl acrylate, acrylamides and methacrylamides, and additional copolymerizable monoethylenically unsaturated monomers, such as, vinyl acetate, acrylonitrile and alkyl vinyl ethers containing 1 to 10 carbon atoms, such as, propyl vinyl ether.
  • the pressure-sensitive acrylic adhesives may comprise copolymers of 2-ethyl-hexyl acrylate, vinyl acetate and acrylic acid sold under such trademarks or tradenames as Gelva RA-788 made by Monsanto, AS-35 * 1 made by Avery Chemical and Aeroset 1085 made by Ashland.
  • the pressure-sensitive rubber-based adnesives may likewise be selected from a variety of compounds of styrene-butadiene-styrene (SBS) and/or styrene-isoprene-styrene (SIS) block copolymers, one or more plasticizers and a stabilizer.
  • SBS styrene-butadiene-styrene
  • SIS styrene-isoprene-styrene
  • Such pressure-sensitive adhesives may include compounds of rubber-based block copolymers such as Kraton 1101 (SBS) or 1107 (SIS) (Shell Chemical Company) , one or more tackifier resins sold under such trademarks or tradenames as Hercolyn D, Piccolyte A-115, Stabilite Ester 10 and Foral 85, and a suitable stabilizer.
  • the pressure-sensitive rubber-based adhesives may comprise from 10 to 30% block copolymers of styrene-butadiene-styrene or styrene-isoprene-styrene, from 30 to 70% tackifying resins and 1 to 3% of a stabilizer.
  • Silicone adhesives may comprise solvent solutions of silicone gum and resin, partially condensed, of the type sold under such trademarks or tradenames as Dow Corning 355, and PSA 595 or PSA 6574 made by General Electric.
  • Thickness and composition of the adhesive layer 18 has been discovered to have an effect on controlling the rate of dissolution of the drug pellet 14 as will subsequently be described. It has thus been found that acrylic adhesives permit faster rates of dissolution than a rubber-based adhesive, and the adhesives may likewise contain tackifying resins, or other additions or fillers. Adhesive layers between 10 and 150 microns in thickness have been found to be effective depending upon the particular drug and application involved. The adhesive layer 18 may be further modified by addition of a drug dissolution vehicle as will be seen from an example to be described.
  • any solid drug which is compressible or handleable in powder form may be employed in its pure form without the addition of any additives.
  • the drug will have a relatively low melting point, on the order of less than 150°C and be relatively soluble in water, in the range of 0.1 to 100 mg/ml.
  • Successful results have been achieved with adrenergics such as timolol and phenylephrine hydrochloride.
  • FIG. 3 there is illustrated a modified form of the bandage 10 wherein the adhesive layer 18 comprises the outer coating of a carrier web 20. As indicated, the carrier web is likewise coated with a layer of adhesive 19 on the inner or pellet side thereof.
  • the adhesive layer 19 may vary in thickness between 20 and 300 microns and may be the same as layer 18, or comprise a different adhesive.
  • carrier web 20 comprises a non-woven fabric composed of nylon, polyethylene, polypropylene, rayon, cellulose-rayon, or polyester and having a fabric weight of from 1 to
  • Choice of carrier web material can have an effect on the rate of dissolution apparently related to the polarit of the material of construction. It has thus been discovered, for example, that a carrier made of a relatively polar molecule, such as nylon, tends to retard the rate of dissolution.
  • FIG. 4 there is illustrated another modified form of the bandage 10.
  • the impermeable backing sfteet 12 is covered by an outer layer 22 to give the bandage a finished feel, look and wearability.
  • the outer layer 22 should be flexible, conformable, lightweight and comfortably wearable.
  • the outer layer 22 may comprise occlusive films of polyethylene, polypropylene, polyvinyl chloride and polyurethane, or non-occlusive woven or non-woven fabrics of the same composition as the carrier web 18 or a perforated film of any of the listed materials, and ranging in thickness from 10 to 200 microns.
  • the bandage 10 preferably includes a protective liner (not shown) , for example, silicone or polyfluoroethylene coated release liners as are well known in the art, removably adhered to pressure sensitive layer 18.
  • a protective liner for example, silicone or polyfluoroethylene coated release liners as are well known in the art, removably adhered to pressure sensitive layer 18.
  • Such a liner may be made of paper or film on the order of 25 to 200 microns thickness and protects the adhesive prior to use and prevents drug migration through the adhesive during storage.
  • Example 1 A bandage for administering the beta-adrenergic blocker timolol transdermally for a period in excess of 80 hours was made in the following manner.
  • a 50 mg wafer-like pellet of timolol was prepared in a standard potassium bromide pellet press, the substantially circular pellet having a diameter of about 1.25 cm and a thickness of about 350 microns.
  • the drug pellet was placed on aluminum foil of 50 microns thickness and this was overlaid with a layer of acrylic adhesive of 50 microns thickness, said adhesive being mass cast from solution (toluene, heptane) at 40-50% solids, wherein the acrylic fraction comprises an acrylic copolymer prepared through reaction of 2-ethyl-hexyl acrylate, vinyl acetate and acrylic acid.
  • In vitro release tests were carried out on the bandage using standard apparatus and techniques, namely Standard U.S.P. Type 2 dissolution apparatus with with a phosphate buffer solution of pH 7.4. Constant release of the drug was sustained over a period in excess of 80 hours, after which the release slowed appreciably and the drug was substantially exhausted. Between 4 and 72 hours, the drug release approached a linear rate.
  • Example 2 A bandage for administering timolol was made.
  • a 50 mg pellet of the drug was prepared and placed on aluminum foil of 50 microns thickness.
  • the pellet was then overlaid with a tackified styrene-butadiene-styrene pressure-sensitive adhesive containing 5% mineral oil, said adhesive being mass cast from- solution (toluene, heptane) at 40-50% solids, wherein the rubber fraction comprises a compound of 18% styrene-butadiene-styrene block copolymer, 15% random styrene-butadiene copolymer, 61% tackifying resins, 5% mineral oil, and 1% stabilizer.
  • the solubility of timolol is about 8 mg/ml in water and about 4 mg/ml in mineral oil.
  • substantially constant release of the drug was sustained for a period in e ' xcess of 120 hours after which the release slowed appreciably and the drug was substantially exhausted. Between 8 and 100 hours, the drug release approached a linear rate.
  • Example 3 A bandage for the administration of timolol was made by preparing a pellet of the drug and placing the same on aluminum foil as in Examples 1 and 2. The pellet was then overlaid with an adhesive carrier web made of non-woven polyester
  • the carrier web had previously been coated on the pellet side with acrylic adhesive, having the same composition as in Example 1, of 25 microns thickness and on the non-pellet, or skin-contact, side with the same acrylic adhesive of 50 microns thickness.
  • acrylic adhesive having the same composition as in Example 1, of 25 microns thickness and on the non-pellet, or skin-contact, side with the same acrylic adhesive of 50 microns thickness.
  • Example 4 A bandage for the administration of the drug phenylephrine hydrochloride was made in the following manner.
  • a 70 mg wafer-like pellet of the drug was prepared in a standard potassium bromide pellet press, the substantially circular pellet having a diameter of about 1.25 cm and a thickness of about 350 microns.
  • the drug pellet was placed on aluminum foil of 50 microns thickness. This was overlaid with an adhesive carrier web made of a non-woven polyester having a fabric weight of
  • the carrier web had previously been coated on the pellet side with tackified styrene-butadiene-styrene pressure-sensitive adhesive, having the same composition as in Example 2, of 25 microns thickness and on the non-pellet, or skin-contact, side with acrylic adhesive, having the same composition as in Example 1, of 50 microns thickness.
  • substantially constant release of the drug was sustained for a period in excess of 35 hours, after which the drug release slowed appreciably and the drug was substantially exhausted. Between about 1 and 32 hours, the drug release approached a linear rate.
  • the invention provides a simple, efficient and inexpensive bandage for the sustained transdermal or topical administration of drugs over an extended period of time.
  • the use of solid drugs advantageously eliminates all matrices, encapsulations and dissolution media of the type heretofore required in bandages of this type.
  • bandage is used in its generic sense to apply to any skin adhesive device whatever its form or shape. While preferred embodiments have been illustrated and described herein, changes and variations may be made by those skilled in the art without departing from the spirit and scope of the appended claims. The invention is defined by the claims that follow.

Abstract

A bandage (10) for the transdermal or topical administration of a drug (14) over an extended period of time comprising an impermeable backing sheet (12), a solid drug pellet (14) on the backing sheet (12), and a layer of contact adhesive (18) covering the pellet (14) and backing sheet (12). In another form, the adhesive (18) is carried by a web (20) made of a non-woven fabric. Control over the rate of dissolution of the solid drug (14) can be achieved by varying the type of web fabric (20), the type of adhesive (18), and the thickness of the adhesive (18).

Description

BANDAGE FOR SUSTAINED DELIVERY OF DRUGS Field of the Invention
This invention relates to bandages and systems for controlled release of transderrnally or topically administered drugs and, more particularly, to an improved bandage in which the patient's normal skin moisture effects dissolution and delivery of the drug. Background of the Invention As used in this application and the appended claims, the word "drugs" is intended in its broadest sense to apply to all medicaments of any type, wnether topical or systemic, applied for therapeutic purposes. In recent years, there have been provided numerous bandages designed for delivery of drugs to the skin or mucosa of the wearer. One group of such prior bandages is represented by U. S. Patent Nos. 3,632,740; 3,769,071; and 3,896,789, which teach the incorporation of specific active agents into a pressure sensitive adhesive for direct contact with skin lesions, and the like. Those bandages had no means for control of the rate of delivery and were objectionable for many applications because of the direct contact of the drug with the skin.
Another group of prior bandages employed specially designed diffusion membranes and drug reservoirs as represented by u. S. Patent Nos. 3,598,122 and 4,069,307. Those bandages were complex, expensive, and involved difficult and precise manufacturing techniques.
An offshoot or refinement of the drug reservoir approach resulted in the micro-encapsulation of fine particles of the drug and the dispersion of the microcapsules within a matrix comprising a discrete layer of a laminar structure. Representative of such bandages are U. S. Patent Nos. 3,996,934; and 3,598,123. Once again, such bandages were complex, costly and difficult to make.
U. S. Patent No. 4,286,592 teaches another laminate bandage in which the drug is dispersed in a dissolution carrier matrix, and discusses the use of an adhesive to control the rate of dissolution and administration of the drug. Here, too, the bandage was complex and costly and required specific manufacturing parameters.
A simpler bandage is shown in Patent No. 4,307,717, but it still required that the drug be dispersed in a matrix and it did not address the question of control of the rate of dissolution. Summary of the Invention
The present invention grows out of the discovery that sustained, substantially constant rate of release over long periods of time can be obtained using drugs in solid form. In its broadest form, the bandage of the invention comprises only a liquid-impermeable backing, a solid drug, preferably in pellet form, and a moisture-permeable skin contact adhesive. Controlled rate dissolution of the solid drug results from contact therewith of water or water vapor emanating from the skin of the wearer.
The solid drug may be used in its pure form and no added excipients, matrices, or dissolution carriers are required. The salutary results achieved derive from the correlation between the body moisture and the solubility of the drug therein and the fact that such moisture can pass through the adhesive up to the drug and the dissolved drug is able to pass back through the adhesive to the skin of the patient.
Further control of the rate of dissolution can be obtained in a number of ways. One method is by varying the composition of the adhesive and/or its thickness. Another method is to incorporate into the adhesive a vehicle in which the drug is soluble, but more or less soluble than in the body moisture of the patient. The bandage may also include a carrier web for the adhesive. The carrier web material can also be selected so that it may have an effect on the rate of dissolution. In all its forms, the inventive bandage is simple, efficient, inexpensive to make, and eliminates the objectionable features of the prior art devices, such as, drug reservoirs, matrices, microencapsulation, diffusion membranes, and the like.
Other features and advantages of the invention will be apparent from the following description and claims and are illustrated in the accompanying drawings which show structure embodying preferred features of tne present invention and the principles thereof. Brief Description of the Drawings
FIG. 1 is a perspective view of a bandage embodying the principles of the invention with portions of the adhesive layer being broken away to reveal internal structure; FIG. 2 is an enlarged vertical sectional view taken on the plane of line 2-2 in FIG. 1;
FIG. 3 is a similar view of a modified form of the bandage;
FIG. 4 is a similar view of another modified form of the bandage; and FIG. 5 is a graph of the dissolution of two representative drugs plotted against time, the drug for the bandages of Examples 1, 2, and 3 being ti olol, and the drug for the bandage of Example 4 being phenylephrine hydrochloride.
Description of the Preferred Embodiments of the Invention Referring with greater particularity to the various figures of the drawings, there is illustrated in FIGS. 1 and 2 the basic bandage structure of the invention indicated generally by the numeral 10. Bandage 10 comprises a flexible liquid-impermeable backing layer or sheet 12. The backing sheet 12 is chosen to prevent migration of the drug therethrough and insure one-way diffusion of the drug when applied. In this regard, the backing sheet may be gas-impermeable as well as liquid-impermeable, it being necessary only that the same be impermeable to the drug in its dissolved or vaporized state. For this purpose, a variety of thin, sheet-like materials are suitable, including aluminum foil, polyester, polypropylene, polyethylene, polyurethane film, and a laminate of aluminum foil and polyester. Desirably, backing sheet 12 is thin and flexible, having a thickness in the range of 6 to 50 microns.
Positioned on the backing sheet 12 is a thin pellet 14 made of a compressed, solid drug. The solid drug pellet 14 may be substantially circular in form and have an inner face 16 of substantially larger dimensions than the pellet's thickness. In this regard, the pellet 14 may range between 0.5 and 10 cm in diameter, 5 and 1,000 microns in thickness, and have a mass between 1 and 1,000 g. The significance of the relatively large surface area 16 will become apparent as the description proceeds. A layer of skin contact adhesive 18 covers the pellet 14 and retains the same on the backing sheet 12. The layer 18 may comprise any of the conventional pressure sensitive adhesives, such as, acrylic copolymer, styrene-butadiene-styrene, styrene-isoprene-styrene and silicone polymer, and may also contain tackifying resins.
The acrylic adhesives may be selected from a variety of pressure-sensitive adhesive copolymers as are well known in the art. Broadly, the useful pressure-sensitive adhesives include the copolymers of acrylic and/or methacrylic acids, alkyl acrylate and methacrylate esters containing 1 to 10 carbon atoms, such as, methyl methacrylate and 2-ethyl-hexyl acrylate, acrylamides and methacrylamides, and additional copolymerizable monoethylenically unsaturated monomers, such as, vinyl acetate, acrylonitrile and alkyl vinyl ethers containing 1 to 10 carbon atoms, such as, propyl vinyl ether. More specifically, the pressure-sensitive acrylic adhesives may comprise copolymers of 2-ethyl-hexyl acrylate, vinyl acetate and acrylic acid sold under such trademarks or tradenames as Gelva RA-788 made by Monsanto, AS-35*1 made by Avery Chemical and Aeroset 1085 made by Ashland.
The pressure-sensitive rubber-based adnesives may likewise be selected from a variety of compounds of styrene-butadiene-styrene (SBS) and/or styrene-isoprene-styrene (SIS) block copolymers, one or more plasticizers and a stabilizer. Such pressure-sensitive adhesives may include compounds of rubber-based block copolymers such as Kraton 1101 (SBS) or 1107 (SIS) (Shell Chemical Company) , one or more tackifier resins sold under such trademarks or tradenames as Hercolyn D, Piccolyte A-115, Stabilite Ester 10 and Foral 85, and a suitable stabilizer.
More specifically, the pressure-sensitive rubber-based adhesives may comprise from 10 to 30% block copolymers of styrene-butadiene-styrene or styrene-isoprene-styrene, from 30 to 70% tackifying resins and 1 to 3% of a stabilizer.
Silicone adhesives may comprise solvent solutions of silicone gum and resin, partially condensed, of the type sold under such trademarks or tradenames as Dow Corning 355, and PSA 595 or PSA 6574 made by General Electric.
Thickness and composition of the adhesive layer 18 has been discovered to have an effect on controlling the rate of dissolution of the drug pellet 14 as will subsequently be described. It has thus been found that acrylic adhesives permit faster rates of dissolution than a rubber-based adhesive, and the adhesives may likewise contain tackifying resins, or other additions or fillers. Adhesive layers between 10 and 150 microns in thickness have been found to be effective depending upon the particular drug and application involved. The adhesive layer 18 may be further modified by addition of a drug dissolution vehicle as will be seen from an example to be described.
Any solid drug which is compressible or handleable in powder form may be employed in its pure form without the addition of any additives. In general, the drug will have a relatively low melting point, on the order of less than 150°C and be relatively soluble in water, in the range of 0.1 to 100 mg/ml. Successful results have been achieved with adrenergics such as timolol and phenylephrine hydrochloride. In FIG. 3, there is illustrated a modified form of the bandage 10 wherein the adhesive layer 18 comprises the outer coating of a carrier web 20. As indicated, the carrier web is likewise coated with a layer of adhesive 19 on the inner or pellet side thereof. The adhesive layer 19 may vary in thickness between 20 and 300 microns and may be the same as layer 18, or comprise a different adhesive. Preferably, carrier web 20 comprises a non-woven fabric composed of nylon, polyethylene, polypropylene, rayon, cellulose-rayon, or polyester and having a fabric weight of from 1 to
2 100 gm/m . Woven fabrics of gauze or cellulosic
2 materials having a weight of from 0.5 to 100 gm/m may also be employed. Choice of carrier web material can have an effect on the rate of dissolution apparently related to the polarit of the material of construction. It has thus been discovered, for example, that a carrier made of a relatively polar molecule, such as nylon, tends to retard the rate of dissolution.
In FIG. 4, there is illustrated another modified form of the bandage 10. In this embodiment, the impermeable backing sfteet 12 is covered by an outer layer 22 to give the bandage a finished feel, look and wearability. The outer layer 22 should be flexible, conformable, lightweight and comfortably wearable. In this regard the outer layer 22 may comprise occlusive films of polyethylene, polypropylene, polyvinyl chloride and polyurethane, or non-occlusive woven or non-woven fabrics of the same composition as the carrier web 18 or a perforated film of any of the listed materials, and ranging in thickness from 10 to 200 microns. As a final finish, the bandage 10 preferably includes a protective liner (not shown) , for example, silicone or polyfluoroethylene coated release liners as are well known in the art, removably adhered to pressure sensitive layer 18. Such a liner may be made of paper or film on the order of 25 to 200 microns thickness and protects the adhesive prior to use and prevents drug migration through the adhesive during storage.
The examples which follow illustrate the invention, but are not intended to limit the invention in any way.
Example 1 A bandage for administering the beta-adrenergic blocker timolol transdermally for a period in excess of 80 hours was made in the following manner. A 50 mg wafer-like pellet of timolol was prepared in a standard potassium bromide pellet press, the substantially circular pellet having a diameter of about 1.25 cm and a thickness of about 350 microns. The drug pellet was placed on aluminum foil of 50 microns thickness and this was overlaid with a layer of acrylic adhesive of 50 microns thickness, said adhesive being mass cast from solution (toluene, heptane) at 40-50% solids, wherein the acrylic fraction comprises an acrylic copolymer prepared through reaction of 2-ethyl-hexyl acrylate, vinyl acetate and acrylic acid. In vitro release tests were carried out on the bandage using standard apparatus and techniques, namely Standard U.S.P. Type 2 dissolution apparatus with with a phosphate buffer solution of pH 7.4. Constant release of the drug was sustained over a period in excess of 80 hours, after which the release slowed appreciably and the drug was substantially exhausted. Between 4 and 72 hours, the drug release approached a linear rate.
Example 2 A bandage for administering timolol was made. As in Example 1, a 50 mg pellet of the drug was prepared and placed on aluminum foil of 50 microns thickness. The pellet was then overlaid with a tackified styrene-butadiene-styrene pressure-sensitive adhesive containing 5% mineral oil, said adhesive being mass cast from- solution (toluene, heptane) at 40-50% solids, wherein the rubber fraction comprises a compound of 18% styrene-butadiene-styrene block copolymer, 15% random styrene-butadiene copolymer, 61% tackifying resins, 5% mineral oil, and 1% stabilizer. For purposes of comparison, the solubility of timolol is about 8 mg/ml in water and about 4 mg/ml in mineral oil. In the same standard in vitro release tests substantially constant release of the drug was sustained for a period in e'xcess of 120 hours after which the release slowed appreciably and the drug was substantially exhausted. Between 8 and 100 hours, the drug release approached a linear rate.
Example 3 A bandage for the administration of timolol was made by preparing a pellet of the drug and placing the same on aluminum foil as in Examples 1 and 2. The pellet was then overlaid with an adhesive carrier web made of non-woven polyester
2 having a fabric weight of 19.9 gm/m . The carrier web had previously been coated on the pellet side with acrylic adhesive, having the same composition as in Example 1, of 25 microns thickness and on the non-pellet, or skin-contact, side with the same acrylic adhesive of 50 microns thickness. In the same standard in vitro release tests substantially constant release of the drug was sustained for a period in excess of 120 hours after which the release slowed appreciably and the drug was substantially exhausted. Between about 15 and 96 hours, the drug release approached a linear rate.
Example 4 A bandage for the administration of the drug phenylephrine hydrochloride was made in the following manner. A 70 mg wafer-like pellet of the drug was prepared in a standard potassium bromide pellet press, the substantially circular pellet having a diameter of about 1.25 cm and a thickness of about 350 microns. The drug pellet was placed on aluminum foil of 50 microns thickness. This was overlaid with an adhesive carrier web made of a non-woven polyester having a fabric weight of
2 19.9 gm/m . The carrier web had previously been coated on the pellet side with tackified styrene-butadiene-styrene pressure-sensitive adhesive, having the same composition as in Example 2, of 25 microns thickness and on the non-pellet, or skin-contact, side with acrylic adhesive, having the same composition as in Example 1, of 50 microns thickness. In the same standard in vitro release tests, substantially constant release of the drug was sustained for a period in excess of 35 hours, after which the drug release slowed appreciably and the drug was substantially exhausted. Between about 1 and 32 hours, the drug release approached a linear rate. -li¬ lt should be apparent from the foregoing that the invention provides a simple, efficient and inexpensive bandage for the sustained transdermal or topical administration of drugs over an extended period of time. The use of solid drugs advantageously eliminates all matrices, encapsulations and dissolution media of the type heretofore required in bandages of this type. It should be appreciated that the term "bandage" is used in its generic sense to apply to any skin adhesive device whatever its form or shape. While preferred embodiments have been illustrated and described herein, changes and variations may be made by those skilled in the art without departing from the spirit and scope of the appended claims. The invention is defined by the claims that follow.

Claims

WHAT IS CLAIMED IS:
1. A bandage for transdermal or topical administration of a drug to the wearer thereof comprising: a liquid-impermeable backing sheet; a solid drug pellet positioned on said backing sheet; and a layer of pressure-sensitive adhesive covering said drug pellet and backing sheet so that all upraised surfaces of said pellet are encased by said adhesive and said pellet makes no physical contact with the wearer during administration of the drug, whereby said adhesive remains in physical contact with the wearer and the drug is administered without puncture of the stratum corneum.
2. The bandage of claim 1 wherein said backing sheet comprises a material selected from the group consisting of aluminum foil, polyester, polypropylene, polyethylene, polyurethane film, and a laminate of aluminum foil and polyester.
3. The bandage of claim 2 wherein said backing sheet has a thickness between 6 and 50 microns.
4. The bandage of claim 1 wherein said drug pellet is substantially circular in configuration and has a diameter between 0.5 and 10 cm and a thickness between 5 and 1,000 microns.
5. The bandage of claim 4 wherein said drug pellet weighs between 1 and 1,000 g.
6. The bandage of claim 1 wherein said pressure-sensitive adhesive comprises an adhesive selected from a group consisting of acrylic copolymer, styrene-butadiene-styrene, styrene-isoprene-styrene, and silicone polymer.
7. The bandage of claim 6 wherein said adhesive layer has a thickness between 10 and 150 microns.
8. The bandage of claim 6 wherein said pressure-sensitive adhesive has mineral oil incorporated therein.
9. A bandage for transdermal or topical administration of a drug to the wearer thereof comprising: a liquid-impermeable backing sheet; a solid drug pellet positioned on the inner surface of said backing sheet; and a carrier web coated with pressure-sensitive adhesive covering said pellet and backing sheet so that all upraised surfaces of said pellet are encased by said carrier web and said pellet makes no physical contact with the wearer during administration of the drug, whereby said adhesive coated web remains in physical contact with the wearer and the drug is administered without puncture of the stratum corneum.
10. The bandage of claim 9 wherein said carrier web comprises a non-woven fabric selected from a group consisting of nylon, polyethylene, polypropylene, rayon, cellulose-rayon, and polyester.
11. The bandage of claim 10 wherein said non-woven fabric has a weight between 1 and 100 mg/m .
12. The bandage of claim 9 wherein said carrier web comprises a woven fabric of gauze or cellulosic materials having a weight of between 0.5
2 and 100 gm/m .
13. The bandage of claim 9 wherein said carrier web is coated with said adhesive on both of its surfaces.
14. The bandage of claim 13 wherein said adhesive comprises an adhesive selected from the group consisting of acrylic copolymer, styrene-butadiene-styrene, styrene-isoprene-styrene, and silicone polymer.
15. The bandage of claim 14 wherein the coating of said adhesive on the skin contact surface of said carrier web has a thickness between 10 and 300 microns and the coating on the inner surface ofsaid web has a thickness of between 10 and 300 microns.
16. The bandage of claim 9 wherein said drug pellet is substantially circular in configuration and has a diameter between 0.5 and 10 cm and a thickness between 5 and 1,000 microns.
17. The bandage of claim 16 wherein said drug pellet weighs between 1 and 1,000 mg.
18. The bandage of claim 15 wherein the adhesive on each of the surfaces of said carrier web comprises acrylic copolymer.
19. The bandage of claim 18 wherein the adhesive coating on the skin contact surface of said carrier web is approximately twice the thickness of the adhesive coating on the inner surface of said web.
20. The bandage of claim 15 wherein the adhesive on the skin contact surface of said carrier web comprises acrylic copolymer and the adhesive on the inner surface of said web comprises styrene-butadiene-styrene.
21. The bandage of claim 20 wherein said acrylate copolymer adhesive coating is approximately twice the thickness of said styrene-butadiene-styrene adhesive coating.
22. The bandage of claim 9 wherein said backing sheet comprises a material selected from the group consisting of aluminum foil, polyester, polypropylene, polyethylene, polyurethane film, and a laminate of aluminum foil and polyester.
23. A bandage for transdermal or topical administration of a drug to the wearer thereof comprising:
. a liquid-impermeable backing sheet; a layer of pressure-sensitive adhesive covering said backing sheet; and a solid drug retained between said backing sheet and adhesive layer and encased by said adhesive so that said drug makes no physical contact with the wearer during administration thereof, whereby said adhesive remains in physical contact with the wearer and the drug is administered without puncture of the stratum corneum.
24. The bandage of claim 23 wherein said backing sheet comprises a material selected from the group consisting of aluminum foil, polyester, polypropylene, polyethylene, polyurethane film, and a laminate of aluminum foil and polyester.
25. The bandage of claim 24 wherein said backing sheet has a thickness between 6 and 50 microns.
26. The bandage of claim 23 wherein said drug pellet is substantially circular in configuration and has a diameter between 0.5 and 10 cm and a thickness between 5 and 1,000 microns.
27. The bandage of claim 26 wherein said drug pellet weighs between 1 and 1,000 mg.
28. The bandage of claim 23 wherein said . pressure-sensitive adhesive comprises an adhesive seleσted from a group consisting of acrylic copolymer, styrene-butadiene-styrene, styrene-isoprene-styrene, and silicone polymer.
29. The bandage of claim 28 wherein said adhesive layer has a thickness between 10 and 150 microns.
30. The bandage of claim 28 wherein said pressure-sensitive adhesive has mineral oil incorporated therein.
PCT/US1985/001295 1984-07-06 1985-07-03 Bandage for sustained delivery of drugs WO1986000536A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DK100586A DK100586D0 (en) 1984-07-06 1986-03-05 PLASTER TO CONTINUOUS DELIVERY OF MEDICINAL PRODUCTS

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US62857784A 1984-07-06 1984-07-06
US628,577 1984-07-06

Publications (1)

Publication Number Publication Date
WO1986000536A1 true WO1986000536A1 (en) 1986-01-30

Family

ID=24519477

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1985/001295 WO1986000536A1 (en) 1984-07-06 1985-07-03 Bandage for sustained delivery of drugs

Country Status (7)

Country Link
EP (1) EP0191783A4 (en)
JP (1) JPS61502683A (en)
AU (1) AU584025B2 (en)
CA (1) CA1253805A (en)
DK (1) DK100586D0 (en)
WO (1) WO1986000536A1 (en)
ZA (1) ZA855137B (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990015568A2 (en) * 1989-06-02 1990-12-27 Stanley Theodore H Apparatus and methods for noninvasive blood glucose monitoring
US5139023A (en) * 1989-06-02 1992-08-18 Theratech Inc. Apparatus and method for noninvasive blood glucose monitoring
US5322695A (en) * 1987-01-09 1994-06-21 Hercon Laboratories Corporation Moisture-vapor-permeable dressing
WO1996038187A1 (en) * 1995-05-29 1996-12-05 Michael Horstmann Transdermal therapeutic system identified without printing inks and process for manufacturing the same
FR2776517A1 (en) * 1998-03-24 1999-10-01 Oreal Patches for applying cosmetics and pharmaceuticals to the skin having an infra red reflecting layer, and a self-adhesive matrix containing topically active ingredients

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4286592A (en) * 1980-02-04 1981-09-01 Alza Corporation Therapeutic system for administering drugs to the skin
US4486193A (en) * 1981-07-22 1984-12-04 Alza Corporation Method for treating ischemic conditions by administering drug by two routes

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR945952A (en) * 1947-04-29 1949-05-19 Auxiliary device for the use of chemicals and minerals for therapeutic purposes
FR2205306A1 (en) * 1972-11-08 1974-05-31 Expl Marques Brevets Soc Medicated dressing for inaccessible site applicant. - permitting diffusion- of powder or tablet to a seat of pain, inflammation or infection
US4207890A (en) * 1977-01-04 1980-06-17 Mcneilab, Inc. Drug-dispensing device and method

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4286592A (en) * 1980-02-04 1981-09-01 Alza Corporation Therapeutic system for administering drugs to the skin
US4486193A (en) * 1981-07-22 1984-12-04 Alza Corporation Method for treating ischemic conditions by administering drug by two routes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP0191783A4 *

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5322695A (en) * 1987-01-09 1994-06-21 Hercon Laboratories Corporation Moisture-vapor-permeable dressing
WO1990015568A2 (en) * 1989-06-02 1990-12-27 Stanley Theodore H Apparatus and methods for noninvasive blood glucose monitoring
WO1990015568A3 (en) * 1989-06-02 1991-04-18 Theodore H Stanley Apparatus and methods for noninvasive blood glucose monitoring
US5139023A (en) * 1989-06-02 1992-08-18 Theratech Inc. Apparatus and method for noninvasive blood glucose monitoring
US5291887A (en) * 1989-06-02 1994-03-08 Anesta Corporation Apparatus and methods for noninvasive blood substance monitoring
WO1996038187A1 (en) * 1995-05-29 1996-12-05 Michael Horstmann Transdermal therapeutic system identified without printing inks and process for manufacturing the same
FR2776517A1 (en) * 1998-03-24 1999-10-01 Oreal Patches for applying cosmetics and pharmaceuticals to the skin having an infra red reflecting layer, and a self-adhesive matrix containing topically active ingredients
EP0958814A1 (en) * 1998-03-24 1999-11-24 L'oreal Patch having a thermal effect and its use
US6191339B1 (en) 1998-03-24 2001-02-20 L'oreal Thermal effect patch and the use thereof

Also Published As

Publication number Publication date
ZA855137B (en) 1986-02-26
CA1253805A (en) 1989-05-09
AU584025B2 (en) 1989-05-11
DK100586A (en) 1986-03-05
DK100586D0 (en) 1986-03-05
JPS61502683A (en) 1986-11-20
EP0191783A4 (en) 1987-12-09
AU4606685A (en) 1986-02-10
EP0191783A1 (en) 1986-08-27

Similar Documents

Publication Publication Date Title
US4655768A (en) Bandage for sustained delivery of drugs
US3731683A (en) Bandage for the controlled metering of topical drugs to the skin
EP1225951B1 (en) A dual adhesive transdermal drug delivery system
JP5977791B2 (en) Transdermal delivery system capable of titration
US4230105A (en) Transdermal delivery of drugs
US5662925A (en) Transdermal delivery system with adhesive overlay and peel seal disc
US3734097A (en) Therapeutic adhesive tape
JP2542026B2 (en) Flat treatment device and its manufacturing method
US4573996A (en) Device for the administration of an active agent to the skin or mucosa
JP2002544157A (en) Drug release device
JP2000514063A (en) Non-occlusive drug delivery device and method of manufacturing the same
JP2567429B2 (en) Transdermal patch activated by user
SK278995B6 (en) Method for producing transdermal therapeutic plaster
AU584025B2 (en) Bandage for sustained delivery of drugs
JPH0472805B2 (en)
JP3575616B2 (en) Patch structure
JP2869167B2 (en) Sustained-release patch preparation
JP2003104874A (en) Device for release controlling medicine
JP2003104875A (en) Device for slow release medicine
JP5512910B2 (en) Tulobuterol-containing percutaneous absorption preparation and patch using the same
JP2557046B2 (en) Layered formulation
JP2697191B2 (en) Transdermal formulation
JP3240184B2 (en) Hygroscopic patch
JP3192829B2 (en) Patch support
JPH07277961A (en) Percutaneous absorption preparation

Legal Events

Date Code Title Description
AK Designated states

Designated state(s): AU BR DK JP

AL Designated countries for regional patents

Designated state(s): BE CH DE FR GB IT NL SE

WWE Wipo information: entry into national phase

Ref document number: 1985903618

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1985903618

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1985903618

Country of ref document: EP