EP0191783A1 - Pansement pour la liberation entretenue de medicaments - Google Patents

Pansement pour la liberation entretenue de medicaments

Info

Publication number
EP0191783A1
EP0191783A1 EP85903618A EP85903618A EP0191783A1 EP 0191783 A1 EP0191783 A1 EP 0191783A1 EP 85903618 A EP85903618 A EP 85903618A EP 85903618 A EP85903618 A EP 85903618A EP 0191783 A1 EP0191783 A1 EP 0191783A1
Authority
EP
European Patent Office
Prior art keywords
bandage
adhesive
drug
styrene
pellet
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP85903618A
Other languages
German (de)
English (en)
Other versions
EP0191783A4 (fr
Inventor
Nelda M. Marecki
Gary A. Avalon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Avery Dennison Corp
Original Assignee
Avery International Corp
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 Corp filed Critical Avery International Corp
Publication of EP0191783A1 publication Critical patent/EP0191783A1/fr
Publication of EP0191783A4 publication Critical patent/EP0191783A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS 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
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive plasters or dressings
    • A61F13/023—Adhesive plasters or dressings wound covering film layers without a fluid handling layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS 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
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive plasters or dressings
    • A61F13/023—Adhesive plasters or dressings wound covering film layers without a fluid handling layer
    • A61F13/0243—Adhesive 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS 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
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/02—Adhesive plasters or dressings
    • A61F13/0246—Adhesive plasters or dressings characterised by the skin adhering layer
    • A61F13/0253—Adhesive plasters or dressings characterised by the skin adhering layer characterized by the adhesive material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal 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
    • A61K9/7084—Transdermal 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

Pansement (10) pour l'administration transdermique ou topique d'un médicament (14) pendant un laps de temps étendu, comportant une feuille de support imperméable (12), une pastille de médicament solide (14) sur la feuille de support (12) et une couche d'adhésif de contact (18) recouvrant la pastille (14) et la feuille de support (12). Dans un autre mode de réalisation, l'adhésif (18) est porté par une bande (20) à base d'un tissu ou d'un non-tissé. Il est possible de réguler la vitesse de dissolution du médicament solide (14) en changeant le type du tissu en bande (20), le type d'adhésif (18) et l'épaisseur de l'adhésif (18).
EP19850903618 1984-07-06 1985-07-03 Pansement pour la liberation entretenue de medicaments. Withdrawn EP0191783A4 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US62857784A 1984-07-06 1984-07-06
US628577 1984-07-06

Publications (2)

Publication Number Publication Date
EP0191783A1 true EP0191783A1 (fr) 1986-08-27
EP0191783A4 EP0191783A4 (fr) 1987-12-09

Family

ID=24519477

Family Applications (1)

Application Number Title Priority Date Filing Date
EP19850903618 Withdrawn EP0191783A4 (fr) 1984-07-06 1985-07-03 Pansement pour la liberation entretenue de medicaments.

Country Status (7)

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

Families Citing this family (5)

* 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
KR920700014A (ko) * 1989-06-02 1992-02-19 테오도르 에이취. 스탠리 비침입적인 혈중 글루코오스의 검사 장치 및 방법
US5139023A (en) * 1989-06-02 1992-08-18 Theratech Inc. Apparatus and method for noninvasive blood glucose monitoring
DE19519593C1 (de) * 1995-05-29 1996-08-29 Horstmann Michael Transdermales Therapeutisches System mit druckfarbenfreier Identifikation und Verfahren zu seiner Herstellung
FR2776517B1 (fr) * 1998-03-24 2000-06-09 Oreal Patch a effet thermique et son utilisation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR945952A (fr) * 1947-04-29 1949-05-19 Dispositif auxiliaire pour l'emploi de produits chimiques et minéraux à des fins thérapeutiques
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

Family Cites Families (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

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR945952A (fr) * 1947-04-29 1949-05-19 Dispositif auxiliaire pour l'emploi de produits chimiques et minéraux à des fins thérapeutiques
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

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO8600536A1 *

Also Published As

Publication number Publication date
AU4606685A (en) 1986-02-10
DK100586A (da) 1986-03-05
ZA855137B (en) 1986-02-26
WO1986000536A1 (fr) 1986-01-30
JPS61502683A (ja) 1986-11-20
AU584025B2 (en) 1989-05-11
EP0191783A4 (fr) 1987-12-09
DK100586D0 (da) 1986-03-05
CA1253805A (fr) 1989-05-09

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