EP1940368A2 - Systeme d'administration transdermique de medicaments avec une composition fonctionnelle acrylate ou methacrylate adhesive sensible a la pression - Google Patents

Systeme d'administration transdermique de medicaments avec une composition fonctionnelle acrylate ou methacrylate adhesive sensible a la pression

Info

Publication number
EP1940368A2
EP1940368A2 EP06826541A EP06826541A EP1940368A2 EP 1940368 A2 EP1940368 A2 EP 1940368A2 EP 06826541 A EP06826541 A EP 06826541A EP 06826541 A EP06826541 A EP 06826541A EP 1940368 A2 EP1940368 A2 EP 1940368A2
Authority
EP
European Patent Office
Prior art keywords
pressure sensitive
sensitive adhesive
set forth
silicon
agent
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Withdrawn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
EP06826541A
Other languages
German (de)
English (en)
Inventor
Timothy P. Mitchell
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.)
Dow Silicones Corp
Original Assignee
Dow Corning 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 Dow Corning Corp filed Critical Dow Corning Corp
Publication of EP1940368A2 publication Critical patent/EP1940368A2/fr
Withdrawn legal-status Critical Current

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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
    • 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

  • the present invention generally relates to a transdermal drug delivery system. More specifically, the present invention relates to a transdermal drug delivery system including a pressure sensitive adhesive composition that is the reaction product of a pressure sensitive adhesive and a silicon-containing capping agent comprising acrylate or methacrylate functionality.
  • Pressure sensitive adhesives also referred to as "PSAs" are known in the art and are commercially available. Silicone pressure sensitive adhesives are typically produced by either blending or condensing together a silicone resin and a silicone polymer, such as a polydiorganosiloxane. Silicone pressure sensitive adhesives are also known in the art and are commercially available. Examples of such pressure sensitive adhesives are disclosed in United States Patent Nos. 2,736,721; 2,814,601, 2,857,356, and 3,528,940. The adhesion of such pressure sensitive adhesives can be varied by altering a ratio of M/Q units in the silicone resin or by altering a ratio of silicone resin to silicone polymer.
  • pressure sensitive adhesives in transdermal drug delivery systems are also known in the art. These systems typically include an active agent and a conventional pressure sensitive adhesive.
  • the active agent for example a pharmaceutical drug, is for controlled transdermal delivery to a substrate, such as the skin of a user of the system.
  • the pressure sensitive adhesive maintains contact between the system and the substrate such that the active agent can be delivered to the substrate. Examples of such systems can be found in United States Patent Nos. 3,731,683; 3,797,494; 4,031,894; and 4,336,243.
  • the pressure sensitive adhesives are designed to ensure contact between the system and the substrate for an extended period of time.
  • the pressure sensitive adhesives are non-irritating and non-sensitizing to the substrate. It is known that, to maintain the stability of pressure sensitive adhesives, and therefore the stability of transdermal drug delivery systems utilizing the pressure sensitive adhesives, the pressure sensitive adhesives must contain a certain content, or concentration, of silicon bonded hydroxyl groups, i.e., silanols. In fact, the silanol content of a pressure sensitive adhesive can be adjusted based on certain factors, such as the particular type of active agent, to control the adhesiveness of the pressure sensitive adhesive. Having too much silanol content or too little silanol content can be undesirable.
  • the transdermal drug delivery systems of the prior art do not sufficiently optimize solubility of the active agent in the pressure sensitive adhesives.
  • the rate at which the active agent is released from the system for delivery to the substrate and also the total amount of the active agent that is ultimately released and delivered to the substrate are not optimized in the prior art.
  • Pressure sensitive adhesives including those used in the systems above, are typically provided in solution with solvent and it is known that residual silanols in the pressure sensitive adhesives can, under certain conditions, react via condensation thereby impacting the stability of these solutions. More specifically, the stability can be impacted because the viscosity of the solution tends to increase over time as a result of the condensation reaction of the residual silanols. This increase in the viscosity is undesirable, especially for long-term shelf-life.
  • the residual silanol content also causes loss of the adhesiveness, also referred to as a loss of tack, of the pressure sensitive adhesive.
  • United States Patent No. RE 35,474 teaches a transdermal drug delivery system for the controlled delivery of amino-functional drugs, as the active agent, to the substrate. It is known that amino-functional drugs interfere with the properties of pressure sensitive adhesives by catalyzing the reaction of silanol groups and, thereby, cause increased shear of the pressure sensitive adhesive and, thus, loss of tack during storage. The '474 patent also teaches that this effect can be inhibited by chemically treating the pressure sensitive adhesives with a treating agent which reduces their silanol content.
  • the amount of the treating agent used to treat the pressure sensitive adhesive must be an amount of at least 0.8 moles triorganosilyl units for every mole of silanol, and that this amount of the treating agent generally reduces the silanol content of the pressure sensitive adhesive to levels below about 7700 parts per million (ppm).
  • the '086 patent focuses on reducing the content of silanol with trimethylsilyl units. Relying strictly on trimethylsilyl units to reduce the content of silanol is deficient because the rate at which an active agent, such as the pharmaceutical drug, is released from the system is not optimized.
  • the trimethylsilyl units relied on in the '086 patent are an example of chemically treating the respective pressure sensitive adhesives with a capping or endblocking agent to reduce their silanol content.
  • Other examples of the use of capping or endblocking agents are disclosed in United States Patent Nos. 4,854,355; 4,858,836; 4,591,622; EP 0529840; and EP 0664328.
  • these examples do not contemplate application of their respective pressure sensitive adhesives in transdermal drug delivery systems.
  • these examples do not employ their respective pressure sensitive adhesives to optimize solubility of any active agent.
  • a transdermal drug delivery system includes an active agent and a pressure sensitive adhesive composition.
  • the active agent is for controlled transdermal delivery to a substrate.
  • the pressure sensitive adhesive composition maintains contact with the substrate.
  • the pressure sensitive adhesive composition includes the reaction product of a pressure sensitive adhesive and a silicon- containing capping agent.
  • the pressure sensitive adhesive is the reaction product of a silicone resin and a silicone polymer.
  • the silicon-containing capping agent comprises acrylate or methacrylate functionality.
  • the particular pressure sensitive adhesive composition utilized in the transdermal drug delivery system of the present invention improves a rate at which the active agent is released from the system for delivery to the substrate, i.e., improves the release rate. As a result of this improvement in the release rate, the total amount of the active agent that is ultimately released and delivered to the substrate is improved. Due to the improved release rate and the improved total delivery of the active agent, it is contemplated that less active agent in the system and/or a smaller size of the system are required which may result in significant cost savings.
  • an additional advantage associated with this invention is that the particular silicon-containing capping agent used in the composition effectively reduces an amount of residual silanol content in the pressure sensitive adhesive as compared to the amount of residual silanol content in conventional silicone pressure sensitive adhesives.
  • the stability of the composition and of the transdermal drug delivery system is improved and adherence between the system and the substrate is maintained, which is obviously an attractive feature in transdermal drug delivery systems.
  • Figure 1 is a line graph illustrating a release rate of 2% niacinamide in ⁇ g/cm 2 at various levels of acrylate post capping as compared to two controls over a time period of from 1 to 24 hours;
  • Figure 2 is a line graph illustrating a release rate of 2% niacinamide in ⁇ g/cm 2 at various levels of acrylate in situ capping as compared to two controls over a time period of from 1 to 24 hours;
  • Figure 3 is a line graph illustrating a release rate of 5% niacinamide in ⁇ g/cm 2 at various levels of acrylate post capping as compared to two controls over a time period of from 1 to 24 hours;
  • Figure 4 is a line graph illustrating a release rate of 5% niacinamide in ⁇ g/cm 2 at various levels of acrylate in situ capping as compared to two controls over a time period of from 1 to 24 hours;
  • Figure 5 is a line graph illustrating a release rate of 10% niacinamide in ⁇ g/cm 2 at various levels of acrylate post capping as compared to two controls over a time period of from 1 to 24 hours;
  • Figure 6 is a line graph illustrating a release rate of 10% niacinamide in ⁇ g/cm 2 at various levels of acrylate in situ capping as compared to two controls over a time period of from 1 to 24 hours;
  • Figure 7 is a line graph illustrating a release rate of 2% ketoconazole in ⁇ g/cm 2 at both 1% and 2.5% acrylate post capping as compared to two controls over a time period of from 1 to 24 hours;
  • Figure 8 is a line graph illustrating a release rate of 5% ketoconazole in ⁇ g/cm 2 at both 1% and 2.5% acrylate post capping as compared to two controls over a time period of from 1 to 24 hours; and [0021] Fig ⁇ re 9 is a line graph illustrating a release rate of 10% ketoconazole in ⁇ g/cm 2 at both 1% and 2.5% acrylate post capping as compared to two controls over a time period of from 1 to 24 hours.
  • a transdermal drug delivery system includes an active agent and a pressure sensitive adhesive composition. Both the active agent and the pressure sensitive adhesive composition are described in detail below. As those skilled in the art appreciate, the system is structural and can be in many forms including, but not limited to, patches, films, multi-layer dressings, reservoir systems, and combinations thereof.
  • the active agent is in the system for controlled transdermal delivery to a substrate. It is also possible, but not required, for the system to include a backing layer for supporting the pressure sensitive adhesive composition, and/or a release liner for protecting the pressure sensitive adhesive composition and/or the active agent prior to the controlled transdermal delivery of the active agent to the substrate.
  • One preferred application of the transdermal drug delivery system of the present invention is to treat a user, or patient, with the active agent. As a result, the substrate is typically the skin of the user and, in this preferred application, the user applies and wears the system on their skin.
  • the active agent can be any component suitable for transdermal delivery to a substrate.
  • Suitable active agents include, but are not limited to, those active agents disclosed and described in United States Patent No. 5,474,783 to Miranda et al., the disclosure of which is incorporated by reference herein in its entirety.
  • active agents include, but are not limited to, cardioactive medications, androgenic steroids, estrogens, hormones, progestational agents, drugs having an action on the central nervous system, nutritional agents, anti-inflammatory agents, antihistamines, respiratory agents, sympathomimetics, miotics, cholinergic agonists, antimuscarinic or muscarinic cholinergic blocking agents, mydriatics, psychicenergizers, anti-infectives, dermatological agents, humoral agents, antispasmodics, antidepressant drugs, antidiabetic, anorectic drugs, anti-allergenics, tranquilizers, antipsychotics, decongestants, antipyretics, antimigrane agents, drugs for treating nausea and vomiting, anti-malarials, anti-ulcerative agents, peptides, drugs for Parkinson's disease, drugs for spasticity, drugs for acute muscle spasms, anti-estrogen, anti-hormone agents, therapeutic agents, and combinations thereof.
  • active agents outlined above that are suitable for implementation as the active agent in the present invention include:
  • Cardioactive medications illustratively, organic nitrates such as nitroglycerin, isosorbide dinitrate and, isosorbide mononitrates; quinidine sulfate; procainamide; thiazides such as bendroflumethiazide, chlorothiazide, and hydrochlorothyazide; nifedipine; nicardipine; adrenergic blocking agents, such as timolol, and propranolol; verapamil; diltiazem; captopril; clonidine and prazosin;
  • organic nitrates such as nitroglycerin, isosorbide dinitrate and, isosorbide mononitrates
  • quinidine sulfate quinidine sulfate
  • procainamide thiazides such as bendroflumethiazide, chlorothiazide, and hydrochlorothyazide
  • Androgenic steroids such as testosterone, methyltestosterone and fluoxymesterone
  • Estrogens such as, conjugated estrogens, esterif ⁇ ed estrogens, quinestrol, estropipate, 17 ⁇ -estradiol, 17 ⁇ -estradiol valerate, equilin, mestranol, estrone, estriol, 17 ⁇ - ethinyl estradiol, and diethylstilbestrol;
  • Progestational agents such as progesterone, 19-norprogesterone, norethindrone, norethindrone acetate, melengestrol, chlormadinone, ethisterone, medroxyprogesterone acetate, hydroxyprogesterone caproate, ethynodiol diacetate, norethynodrel, 17-alpha-hydroxyprogesterone, dydrogesterone, dimethisterone, ethinylestrenol, norgestrel, demegestone, promegestone, and megestrol acetate;
  • Drugs having an action on the central nervous system for example sedatives, hyponotics, antianxiety agents, analgesics and anesthetics, such as chloral, buprenorphine, naloxone, haloperidol, fluphenazine, pentobarbital, phenobarbital, secobarbital, codeine, lidocaine, tetracaine, dyclonine, dibucaine, cocaine, procaine, mepivacaine, bupivacaine, etidocaine, prilocaine, benzocaine, fentanyl, and nicotine;
  • analgesics and anesthetics such as chloral, buprenorphine, naloxone, haloperidol, fluphenazine, pentobarbital, phenobarbital, secobarbital, codeine, lidocaine, tetracaine, dyclonine, dibucaine, cocaine, procaine,
  • Nutritional agents such as vitamins (e.g. niacinamide), essential amino acids and essential fats;
  • Anti-inflammatory agents such as hydrocortisone, cortisone, dexamethasone, fluocinolone, triamcinolone, medrysone, prednisolone, flurandrenolide, prednisone, halcinonide, methylprednisolone, fludrocortisone, corticosterone, paramethasone, betamethasone, ibuprofen, naproxen, fenoprofen, fenbufen, flurbiprofen, acetaminophen, indoprofen, ketoprofen, suprofen, indomethacin, piroxicam, aspirin, salicylic acid, diflunisal, methyl salicylate, phenylbutazone, sulindac, mefenamic acid, meclofenamate sodium, naproxen, and the like;
  • External analgesics such as camphor, menthol, capsicum extract, frankincense, green tea, juniper tea, and caffeine;
  • Antihistamines such as diphenhydramine, dimenhydrinate, perphenazine, triprolidine, pyrilamine, chlorcyclizine, promethazine, carbinoxamine, tripelennamine, brompheniramine, hydroxyzine, cyclizine, meclizine, terrenadine, and chlorpheniramine;
  • Respiratory agents such as theophylline and Beta-adrenergic agonists such as albuterol, terbutaline, metaproterenol, ritodrine, carbuterol, fenoterol, quinterenol, rimiterol, solmefamol, soterenol, and tretoquinol;
  • Sympathomimetics such as dopamine, norepinephrine, phenylpropanolamine, phenylephrine, pseudoephedrine, amphetamine, propylhexedrine and epinephrine;
  • Miotics such as pilocarpine, and the like
  • Cholinergic agonists such as choline, acetylcholine, methacholine, carbachol, bethanechol, pilocarpine, muscarine, and arecoline;
  • Antimuscarinic or muscarinic cholinergic blocking agents such as atropine, scopolamine, homatropine, methscopolamine, homatropine methylbromide, methantheline, cyclopentolate, tropicamide, propantheline, anisotropine, dicyclomine, and eucatropine;
  • Mydriatics such as atropine, cyclopentolate, homatropine, scopolamine, tropicamide, eucatropine and hydroxyamphetamine;
  • Psychicenergizers such as 3-(2-aminopropy)indole, 3-(2- ammobutyl)indole, and the like;
  • Anti-infectives such as antibiotics, including penicillin, tetracycline, chloramphenicol, sulfacetamide, sulfadiazine, sulfamethoxazole and sulf ⁇ soxazole; antivirals, including idoxuridine; antibacterials, such as erythromycin and clarithromycin; anti-fungals, such as ketoconazole, and other anti-infectives including nitrofurazone, cyclopirox, terbafine, witch hazel, and the like;
  • Dermatological agents such as retinoids; vitamins C and E; benzoyl peroxide and dapsone;
  • Humoral agents such as the prostaglandins, natural and synthetic, for example PGEl, PGE 2-al ⁇ ha, and PGF 2-al ⁇ ha, and the PGEl analog misoprostol;
  • Antispasmodics such as atropine, methantheline, papaverine, cinnamedrine, and methscopolamine;
  • Antidepressant drugs such as paroxetine, phenelzine, tranylcypromine, imipramine, amitriptyline, trimipramine, doxepin, desipramine, nortriptyline, protriptyline, amoxapine, maprotiline, and trazodone;
  • Anti-diabetics such as insulin, and anticancer drugs such as tamoxifen and methotrexate;
  • Anorectic drugs such as, dextroamphetamine, methamphetamine, phenylpropanolamine, fenfluramine, diethylpropion, mazindol, and phentermine.
  • Anti-allergenics such as antazoline, methapyrilene, chlorpheniramine, pyrilamine and pheniramine;
  • Tranquilizers such as reserpine, chlorpromazine, and antianxiety benzodiazepines such as alprazolam, chlordiazepoxide, clorazeptate, halazepam, oxazepam, prazepam, clonazepam, flurazepam, triazolam, lorazepam and diazepam;
  • Antipsychotics such as thiopropazate, chlorpromazine, triflupromazine, mesoridazine, piperacetazine, thioridazine, acetophenazine, fluphenazine, perphenazine, trifluoperazine, chlorprothixene, thiothixene, haloperidol, bromperidol, loxapine, and molindone;
  • Decongestants such as phenylephrine, ephedrine, naphazoline, tetrahydrozoline;
  • Antipyretics such as aspirin, salicylamide, and the like;
  • Antimigrane agents such as dihydroergotamine and pizotyline
  • Drugs for treating nausea and vomiting such as chlorpromazine, perphenazine, prochlorperazine, promethazine, triethylperazine, triflupromazine, and trimeprazine;
  • Anti-malarials such as the 4-aminoquinolines, alphaaminoquinolines, chloroquine, and pyrimethamine;
  • Anti-ulcerative agents such as misoprostol, omeprazole, and enprostil;
  • Peptides such as growth releasing factor
  • Drugs for Parkinson's disease, spasticity, and acute muscle spasms such as levodopa, carbidopa, amantadine, apomorphine, bromocriptine, selegiline (deprenyl), trihexyphenidyl hydrochloride, benztropine mesylate, procyclidine hydrochloride, baclofen, diazepam, and dantrolene; and
  • Anti-estrogen or hormone agents such as tamoxifen or human chorionic gonadotropin.
  • the particular active agent is not limited to those recited above.
  • suitable active agents for use in the systems will be apparent to those skilled in the art (See, for example, pages 149-217 of Yie Chien's treatise entitled "Novel Drug Delivery Systems” which is Volume 14 of Drugs and the Pharmaceutical Sciences, Marcel Dekker, Inc., New York, NY. 10016 (1982)).
  • the active agents can be present in the system in different forms, depending on which form yields optimum delivery characteristic, such as the release rate and the total amount released as described below.
  • the drug can be in its free base or acid form, or in the form of salts, esters, or any other pharmacologically acceptable derivatives, or even as components of molecular complexes.
  • the amount of the active agent incorporated into the system varies depending on many factors including, but not limited to, the particular active agent, the desired therapeutic effect, and the time span for which the system is to provide therapy.
  • the passage of the active agent through the skin is the rate- limiting step in transdermal delivery.
  • the amount of the active agent and the rate of release are typically selected so as to provide transdermal delivery characterized by a zero order time dependency for a prolonged period of time.
  • the minimum amount of active agent in the system is selected based on the amount of active agent which passes through the skin, or other substrate, in the time span for which the system is to provide therapy.
  • the amount of active agent in the system varies from about 0.1% up to about 60% by weight of the system, more preferably from about 0.3% up to about 50% by weight of the system, and for the lower drug doses permitted by this invention, most preferably from about 1.0% up to about 30% by weight of the system.
  • the weight of the system is, at a minimum, the combined weight of the active agent and the pressure sensitive adhesive composition.
  • the active agent is most typically disposed in the pressure sensitive adhesive composition.
  • the active agent and said pressure sensitive adhesive composition may coexist in the system in discrete layers. That is, in certain embodiments, the active agent is not disposed, or directly incorporated, into the pressure sensitive adhesive composition.
  • the transdermal drug delivery system can also contain other agents known to accelerate the delivery of the active agent through the skin or other substrate.
  • agents are also referred to in the art as skin-penetration or permeation enhancers, accelerants, adjuvants, and sorption promoters, and are collectively referred herein simply as "enhancers”.
  • enhancers includes those with diverse mechanisms of action including those which have the function of improving the solubility and diffusibility of the active agent within the pressure sensitive adhesive composition and those which improve percutaneous absorption, for example, by changing the ability of the stratum corneum to retain moisture, softening the skin, improving the skin's permeability, acting as penetration assistants or hair-follicle openers or changing the state of the skin including the boundary layer.
  • Some of these enhancers have more than one mechanism of action, but in essence they serve to enhance the delivery of the active agent to the substrate.
  • enhancers are polyhydric alcohols such as dipropylene glycol, propylene glycol, and polyethylene glycol which enhance solubility of the active
  • oils such as olive oil, squalene, and lanolin; fatty ethers such as cetyl ether and oleyl ether; fatty acid esters such as isopropyl myristate which enhance diffusibility of the active agent; urea and urea derivatives such as allantoin which affect the ability of keratin to retain moisture; polar solvents such as dimethyldecylphosphoxide, methyloctylsulfoxide, dimethyllaurylamide, dodecylpyrrolidone, isosorbitol, dimethylacetonide, dimethylsulfoxide, decylmethylsulfoxide, and dimethylformamide which affect keratin permeability; salicylic acid which softens the keratin; amino acids which are penetration assistants; benzyl nicotinate which is a hair follicle opener; and higher molecular weight aliphatic surfactants such as lauryl sulfate salts
  • agents include oleic and linoleic acids, ascorbic acid, panthenol, butylated hydroxytoluene, tocopherol, tocopheryl acetate, tocopheryl linoleate, propyl oleate, and isopropyl palmitate.
  • a plasticizer or tackifying agent may be incorporated into the system, preferably into the composition, to improve the adhesive characteristics of the pressure sensitive adhesive composition.
  • a tackifying agent is particularly useful in those embodiments in which the active agent does not plasticize the silicone polymer.
  • Suitable tackifying agents are those known in the art including: (1) aliphatic hydrocarbons; (2) mixed aliphatic and aromatic hydrocarbons; (3) aromatic hydrocarbons; (4) substituted aromatic hydrocarbons; (5) hydrogenated esters; (6) polyterpenes; and (7) hydrogenated wood rosins.
  • the tackifying agent employed is preferably compatible with the other components in the composition.
  • Suitable tackifying agents are silicone fluid (e.g., Q7-9120 Silicone Fluid, available from Dow Corning Corporation, Midland, Michigan) or mineral oil. Silicone fluid is useful for blends comprising polysiloxane as a major component. In other embodiments, where a synthetic rubber, for example, is a major component, mineral oil is a useful tackifying agent.
  • silicone fluid e.g., Q7-9120 Silicone Fluid, available from Dow Corning Corporation, Midland, Michigan
  • mineral oil is a useful tackifying agent.
  • active agents such as vasodilator nitroglycerin
  • plasticizers for active agents which are not readily soluble in the in the components, a co-solvent for the active agent and other components can be added.
  • Co-solvents such as lecithin, retinol derivatives, tocopherol, dipropylene glycol, triacetin, propylene glycol, saturated and unsaturated fatty acids, mineral oil, silicone fluid, alcohols, butyl benzyl phthalate, and the like are useful in the practice of the instant invention depending on the solubility of the active agent in the composition.
  • the pressure sensitive adhesive composition maintains contact between the system and the substrate.
  • the pressure sensitive adhesive composition also referred to throughout simply as the composition, is an adhesive that possesses sufficient tack and cohesive strength so that it can be adhered with mild pressure and also removed and the adhered again (to the same or another).
  • the pressure sensitive adhesive composition more specifically includes the reaction product of a pressure sensitive adhesive and a silicon-containing capping agent.
  • the silicon-containing capping agent and the pressure sensitive adhesive reaction to form the composition.
  • the silicon-containing capping agent comprises acrylate or methacrylate functionality and is described additionally below.
  • the pressure sensitive adhesive is preferably present in the composition in an amount of from 85.0 to 99.9 parts by weight based on weight % solids of the pressure sensitive adhesive
  • the silicon-containing capping agent is preferably present in the composition in an amount of from 0.1 to 15 parts by weight based on weight % solids of the pressure sensitive adhesive. More preferably, the pressure sensitive adhesive is present in the composition in an amount of from 85.0 to 99.8 parts by weight based on weight % solids of the pressure sensitive adhesive
  • the silicon-containing capping agent is present in the composition in an amount of from 0.2 to 15 parts by weight based on weight % solids of the pressure sensitive adhesive.
  • the pressure sensitive adhesive is present in the composition in an amount of from 90.0 to 99.25 parts by weight based on weight % solids of the pressure sensitive adhesive, and the silicon-containing capping agent is more preferably present in the composition in an amount of from 0.75 to 10 parts by weight based on weight % solids of the pressure sensitive adhesive.
  • the pressure sensitive adhesive is present in the composition is present in the composition in an amount of from 85.0 to 99.5 parts by weight based on weight % solids of the pressure sensitive adhesive, and the silicon-containing capping agent is present in the composition in an amount of from 0.5 to 15 parts by weight based on weight % solids of the pressure sensitive adhesive.
  • the pressure sensitive adhesive is present in the composition in an amount of from 85.0 to 99.25 parts by weight based on weight % solids of the pressure sensitive adhesive, and the silicon-containing capping agent is present in the composition in an amount of from 0.75 to 15 parts by weight based on weight % solids of the pressure sensitive adhesive.
  • the pressure sensitive adhesive has a weight % solids of from 50 to 65%, more typically 60%.
  • the pressure sensitive adhesive includes the reaction product of a silicone resin and a silicone polymer.
  • the silicone resin reacts in an amount of from 40 to 70 parts by weight to form the pressure sensitive adhesive
  • the silicone polymer reacts in an amount of from 30 to 60 parts by weight to form the pressure sensitive adhesive. Both of these parts by weight are based on 100 parts by weight of the pressure sensitive adhesive.
  • the pressure sensitive adhesive may comprise a catalytic amount of a condensation catalyst.
  • a condensation catalyst Those skilled in the art readily appreciate the wide variety of catalysts that can be used to catalyze condensation between the silicone resin and the silicone polymer. Typically, these catalysts are simple bases or acids.
  • One, non-limiting examples of such a condensation catalyst is potassium hydroxide.
  • the catalytic amount of the condensation catalyst varies based on a wide variety of factors including, but not limited to, the particular condensation catalyst, the particular silicone resin, and the particular silicone polymer used.
  • silicone resins and silicone polymers include, but are not limited to, those disclosed and described in United States Patent No. 6,337,086 to Kanios et al., the disclosure of which is incorporated by reference herein in its entirety.
  • a preferred silicone resin comprises a copolymer comprising triorganosiloxy units of the formula R 3 S SiO 1Z2 and tetrafunctional siloxy units of the formula SiO 4/2 in a ratio of about 0.6 to 0.9 triorganosiloxy units for each tetrafunctional siloxy unit, wherein each R 3 independently denotes a monovalent hydrocarbon radical having from 1 to 6 carbon atoms, and a preferred silicone polymer comprises at least one polydiorganosiloxane comprising AR 3 SiO units terminated with endblocking TR 3 ASi01/2 units, wherein the polydiorganosiloxane has a viscosity of from about 100 centipoise to about 30,000,000 centipoise at 25 0 C, each A radical is independently selected from R 3 or halohydro-carbon radicals having from 1 to 6 carbon atoms, each T radical is independently selected from the group consisting of R 3 , OH, H or OR 4 , and each R 4 is
  • one type of pressure sensitive adhesive is made by: [0074] mixing (i) from 40 to 70 inclusive parts by weight of at least one resin copolymer containing silicon-bonded hydroxyl radicals and consisting essentially of units for each SiO 4 / 2 unit present, (ii) between about 30 and about 60 parts by weight of at least one polydiorganosiloxane comprising AR 3 SiO units terminated with endblocking TR 3 ASi01/2 units, wherein the polydiorganosiloxane has a viscosity of from about 100 centipoise to about 30,000,000 centipoise at 25 0 C and each R 3 is a monovalent organic radical selected from the group consisting of hydrocarbon radicals of from 1 to 6 inclusive carbon atoms, each A radical is independently selected from R 3 or halohydrocarbon radicals having from 1 to 6 inclusive carbon atoms, each T radical is independently selected from the group consisting of R 3 ,
  • Additional organosilicon endblocking agents can be used in conjunction with the silicon-containing capping agent or agents (iii) of the present invention.
  • additional organosilicon endblocking agents also referred to herein as a second silicon-containing capping agent, are described additionally below.
  • the pressure sensitive adhesives are made in accordance with the present invention using from 40 to 70 inclusive parts by weight of silicone copolymer resins (i) and from 30 to 60 parts by weight of polydiorganosiloxane (ii) of the type which have been used in the past to make such adhesives. More preferred are compositions employing from 50 to 65 parts by weight of resin copolymer (i) and from 35 to 50 parts by weight of polydiorganosiloxane (ii).
  • the silicone resin copolymers (i) are well-known materials. They contain silicon-bonded hydroxyl radicals in amounts which typically range from about 1 to 4 weight percent of silicon-bonded hydroxyl radicals and comprise triorganosiloxy units of the formula R 3 3 SiOi /2 and tetrafunctional siloxy units of the formula SiO 4/2 in a mole ratio of from 0.6 to 0.9 R 3 B SiO 1 Z 2 units for each SiO 4/2 unit present. Blends of two or more such copolymers may also be used.
  • resin copolymers are generally benzene-soluble resinous materials which are typically solids at room temperature and are prepared as, and usually, but not necessarily used as, a solution in an organic solvent.
  • Typical organic solvents used to dissolve resin copolymer (i) include benzene, toluene, xylene, methylene chloride, perchloroethylene, naphtha mineral spirits and mixtures of these.
  • Resin copolymer (i) consists essentially of from 0.6 to 0.9 R ⁇ SiO units for every SiO 4/2 unit in the copolymer. There may also be a few mole percent of R 3 2 Si0 units present in the copolymer provided that the presence of such units does not cause the ultimate product of this process to lose its ability to function as a PSA.
  • R 3 denotes, independently, a monovalent hydrocarbon radical having from 1 to 6 inclusive carbon atoms such as methyl, ethyl, propyl, isopropyl, hexyl, cyclohexyl, vinyl, allyl, propenyl and phenyl.
  • the R 3 3 SiOi/2 units are Me 3 SiOy 2 units anoVor Me 2 R 1 SiOy 2 units wherein is R 1 is a vinyl ("Vi") or phenyl ("Ph") radical. More preferably, no more than 10 mole percent of the R 3 Si0y 2 units present in resin copolymer (i) are Me 2 R SiOy 2 units and the remaining units are Me 3 SiOy 2 units where each R 2 is a vinyl radical. Most preferably, the R 3 3 Si0y 2 units are Me 3 SiOy 2 units.
  • the mole ratio of R 3 3 Si0y 2 and SiO 4/2 units can be determined simply from a knowledge of the identity of the R 3 radicals in the R 3 3 SiOy 2 units and the percent carbon analysis of the resin copolymer.
  • the carbon analysis has a value of from 19.8 to 24.4 percent by weight.
  • Resin copolymer (i) may be prepared according to Daudt et al., U.S. Pat.
  • a mixture of suitable hydrolyzable silanes free of R 3 radicals may be cohydrolyzed and condensed.
  • a suitable silylating agent such as hexamethyldisilazane or divinyltetramethyldisilazane, to reduce the silicon-bonded hydroxyl content of the copolymer product to less that 1 percent by weight.
  • the resin copolymers employed contain from about 1 to 4 weight percent of silicon-bonded hydroxyl radicals.
  • Ingredient (ii) is also a well-known material and is one or more polydiorganosiloxanes comprising AR 3 SiO units terminated with endblocking TR 3 ASi01/2 units, each of which polydiorganosiloxanes has a viscosity of from 100 centipoise to 30,000,000 centipoise at 25 0 C (100 millipascal-seconds to 30,000 pascal seconds (Pa.s) where 1 centipoise equals 1 millipascal second).
  • viscosity is directly related to the average number of diorganosiloxane units present for a series of polydiorganosiloxanes of varying molecular weights which have the same endblocking units.
  • Polydiorganosiloxanes having a viscosity of from about 100 to 100,000 centipoise at 25 0 C range from fluids to somewhat viscous polymers.
  • These polydiorganosiloxanes are preferably prereacted with resin copolymer (i) prior to condensation in the presence of endblocking agent (iii) to improve the tack and adhesion properties of the resulting PSA as will be further described.
  • Polydiorganosiloxanes having viscosities in excess of 100,000 centipoise can typically be subjected to the condensation/endblocking step (II) of the present invention without prereaction.
  • Polydiorganosiloxanes having viscosities in excess of 1,000,000 centipoise are highly viscous products often referred to as gums and the viscosity is often expressed in terms of a Williams Plasticity value (polydimethylsiloxane gums of about 10,000,000 centipoise viscosity typically have a Williams Plasticity Value of about 50 mils (1.27 mm) or more at 25°C).
  • the polydiorganosiloxanes of (ii) consist essentially of AR 3 SiO units where each R 3 is as defined above.
  • Each A radical is selected from radicals such as R 3 or halohydrocarbon radicals of from 1 to 6 inclusive carbon atoms such a chloromethyl, chloropropyl, l-chloro-2-methylpropyl, 3,3,3-trifluoropropyl and F 3 C(CH 2 )S radicals.
  • the polydiorganosiloxane can contain Me 2 SiO units, PhMeSiO units, MeViSiO units, Ph 2 SiO units, methylethylsiloxy units, 3,3,3-trifluoropropyl units and 1-chloro, 2- methylpropyl units and the like.
  • the AR 3 SiO units are selected from the group consisting of R 3 2 Si0R 3 R 4 Si0 units, Ph 2 SiO units and combinations of both where R 3 and R 4 are as above, at least 50 mole percent of the R 4 radicals present in the polydiorganosiloxane (ii) are methyl radicals and no more than 50 mole percent of the total moles of AR 3 SiO units present in each polydiorganosiloxane of (ii) are Ph 2 SiO units.
  • no more than 10 mole percent of the AR 3 SiO units present in each polydiorganosiloxane (ii) are MeR 3 SiO units where R 3 is as above defined and the remaining AR 3 SiO units present in each polydiorganosiloxane are Me 2 SiO units.
  • each polydiorganosiloxane (ii) is terminated with endblocking units of the unit formula TR 3 ASiO 1Z2 where R 3 and A are as defined above and each T radical is R 3 , OH, H or OR 4 radicals where each R 4 is an alkyl radical of from 1 to 4 inclusive carbon atoms such as methyl, ethyl, n-propyl, and isobutyl radicals, H, OH and OR 4 provide a site for reaction with the acrylate or methacrylate functional silicon-containing capping agent of the present invention (iii) and also provide a site for condensation with other such radicals on polydiorganosiloxanes (ii) or with the silicon-bonded hydroxyl groups present in resin copolymer (i).
  • polydiorganosiloxanes where T is OH are most preferred because the polydiorganosiloxane (ii) can then readily copolymerize with the resin copolymer (i).
  • an appropriate catalyst such as HCl, which is generated when chlorosilanes are used, or ammonia, which is generated when organosilazanes are used as endblocking agents
  • triorganosiloxy e.g., R 3 3 SiOi/ 2 such as (CH 3 ) 3 SiOj/2 or CH 2 CH(CHs) 2 SiOy 2
  • R 3 3 SiOi/ 2 such as (CH 3 ) 3 SiOj/2 or CH 2 CH(CHs) 2 SiOy 2
  • the cleavage exposes a silicon-bonded hydroxyl radical which can then condense with silicon-bonded hydroxyl radicals in the copolymer resin, with endblocking triorganosilyl units or with other polydiorganosiloxanes containing H, OH or OR 4 radicals or silicon-bonded hydroxyl radicals exposed by cleavage reactions. Mixtures of polydiorganosiloxanes containing different substituent radicals may also be used.
  • the pressure sensitive adhesive comprises a concentration of silicon bonded hydroxyl groups (i.e., silanols) and the silicon-containing capping agent is further defined as an endblocking agent.
  • the terms endblocking agents and capping agents are used interchangeably throughout the art and in the subject description.
  • the endblocking agent and the pressure sensitive adhesive are condensed to produce the pressure sensitive adhesive composition. More specifically, the endblocking agent reacts with the concentration of silicon bonded hydroxyl groups to cap the pressure sensitive adhesive.
  • the concentration of silanols in the composition is from 5,000 to 15,000, more typically from 8,000 to 13,000, ppm.
  • the endblocking agent can be introduced to react with the pressure sensitive adhesive after the pressure sensitive adhesive has already been formed, i.e., after the silicone resin and the silicone polymer which make up the pressure sensitive adhesive have reacted.
  • This technique may be generally referred to as post capping.
  • the endblocking agent can be reacted in situ with the silicone resin and the silicone polymer such that the endblocking agent is present as the silicone resin and the silicone polymer are reacting. That is, the endblocking agent is introduced either prior to or during the reaction of the silicone resin and the silicone polymer. In either case, the silicone resin and the silicone polymer are reacted in the presence of the silicon- containing capping agent.
  • the silicon-containing capping agent is selected from the group of acrylate functional silanes, acrylate functional silazanes, acrylate functional disilazanes, acrylate functional disiloxanes, methacrylate functional silanes, methacrylate functional silazanes, methacrylate functional disilazanes, methacrylate functional disiloxanes, and combinations thereof.
  • the endblocking agent may be described to be of the general formula (XYR 2 Si) 2 D wherein X is a monovalent radical of the general formula AE- where E is -O- or -NH- and A is an acryl group or a methacryl group, Y is a divalent alkylene radical having from 1 to 6 carbon atoms, R is a methyl or a phenyl radical, and D is a divalent or a trivalent organic hydrolyzable radical.
  • D is -O- or -NH-.
  • this particular endblocking agent is selected from the group of Bis(3- methacryloxypropyl)tetramethyldisilazane, Bis(3-acryloxypropyl)tetramethyldisilazane, Bis(3 -methacryloxypropyl)tetramethyldisiloxane, Bis(3 -acryloxypropy 1) tetramethyldisiloxane, and combinations thereof.
  • the acryl group provides the silicon-containing capping agent with acrylate functionality and the methacryl group provides the silicon-containing capping agent with the methacrylate functionality.
  • the acryl group can be generically represented as
  • the methacryl group can be generally represented as
  • the endblocking agent may be described to be of the general formula XYR' b SiZ 3-b wherein X is a monovalent radical of the general formula AE- where E is -O- or -NH- and A is an acryl group or a methacryl group as set forth above, Y is a divalent alkylene radical having from 1 to 6 carbon atoms, R' is a methyl or a phenyl radical, Z is a monovalent hydrolyzable organic radical or a halogen, and b is 0, 1, or 2.
  • the monovalent hydrolyzable organic radical is of the general formula R" O- where R" is an alkylene radical.
  • this particular endblocking agent is selected from the group of 3-methacryloxypropyldimethylchlorosilane, 3- methacryloxypropyldichlorosilane, 3-methacryloxypropyltrichlorosilane, 3- methacryloxypropyldimethylmethoxysilane, 3 - methacryloxypropylmethyldimethoxysilane, 3 -methacryloxypropyltrimethoxysilane, 3 - methacryloxypropyldimethylethoxysilane, 3-methacryloxypropylmethyldiethoxysilane, 3-methacryloxypropyltriethoxysilane, (methacryloxymethyl)dimethylmethoxysilane, (metliacryloxymethyl)metliyldimethoxysilane, (methacryloxymethyl)tximethoxysilane, (methacryloxymethyl)dimetliyletlioxysilane, (methacryloxymethyl)
  • the second silicon-containing capping agent can be used in conjunction with the silicon-containing capping, or endblocking, agent of the present invention.
  • This second silicon-containing capping agent is distinguishable from the silicon-containing capping agent in that the second silicon-containing capping agent is free of acrylate and methacrylate functionality.
  • the second silicon- containing capping agent, an organosilicon endblocking agent is along with the silicon- containing capping agent and the pressure sensitive adhesive a reaction product that forms the composition.
  • the second silicon-containing capping agent is capable of generating an endblocking triorganosilyl unit.
  • Suitable second silicon-containing capping agents include, but are not limited to, those described in United States Patent No. 6,337,086 to Kanios et al., the disclosure of which has already been incorporated by reference in its entirety.
  • Two of the active agents described above are niacinamide and ketoconazole.
  • the active agent comprises niacinamide in amount of 1.5 to 2.5, preferably 2, parts by weight based on 100 parts by weight of the system and the silicon- containing capping agent is post capped
  • the niacinamide is released from the system at a rate of 50 to 350, preferably 75 to 300, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 1 and spans acrylate capping levels from 0.5 to 5% by weight solids of PSA.
  • the active agent comprises niacinamide in amount of 1.5 to 2.5, preferably 2, parts by weight based on 100 parts by weight of the system and the silicon-containing capping agent is capped in situ
  • the niacinamide is released from the system at a rate of 50 to 500, preferably 65 to 450, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 2 and spans acrylate capping levels from 0.5 to 5% by weight solids PSA.
  • the active agent comprises niacinamide in amount of 4 to 6, preferably 5, parts by weight based on 100 parts by weight of the system and the silicon- containing capping agent is post capped
  • the niacinamide is released from the system at a rate of 170 to 800, preferably 200 to 750, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 3 and spans acrylate capping levels from 0.5 to 5% by weight solids of PSA.
  • the active agent comprises niacinamide in amount of 4 to 6, preferably 5, parts by weight based on 100 parts by weight of the system and the silicon-containing capping agent is capped in situ
  • the niacinamide is released from the system at a rate of 150 to 1000, preferably 200 to 875, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 4 and spans acrylate capping levels from 0.5 to 5% by weight solids of PSA.
  • the active agent comprises niacinamide in amount of 7 to 13, preferably 10, parts by weight based on 100 parts by weight of the system and the silicon- containing capping agent is post capped
  • the niacinamide is released from the system at a rate of 250 to 1300, preferably 300 to 1250, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 5 and spans acrylate capping levels from 0.5 to 5% by weight solids of PSA.
  • the active agent comprises niacinamide in amount of 7 to 13, preferably 10, parts by weight based on 100 parts by weight of the system and the silicon-containing capping agent is capped in situ
  • the niacinamide is released from the system at a rate of 300 to 1500, preferably 350 to 1400, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 6 and spans acrylate capping levels from 0.5 to 5% by weight solids of PSA.
  • the active agent comprises ketoconazole in amount of 1.5 to 2.5, preferably 2, parts by weight based on 100 parts by weight of the system and the silicon- containing capping agent is post capped
  • the ketoconazole is released from the system at a rate of 5 to 90, preferably 7 to 80, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 7 and includes acrylate capping levels of 1% and 2.5% by weight solids of PSA.
  • the ketoconazole is released from the system at a rate of from 4 to 90, preferably 6 to 80, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 8 and includes acrylate capping levels of 1% and 2.5% by weight solids of PSA.
  • the active agent comprises ketoconazole in amount of 7 to 13, preferably 10, parts by weight based on 100 parts by weight of the system and the silicon-containing capping agent is post capped
  • the ketoconazole is released from the system at a rate of 6 to 90, preferably 7 to 80, ⁇ g/cm 2 over a time period of 1 to 24 hours.
  • This particular release rate is illustrated in Figure 9 and includes acrylate capping levels of 1% and 2.5% by weight solids of PSA.
  • Control Example 1 also referred to below as PSA 1, is a conventional, i.e., uncapped, silicone PSA that is produced through a condensation reaction of a silanol endblocked polydimethylsiloxane (PDMS) with a silicate resin and that is 60% solids in ethyl acetate.
  • PDMS silanol endblocked polydimethylsiloxane
  • Control Example 2 is an amine-compatible, silicone PSA that is produced through a condensation reaction of a silanol endblocked polydimethylsiloxane (PDMS) with a silicate resin and that is fully capped with trimethylsiloxy groups and is 60% solids in ethyl acetate.
  • PDMS silanol endblocked polydimethylsiloxane
  • HCl was immediate as indicated by pH paper color change. Material was allowed to mix overnight on a mixing wheel. The next day, 150 g of sodium bicarbonate was added to the material to aid in the neutralization of the HCl. Sample was allowed to mix overnight. The pressure sensitive adhesive composition was then pressure filtered the next day to remove particulate.
  • HCl was immediate as indicated by pH paper color change. Material was allowed to mix overnight on a mixing wheel. The next'day, 150 g of sodium bicarbonate was added to the material to aid in the neutralization of the HCl. Sample was allowed to mix overnight. The pressure sensitive adhesive composition was then pressure filtered the next day to remove particulate.
  • HCl was immediate as indicated by pH paper color change. Material was allowed to mix overnight on a mixing wheel. The next day, 126 g of sodium bicarbonate was added to the material to aid in the neutralization of the HCl. Sample was allowed to mix overnight. The pressure sensitive adhesive composition was then pressure filtered the next day to remove particulate.
  • HCl was immediate as indicated by pH paper color change. Material was allowed to mix overnight on a mixing wheel. The next day, 125 g of sodium bicarbonate was added to the material to aid in the neutralization of the HCl. Sample was allowed to mix overnight. The pressure sensitive adhesive composition was then pressure filtered the next day to remove particulate.
  • Example 5 Post Capping / 5.0% Acrylate capping by weight solids of PSA [00105] To a 32 ounce jar, 500.0 g of PSA 1 and 15.0 g of CA-I were added.
  • HCl was immediate as indicated by pH paper color change. Material was allowed to mix overnight on a mixing wheel. The next day, 100 g of sodium bicarbonate was added to the material to aid in the neutralization of the HCl. Sample was allowed to mix overnight. The pressure sensitive adhesive composition was then pressure filtered the next day to remove particulate.
  • Example 6 In Situ Capping / 0.5% Acrylate capping by weight solids of PSA [00106] 274.43 g of Resin-1 (71.79% solids solution in xylene comprising trimethylsiloxy and hydroxy end-blocked silicate resin in a three dimensional structure), 161.19 g of Polymer- 1 (hydroxy end-blocked polydimethylsiloxane with a viscosity of 13,500 cp at 25 0 C and non-volatile content minimum of 99%) and 162.58 g of xylene were blended together to yield a nominal 60% solids mixture. The mixture was placed into a glass reactor and 1.8 g of CA-2 were added to this mixture.
  • Resin-1 71.79% solids solution in xylene comprising trimethylsiloxy and hydroxy end-blocked silicate resin in a three dimensional structure
  • 161.19 g of Polymer- 1 hydroxy end-blocked polydimethylsiloxane with a viscosity of 13,500 cp at
  • the reactor was equipped with a bottom discharge, thermometer, nitrogen inlet, Dean-Starke trap, water- cooled condenser, a stirring paddle and a heating mantle. Under mixing and a nitrogen purge, the reactor was heated to 145°C. A condensation catalyst, anhydrous ammonia, was bubbled through the reaction mixture. As the material started to condense, water was collected as an azeotrope in the Dean-Starke trap. The reaction was continued for 4 hours at which time the addition of ammonia was discontinued. The mixture was allowed to continue to reflux at 145 0 C to remove any residual ammonia. The refluxing was complete when the solution pH was neutral. At that time, the heat was discontinued and the material, the pressure sensitive adhesive composition, was allowed to cool to less than 5O 0 C.
  • Example 7 In Situ Capping / 0.75% Acrylate capping by weight solids of PSA
  • the pressure sensitive adhesive composition of the present invention was prepared similar to the description above in Example 6, but containing a higher level of silicon-containing capping agent. 273.74 g of Resin-1, 160.79 g of Polymer- 1, 162.77 g of xylene, and 2.7 g of CA-2 were used to prepare the composition.
  • Example 8 - In Situ Capping / 1.0% Acrylate capping by weight solids of PSA
  • the pressure sensitive adhesive composition of the present invention was prepared similar to the description above in Example 6, but containing a higher level of silicon-containing capping agent.
  • Example 10 In Situ Capping / 5.0% Acrylate capping by weight solids of PSA
  • the pressure sensitive adhesive composition of the present invention was prepared similar to the description above in Example 6, but containing a higher level of silicon-containing capping agent. 262.01 g of Resin-1, 153.9 g of Polymer-1, 166.09 g of xylene, and 18.0 g of CA-2 were used to prepare the composition.
  • Example 11 - In Situ Capping / 1.0% Acrylate capping by weight solids of PSA
  • the pressure sensitive adhesive composition of the present invention was prepared similar to the description above in Example 6, but containing a higher level of silicon-containing capping agent.
  • Example 12 In Situ Capping / 2.5% Acrylate capping by weight solids of PSA [00112]
  • the pressure sensitive adhesive composition of the present invention was prepared similar to the description above in Example 6, but containing a higher level of silicon-containing capping agent. 268.95 g of Resin-1, 157.95 g of Polymer-1, 164.14 g of xylene, and 9.0 g of CA-3 were used to prepare the composition.
  • Example 13 In Situ Capping / 5.0% Acrylate capping by weight solids of PSA
  • the pressure sensitive adhesive composition of the present invention was prepared similar to the description above in Example 6, but containing a higher level of silicon-containing capping agent. 262.01 g of Resin-1, 153.9 g of
  • Polymer-1 166.09 g of xylene, and 18.0 g of CA-3 were used to prepare the composition.
  • the silicon-containing capping agent, CA-I is 3- methacryloxypropyldimethylchlorosilane commercially available from Gelest,
  • the silicon-containing capping agent, CA-2 is 3- methacryloxypropyltrimethoxysilane commercially available from Dow Corning
  • the silicon-containing capping agent, CA-3 is 3- methacryloxypropylmethyldimethoxysilane commercially available from Gelest.
  • Example 13 are known and were measured according to the following Test Procedures.
  • non- volatile contents were determined by placing 2-4 grams (A) of the particular Example in an aluminum foil dish and heating the sample for 1 hour at
  • NVC in percent, is equal to 100*B/A.
  • Samples were prepared as follows: The particular Example was cast directly on 2.0 mil thick polyester sheets with the appropriate casting bar to afford a final adhesive thickness of 1.0 mil. Once cast, the sample was dried in an air-circulating oven at HO 0 C for 5 minutes. After cooling, the samples were cut into 1 inch wide strips. The strips were then applied to a stainless steel panel by rolling with 2 passes with a 4.5# steel roller. After equilibrating for 20 minutes on the stainless steel panel, the samples were then tested for 180 Degree Peel Adhesion at a rate of 12 inches per minute. Testing for 180 Degree Peel Adhesion is further understood by those skilled in the art with particular reference to ASTM D3330 and/or PSTC (Pressure Sensitive Tape Council)- 1, which are typical standards for the 180 Degree Peel Adhesion.
  • ASTM D3330 and/or PSTC Pressure Sensitive Tape Council
  • exemplary transdermal drug delivery systems were formed using niacinamide and ketoconazole as active agents.
  • the niacinamide was loaded into the Control Examples and into the particular Examples of the invention at levels of 2% ( Figures 1 and 2), 5% ( Figures 3 and 4), and 10% ( Figures 5 and 6).
  • Figures 1, 3, and 5 involve post capping of the capping agent
  • Figures 2, 4, and 6 involve in situ capping of the capping agent.
  • the ketoconazole was loaded into the Control Examples and into Examples 3 and 4 of the invention at levels of 2% ( Figure 7), 5% ( Figure 8), and 10% (Figure 9).
  • Figures 7-9 all involve post capping of the capping agent. Loading of the respective active agent is based on the total weight of the system.
  • samples were prepared by thoroughly mixing the respective active agent into the particular Example prior to casting and drying as generally described above under the ISO Degree Peel Adhesion Test Procedure.
  • the release rate testing was performed using Franz static diffusion cells with the receptor fluid being specific for each drug.
  • the receptor fluid was 0.9% saline, and for ketoconazole, the receptor fluid was 40% PEG.
  • Sampling time periods were from 1 to 24 hours, more specifically 1, 2, 3, 4, 6, 8 and 24 hours, with full receptor fluid replacement.
  • Time' ⁇ i.e., the square root of the time.
  • Analysis on the receptor fluid was conducted using a UV spectrophotometer at a wavelength specific for each active agent.
  • the specific wavelength was 261 nm and for ketoconazole, the specific wavelength was 269 nm.

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Abstract

L'invention concerne un système d'administration transdermique de médicament qui comporte un agent actif et une composition adhésive sensible à la pression. L'agent actif est destiné à l'administration transdermique régulée à la peau de l'utilisateur de ce système, et la composition adhésive sensible à la pression est destinée à maintenir le système en contact avec la peau. Ladite composition est une composition fonctionnelle acrylate ou méthacrylate adhésive sensible à la pression qui est le produit de la réaction d'un adhésif sensible à la pression et d'un agent de coiffe contenant du silicium. En d'autres termes, l'agent de coiffe contenant du silicium et l'adhésif sensible à la pression réagissent pour former la composition adhésive sensible à la pression. L'agent de coiffe contenant du silicium comprend la fonctionnalité acrylate ou méthacrylate, fonctionnalité qui fournit la composition adhésive sensible à la pression avec sa fonctionnalité acrylate ou méthacrylate. L'adhésif sensible à la pression est lui-même le produit de la réaction d'une résine de silicone et d'un polymère de silicone.
EP06826541A 2005-10-25 2006-10-24 Systeme d'administration transdermique de medicaments avec une composition fonctionnelle acrylate ou methacrylate adhesive sensible a la pression Withdrawn EP1940368A2 (fr)

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