US 201100973 84Al (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0097384 A1 Kanios et al. 43 Pub. Date: A r. 28 9 201 1 (54) TRANSDERMAL DRUG DELIVERY DEVICE Publication Classi?cation INCLUDING AN OCCLUSIVE BACKING (51) Int. Cl. (75) Inventors: DavidJuan A. Kanios, Mantelle, Miami, Miami, FL (US);FL (US); A611, 9/12 168 (200601) Viet Nguyen, Miami, FL (US) ( ' ) A61P 25/00 (2006.01) (73)(21) Assignee:Appl. No.: Noven12/981,126 Pharmaceuticals, Inc. (52) US. Cl. ....................................... .. 424/448; 514/398 (22) Filed: Dec. 29, 2010 (57) ABSTRACT _ _ A transdermal drug delivery system for the topical applica Related U‘s‘ Apphcatlon Data tion of one or more active agents contained in one or more (62) Division of application No. 11/245,190, ?led on Oct. Polymeric and/Or adhesive Carrier layers, proximate to a non‘ 7, 2005, now pat No_ 7,620,487' drug containing polymeric backing layer Which can control the delivery rate and pro?le of the transdermal drug delivery (60) Provisional application No, 60/616,861, ?led on Oct system by adjusting the moisture vapor transmission rate of 8, 2004. the polymeric backing layer. Patent Application Publication Apr. 28, 2011 Sheet 1 0f 2 US 2011/0097384 A1 K270i. Patent Application Publication Apr. 28, 2011 Sheet 2 0f 2 US 2011/0097384 A1 23 -§ -§ -§ ~... -% E -& 1" -a N s: =1 "a g: g ‘:2 + .gFE g -s + 4 ~22 -§' ~21 a 3 2 go US 2011/0097384 A1 Apr. 28, 2011 TRANSDERMAL DRUG DELIVERY DEVICE the reservoir-type device, the active agent is generally kept INCLUDING AN OCCLUSIVE BACKING separate from the adhesive. The device has a pocket or “res ervoir” Which physically serves to hold the active agent and carrier, and Which is formed in or by a backing layer. A [0001] This application claims the bene?t of provisional peripheral adhesive layer is then used to af?x the device to the application 60/616,861 ?led Oct. 8, 2004, Which is hereby user. incorporated by reference in its entirety. [0009] The reservoir-type devices have a number of disad vantages including a non-uniform drug release pro?le Where FIELD OF THE INVENTION a high dose of drug is initially released upon application to the user, often described as a “burst effect.” This burst or high [0002] This invention relates generally to transdermal drug initial release of drug then drops off after a period of time to delivery systems, and more particularly to pharmaceutically a rate that necessary to achieve a therapeutically effective acceptable adhesive matrix compositions. The invention amount. Drug delivery according to this pro?le is generally additionally relates to transdermal drug delivery systems pro described as ?rst order release. viding acceptable drug release pro?les for an extended period [0010] While classic reservoir-type devices are still in use of time of up to seven days or longer. today, the term reservoir is being used interchangeably herein [0003] In particular, the present invention is directed to a transdermal drug delivery system for the topical application With matrix-type devices Which still rely upon a separate adhesive means used to af?x the device to the user. of one or more active agents contained in one or more poly meric and/ or adhesive carrier layers, proximate to a non-drug [0011] In a matrix-type device, the active agent is dissolved containing polymeric backing layer. The backing layer can be or dispersed in a carrier that typically is in a ?nite carrier form. processed or manufactured separately from the polymeric The carrier form can be self-adhesive or non-adhesive. Non and/or adhesive drug carrier layer(s) to prevent or minimize adhesive matrix-type devices, that is, those Which still rely on loss of drug or other system components, and combined prior a separate adhesive means to af?x the device to the user, to topical application. In the alternative, the backing device employ a drug permeable adhesive layer (often referred to as can be processed together With the polymeric and/ or adhesive an “in-line adhesive” since the drug must pass through this drug carrier layer(s). The drug delivery rate and pro?le can be layer) applied over the drug matrix carrier layer. To better controlled by adjusting certain characteristics of the poly control the release rate of the drug, the non-adhesive matrix meric backing layer. type devices often employ one or more additional drug per meable layers such as, for example, rate controlling mem BACKGROUND OF THE INVENTION branes. The non-adhesive matrix-type devices often contain excipients, such as drug delivery enhancers, to help control [0004] The use of transdermal drug delivery systems to the release rate. These devices are often referred to as multi topically administer an active agent is Well knoWn. These layer or multilaminate. systems incorporate the active agent into a carrier composi [0012] In a “monolithic” or “monolayer” matrix-type tion, such as a polymeric and/or pressure-sensitive adhesive device, the active agent is typically solubiliZed or homog composition, from Which the active agent is delivered through enously blended in an adhesive carrier composition, typically the skin or mucosa of the user. a pressure-sensitive adhesive orbioadhesive, Which functions [0005] Many factors in?uence the design and performance as both the drug carrier and the means of af?xing the system of such drug delivery devices, such as the individual drugs to the skin or mucosa. Such devices, commonly referred to as themselves, the physical/ chemical characteristics of the sys drug-in-adhesive devices, are described, for example, in Us. tem’s components and the performance/behavior relative to Pat. Nos. 4,994,267; 5,446,070; 5,474,783 and 5,656,286, all other system components once combined, external/environ of Which are assigned to Noven Pharmaceuticals, Inc., mental conditions during manufacturing and storage thereaf Miami, Fla. and herein incorporated by reference. ter, the properties of the topical site of application, the desired [0013] While matrix-type devices, especially drug-in-ad rate of drug delivery and onset, the drug delivery pro?le, and hesive devices, achieve more uniform and controlled drug the intended duration of delivery. Cost, appearance, siZe and deliver rates over longer periods of time, most transdermal ease of manufacturing are also important considerations. systems remain subject to a higher initial drug release than is [0006] Active-ingredient-containing transdermal drug required to achieve therapeutic ef?cacy. For many drugs and/ delivery systems (“patches”) are essentially divided into tWo or therapeutic situations, it Would be advantageous to elimi major technical systems: reservoir systems and matrix sys nate or suppress this higher initial release and achieve a tems. The present invention relates to matrix systems Where “steady state” (Zero order) release pro?le Which uniformly the active ingredient(s) are embedded in a semi-solid matrix delivers a therapeutically effective amount of drug over the made up of a single polymer or a blend of polymers. extended duration of device’s desired use, preferably up to 7 [0007] Both types of devices employ a backing layer that days or more. forms the protective outer surface of the ?nished transdermal [0014] The high initial blood level concentration of certain system and Which is exposed to the environment during use. drugs may cause adverse or undesired effects, or create tox A release liner or protective layer that forms the inner surface icity concerns, thereby limiting the use of transdermal admin covers the polymeric adhesive Which is employed for af?xing istration. In other instances, the higher initial blood level the system to the skin or mucosa of a user. The release liner or concentration may reduce the amount of drug required for protective layer is removed prior to application, exposing the treatment to the point of risking under dosing, or the higher adhesive, typically a pressure-sensitive adhesive. initial blood level concentration may make it impractical to [0008] In the “classic” reservoir-type device, the active increase the duration of the device’s application While retain agent is typically dissolved or dispersed in a carrier to yield a ing therapeutic effectiveness. Reducing the frequency of non-?nite carrier form, such as, for example, a ?uid or gel. In replacing the transdermal drug delivery system Would US 2011/0097384 A1 Apr. 28, 2011 increase user compliance, reduce any lag or drop off in e?i one or more polymeric and/or adhesive carrier layers, proxi cacious blood levels, and reduce the amount of drug required mate to a non-drug containing polymeric backing layer Which for treatment (also provided by reducing the higher initial is manufactured to optimiZe drug loading While providing blood level associated With the higher release rate). desirable adhesion to skin or mucosa as Well as providing [0015] Drug concentration in transdermal delivery systems modulation of the drug delivery and pro?le. The polymeric can vary Widely depending on the drug and polymers used. backing layer is designed to provide control of permeation LoW drug concentrations in the adhesive can result in di?i rate, onset and pro?le of the active agent from the system. culties in achieving an acceptable delivery rate of the medi [0022] The transdermal delivery device may comprise at cament, preferably one approximating Zero order kinetics. least one layer formed of a single polymer or a blend of High drug concentrations, on the other hand, frequently affect polymers to serve as a pressure-sensitive adhesive composi the adhesion properties of the adhesives, and tend to promote tion for applying the system to the dermis.