Transdermal norelgestromin delivery system

a norelgestromin and delivery system technology, applied in the field of medical patches, can solve the problems of high affinity for lint and dirt to adhere to the edge of the patch, severe cold flow, etc., and achieve the effects of low cost, high flux rate, and high loading rate of permeation enhancer

Inactive Publication Date: 2007-05-03
ALZA CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009] The present invention provides a method and a device for transdermal delivery of an effective amount of NGMN, an estrogen, or NGMN in combination with an estrogen (for contraceptive effect or for providing hormone replacement) to an individual in need thereof. In one aspect, a patch with polyacrylate reservoir suitable for multiple day delivery of NGMN is provided. In another aspect, a high loading of permeation enhancer enables high flux rate with a relatively small area, suitable for a transdermal patch that can be maintained adhesively on the body surface for an extensive period of time, such as 3, 7 days, and even longer, with acceptable rheological and adhesive properties and better appearance.
[0010] The preparation of formulations with polyacrylate for adhesion rather than PIB results in improved cold-flow resistance. This feature in turn results in an improvement in both patch aesthetics, ease of removal and improved patient compliance. The use of polyacrylate also results in formulations that are and remain translucent (versus opaque in appearance due to undissolved PVP particles and moisture uptake during 7 day wear) which, when combined with a transparent or translucent backing, have an improved translucent appearance after application and during wear. Although PVP, either dissolved, dispersed (e.g., in micronized form), or combination thereof, can be used, it is not required for the formulation of the present invention to adhere to the body surface. Further, the increased drug flux per unit area also results in a smaller patch size, again improving aesthetics and patient acceptability, and reducing the likelihood of unintentional detachment.
[0011] In the currently commercially available 7-day wear patches, the amount of NGMN and EE loaded into the adhesive drug layer resulting in adhesive layer about 0.006 inch (0.15 mm) to 0.008 inch (0.20 mm) thick. The thicker adhesive layer requires the addition of a non-woven backing for structural support during manufacturing, patch application and patch removal. The thicker adhesive layer also results in severe cold flow during storage in the pouch, and higher affinity for lint and dirt to adhere to the edge of the patch during wear. The currently available ORTHO EVRA® patches utilizes less than 20% of the NGMN and EE loaded into the patch during 7 days of wear. The effective dose of NGMN and EE in an ORTHO EVRA® contraceptive patch is 150 μg/day of NGMN and 20 μg/day of EE having a basal surface area (i.e. the area in diffusional contact with the skin) of 20 cm2. ORTHO EVRA® patches deliver the NGMN at a flux of 0.3 μg/cm2-h, and EE at a flux of 0.04 μg/cm2-h.
[0012] The use of polyacrylates results in a simpler, less complex manufacturing process as the drug/adhesive layer is thinner remo...

Problems solved by technology

The thicker adhesive layer also results in severe cold flow during storage in the po...

Method used

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  • Transdermal norelgestromin delivery system
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  • Transdermal norelgestromin delivery system

Examples

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example 1

[0081] A monomer mix containing butyl acrylate, 2-hydroxyethyl acrylate, t-octyl acrylamide, acrylic acid, ethyl acetate (solvent), and 2,2′-azobisisobutyronitrile (AIBN) (polymerization initiator) was prepared. A fraction was charged to an appropriate vessel and heated to reflux with stirring. The remainder was added to the vessel over time. The ratios of the monomers and initiator added totally, i.e., butyl acrylate: 2-hydroxyethyl acrylate: t-octyl acrylamide: acrylic acid: AIBN were 59: 25.5: 9.5: 6: 2. The material was then held at reflux for a suitable period of time. At the end of the hold period, the contents were cooled to room temperature and the solution polymer discharged. The dry film made from this polyacrylate formulation had storage modulus of around 9×105 dyn / cm2, creep compliance of around 7×10−5 cm2 / dyn, and glass transition temperature of −8° C., and consequently was too stiff to provide adequate adhesive properties alone. This formed a proadhesive.

example 2

[0082] A monomer mix containing butyl acrylate, 2-hydroxypropyl acrylate, t-octyl acrylamide, acrylic acid, ethyl acetate (solvent), and 2,2′-azobisisobutyronitrile (AIBN) (polymerization initiator) was prepared. A fraction was charged to an appropriate vessel and heated to reflux with stirring. The remainder was added to the vessel over time. The material was held at reflux for a suitable period of time. The ratios of the monomers and initiator added totally, i.e., butyl acrylate: 2-hydroxypropyl acrylate: t-octyl acrylamide: acrylic acid: AIBN were 59: 25.5: 9.5: 6: 2. At the end of the hold period, the contents were cooled to room temperature and the solution polymer discharged. The dry film made from this polyacrylate formulation had storage modulus of around 8×105 dyn / cm2, creep compliance of around 4×10−5 cm2 / dyn, and glass transition temperature of −8° C., and consequently was too stiff to provide adequate adhesive properties alone. This formed a proadhesive.

example 3

[0083] A monomer mix containing vinyl acetate, 2-hydroxyethyl acrylate, 2-ethylhexyl acrylate, ethyl acetate (solvent), and 2,2′-azobisisobutyronitrile (AIBN) (polymerization initiator) was prepared. A fraction was charged to an appropriate vessel and heated to reflux with stirring. The remainder was added to the vessel over time. The material was held at reflux for a suitable period of time. The ratios of the monomers and initiator added totally, i.e., vinyl acetate: 2-hydroxyethyl acrylate: 2-ethylhexyl acrylate: AIBN were 50: 10: 40: 1.2. At the end of the hold period, the contents were cooled to room temperature and the solution polymer discharged. The dry film made from this polyacrylate formulation had storage modulus of around 2×106 dyn / cm2, creep compliance of around 4×10−6 cm2 / dyn, and glass transition temperature of −14° C., and consequently was too stiff to provide adequate adhesive properties alone. This formed a proadhesive.

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Abstract

A system for transdermal delivery of norelgestromin (NGMN) to an individual. The system has a high NGMN loading with suitable permeation enhancers to effect therapeutic flux rate. Polyacrylate drug reservoir with the NGMN and high loading of one or more of permeation enhancers and NGMN dissolved therein provides desirable adhesive characteristics and effective transdermal therapeutic properties. Estrogen can be delivered with the NGMN.

Description

CROSS REFERENCE TO RELATED U.S. APPLICATION DATA [0001] The present application is derived from and claims priority to provisional application U.S. Ser. No. 60 / 720,200, filed Sep. 23, 2005, which is herein incorporated by reference in its entirety.TECHNICAL FIELD [0002] This invention relates to a medical patch for transdermal administration of norelgestromin (NGMN) and to a method of treating a subject by administering norelgestromin (NGMN) thereto with the medical patch. In particular, the invention relates to transdermal systems for administration of NGMN preferably in combination with an estrogen with adhesive system having high enhancer tolerance when used in transdermal drug delivery. BACKGROUND [0003] Transdermnal devices for the delivery of biologically active agents have been used for maintaining health and therapeutically treating a wide variety of ailments. For example, analgesics, steroids, etc., have been delivered with such devices. Such transdermal devices include pat...

Claims

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Application Information

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IPC IPC(8): A61K9/70A61K31/56
CPCA61K9/7061A61K31/56A61K31/4439C09J7/385C09J7/255C09J133/06C09J2467/006
Inventor WESTCOTT, TYLER D.STEPIC, JANEIMBERT, DELPHINE C.AUDETT, JAYWEN, JIANYELUCIANO, ALLISONSILVERBERG, ERIC N.FOREMAN, PAUL B.
Owner ALZA CORP
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