Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
2001-01-17
2002-04-02
Dodson, Shelley A. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S447000, C424S448000
Reexamination Certificate
active
06365178
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to methods of preparing pressure sensitive adhesive matrix patch devices for transdermal drug delivery. More particularly, the invention relates to the preparation of pressure sensitive adhesive matrix patches by dissolving hydrophilic salts of hydrophobic drugs that are crystalline at room temperature in aqueous dispersions of hydrophobic pressure sensitive adhesive polymers. These patches are surprisingly free from drug crystals upon drying and exhibit unusually good physical stability without the use of a solubilizing agent or crystal growth inhibitor.
Transdermal delivery of various drugs and pressure sensitive adhesive matrix patches for transdermal delivery of such drugs are well known in the art of drug delivery. These matrix patches include a pressure sensitive adhesive layer for affixing the patch to the skin and for carrying the drug and any excipients that are directly incorporated into this adhesive layer. These adhesive matrix patches also typically include an inert, impervious backing layer and a release liner that is peeled off and discarded before applying the patch to the skin. These patches are distinguished from reservoir patches in that the drug in a reservoir patch is incorporated in a layer or compartment separate from the pressure sensitive adhesive layer. An example of a reservoir transdermal patch is described in U.S. Pat. No. 5,120,546 to Hansen et al.
The polymers used to form pressure sensitive adhesives are well known to those skilled in the art and will be discussed in greater detail below. Since these polymers are hydrophobic in nature, they are typically supplied in liquid form, either dissolved in organic solvents (solvent-based adhesives) or as two-phase aqueous dispersions of water-insoluble polymer particles (water-based adhesives). I. Benedek & J. L. Heymans, Pressure-Sensitive Adhesives Technology 34 (1997).
Drugs or pharmaceutical agents that are incorporated into pressure sensitive adhesive matrix patches are often available as either hydrophobic water-insoluble free drugs or as hydrophilic water-soluble salts. These hydrophilic drug salt derivatives are well known in the art and are often the forms that are developed for oral delivery.
In some patents it is suggested that the hydrophobic free drug form of a drug and the hydrophilic salt form of a drug may be freely substituted in a transdermal pressure sensitive adhesive matrix patch. For example, U.S. Pat. No. 5,149,538 to Granger discloses a pressure sensitive adhesive matrix incorporating opioids or their pharmaceutically acceptable salts, however, no mention is made of the means of manufacture or the specific types of adhesives that might be compatible with such opioid drugs or drug salts. Free form drugs and their corresponding salts will normally differ in their physico-chemical properties such as solubility and hydrophobicity. Therefore, it is unlikely that the free drug and salt forms can be freely substituted in a given adhesive. The free drug form is likely to be insoluble in the water phase of an aqueous emulsion pressure sensitive adhesive, while the hydrophilic salt form is likely to be insoluble in the organic solvents of a solvent-based pressure sensitive adhesive.
It is well known in the art that a transdermal delivery system suitable for one drug or drug form may not be suitable for use with another drug or drug form. For example, U.S. Pat. No. 5,633,009 to Kenealy et al. suggests that azapirones and azapirone salts may be freely interchanged in pressure sensitive matrix patches, but discloses only techniques for incorporating hydrophobic azapirone free base in a solvent-based hydrophobic polyisobutylene adhesive. U.S. Pat. No. 5,589,498 to Mohr et al. suggests that ketorolac and ketorolac salts may be freely substituted in transdermal matrix devices, but only discloses techniques for incorporating hydrophobic ketorolac free acid in a hydrophobic solvent-based pressure sensitive acrylic adhesive and techniques for incorporating hydrophilic ketorolac tromethamine in hydrophilic polymers (hydrogels, polyurethane, or pectin/gelatin blends). These examples serve to illustrate that hydrophilic salt forms of drugs are known in the art to be compatible with water-soluble hydrophilic polymers and hydrophobic drug forms are known to be compatible with solvent-based hydrophobic polymers such as are used in typical pressure sensitive adhesives.
For manufacturing transdernal pressure sensitive matrix patches using hydrophilic drug salts, the hydrophilic salt is commonly converted to the hydrophobic free base This conversion and subsequent incorporation in a solvent-based hydrophobic pressure sensitive adhesive polymer is well known in the art. U.S. Pat. No. 5,002,773 to Keshary et al. describes transdermal delivery of a calcium antagonist compound, “TA-3090.” Keshary states that the free base form of TA-3090 can be incorporated in polymeric matrix materials in a higher concentration than the maleate salt of TA-3090 and that the free base form is preferred for transdermal delivery. U.S. Pat. No. 4,201,211 to Chandrasekaran et al. discloses a gelled mineral oil-polyisobutylene skin patch for transdermal delivery that incorporates clonidine free base. Oral clonidine tablets, however, are manufactured with the clonidine hydrochloride salt. U.S. Pat. No. 4,262,003 to Urquhart et al. describes a gelled mineral oil-polyisobutylene-scopolamine free base transdermal patch for the administration of scopolamine base. U.S. Pat. No. 4,956,171 to Chang provides examples of the conversion of buprenorphine salts into buprenorphine free base for incorporation into an organic solvent-based pressures sensitive adhesive. These examples serve to illustrate the conversion of a hydrophilic salt form of a drug into the more hydrophobic free base form to render it compatible for incorporation into a hydrophobic pressure sensitive adhesive matrix patch.
Water-based hydrophobic pressure sensitive adhesives are also known in the art. These are two-phase systems wherein the hydrophobic pressure sensitive adhesive polymer is dispersed as particles in water. U.S. Pat. No. 4,564,010 to Coughlan et al. discloses a water-based pressure sensitive adhesive emulsion film for medical use comprising a base layer laminated to a water-based pressure sensitive adhesive coating formed of a mixture of a polyacrylic latex, an ester resin, and a thickening agent. Coughlan teaches that such films can be used in transdermal delivery systems as peripheral adhesives, with the drug being incorporated in a separate element. The possibility of incorporating the drug and optional permeation enhancers into the water-based pressure sensitive layer is not considered. U.S. Pat. No. 4,409,206 to Stricker et al. discloses a means of manufacturing a patch for transdermal drug delivery using acrylic polymer dispersions. In this invention the acrylic dispersion is dried and the hydrophobic drug substances are then allowed to diff-use into the dried film from drug solutions or suspensions in organic solvents, which are subsequently evaporated. The mixing of a water soluble drug salt in an aqueous dispersion and preparing a polymer matrix film in a single coating and drying step was not recognized or discussed.
The manufacture of transdermal matrix patch devices that use water-based pressure sensitive adhesive dispersions has been contemplated in the art, but the incorporation of hydrophilic salts of crystalline drugs in such dispersions has not been considered. U.S. Pat. No. 5,230,896 to Yeh et al. discloses a transdermal delivery system for administration of nicotine comprising nicotine base, an acrylic polymer adhesive, a stabilizer, and a polyester film backing. It is stated that a nicotine salt is also contemplated in the practice of the invention. Such a nicotine salt is used to reduce volatility of the drug and is formed in situ by addition of acid. Nicotine is an unusual compound in that the free base is quite hydrophilic and is a liquid at room temperature. Both nicotine free base and
Ebert Charles D.
Fikstad David
Venkateshwaran Srinivasan
Dodson Shelley A.
Koneru Phanesh
Thorpe North & Western
Tran Paul B.
Watson Pharmaceuticals, Inc.
LandOfFree
Method of making pressure sensitive adhesive matrix patches... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method of making pressure sensitive adhesive matrix patches..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method of making pressure sensitive adhesive matrix patches... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2872691