Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1998-05-01
2001-11-06
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S449000, C424S487000
Reexamination Certificate
active
06312715
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to transdermal drug delivery compositions that contain pressure sensitive adhesive microspheres containing a softening agent and/or a therapeutic agent. The invention additionally relates to an in-situ method of preparing pressure sensitive adhesive microspheres that contain a softening agent and/or a therapeutic agent.
BACKGROUND OF THE INVENTION
Inherently tacky pressure sensitive adhesive microspheres are known in the art to be useful in repositionable pressure sensitive adhesive applications and there are numerous references discussing the preparation and/or use of inherently tacky, elastomeric polymeric microspheres. Pressure sensitive adhesive microspheres may be solid or hollow and are generally crosslinked to an extent such that the particulate nature of the adhesive is maintained throughout processing and use. Typically, pressure sensitive adhesive microspheres are prepared via suspension polymerization of one or more free radically polymerizable monomers in the presence of surfactants and/or suspension stabilizers. Choice of surfactants and/or suspension stabilizers and their specific combinations with specific monomers can determine suspension stability, desired particle morphology, performance characteristics, and the like.
Various copolymerizable monomeric components have been added to the free radically polymerizable monomers, suspension stabilizers and/or surfactants to modify the adhesive properties of these suspension polymerized microspheres. For example, nitrogen-containing polar monomers have been added to acid-free acrylate suspension polymerization mixtures to form adhesive microspheres containing multiple internal voids. Polar comonomers having no dissociable protons or low levels of dissociable protons, when used along with particular surfactant and polymeric stabilizer combinations, can be added to suspension polymerizable formulations to yield adhesive microspheres having enhanced adhesive properties while maintaining their repositionable and self cleaning qualities against a variety of surfaces.
Copolymerizable or otherwise incorporated oligomeric and polymeric additives have also been employed in suspension polymerized adhesive microspheres to alter microsphere adhesive properties and other performance characteristics. Hydrophilic oligomers and polymers have been included in suspension polymerizable adhesive microsphere formulations to provide improved microsphere stability and, in some formulations, water dispersibility. Water insoluble polymeric components have also been incorporated into adhesive microspheres by suspension polymerization of alkyl(meth)acrylate and other comonomers in the presence of such polymeric components. This method of incorporation allows for the inclusion of water insoluble polymer components into adhesive microspheres that could not typically be incorporated under standard free radical suspension polymerization conditions. Another advantage of this water insoluble polymer incorporation is to modify the physical and adhesive properties of the microspheres. Finally, crystalline polymers or crystallizable monomers have also been added during suspension polymerization to provide adhesive microspheres having thermally controllable shape memory.
Drugs and other therapeutically active agents have been administered transdermally or percutaneously using a variety of methods and devices. One known method is to incorporate the drug into a continuous adhesive matrix, either alone or in combination with one or more excipients that enhance the delivery of drug across the skin. Examples of such systems are found, for example in Nelson et al., U.S. Pat. No. 5,223,261 and Peterson, U.S. Pat. No. 5,494,680.
There have been some attempts in the prior art to develop transdernal drug delivery systems that use pressure sensitive adhesive particles in place of a continuous adhesive matrix. For example, JP 58-12255 describes an adhesive tape or sheet made up of acrylic polymer particles that contain a drug such as a steroid. EP 793,972 describes a transdermal drug delivery device that contains finely pulverized acrylate adhesive particles in combination with a drug.
SUMMARY OF THE INVENTION
The transdermal drug delivery composition of the present invention comprises pressure sensitive adhesive microspheres comprising (a) at least 10 wt-% of a softening agent incorporated within the microspheres and optionally comprising (b) a therapeutically effective amount of a drug.
The use of polymeric microspheres as described herein provides a high degree of flexibility in formulating transdermal drug delivery compositions. In particular, the transdermal drug delivery compositions of the invention can tolerate the inclusion of a relatively large amount of a softening agent without undue loss of cohesive strength. This tolerance for softening agents or excipients allows one to achieve excellent delivery of drug through the skin without sacrificing adhesive properties.
The invention also provides a transdermal drug delivery device comprising a transdermal drug delivery composition comprised of pressure sensitive adhesive microspheres comprising (a) at least 10 wt-% of a softening agent incorporated within the microspheres and optionally comprising (b) a therapeutically effective amount of a drug disposed upon a backing.
Another aspect of the invention provides a method of preparing a transdermal drug delivery composition comprising the steps of:
a) forming an oil phase comprising one or more acrylic acid ester, methacrylic acid ester, or vinyl ester monomers alone or in any combination; a non-reactive, oil soluble softening agent and/or drug; and an oil soluble free radical initiator in an aqueous phase comprising an aqueous medium comprising at least one suspension stabilizer or surfactant and
b) initiating polymerization of the oil phase in the aqueous phase, thereby forming an adhesive microsphere transdermal drug delivery composition.
Unless otherwise indicated, all weight percentages are based on the total weight of the transdermal drug delivery composition.
DETAILED DESCRIPTION OF THE INVENTION
The transdermal drug delivery composition of the invention can be formed by a “post-addition” method, wherein the polymerized microsphere component is blended with the softening agent and/or drug under such conditions as to cause the softening agent and/or drug to be incorporated into the microsphere. This post-addition method of preparing the transdermal drug delivery composition of the invention comprises the steps of:
(a) providing a polymeric microsphere component;
(b) blending the polymeric microsphere component with a softening agent and/or a drug and, optionally, a solvent capable of dissolving the softening agent and/or drug and/or of swelling the polymeric microsphere component; and
(c) removing the solvent.
The polymeric microsphere component of the inventive compositions can be prepared by suspension, dispersion, direct emulsion and modified emulsion techniques. Preferably, the polymeric microsphere component is prepared according to the suspension polymerization methods described in, for example, U.S. Pat. Nos. 3,691,140; 4,166,152; 4,495,318; 4,786,696; 4,988,467; 5,045,569; 5,508,313; and 5,571,617 and PCT Pat. Appls. WO 96/01280; WO 97/46633; and WO 97/46634, the disclosures of which are incorporated herein by reference. The preferred polymeric microsphere components are comprised of acrylate or vinyl ester microspheres.
In the preferred suspension polymerization methods, the acrylate or vinyl ester microspheres can typically be prepared by forming an oil phase comprising (meth)acrylic acid ester and/or vinyl ester monomers, optionally also containing free radically polymerizable polar comonomers, and an oil soluble free radical initiator in a water phase that comprises an aqueous medium having at least one suspension stabilizer or surfactant. Depending on the types and amounts of monomers, comonomers, crosslinking agents, oligomeric or polymeric additives, stabilizers, surfactants, reaction condition
Cantor Adam S.
Choi Hye-Ok
Delgado Joaquin
Ko Chan U.
Tran Thu-Van
3M Innovative Properties Company
Howard MarySusan
Page Thurman K.
Ringsred Ted K.
Sprague Robert W.
LandOfFree
Adhesive microsphere drug delivery composition does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Adhesive microsphere drug delivery composition, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Adhesive microsphere drug delivery composition will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2588590