TECHNICAL FIELD:
The present disclosure broadly lies in the field of pharmaceuticals, specifically in New Drug Delivery Systems (NDDS). This disclosure is related to improved adhesive preparations and transdermal patches comprising those preparations.
BACKGROUND OF THE ART:
A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. Often, this promotes healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types of medication delivery such as oral, topical, intravenous, intramuscular, etc. is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive.
The transdermal patches already available in the prior art encounter various drawbacks. It is evident from the existing transdermal patches and the literature associate with the same that loading of active compounds above a certain concentration has detrimental effects on the base adhesive as the adhesive starts breaking apart and in turn would leave some residue on the skin of patients. This is particularly the case when the actives are in an oil state wherein the actives themselves act as plasticizers and impact the cross-linking of the polymer and tackifier compounds. Therefore, the active oils have been limited in concentration to less than or equal to 20% of the base adhesive. The present invention describes composition and preparation of adhesive complex capable of incorporating up to 35% of active medicine.
Another common problem with Transdermal patches is that the patches fall of or lose tack in contact with water. This is a major problem when the patient perspires wherein the sweat forms a barrier layer between the skin and the adhesive causing the patch to fall off. This is the case as hot melt adhesives are inherently hydrophobic in nature. The present invention describes composition of an adhesive complex that has a part hydrophilic characteristic to maintain adhesion during perspiration.

The final major issue with existing Transdermal formulations is that since hot melt adhesives are oil based, it is not possible to incorporate oil insoluble actives, more specifically water soluble active compounds. This is a major challenge with patches containing herbal medicines which water soluble such as Turmeric and Boswellia Serrata. The present invention describes the composition of an adhesive that can in part incorporate water soluble active compounds.
In a nutshell, the present invention has been completed in consideration of the above problems with adhesive preparations of Transdermal patches. These are namely, adhesive structure breaking with high dosage of active compounds in an oil form, inability of incorporating water-soluble compounds / actives in the adhesives and hydrophobic characteristic of such adhesives.
OBJECT OF THE INVENTION
The object of the present invention is to provide an adhesive preparation which can be employed
for the construction of improved transdermal patches for targeted and sustained release of active
compounds.
Another objective of the present invention is to provide improved transdermal patches.
Yet another objective of the present invention is to provide sweat proof patches.
Yet another important objective of the present invention is to provide transdermal patches for pain
and wound healing.
BRIEF DESCRIPTION OF FIGURES AND DRAWINGS
The accompanying drawings illustrate some of the embodiments of the present invention and, together with the descriptions, serve to explain the invention. These drawings are offered by way of illustration and not by way of limitation.
Figure 1 illustrates Transdermal patch having fully coated adhesive layer. Figure 2 illustrates a layout profile of layers of Transdermal patch.
Figure 3 illustrates Transdermal patch having alternate hydrophilic and hydrophobic layers.

SUMMARY:
The present invention provides improved adhesive preparations and are employed for preparing transdermal patches. The patch of the present invention comprises a backing layer, an adhesive layer and a release liner.
The adhesive layer of the transdermal patch of the present invention contains a thermoplastic styrenic block elastomer based on Styrene-Isoprene-Styrene (SIS) or Styrene-Butadiene-Styrene (SBS) or Styrene- Ethylene/Butylene-Styrene (SEBS) block copolymers or Linear Triblock Copolymer. Further, adhesive layer comprises a tackifier component such as a petroleum-based resin including aliphatic and aromatic resins obtained as by-products of naptha-cracking. The adhesive layer also comprises a plasticizer component and an anti-oxidant so that the adhesive layer is stable in contact with air and does not char upon re-melting. The final component of the adhesive mass is the active medicine selected from Methyl Salicylate, Menthol, Camphor, Eucalyptus Oil and Clove Oil, and Turmeric Oil and combinations thereof. The transdermal patch of the present is sweat proof. The said patch also relieves pain and heals wounds.
DETAILED DESCRIPTION:
Accordingly, the present invention provides improved adhesive preparations and are employed
for preparing transdermal patches. The patch of the present invention comprises a backing layer,
an adhesive layer and a release liner.
In an embodiment, the present invention provides a transdermal drug delivery patch comprising:
a backing layer having thickness in a range of 100 to 300 microns;
an adhesive layer having a thickness of 150 to 200 gram per square meter (gsm);
a release liner having thickness in a range of 80 to 150 microns, wherein said release liner is a
removable transparent protective film.
In another embodiment said backing layer is comprised of knitted polyester fabrics, knitted cotton fabrics, woven cotton fabrics, nylon fabrics, polypropylene non-woven fabrics, viscose cotton / polyester non-woven fabrics, polyurethane films and multilayer LDPE based films and combinations thereof.

In yet another embodiment said adhesive layer is comprised of an adhesive preparation
comprising:
a thermoplastic styrenic block elastomer;
a tackifier;
a plasticizer;
an anti-oxidant;
an active medicine and optionally a super absorbent polymer (SAP) in various combinations.
In one embodiment said thermoplastic styrenic block elastomer is based on Styrene-Isoprene-Styrene (SIS) or Styrene-Butadiene-Styrene (SBS) or Styrene- Ethylene/Butylene-Styrene (SEBS) block copolymers or Linear Triblock Copolymer.
In yet another embodiment said thermoplastic styrenic block elastomer is in the range of 20% to 35% of the adhesive mass.
In one embodiment said tackifier is a petroleum-based resin including aliphatic and aromatic resins obtained as by-products of naptha-cracking.
In an embodiment, said tackifier is in the range of 20% to 60% of the adhesive mass.
In another embodiment said plasticizer is selected from Napthenic Oil, White Mineral Oil, Paraffinic Oils, Silicon Oils or Plant Oils.
In yet another embodiment said plasticizer is in the range of 5% to 20% of the adhesive mass.
In a further embodiment said anti-oxidant is selected from Irganox 1010 and Irganox 1098.
In still another embodiment said anti-oxidant is in the range of 0.1% to 2% of the adhesive mass.
In an embodiment, said active medicine comprises Methyl Salicylate, Menthol, Camphor, Eucalyptus Oil, Clove Oil, Turmeric Oil and combinations thereof.

In another embodiment, said active medicine is in the range of 25-35% of the adhesive mass.
In yet another embodiment said adhesive preparation optionally comprises penetration enhancer selected from Menthol and Oleic Acid in a range of 5% to 10% of the adhesive mass.
In still another embodiment said adhesive preparation optionally comprises a skin protective agent selected from zinc oxide and boric acid.
In an embodiment said super absorbent polymer is carboxymethylcellulose (CMC).
In one embodiment the adhesive layer is either coated on complete surface or in form of strips.
In another embodiment, the transdermal patch with strips is a sweat proof transdermal patch having alternate hydrophilic and hydrophobic channels.
In a further embodiment, said release liner is selected from Glasine or Clay Coated Craft Silicon Release Papers, or Platinum Coated Polyester Release films and combinations thereof.
In yet another embodiment, the present invention provides a method of preparing a transdermal patch as claimed in claim 1, wherein said method comprises the steps of:
providing the components of the adhesive layer in a high shear mixer pre-heated to 140°C; mixing said component in a 50kg total batch size for 1 hour at 150 rpm stirrer speed; extruding the melt and coating the same onto the release liner at 140°C; laminating the backing layer with extruded melt;
feeding the coated laminate into a die-cutting machine to cut patches of the required size; packing the finished products in three-layer aluminium foil pouches.
In still another embodiment, said size of patch is 22.5 cm2, 50 cm2, 75 cm2, 140 cm2, 200 cm2 or 220 cm2.

In another embodiment, the transdermal patch relieves muscular pain, stiffness and joint pain. In a further embodiment said transdermal patch comprises turmeric oil as an active medicine and is capable of healing wounds.
The below table depicts the constitution of the transdermal patch of the present invention:

Component Description Ratio
Backing Layer Backing Layer
Polyethylene, Polyurethane, Knitted Fabric, Woven Fabric or
blends of above 50- 150 gsm
Adhesive Layer Styrene-Isoprene-Styrene block copolymer Liner or Radial Diblock or Triblock Polystyrene Content 10% to 40% 20% - 40%

Aliphatic Hydrocarbon Resin (Softening point of 90-130°C) 20% - 40%

Antioxidant - Irganox 1010 1 - 3%

Active Medicine 0 - 30%
Release Liner Release Liner
Polyester or Paper coated with Silicon / Platinum 30-140 gsm
The above elastomers impart a backbone to the adhesive layer and impart elasticity to the adhesive compound. For imparting the characteristic to absorb a higher concentration of active medicine (in the form of an oil), it is recommended for the elastomer to have a high styrene content (>15%). High styrene content enables the elastomer to hold a higher dosage of oil without compromising on the cohesiveness of the adhesive. For imparting a hydrophilic characteristic to the adhesive, it is recommended to use a radial elastomer (Such as Kraton Dl 126) which increases the surface tension of the adhesive, in turn making it more wettable. It is preferred that the content of the above elastomer is in between 20% to 35% of the adhesive mass.
The aliphatic and aromatic resins as mentioned above can be hydrogenated to decrease its color and improve its stability towards heat, oxygen, and ultraviolet light. As an alternative to aliphatic and aromatic resins, rosin esters produced by the reaction between rosin acids and alcohols, can

be used as a tackifier component in the adhesive composition. For imparting the characteristic to absorb a higher concentration of active medicine (in the form of an oil), it is recommended for the tackifier to have a high softening point (preferably >110°C) so that the cohesiveness of the adhesive is not compromised as the content of the oil is increased. It is preferred that the content of the above tackifier is in between 20% to 60% of the adhesive mass.
In order to impart a hydrophilic characteristic to the adhesive, it is recommended to also add a Super Absorbent Polymer (SAP) to the adhesive. The SAP would absorb the water (or sweat) and from a gelling substance thereby preventing it forming a barrier between the skin and the adhesive. Recommended SAPs for the particular application would include Carboxymethylcellulose (CMC) and derivatives. It is preferred that the content of the SAP is in between 5% to 10% of the adhesive mass.
The above-mentioned penetration enhancer increases the topical porosity of the skin and allow better permeation of the active medicine. In the present invention, Menthol and Oleic Acid have been shown to have effective penetration enhancer properties. It is preferred that the content of the penetration enhancer is in between 5% to 10% of the adhesive mass.
The final component of the adhesive mass is the active medicine. The active medicine depends on the end application and suitability with the adhesive would depend on the cross-linking capability with the elastomer-tackifier complex. In one particular example, the actives consist of Methyl Salicylate, Menthol, Camphor, Eucalyptus Oil, Clove Oil and Turmeric oil. The total content of the above actives was 25-35% of the adhesive mass.
While the above is an example where the actives are in the form of an oil, wherever water soluble actives need to be incorporated, it is essential to add an emulsifier (such as Polyoxyethylene (20) sorbitan monooleate) to blend the active with plasticizer oil (whichever preferred among the plasticizers detailed above) and incorporate the same in the adhesive layer.
The total thickness of the adhesive layer depends on the rate of release and the duration of the Transdermal patch. This in turn depends on the molecular weight of the active compounds and the

concentration of the penetration enhancer in the composition of the patch. For the composition described in the example, the thickness of the adhesive layer is recommended to be in the range of 150to200gsm.
The transdermal patch prepared using the adhesive composition of the present invention comprises an elastic backing, the above described adhesive layer coated on one side of the backing and laminated with a release liner, wherein the stretchable support comprises a knitted fabric, the adhesive layer contains a hot melt adhesive coating and the release liner contains a silicon or platinum coated clay coated craft or glassine release paper or alternatively silicon or platinum coated polyester film.
The elastic backing may be suitable for anchoring the adhesive so that when applied on the skin, the adhesive layer does not detach from the backing. Suitable backing materials for the same include, knitted polyester fabrics, knitted cotton fabrics, woven cotton fabrics, nylon fabrics, polypropylene non-woven fabrics, viscose cotton / polyester non-woven fabrics, polyurethane films and multilayer LDPE based films. It is recommended for the backing layer to be elastic in nature (30 to 100%) so that it can conform to the bends of the body joints (such as knee or elbow). It is also recommended for the backing layer to be selectively porous (porous towards air and impermeable towards water). The thickness of the backing layer is recommended to be in the range of 100 to 300 microns.
The release liner provides a substrate to coat the adhesive layer on and also to provide a protective barrier to the adhesive layer. The release liner has a coating of a non-stick polymer such as Silicon or Platinum. These can be peeled off when the patch is intended to be used. Examples of release liners include Glasine or Clay Coated Craft Silicon Release Papers, or Platinum Coated Polyester Release films. The thickness of the release lines is recommended to be in the range of 80 to 150 microns.
Further, the transdermal patch of the present invention contains a blend of 5 powerful herbal pain relievers that provide instant and long-lasting relief from muscular pain, stiffness and joint pain.

The patch easily fits in a pocket and can be applied anytime, anywhere under the clothing without any greasiness, stickiness or smell.
As discussed earlier most of the transdermal patches come off due to perspiration - this is because the sweat from inside the body forms a barrier between the skin and the patch which causes the patch to lose contact with the skin. In one embodiment, the transdermal patch of the present invention has unique alternate layering of hydrophilic (water absorbent) and hydrophobic (water repelling) coats. The sweat is pushed out to the hydrophilic channels and therefore does not form a barrier between the patch and the skin, hence preventing the patch from coming off while excessive perspiration such as during exercise etc.
EXAMPLES:
The following products were made using the components and respective proportions as indicated in the Tables below: Example 1:

Component Description Ratio
Backing Layer Knitted Polyester Fabric 150 gsm
Adhesive Layer Radial Styrene-Isoprene-Styrene block copolymer with 18% Styrene Content 20%

Aliphatic Hydrocarbon Resin with a softening point of 115°C 30%

Carboxy Methyl Cellulose 5%

Antioxidant - Irganox 1010 2%

Napthenic Oil 10%

Methyl Salicylate 10%

Menthol 10%

Camphor 10%

Eucalyptus Oil 1.5%

Clove Oil 1.5%
Release Liner Platinum coated Polyester Release Liner 100 micron 141 gsm
Example 2:

Component Description Ratio

Backing Layer Knitted Polyester Fabric 150 gsm
Adhesive Layer Radial Styrene-Isoprene-Styrene block copolymer with 18% Styrene Content 25%

Aliphatic Hydrocarbon Resin with a softening point of 115°C 25%

Carboxy Methyl Cellulose 5%

Antioxidant - Irganox 1010 1%

Napthenic Oil 32%

Turmeric Powder 10%

Tween 80 2%
Release Liner Platinum coated Polyester Release Liner 100 micron 141 gsm
Example 3:

Component Description Ratio
Backing Layer Knitted Polyester Fabric 150 gsm
Adhesive Layer Radial Styrene-Isoprene-Styrene block copolymer with 18% Styrene Content 30%

Aliphatic Hydrocarbon Resin with a softening point of 115°C 34.9%

Antioxidant - Irganox 1010 2%

Mineral Oil 10%

Methyl Salicylate 7.0%

Menthol 7.0%

Camphor 7.0%

Eucalyptus Oil 1.05%

Clove Oil 1.05%
Release Liner Platinum coated Polyester Release Liner 100 micron 141 gsm
Example 4:

Component Description Ratio
Backing Layer , Knitted Polyester Fabric 150 gsm
Adhesive
Layer
Release
Liner
Component Linear Triblock Copolymer with Polystyrene content 15% 25%

Aliphatic Hydrocarbon Resin with a softening point of 115°C 25%

Antioxidant - Irganox 1010 1%

Mineral Oil 32%

Turmeric Oil 10%

Zinc Oxide 5%

Boric Acid 2%
Release Liner Glasine Release Paper 90 gsm
PROCESS FOR MAKING THE PRODUCT
The components of the adhesive layer shown in the above Table are put in a high shear mixer pre¬heated to 140°C in the following order: Napthenic Oil -> Aliphatic Hydrocarbon Resin -> Styrenic Block Copolymer -> Anti-oxidant -> CMC -> Actives. The mixing is carried out for a 50 kg total batch size for 1 hour at 150 rpm stirrer speed. The melt is then extruded out, coated onto the release liner at 140°C and laminated onto the backing layer. The coated laminate is then fed into a die-cutting machine to cut patches of the required size. The finished products are packed in 3 layer aluminium foil pouches.
ADVANTAGES
1. The present invention has an advantage that it describes a composition and preparation of such composition (having an adhesive medium capable of incorporating up to 35% of active medicine), without any disruption of adhesive composition.
2. The present invention describes composition of an adhesive medium that has a part hydrophilic characteristic to maintain adhesion during perspiration, hence overcoming the prior art problem.
3. The present invention describes the composition of an adhesive that can in part incorporate water soluble active compounds.
4. The transdermal patch of the present invention is sweat proof and efficient in relieving pain and healing wounds.

We claim:
1. A transdermal drug delivery patch comprising:
a backing layer having thickness in a range of 100 to 300 microns;
an adhesive layer having a thickness of 150 to 200 gsm;
a release liner having thickness in a range of 80 to 150 microns, wherein said release liner
is a removable transparent protective film.
2. The transdermal drug delivery patch as claimed in claim 1, wherein said backing layer is comprised of knitted polyester fabrics, knitted cotton fabrics, woven cotton fabrics, nylon fabrics, polypropylene non-woven fabrics, viscose cotton / polyester non-woven fabrics, polyurethane films and multilayer LDPE based films and combinations thereof.
3. The transdermal drug delivery patch as claimed in claim 1, wherein said adhesive layer is comprised of an adhesive preparation comprising:
a thermoplastic styrenic block elastomer;
a tackifier;
a plasticizer;
an anti-oxidant;
an active medicine and optionally a super absorbent polymer (SAP) in various
combinations.
4. The transdermal patch as claimed in claim 3, wherein said thermoplastic styrenic block elastomer is based on Styrene-Isoprene-Styrene (SIS) or Styrene-Butadiene-Styrene (SBS) or Styrene- Ethylene/Butylene-Styrene (SEBS) block copolymers or Linear Triblock Copolymer.
5. The transdermal patch as claimed in claim 4, wherein said thermoplastic styrenic block elastomer is in the range of 20% to 35% of the adhesive mass.
6. The transdermal patch as claimed in claim 3, wherein said tackifier is a petroleum-based resin including aliphatic and aromatic resins obtained as by-products of naptha-cracking.
7. The transdermal patch as claimed in claim 6, wherein said tackifier is in the range of 20% to 60% of the adhesive mass.

The transdermal patch as claimed in claim 3, wherein said plasticizer is selected from Napthenic Oil, White Mineral Oil, Paraffinic Oils, Silicon Oils or Plant Oils.
The transdermal patch as claimed in claim 8, wherein said plasticizer is in the range of 5% to 20% of the adhesive mass.
The transdermal patch as claimed in claim 3, wherein said anti-oxidant is selected from Irganox 1010 and Irganox 1098.
The transdermal patch as claimed in claim 10, wherein said anti-oxidant is in the range of 0.1% to 2% of the adhesive mass.
The transdermal patch as claimed in claim 3, wherein said active medicine comprises Methyl Salicylate, Menthol, Camphor, Eucalyptus Oil, Clove Oil, Turmeric Oil and combinations thereof.
The transdermal patch as claimed in claim 12, wherein said active medicine is in the range of 25-35% of the adhesive mass.
The transdermal patch as claimed in claim 3, wherein said adhesive preparation optionally comprises penetration enhancer selected from Menthol and Oleic Acid in a range of 5% to 10% of the adhesive mass.
The transdermal patch as claimed in claim 3, wherein said adhesive preparation optionally comprises a skin protective agent selected from zinc oxide and boric acid.
The transdermal patch as claimed in claim 3, wherein said super absorbent polymer is carboxymethylcellulose (CMC).
The transdermal patch as claimed in claim 1, wherein the adhesive layer is either coated on complete surface or in form of strips.

18. The transdermal patch as claimed in claim 17, wherein the transdermal patch with strips is a sweat proof transdermal patch having alternate hydrophilic and hydrophobic channels.
19. The transdermal patch as claimed in claim 1, wherein said release liner is selected from Glasine or Clay Coated Craft Silicon Release Papers, or Platinum Coated Polyester Release films and combinations thereof.
20. A method of preparing a sweat proof transdermal patch as claimed in claim 1, wherein said method comprises the steps of:
providing the components of the adhesive layer in a high shear mixer pre-heated to 140°C;
mixing said component in a 50kg total batch size for 1 hour at 150 rpm stirrer speed; extruding the melt and coating the same onto the release liner at 140°C; laminating the backing layer with extruded melt;
feeding the coated laminate into a die-cutting machine to cut patches of the required size; packing the finished products in three-layer aluminium foil pouches.
21. The method of preparing a sweat proof transdermal patch as claimed in claim 18, wherein in said size of patch is 22.5 cm2, 50 cm2, 75 cm2, 140 cm2, 200 cm2 or 220 cm2.
22. The transdermal patch as claimed in claim 1 for relieving muscular pain, stiffness and joint pain.
23. The transdermal patch as claimed in claim 1, wherein said transdermal patch comprises turmeric oil as an active medicine and is capable of healing wounds.