CA2228034A1 - Transdermal patch containing aspirin - Google Patents
Transdermal patch containing aspirin Download PDFInfo
- Publication number
- CA2228034A1 CA2228034A1 CA 2228034 CA2228034A CA2228034A1 CA 2228034 A1 CA2228034 A1 CA 2228034A1 CA 2228034 CA2228034 CA 2228034 CA 2228034 A CA2228034 A CA 2228034A CA 2228034 A1 CA2228034 A1 CA 2228034A1
- Authority
- CA
- Canada
- Prior art keywords
- adhesive
- patch
- transdermal patch
- aspirin
- transdermal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 229960001138 acetylsalicylic acid Drugs 0.000 title claims abstract description 39
- 239000000853 adhesive Substances 0.000 claims abstract description 32
- 230000001070 adhesive effect Effects 0.000 claims abstract description 32
- 238000005406 washing Methods 0.000 claims abstract description 9
- 230000000694 effects Effects 0.000 claims description 10
- 229920000728 polyester Polymers 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000012466 permeate Substances 0.000 claims description 6
- 230000036470 plasma concentration Effects 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 5
- 238000009792 diffusion process Methods 0.000 claims description 4
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 claims description 4
- 229920002126 Acrylic acid copolymer Polymers 0.000 claims description 3
- 239000003961 penetration enhancing agent Substances 0.000 claims description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 claims description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 claims description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 claims description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000005642 Oleic acid Substances 0.000 claims description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 claims description 2
- 229940087305 limonene Drugs 0.000 claims description 2
- 235000001510 limonene Nutrition 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- 230000002459 sustained effect Effects 0.000 claims description 2
- 239000011248 coating agent Substances 0.000 claims 1
- 238000000576 coating method Methods 0.000 claims 1
- 229940079593 drug Drugs 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 239000010410 layer Substances 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 238000010579 first pass effect Methods 0.000 description 3
- 230000001839 systemic circulation Effects 0.000 description 3
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 3
- 230000037317 transdermal delivery Effects 0.000 description 3
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229920001296 polysiloxane Polymers 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 206010002388 Angina unstable Diseases 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010017788 Gastric haemorrhage Diseases 0.000 description 1
- 229920002367 Polyisobutene Polymers 0.000 description 1
- 208000007718 Stable Angina Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 206010000891 acute myocardial infarction Diseases 0.000 description 1
- 239000002313 adhesive film Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000702 anti-platelet effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960002380 dibutyl phthalate Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000000328 pro-aggregatory effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 150000003595 thromboxanes Chemical class 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/612—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid
- A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
- A61K31/618—Salicylic acid; Derivatives thereof having the carboxyl group in position 1 esterified, e.g. salsalate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
- A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
- A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
- A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
- A61K9/7061—Polyacrylates
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
A transdermal patch contains aspirin as a pharmaceutically active product having platelet washing properties. The patch comprises a backing, an adhesive for applying the patch and a liner which is released to app ly the patch. The aspirin is incorporated into the adhesive.
Description
W O 97/04759 - 1 - PcT/~ col5 TRANS~t~ ~L PATCH CONTAINING ASPIRIN
The invention relates to a transdermal delivery system.
? Aspirin, which has been available for about 100 years, possesses analgesic, anti-inflammatory and antipyretic ~ properties. This compound has also been shown to be effective in cardiovascular disease and this action is dependent upon its effects on platelet function. Aspirin can improve the mortality figures associated with acute myocardial infarction and reduces the risk of this in patients with unstable angina by between 30 and 50%. It is used to prevent re-occurrence in those patients after recovery from myocardial infarction. It is also likely to be of benefit to individuals suffering from stable angina since it reduces the risk of myocardial infarction in apparently healthy, middle-aged men. Aspirin is used to reduce the likelihood of stroke in patients with transient cerebral ischaemic attacks. It also lowers the risk of thromboembolism in patients with atrial fibrillation and following valve replacement.
Aspirin reduces platelet aggregation by irreversibly inhibiting fatty acid cyclo-oxygenase, a precursor in the biosynthesis of prostaglandins and thromboxanes. This occurs by acetylation of a serine residue and thus prevents access of arachidonic acid to the active site by steric hindrance. Thromboxane A2 is the main cyclo-oxygenase produce of activated platelets and is proaggregatory and a vasoconstrictor. Therefore, aspirin exerts its antithrombotic action by preventing thromboxane A2 biosynthesis. Although other non-steroidal anti-inflammatory drugs also possess this effect they are much less effective because, unlike aspirin, they reversibly inhibit the enzyme.
W O 97/04759 PCT~E96~ 9 Although the use of oral aspirin has been used for these conditions, there are a number of disadvantages associated with this treatment. The compound has been associated with various gastrointestinal side effects the most severe of which can be gastric bleeding occurring in about 70% of patients taking oral aspirin. Furthermore, the drug is extensively hydrolysed by first-pass metabolism and possesses a half life of about 15 minutes. Salicylic acid, a metabolite of aspirin, has no anti-platelet activity.
Therefore, the development of a suitable transdermal delivery system for aspirin would avoid the side-effects detailed above and would also prevent first-pass metabolism.
According to the invention, there is provided a transdermal patch cont~ining aspirin as a pharmaceutically active product having platelet washing properties, the patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch, wherein the aspirin is incorporated into the adhesive.
The invention also provides a transdermal patch for sustained transdermal administration of aspirin to a patient in need of platelet washing effect comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
The invention further provides use of aspirin for preparing a transdermal patch comprising a backing, an adhe~ive for applying the patch, and a liner which is released to apply the patch, in which aspirin i8 W O 97/04759 PCT/1~5Gl'~lg incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
In another aspect, the invention provides a method for S achieving a platelet washing effect in a patient comprising the step of applying a transdermal patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch to the patient's skin, aspirin being incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
Preferably the adhesive is a pressure sensitive adhesive, based, for example, on acrylic acid copolymers.
In one embodiment of the invention, the adhesive is applied to the release liner. Typically, the release liner is a fluoro-polymeric-coated polyester.
Preferably, the backing comprises a backing layer attached to the adhesive. Typically the backing layer comprises aluminised polyester. In one case the aluminised polyester is sputter coated onto the adhesive.
In another embodiment of the invention the patch includes a penetration enhancer to promote the diffusion of the ph~r~ceutically active product.
The invention also provides a method for producing a transdermal patch comprising the steps of incorporating a pharmaceutically active product having platelet washing properties into an adhesive.
The invention further provides a transdermal patch whenever produced by the method of the invention.
W O 97/04759 . PCTil~5/ -_19 In another aspect, the invention provides a method for reducing platelet aggregation in a patient comprising the step of applying to a patient a transdermal patch of the invention.
The purpose of the present invention is to develop a stable transdermal patch system which will deliver sufficient aspirin to the systemic circulation to reduce platelet aggregation. It i8 a further purpose of this invention to deliver sufficient aspirin to inhibit thromboxane A2 production associated with the platelets but not prostacyline production occurring within the venous endothelium.
The invention will be more clearly understood from the following description thereof given by way of example only with reference to Fig. 1 which is a diagrammatic cross sectional view of a transdermal patch according to the invention.
Referring to Fig. 1, there is illustrated a transdermal patch according to the invention comprising a pressure sensitive adhesive layer (b) into which the aspirin is incorporated, a release liner (c) and a backing (a).
Aspirin has been incorporated directly into a pressure sensitive adhesive such as, but not limited to, acrylic acid copolymers (b). This mixture can then be cast, rolled or knife-coated onto a suitable release-liner such as, but not limited to, a siliconised polyester (c). A
backing-layer such as, but not limited to, a sputter-coated aluminised polyester (to prevent drug strike through) can then be attached (a). The release-liner (c) is ~ ,ved before the drug contAining adhesive is presented to the skin.
W O 97/04759 PCT~E9G~ 19 S
Unusually, this patch has been designed so that skin acts as the rate-determining membrane to drug diffusion. The advantage of this type of system is that it provides the most efficient delivery of drug through the skin. This, in turn, will provide the smallest unit area of skin for drug delivery and hence the smallest patch size. This is an important consideration given the possible daily amounts of drug required by the transdermal route. A
further advantage of this invention is that aspirin can be delivered systemically avoiding first-pass metabolism.
Furthermore, delivering aspirin transdermally will also prevent adverse side-effects on the gastrointestinal tract.
A further aspect to this invention is the use of various penetration enhancers to promote the diffusion of aspirin through the skin to the systemic circulation. This would also reduce the size (area) of patch required to deliver a given amount of aspirin to the systemic circulation.
Examples of such penetration enhancers include, but is not limited to, propylene glycol, oleic acid, isopropyl myristate, dimethylsulphoxide, ethanol, and/or limonene.
A variety of suitable matrices may be used as a drug reservoir. These include the above mentioned acrylate co-polymers, polyisobutylenes and silicone-based adhesives.
Other excipients present in the formulation may include plasticisers such as diethylphthalate, dibutylphthalate, glycerol.
Example 1 A transdermal delivery system for aspirin was prepared in the following way. A pressure sensitive adhesive solution (PSA) was prepared using Duro-Tak 387-2054 dissolved in ethyl acetate. Aspirin (200 mg) was dissolved in 20 g of W O 97/04759 . PCT/lh~G~ 9 PSA and cast onto a siliconised release liner using a 10 x 10 cm template. The film was oven dried after which an aluminium sputter-coated polyester backing layer was attached to the exposed, drug-containing, adhesive film (dry weight 5 g). Thereafter, 1 cm2 sections were cut from the laminate and examined for drug release using silicone-based (Silescol) sheeting in a modified Franz cell (Fig.
2).
Patches (5 x 5 cm2) were also applied to 5 human volunteers for a 24 hour period. Thereafter, the patches were removed and extracted for remaining aspirin. It can be seen from Fig. 3 that, typically 30 - 40~ of the drug had been absorbed from the patches within a 24 hour period.
DURO-TAK sre a range of adhesives available from National Starch.
Silescol is manufactured by Esco Rubber and is available from Bibby Sterilin.
The invention is not limited to the embodiments hereinbefore described which may be varied in detail.
The invention relates to a transdermal delivery system.
? Aspirin, which has been available for about 100 years, possesses analgesic, anti-inflammatory and antipyretic ~ properties. This compound has also been shown to be effective in cardiovascular disease and this action is dependent upon its effects on platelet function. Aspirin can improve the mortality figures associated with acute myocardial infarction and reduces the risk of this in patients with unstable angina by between 30 and 50%. It is used to prevent re-occurrence in those patients after recovery from myocardial infarction. It is also likely to be of benefit to individuals suffering from stable angina since it reduces the risk of myocardial infarction in apparently healthy, middle-aged men. Aspirin is used to reduce the likelihood of stroke in patients with transient cerebral ischaemic attacks. It also lowers the risk of thromboembolism in patients with atrial fibrillation and following valve replacement.
Aspirin reduces platelet aggregation by irreversibly inhibiting fatty acid cyclo-oxygenase, a precursor in the biosynthesis of prostaglandins and thromboxanes. This occurs by acetylation of a serine residue and thus prevents access of arachidonic acid to the active site by steric hindrance. Thromboxane A2 is the main cyclo-oxygenase produce of activated platelets and is proaggregatory and a vasoconstrictor. Therefore, aspirin exerts its antithrombotic action by preventing thromboxane A2 biosynthesis. Although other non-steroidal anti-inflammatory drugs also possess this effect they are much less effective because, unlike aspirin, they reversibly inhibit the enzyme.
W O 97/04759 PCT~E96~ 9 Although the use of oral aspirin has been used for these conditions, there are a number of disadvantages associated with this treatment. The compound has been associated with various gastrointestinal side effects the most severe of which can be gastric bleeding occurring in about 70% of patients taking oral aspirin. Furthermore, the drug is extensively hydrolysed by first-pass metabolism and possesses a half life of about 15 minutes. Salicylic acid, a metabolite of aspirin, has no anti-platelet activity.
Therefore, the development of a suitable transdermal delivery system for aspirin would avoid the side-effects detailed above and would also prevent first-pass metabolism.
According to the invention, there is provided a transdermal patch cont~ining aspirin as a pharmaceutically active product having platelet washing properties, the patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch, wherein the aspirin is incorporated into the adhesive.
The invention also provides a transdermal patch for sustained transdermal administration of aspirin to a patient in need of platelet washing effect comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
The invention further provides use of aspirin for preparing a transdermal patch comprising a backing, an adhe~ive for applying the patch, and a liner which is released to apply the patch, in which aspirin i8 W O 97/04759 PCT/1~5Gl'~lg incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
In another aspect, the invention provides a method for S achieving a platelet washing effect in a patient comprising the step of applying a transdermal patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch to the patient's skin, aspirin being incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
Preferably the adhesive is a pressure sensitive adhesive, based, for example, on acrylic acid copolymers.
In one embodiment of the invention, the adhesive is applied to the release liner. Typically, the release liner is a fluoro-polymeric-coated polyester.
Preferably, the backing comprises a backing layer attached to the adhesive. Typically the backing layer comprises aluminised polyester. In one case the aluminised polyester is sputter coated onto the adhesive.
In another embodiment of the invention the patch includes a penetration enhancer to promote the diffusion of the ph~r~ceutically active product.
The invention also provides a method for producing a transdermal patch comprising the steps of incorporating a pharmaceutically active product having platelet washing properties into an adhesive.
The invention further provides a transdermal patch whenever produced by the method of the invention.
W O 97/04759 . PCTil~5/ -_19 In another aspect, the invention provides a method for reducing platelet aggregation in a patient comprising the step of applying to a patient a transdermal patch of the invention.
The purpose of the present invention is to develop a stable transdermal patch system which will deliver sufficient aspirin to the systemic circulation to reduce platelet aggregation. It i8 a further purpose of this invention to deliver sufficient aspirin to inhibit thromboxane A2 production associated with the platelets but not prostacyline production occurring within the venous endothelium.
The invention will be more clearly understood from the following description thereof given by way of example only with reference to Fig. 1 which is a diagrammatic cross sectional view of a transdermal patch according to the invention.
Referring to Fig. 1, there is illustrated a transdermal patch according to the invention comprising a pressure sensitive adhesive layer (b) into which the aspirin is incorporated, a release liner (c) and a backing (a).
Aspirin has been incorporated directly into a pressure sensitive adhesive such as, but not limited to, acrylic acid copolymers (b). This mixture can then be cast, rolled or knife-coated onto a suitable release-liner such as, but not limited to, a siliconised polyester (c). A
backing-layer such as, but not limited to, a sputter-coated aluminised polyester (to prevent drug strike through) can then be attached (a). The release-liner (c) is ~ ,ved before the drug contAining adhesive is presented to the skin.
W O 97/04759 PCT~E9G~ 19 S
Unusually, this patch has been designed so that skin acts as the rate-determining membrane to drug diffusion. The advantage of this type of system is that it provides the most efficient delivery of drug through the skin. This, in turn, will provide the smallest unit area of skin for drug delivery and hence the smallest patch size. This is an important consideration given the possible daily amounts of drug required by the transdermal route. A
further advantage of this invention is that aspirin can be delivered systemically avoiding first-pass metabolism.
Furthermore, delivering aspirin transdermally will also prevent adverse side-effects on the gastrointestinal tract.
A further aspect to this invention is the use of various penetration enhancers to promote the diffusion of aspirin through the skin to the systemic circulation. This would also reduce the size (area) of patch required to deliver a given amount of aspirin to the systemic circulation.
Examples of such penetration enhancers include, but is not limited to, propylene glycol, oleic acid, isopropyl myristate, dimethylsulphoxide, ethanol, and/or limonene.
A variety of suitable matrices may be used as a drug reservoir. These include the above mentioned acrylate co-polymers, polyisobutylenes and silicone-based adhesives.
Other excipients present in the formulation may include plasticisers such as diethylphthalate, dibutylphthalate, glycerol.
Example 1 A transdermal delivery system for aspirin was prepared in the following way. A pressure sensitive adhesive solution (PSA) was prepared using Duro-Tak 387-2054 dissolved in ethyl acetate. Aspirin (200 mg) was dissolved in 20 g of W O 97/04759 . PCT/lh~G~ 9 PSA and cast onto a siliconised release liner using a 10 x 10 cm template. The film was oven dried after which an aluminium sputter-coated polyester backing layer was attached to the exposed, drug-containing, adhesive film (dry weight 5 g). Thereafter, 1 cm2 sections were cut from the laminate and examined for drug release using silicone-based (Silescol) sheeting in a modified Franz cell (Fig.
2).
Patches (5 x 5 cm2) were also applied to 5 human volunteers for a 24 hour period. Thereafter, the patches were removed and extracted for remaining aspirin. It can be seen from Fig. 3 that, typically 30 - 40~ of the drug had been absorbed from the patches within a 24 hour period.
DURO-TAK sre a range of adhesives available from National Starch.
Silescol is manufactured by Esco Rubber and is available from Bibby Sterilin.
The invention is not limited to the embodiments hereinbefore described which may be varied in detail.
Claims (20)
1. A transdermal patch containing aspirin as a pharmaceutically active product having platelet washing properties, the patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch, wherein the aspirin is incorporated into the adhesive.
2. A transdermal patch as claimed claim 1 wherein the adhesive is a pressure sensitive adhesive.
3. A transdermal patch as claimed in claim 2 wherein the adhesive is based on acrylic acid copolymers.
4. A transdermal patch as claimed in any preceding claim wherein the adhesive is applied to the release liner.
5. A transdermal patch as claimed in any preceding claim wherein the release liner is a fluoropolymeric-coated polyester.
6. A transdermal patch as claimed in claim 5 wherein the liner is a siliconised release liner.
7. A transdermal patch as claimed in any preceding claim wherein the backing comprises a backing layer attached to the adhesive.
8. A transdermal patch as claimed in any preceding claim wherein the backing layer comprises aluminised polyester.
9. A transdermal patch as claimed in claim 8 wherein the aluminised polyester is sputter coated onto the adhesive.
10. A transdermal patch as claimed in any preceding claim including a penetration enhancer to promote the diffusion of the pharmaceutically active product.
11. A transdermal patch as claimed in claim 10 wherein the penetration enhancer is selected from one or more of propylene glycol, oleic acid, isopropyl myristate, dimethylsulphoxide, ethanol and/or limonene.
12. A transdermal patch substantially as hereinbefore described with reference to the example and drawings.
13. A method for producing a transdermal patch comprising the steps of incorporating a pharmaceutically active product having platelet washing properties into an adhesive, coating the adhesive onto a release liner, and applying a backing layer.
14. A method for producing a transdermal patch substantially as hereinbefore described with reference to the examples and drawings.
15. A transdermal patch whenever produced by a method as claimed in claim 13 or 14.
16. A method for reducing platelet aggregation in a patient comprising the step of applying to a patient a transdermal patch as claimed in any of claims 1 to 12 or 15.
17. A method for reducing platelet aggregation in a patient substantially as hereinbefore described with reference to the examples and drawings.
18. A transdermal patch for sustained transdermal administration of aspirin to a patient in need of platelet washing effect comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
19. Use of aspirin for preparing a transdermal patch comprising a backing, an adhesive for applying the patch, and a liner which is released to apply the patch, in which aspirin is incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
20. A method for achieving a platelet washing effect in a patient comprising the step of applying a transdermal patch comprising a backing, an adhesive for applying the patch and a liner which is released to apply the patch to the patient's skin, aspirin being incorporated in the adhesive in an amount sufficient to transdermally permeate the skin and achieve desired plasma levels.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE950575 | 1995-07-26 | ||
| IE950575 | 1995-07-27 | ||
| IE960368 | 1996-05-27 | ||
| IE960368 | 1996-05-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2228034A1 true CA2228034A1 (en) | 1997-02-13 |
Family
ID=26319840
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2228034 Abandoned CA2228034A1 (en) | 1995-07-26 | 1996-07-26 | Transdermal patch containing aspirin |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0840600A1 (en) |
| JP (1) | JPH11510157A (en) |
| AU (1) | AU6709196A (en) |
| CA (1) | CA2228034A1 (en) |
| GB (1) | GB2319473A (en) |
| WO (1) | WO1997004759A1 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19616539A1 (en) * | 1996-04-25 | 1997-11-06 | Luitpold Pharma Gmbh | Alcoholic solutions containing acetylsalicylic acid for percutaneous use, their use for antithrombotic therapy and medicines |
| JPH1112177A (en) * | 1997-06-25 | 1999-01-19 | Teikoku Seiyaku Co Ltd | Stable aspirin-containing preparation for external use |
| DE19959913A1 (en) * | 1999-12-11 | 2001-06-28 | Lohmann Therapie Syst Lts | Transdermal system for the treatment of migraines containing acetylsalicylic acid |
| FR2924349B1 (en) | 2007-12-03 | 2010-01-01 | Dbv Tech | ALLERGEN DISENSIBILITY METHOD |
| FR2926466B1 (en) * | 2008-01-23 | 2010-11-12 | Dbv Tech | METHOD FOR MANUFACTURING PATCHES BY ELECTROSPRAY |
| WO2011076401A1 (en) | 2009-12-23 | 2011-06-30 | Holger Schankin | Substantially water-free pharmaceutical compositions containing acetylsalicylic acid |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP921157A2 (en) * | 1991-12-20 | 1994-10-31 | Lohmann Therapie Syst Lts | Transdermal system of applying acetilsalicilyc acid in antithrombosys therapy |
| DE4332093C2 (en) * | 1993-09-22 | 1995-07-13 | Lohmann Therapie Syst Lts | Transdermal therapeutic system with the active ingredient acetylsalicylic acid and process for its preparation |
-
1996
- 1996-07-26 AU AU67091/96A patent/AU6709196A/en not_active Abandoned
- 1996-07-26 JP JP9507419A patent/JPH11510157A/en active Pending
- 1996-07-26 CA CA 2228034 patent/CA2228034A1/en not_active Abandoned
- 1996-07-26 EP EP96927180A patent/EP0840600A1/en not_active Withdrawn
- 1996-07-26 GB GB9801409A patent/GB2319473A/en not_active Withdrawn
- 1996-07-26 WO PCT/IE1996/000049 patent/WO1997004759A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| JPH11510157A (en) | 1999-09-07 |
| WO1997004759A1 (en) | 1997-02-13 |
| EP0840600A1 (en) | 1998-05-13 |
| GB9801409D0 (en) | 1998-03-18 |
| GB2319473A (en) | 1998-05-27 |
| AU6709196A (en) | 1997-02-26 |
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