Drug – bio-affecting and body treating compositions – Designated organic nonactive ingredient containing other... – Solid synthetic organic polymer
Reexamination Certificate
1999-05-21
2001-04-03
Kulkosky, Peter F. (Department: 1615)
Drug, bio-affecting and body treating compositions
Designated organic nonactive ingredient containing other...
Solid synthetic organic polymer
C514S946000, C424S449000
Reexamination Certificate
active
06211250
ABSTRACT:
FIELD OF THE INVENTION
The present invention is concerned with a system suitable for the percutaneous delivery, particularly transdermal delivery of active agent. The invention also relates to a method of percutaneous delivery of actives and to therapeutic or prophylactic methods of treatment of a subject by percutaneous delivery of an active agent.
BACKGROUND TO THE INVENTION
The term “active agent” as used herein is intended to denote substances that have a physiological effect, for example, a drug. The term “homogenous” as used herein is intended to mean uniform throughout. The term “film forming” as used herein is intended to mean a substance capable of forming a thin layer on the surface to which it is applied and when exposed to ambient conditions. The term “liquid” as used herein is intended to mean a substance which is flowable. The term “percutaneous” as used herein is intended to mean any route of administering an active agent onto, into or through the skin of a subject so as to achieve one or more of a topical, local or systemic physiological effect.
The use of the skin as a route for delivery of drugs is of relatively recent origin. One form of delivery system is that based on the use of an adhesive transdermal patch. These transdermal patches provide an alternative non-invasive parenteral route for the delivery of drugs which may or may not be suitable for oral administration. An example of an early form of a transdermal patch is described in U.S. Pat. No. 3,598,122 where the patch is in the form of a bandage.
Conventional routes of drug administration suffer several disadvantages when compared to the percutaneous route of drug administration. The percutaneous route of delivery may allow for the controlled release of an active agent into the systemic circulation. Many drugs are poorly absorbed by traditional routes of delivery and it has been found that the percutaneous route provides an effective method of achieving improved bioavailability for those active agents.
Examples of the uses of transdermal patches include treatment of nicotine addiction using nicotine containing patches, hormone replacement therapy, treatment of travel sickness using hyoscine, angina using glyceryltrinitrate, treatment of rheumatism using flurbiprofen or ibuprofen, and intractable pain relief using fentanyl. Other examples of transdermal patches are clonidine patches for vasoconstrictor therapy and treatment of migraine (see, for example, U.S. Pat. No. 4,201,211), oestradiol patches for treatment of osteoporosis, oestradiol
orethisterone patches, and oestrogen/progesterone patches. The world therapeutic patch market is expected to increase significantly over the next few years.
Existing transdermal patches usually comprise a layer including the active and an adhesive layer and rely on the adhesive layer for attachment of the patch to the skin of a subject. This delivery system involves incorporation of the medicament into a carrier such as a polymeric matrix and/or pressure-sensitive adhesive formulation. The adhesive must adhere to the skin and permit migration of the medicament from the carrier through the skin into the bloodstream of the subject. The medicament may be included in the polymeric matrix or the adhesive layer or both.
An example of an adhesive transdermal delivery system is described in Australian patent 670033. This patent describes a dermal composition comprising a blend of a polyacrylate and a second polymer selected from polysiloxane or a hydrocarbon polymer, wherein the polyacrylate and the second polymer are mutually insoluble or immiscible polymers and a drug wherein the composition is a pressure-sensitive adhesive.
Adhesive based transdermal systems suffer a number of disadvantages. A major disadvantage is that the adhesive is responsible for an adverse skin reaction in about 30% of individuals. Current skin patches are occlusive and prevent the skin from transpiring. Moreover the skin area to which the adhesive patch may be applied is restricted to a non-hairy area of the skin that is substantially free of wrinkles, crease and folds. Furthermore, the wearer of an adhesive patch is aware of its presence because of the its inability to stretch with the skin on body movement.
In a related art there exist topical creams for delivery of active agents for treatment of certain skin diseases. One such disclosure is that of U.S. Pat. No. 4,935,241 in the name of SHIONOGI & CO LTD. This patent describes a pharmaceutical formulation for localised treatment of tinea pedis which comprises a topical cream including an active agent and an ethyl acrylate-methyl methacrylate copolymer.
An objective of the present invention is to provide a system for the percutaneous delivery of one or more active agents which system avoids, or mitigates at least in part, one or more of the disadvantages attending prior art adhesive transdermal patches. In particular, the compositions developed should be non-occlusive, rate variable and effective in delivering an active agent to have a systemic, topical or local effect upon a subject.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides, in one aspect, a substantially homogenous liquid composition capable of percutaneous delivery of one or more physiologically active agents, the composition including at least one rate modulating polymer, a volatile solvent and at least one physiologically active agent, said rate modulating polymer being selected to enable modulation of the rate of delivery of said physiologically active agent.
An advantage of the present invention is that the composition of the invention can be dispensed onto, and rubbed into the skin of a subject to form a thin film on the skin surface, this film providing for the percutaneous delivery of the one or more actives contained in the composition. The composition may be applied to the selected skin surface of skin and rubbed onto the skin until a suitable thickness of film is formed. Unlike conventional transdermal patches, the transdermal system of the present invention does not require the use of an adhesive layer. Moreover, it is robust (resistant to accidental removal), waterproof and has good substantivity on the skin. It has additionally been found that the formulations according to the invention can be varied by altering the nature of the modulating polymer to alter the rate of release of the active agent into the skin of the patient. In particular it is found that the use of the modulating polymer enables the formation of a reservoir of active agent on the skin of the patient which can be absorbed by the skin at a varying rate depending on the other components of the formulation.
Although it is preferred that the skin surface be non-hairy, the presence of hair does not create as significant a problem as is the case with adhesive patches. Similarly the presence of wrinkles, creases and folds in the skin are not an impediment to the application of the composition of the invention to a particular area of the body, although it is preferable to avoid areas that have significant creasing or folds. Moreover the film that is formed is unobtrusive to the subject in that the subject is not significantly aware of its presence on the skin.
The composition according to the invention may also preferably include a second polymer which may be of opposite water affinity to the first polymer. For example, where the first polymer is hydrophobic, the second polymer may be hydrophilic and vice versa. The percutaneous composition of the invention preferably includes at least one hydrophobic polymer and at least one hydrophilic polymer, one of which is selected to enable modulation of the rate of delivery of said physiologically active agent.
Where a hydrophobic polymer and a hydrophilic polymer are used, the composition may be such that when applied to the skin, the volatile solvent may evaporate leaving a two-phase film. The formed film may include a continuous phase and a dispersed phase. The hydrophilic polymer may form the continuous phase and the hydrophobic polymer may form
Davey Greg
Tomlinson Rod
Kulkosky Peter F.
Ostrolenk Faber Gerb & Soffen, LLP
Soltec Research Pty Ltd.
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