Although there are several skin patch compositions available on the market, which can be used for forming a protective film over a wound, they are associated with a number of problems. The spray-on skin patches presently known basically take the form of a water insoluble polymer dissolved in an organic solvent, with an appropriate propellant that will allow it to be applied in an aerosol form. A significant disadvantage with such compositions is that after being applied to the skin and being left to dry a non-porous film structure is formed that prevents the passage across it of gasses or moisture. The failure to allow moisture to move away from the wound results in excess moisture being trapped beneath the film surface causing depredation of the wound, and the possibility of infection.
It is also problematic that due to delivery via an aerosol means with the aid of a propellant, the spray-on skin patch is applied at a high pressure and can cause pain or discomfort to the patient when applied to a wound area. It has previously not been thought possible to eliminate the propellant from such compositions in order that the composition can be administered under lower pressure, the reason being that it was generally believed the presence of propellant was essential to prevent the clogging of the spraying nozzle through which the composition is applied.
Use of known spray-on skin patch composition has also been demonstrated in the past to allow the growth of microorganisms beneath the film covering that can lead to wound infection as indicated above.
The prevention or treatment of local or topical disease states or conditions of the skin has traditionally used simple non-occlusive delivery systems. These drug delivery systems usually include a volatile and/or non-volatile medium where a composition of the drug and medium is topically applied to the skin, in the vicinity of or directly on the area of skin to be treated. These delivery systems usually take the form of emulsion, creams, ointments, foams, gels, liquids, sprays and aerosols. Such delivery systems are generally used to treat skin inflammations, fungal and bacterial topical infection, soft-tissue contusions, parasites and topical analgesia. The limitation with this type of delivery system is that systemic drugs are generally not suitable for this type of administration, due to various factors possibly including the short interval of application. Some major problems with the current state of the art relate to a lack of efficacy of systemic drugs because of the low drug flux across the skin, inability to adequately control the rate of drug delivery, or the requirement for a very large application area. Problems with the poor dermal penetration of drugs is that the drug can be easily washed off, or transferred to clothes, other surfaces.
The dermal delivery of drugs may represent one of the oldest form of drug delivery in human history. Resins and animal fats were probably used by humans in early times to treat damage to the skin resulting from injuries and burns. Such substances for local delivery of active substances remained largely unchanged until as late as this century. The concept of transdermal systemic drug delivery was first seriously advocated by Dr. Alejandro Zaffaroni, for example, in U.S. Pat. Nos. 3,598,122 and 3,731,683 from the early 1970s. Transdermal systemic drug delivery provides an effective method of achieving improved bioavailability for physiologically active substances where the drugs are poorly absorbed by traditional routes of delivery, and/or when oral dosing is poorly tolerated or not possible.
Transdermal formulations are however limited. For example, polar drugs tend to penetrate the skin too slowly. Since most drugs are of a polar nature this limitation is significant, as is the fact that many drugs cause irritation at the site of topical application.
One common method known for assisting the rate of penetration of drugs across the skin is to increase the thermodynamic activity of the drug. The thermodynamic activity of a drug is proportional to the concentration of the drug and the selection of the vehicle. According to the laws of thermodynamics, the maximum activity of a drug is related to that of the pure drug crystal.
From the 1970s a principal focus of transdermal systemic drug delivery has been, and remains, on transdermal patch devices. These patch devices are like bandages which are attached to the surface of intact skin for prolonged periods of time to allow a desired systemic delivery of a drug or other physiologically active agent. These transdermal patch devices occlude the skin and trap the drug, together with volatiles and vehicle excipients, between the skin and an outer impermeable backing membrane. The membrane prevents the evaporation or diffusion of vehicle excipients, volatiles and drag into an environment other than the specific target skin site. The prolonged length of time required for transfer of the drug and excipients from the patch into the skin often results in local skin irritation. The irritation is caused by prolonged contact on the skin by the drug, volatiles, vehicle excipients, or the adhesive used to attach the patch device to the skin. The occlusive nature of the patch device also restricts the natural ability of the skin to “breathe”, this being uncomfortable and increasing the risk of irritation. With added problems of complex and costly manufacturing processes for transdermal patch devices there is a need for improved transdermal drug delivery systems which allow ease of administration, simple preparation and comparatively low cost preparation.
The thermodynamic activity of a drug can be increased by employing supersaturated systems which give rise to unusually high thermodynamic potentials (Coldman, et al, J. Pharm Sci. 58(9): 119, 1969). However, topical vehicles relying on supersaturation have the major limitation of formulation instability, both prior to and during application to the skin. As such, they are of limited clinical value within a non-occlusive volatile:non-volatile delivery vehicle, because as soon as the formulation comes into contact with a person's clothing or the like, the drug often precipitates; hence the formulation is no longer supersaturated and any enhanced percutaneous absorption ceases.
Other workers such as Kondo, et al (J. Pharmacobio-Dyn., 10:743 1987) who were using supersaturation to achieve enhanced transdermal drug delivery, have relied on the use of anti-nucleating polymers to stabilize the formulation. However, the applied drug formulations stabilized with polymers formed an appreciable surface mass on the skin which remained there over a prolonged duration of many hours, not a few minutes. So, while Kondo advocated the use of a metered spray to deliver these formulations, in reality it would be impossible to obtain a non-occlusive delivery system with a short application time and still maintain a clinically useful transdermal penetration enhancement.
It is accordingly an object of the present invention to provide a spray-on skin patch composition that overcomes some of the problems associated with prior art compositions and systems. Other objects of the present invention will become apparent from the following detailed description.
USPTO Backgrounds
USPTO Backgrounds