Oral transmucosal delivery of drugs or any other ingredients via the inner buccal cavity

Abstract

A device and method for the oral transmucosal delivery of active substances to the oral cavity utilizing an unplasticized polyvinyl pyrrolidone polymer (PVP) as the primary mucoadhesive. The device is applied and adheres to the mucosa of the oral cavity without causing side effects or leaving an unpleasant taste. Preferably the device is a bilayer tablet having a mucoadhesive layer and an overlying active substance containing layer. The mucoadhesive layer may contain PVP as the only adhesive or may be combined with other hydrophilic polymeric substances. The active layer also contains a hydrophilic polymer carrier. The layers in the device dissolve and release the active substance to the oral cavity and is particularly adapted for the delivery of substances active in the oral cavity such as breath fresheners and substances to combat dry mouth. It is also useful for the delivery of ionic drugs such as peptides.

Description

[0001] This application is a continuation of application Ser. No. 09 / 285,018 filed Apr. 1, 1999.[0002] This invention relates to a composition and a method for oral transmucosal delivery of active substances to a human or animal via the inner buccal cavity. More particularly, this invention relates to an improved dosage form which can easily adhere to the inner buccal cavity and sustain transmucosal release of drugs, odorants or any other ingredients and exhibit the activity effectively.[0003] The sustained delivery of certain active substances, especially ionic peptide-based drugs, presents one of the greatest challenges in pharmaceutical science. Oral administration of pharmaceutical compositions has some drawbacks. For instance, it is difficult to keep the medicament at the desired location so that it can be absorbed, it is easily metabolized in the liver, and it is easily decomposed in the stomach. Accordingly, there has been much interest in the use of the mucosal lining of bod...

AI Technical Summary

Benefits of technology

[0016] It is another object of the present invention to provide a transmucosal device for the delivery of active substances utilizing a mucoadhesive that is fully soluble in the secretions present in buccal cavity without having an objectionable taste or causing irritation.

[0048] Extended delivery of active substances can be obtained according to the bilayered or multilayered device according to the present invention. The rate of release of the active substances within the oral cavity can be specified by selection of particular polymer or polymer combinations. The device according to the present invention is capable of adhering to contoured surfaces such as the gum or the roof of the mouth. The device can deliver the active substances over a period of up to 2 hours or longer from a single device, and can dissolve without leaving any bad taste or causing sustained irritation. The device according to this invention is particularly useful in delivering charged drugs such as polypeptide based drugs because the PVP mucoadhesive is non-ionic which does not interact with ionic drugs to be delivered. Further, the device is particularly adaptable for the delivery of odorants or other active agents for the treatment of halitosis or dryness of the mouth.

Problems solved by technology

The sustained delivery of certain active substances, especially ionic peptide-based drugs, presents one of the greatest challenges in pharmaceutical science.

For instance, it is difficult to keep the medicament at the desired location so that it can be absorbed, it is easily metabolized in the liver, and it is easily decomposed in the stomach.

Therefore, charged drugs, such as ionized polypeptide based drugs, present a significant challenge to absorption through the oral mucosa.

Such forms remain in the oral cavity only for short periods of time, generally not more than about 10 to 20 minutes, and they cannot always provide for effective sustained delivery of the substance.

Moreover, the presence of a lozenge or troche in the user's mouth can be annoying or distracting, and may interfere with speech or with the ingestion of fluids.

Holding the lozenge in the mouth to avoid either swallowing it or spitting it out requires conscious effort, and inadvertent loss can be embarrassing.

However, these known bioadhesives have several drawbacks.

For example, adhesives in the form of pastes, creams or ointments are messy and inconvenient to use, and generally adhere poorly or not at all and are not suitable for extended periods of use.

Some forms of adhesives, such as Carbopol (carboxyvinyl polymers), are not water soluble thus leave a tacky, greasy residue in the oral cavity of the wearer, and can cause sustained oral irritation.

On the other hand, some forms of adhesives remain in the oral cavity for only short periods of time, e.g. generally not more than about 10 or 20 minutes, and therefore cannot provide for delivery of a substanceover an extended period of time.

The presence of the plasticizer negatively affects the palatability and stability of the mucoadhesive.

In addition to undesirable interaction with the ionic active substances, the presence of plasticizers or other ionic polymers in the mucoadhesive may also cause undesirable wearing properties or irritation.