Drug delivery device

Details Drug delivery device Drug delivery device

2001-04-20

2004-07-06

Calvert, John J. (Department: 3761)

Surgery

Means and methods for collecting body fluids or waste material

Absorbent pad for external or internal application and...

C604S385170, C604S904000, C604S514000, C424S731000

Reexamination Certificate

active

06758840

ABSTRACT:

This invention concerns drug delivery devices for insertion into the vagina, rectum or nasal cavity. The devices exploit the highly vascularised nature of the vaginal, nasal and rectal mucosal tissue to deliver pharmaceutical agents to localised areas and/or into underlying tissues.
The vagina, rectum and nasal cavity provide an excellent route for the administration of pharmaceutical agents due to the copious blood supply in these regions. Delivery of the agent through the tissue wall is generally fast. Any one of vaginal, rectal and nasal administration can be a preferred route when drug can be destroyed by local conditions such as those encountered in the stomach. Other very important situations when the oral route is precluded are when vomiting has occurred, or is likely to occur, when the patient is unable to swallow successfully and when the patient is unconscious.
The vaginal delivery route is known to be useful for the delivery of pharmaceutical agents which have their site of action within tissues or organs close to the vagina, in particular, for administration to the vaginal tissues, uterus, ovaries and Fallopian tubes and other tissues and organs within the peritoneal cavity. Pathological lesions within and around these organs may also be treated in this manner.
The vagina may also be used for the delivery of pharmaceutical agents intended for use in other regions of the body. Administration through the vaginal cavity is particularly useful where other formulations are unsuitable, for example, in situations where pharmaceutical agents aggravate or upset the stomach, or are difficult or impossible to administer orally. Such agents may conveniently be administered intra-vaginally.
Intra-vaginal devices for the delivery of pharmaceutical agents and other materials into the vaginal cavity are known. Such devices are either of the type where a medicament is impregnated into the device, or of the type that carries an encapsulated medicament.
For example, U.S. Pat. No. 4,309,997 discloses a moist, medicated vaginal tampon that is impregnated with a contraceptive agent and a medicament for the control of venereal disease.
U.S. Pat. No. 4,318,405 discloses a tampon which has a capsule of disintegratable material partially embedded in one end. This tampon is inserted into the vagina and serves both to deliver and to retain the encapsulated medicament in the vaginal cavity. This patent also discloses a means for prewetting the tampon in order to activate the capsule.
U.S. Pat. No. 5,527,534 discloses a sponge, impregnated with a liquid containing an effective amount of an active pharmaceutical agent, for insertion into the vaginal cavity.
U.S. Pat. No. 5,273,521 discloses a tampon assembly that is adapted for carrying a medicament within a longitudinal bore formed within the tampon. The medicament can be selectively expelled into the vaginal cavity from the bore using a tubular inserter.
One disadvantage of the intra-vaginal devices described above is that, where the tampon or sponge comprises an absorbent material, it will itself absorb much of the pharmaceutical agent. On the other hand, where the intra-vaginal device comprises non-absorbent material, or is saturated with a medicament, then the natural tendency of the vaginal cavity to flush fluid away will result in the expulsion of much of the medicament from the vagina, particularly during menstruation.
Movement of pharmaceutical molecules from the vaginal cavity into the surrounding tissues is usually via a simple diffusion process. Net diffusion may be given by the equation:
Net diffusion=
k.D.
(
C
vag
−C
tiss
);
where k is a constant, D is the diffusion constant for the molecule, C
vag
is the molecular concentration in the vagina at the surface of the mucosa and C
tiss
is the molecular concentration in the tissue surrounding the vagina.
Hence, if C
vag
drops due to absorption into an intra-vaginal device or due to the flushing away of pharmaceutical agent with vaginal fluids, then the net diffusion of molecules of the pharmaceutical agent across the vaginal mucosa will also fall. Therefore, in order to achieve maximum rates of uptake of pharmaceuticals from the vaginal cavity across the vaginal mucosa and into the surrounding tissues and body fluids, C
vag
should be maintained at as high a level as possible.
Conventional intra-vaginal devices do not achieve this result. For example, U.S. Pat. No. 5,299,581 attempts to get around this problem by using an intra-vaginal device having a sheet-like cover which is impervious to vaginal fluid. The device comprises a means to expel a medicament once the device has been inserted into the vagina. There is also a means to restrict the escape of excess fluid from the vagina, which in a preferred embodiment is in the form of a sponge or leaf tampon at the lower end of the device. These devices thus reduce absorption of the medicament into the device core to some extent. However, a requirement of this device is that medicaments must be in a liquid form. Such devices are thus not suitable for the sustained release of pharmaceuticals. Furthermore, after insertion of the device, the medicament must be actively introduced into the vagina through a tube within the device. This is cumbersome and inconvenient for the user. Additionally, although the devices are adapted to absorb excess fluid, they are unsuitable for use during menstruation in place of a conventional absorbent article.
The nasal and rectal mucosa also provide a useful anatomical site for systemic drug delivery. The nasal tissue is highly vascularized, providing an attractive site for rapid and efficient systemic absorption. The adult nasal cavity has a capacity of around 20 ml, with a large surface area (approximately 180 cm
2
) for drug absorption afforded by the microvilli present along the pseudostratified columnar epithelial cells of the nasal mucosa. For non-peptide small molecular compounds, intranasal bioavailability has been shown to be comparable to that of injections. The nasal mucosa has been shown to be amenable to the systemic absorption of certain peptides, as well as to nonpeptide drug molecules. The nasal route is advantageous for nonpeptide drugs that are poorly absorbed orally. One additional advantage to nasal absorption is that it avoids first-pass metabolism by the liver.
The nasal route also offers advantages when rapid and regulated uptake of pharmaceutical is required, such as in the control of acute inflammation, acute respiratory disturbance, emesis, migraine and acute cardiological events.
The present invention aims to provide improved devices for the administration of pharmaceutical agents through the vaginal, nasal or rectal walls. In particular, the present invention aims to provide a simple to use and comfortable device, which provides enhanced uptake of pharmaceutical and which may be employed irrespective of local conditions within the vagina, rectum or nasal cavity.
According to the present invention there is provided a device adapted for insertion into the vagina, rectum or nasal cavity, said device comprising a body, a layer of fluid-impermeable material on at least part of said body and one or more pharmaceutical agents disposed on the surface of said material remote from said body. Preferably, said body comprises an absorbent material.
The fluid-impermeable material forms a layer between the pharmaceutical agent and the body of the device. This layer prevents direct diffusion of the pharmaceutical agent into the device itself, therefore maintaining a high concentration of pharmaceutical agent in the vicinity of the tissue wall and increasing the net diffusion of the pharmaceutical across the mucosa. The presence of the fluid-impermeable layer reduces the inverse dependence of the uptake of the drug on the movement of fluid into and through the vaginal, rectal or nasal cavity. In the case of the intra-vaginal device of the invention, this fluid impermeable layer allows enhanced pharmaceutical uptake to be maintained during menstruation, irrespective of the volume of men

Affiliated with

Also associated with

Rating

Drug delivery device does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Drug delivery device, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Drug delivery device will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3195417