Pharmaceutical delivery system

Abstract

A pharmaceutical formulation to treat vaginal conditions in a human patient comprises: at least one active agent; a modified release dosage form which provides extended release of the anti-infective agent upon vaginal administration to the patient; and wherein the formulation, when containing a total dose of the anti-infective agent of about 25 μg to about 500 mg based on the active agent will produce a plasma concentration versus time curve (ng / mL versus hours) having an area under the curve (AUC) of less than about 600 ng / mL.hr.

Description

BACKGROUND OF THE INVENTION [0001] 1. Field of the Invention [0002] The present invention is directed to delivery systems, which stabilize surface active therapeutic agents, or those therapeutic agents which obtain surface active properties in a delivery system. These systems are suitable for use in the vaginal cavity, as well as other mucosal cavities of the body. The invention is additionally concerned with preparations demonstrating a modified, controlled, extended or sustained release of the active and / or therapeutic agent and a minimal number of administrations to produce efficacy upon administration of said delivery system. [0003] 2. Description of the Related Art [0004] One significant aspect of medicine is the treatment of the female reproductive system for the prevention, treatment, mitigation, diagnosis and cure of diseases and the prevention of conception. Usually, this involves the delivery of active agents to the vaginal cavity and its environs. Systems to affect the de...

AI Technical Summary

Benefits of technology

[0023] Still a further embodiment is drawn to a method of reducing adverse effects of an active pharmaceutical ingredient formulation comprising administering to a patient in need thereof a pharmaceutical formulation comprising an active pharmaceutical having surfactant properties to a patient in need thereof.

[0024] In currently available products, containing clindamycin phosphate for use intravaginally in the treatment of bacterial vaginosis, the common system of delivery is a semi-solid cream. The dosage form is conventional in that it consists of a continuous aqueous phase and a disperse non-aqueous phase. The active drug being solubilized, or dispersed in the aqueous phase which allows immediate contact of active pharmaceutical ingredients with surfaces which are in need of relief from microbial insult. It also allows dilution, rinsing and leakage of the product from these surfaces and does not allow the optimum contact time required to effectively impact the life cycle of those organisms which are infecting the surrounding tissues. Subsequent to this, multiple applications of the product 3 to 7 times a week are needed to provide relief and cure of the condition. The required repeated application of the active pharmaceutical ingredients (API's) using this system increases the potential for systemic uptake and also increases the likelihood of tissue irritation.

[0025] In order to increase the contact time of the API to be more effective against microorganisms and at the same time reduce the systemic uptake and irritation potential, the reduction of multiple doses is a desired strategy. In order to reduce the dosage requirement one must overcome the physical loss of the delivery system through dilution, rinsing or leakage caused by indigenous fluids and temperature. A system that will adhere to the mucosal surfaces and resist rinsing through aqueous fluids while at the same time release levels of the active pharmaceutical ingredient at a rate which will minimize systemic uptake but stay in contact with infected surfaces long enough to interfere with the infecting organisms life cycle would reduce the number of applications needed.

[0028] It has been unexpectedly found that phospholipids in combination with surfactants from a system previously destabilized with Clindamycin phosphate became physically stable.

Problems solved by technology

These delivery systems, regardless of formulation or method of manufacture, have not reliably demonstrated the ability to deliver active agents in a controlled manner with lower systemic absorption within the vaginal cavity for long periods of time, and particularly for 12 hours or longer.

The vaginal cavity is subject to conditions rendering it a target for disease and infection; however, as previously noted, it is extremely difficult to deliver an active agent to this area for an extended period of time.

The vaginal cavity is also subject to considerable physical deformation, such as during sexual intercourse or during the insertion of tampons.

Although pharmaceutically active agents have been developed, it has been difficult to achieve optimal potential effectiveness from these agents due to the inadequacy of currently available drug delivery systems.

Often, this is believed to be due to their water miscibility and / or their lack of physical stability at 37 degrees C.

Further, the nature of the active / therapeutic agent itself can cause the delivery system to deteriorate.

Many known systems exhibit limited effectiveness since they rapidly release their active agents in an uncontrolled manner and rapid manner.

Further, conventional systems also result in a relatively high systemic absorption of the active agent, which may be due in part to the instability of the system.

Unfortunately, the controlled release systems known in the art do not affect the total number of days that are required to treat a condition.

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