Formulations for oral administration of cromolyn sodium

Abstract

An oral dosage form comprises cromolyn sodium (sodium or disodium cromoglycate), and an acylated amino acid delivery agent.

Description

[0001] This invention relates to delivery of therapeutic polar organic compounds in a bioavailable and bioactive form. This invention further relates to oral administration of polar organic compounds as active agents as part of a therapeutic regimen. This invention further relates to the oral administration of cromolyn in a bioavailable and bioactive form for the treatment of asthma, allergies and viral infections.[0002] This invention is directed to formulations of a delivery agent and cromolyn for oral administration. This invention further relates to formulations of a delivery agent and cromolyn for oral administration that releases cromolyn which is both bioavailable and bioactive for the treatment of asthma, allergies and viral infections.[0003] This invention relates to providing methods for the granulation and encapsulation of a formulation comprising a delivery agent and cromolyn for oral administration. This invention further relates to providing methods for the granulation...

AI Technical Summary

Benefits of technology

0176] Due to the greater levels of systemic absorption afforded to cromolyn sodium by the oral dosage forms of the present invention, it is contemplated that the duration of action may be dependent on the total amount of drug absorbed from the gastrointestinal tract. Therefore, it is contemplated that the oral dosage forms of the present invention may provide the prolonged activity of cromolyn sodium in comparison to other cromolyn sodium treatments used to date. However, it is also contemplated that, in certain circumstances, e.g., in the treatment of severe inflammatory conditions, the oral dosage forms of the present invention may be administered as often as every 4 hours to human patients. It is further contemplated that the oral dosage forms of the present invention may be administered on a less frequent basis, e.g., 4 times a day, 3 times a day, twice a day, and once a day.

0177] In certain preferred embodiments of the present invention, the oral dosage form is a solid dosage form which contains the cromolyn sodium in an effective amount together with the drug delivery agents of the present invention in a requisite ratio to provide suitably enhanced absorptivity of the cromolyn sodium from the gastrointestinal tract upon oral administration. In embodiments of the present invention wherein a relatively large amount of cromolyn sodium is administered together with the requisite amount of drug delivery agent, or wherein a large amount of drug delivery is required to provide the requisite absorptivity, it is further contemplated that the dose may be divided into multiple capsules or tablets and administered to the patient at the same time. In this manner, even large amounts of drug / delivery agent combinations can be administered orally to the patient without patient experiences problems swallowing the dose. In yet other embodiments of the invention contemplated herein, the cromolyn sodium / drug delivery agent combination may be prepared in the form of a dry powder which is suspended in a liquid for oral administration prior to use, thereby negating the necessity of administering multiple unit doses of the dosage forms of the present invention in order to attain the desired dosage level of drug.

Problems solved by technology

Conventional means for delivering active agents are often severely limited by biological, chemical, and physical barriers.

Biologically or chemically active agents are particularly vulnerable to such barriers.

These agents are rapidly rendered partially or totally ineffective, pass through partially or totally unabsorbed, or are partially or totally destroyed in the gastrointestinal tract by acid hydrolysis, enzymes, or the like.

Absorption of drugs via the gastrointestinal (GI) tract, however, is hampered by natural barriers including acid-induced hydrolysis in the stomach, enzymatic degradation throughout the GI tract, poor solubility in the intestinal environment, and lack of permeation through the epithelial cells.

The latter is particularly problematic because it can exclude the passage of compounds across the tissue based on size, charge and / or lipophilicity.

These systems, however, are highly inefficient and have been shown to cause transient to long-lasting membrane damage.

Such membrane effects have the added disadvantage of allowing nonselective transport of toxic materials.

Cromolyn has a high safety profile but exhibits poor absorption from the gastrointestinal tract.

Cromolyn, when given orally, is poorly absorbed from the gastrointestinal tract because it is highly lipid-insoluble and mainly ionized.

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