A PHARMACEUTICAL COMPOSITION COMPRISING MONTELUKAST SODIUM AND LEVOCETIRIZINE DIHYDROCHLORIDE IN A SINGLE DOSAGE FORM

Abstract

Cetirizine is a second generation H₁ histamine receptor antagonist.  In its racemic form, it generally offers some significant advantages over the first generation antihistaminics.

U.S. Patent No. 5,698,558 discloses that the administration of optically pure enantiomer (-) cetirizine i.e. levocetirizine can reduce or avoid adverse side effects associated with the use of racemic cetirizine.  These side effects include sedation, somnolence, headache, gastrointestinal disturbance, dizziness, nausea, cardiac arrhythmias, and other cardiovascular effects.  

Montelukast is a leukotriene antagonists and inhibitor of leukotriene biosynthesis. U.S. Patent No. 5,565,473 discloses montelukast and use of montelukast in pulmonary disorders including diseases such as asthma, chronic bronchitis, and related obstructive airway diseases, allergies and allergic reactions such as allergic rhinitis, contact dermatitis, allergic conjunctivitis, inflammation such as arthritis or inflammatory bowel disease, pain, skin disorders such as psoriasis, atopic eczema,  cardiovascular disorders such as angina, myocardial ischemia, hypertension, platelet aggregation and the like. 

There have been several reports on the combination of cetirizine, or its enantiomer or salt with one or more leukotriene inhibitors provides synergistic effect for the treatment or prevention of inflammation, asthma or allergic disorder.  Furthermore, said combination also avoids or reduces certain side effects associated with H₁ histamine receptor antagonists.

U.S. Patent No. 6,384,038 discloses a combination of cetirizine and a leukotriene inhibitor for the treatment or prevention of inflammation, asthma or allergic disorder.

WO 99/32125 discloses a combination of montelukast and antihistaminic drugs for the treatment of inflammation, asthma or allergic disorder and the like.

However, none of the prior art disclose a pharmaceutical composition comprising montelukast sodium and levocetirizine dihydrochloride.

In an attempt to prepare a pharmaceutical composition of montelukast sodium and levocetirizine dihydrochloride, we observed that incomplete in vitro release for montelukast sodium is attained when both the drugs are mixed and granulated together.

Unexpectedly, we have now found that desired in vitro release is attained when a combination of montelukast sodium and levocetirizine dihydrochloride is formulated in a single dosage form, in a manner to minimize observed interaction between the two drugs.

Hence, the present discl...