Pharmaceutical compositions containing venlafaxine

Abstract

The invention provides a delayed burst release formulation comprising a core formed as a compressed tablet and an outer coating that surrounds the core; said core comprising venlafaxine, or a pharmaceutically acceptable salt thereof, at least one burst controlling agent and a disintegrant; and said outer coating comprising a water insoluble hydrophobic carrier and water-insoluble but hydrophilic particulate matter.

Description

FIELD OF THE INVENTION [0001] The present invention relates to a formulation and method for the delayed burst release of venlafaxine. BACKGROUND OF THE INVENTION [0002] Venlafaxine, 1-[(2-dimethylamino)-1-(4-methoxyphenyl) ethyl] cyclohexanol, is an important drug for the treatment of depression. Venlafaxine and the acid salts thereof are disclosed in U.S. Pat. No. 4,535,186, which is hereby incorporated by reference as if fully set forth herein. Venlafaxine hydrochloride is presently administered to adults in compressed tablet form in doses ranging from 75 to 350 mg / day, in divided doses two or three times a day. Currently, in therapeutic dosing with venlafaxine hydrochloride tablets, rapid dissolution results in a rapid increase in blood plasma levels of the active compound shortly after administration followed by a decrease in blood plasma levels over several hours as the active compound is eliminated or metabolized, until subtherapeutic plasma levels are approached after about t...

AI Technical Summary

Benefits of technology

[0021] The delivery system of the present invention also advantageously uses the unique continuous absorption characterizing the colon, which results in more flat, consistent concentration levels of the drug in blood. Such an absorption, of course, can significantly contribute to reduce the fluctuations in blood drug concentration thus to prevent the side effects which may appear significantly upon using either immediate or conventional controlled release formulations, thereby improving compliance.

[0026] Even more surprisingly, as can be seen from FIGS. 12 and 13, and the description thereof presented hereinafter, the formulations of the present invention allow for the use of lower dosages since a formulation comprising about 60 mg according to the present invention provides bioequivalence of Efexor XR 75 mg and provides similar bioavailability in the area under the concentration-time curve to Efexor XR 75 mg while formulations comprising about 120 mg according to the present invention provides bioequivalence of Efexor XR 150 mg and provides similar bioavailability in the area under the concentration-time curve to Efexor XR 150 mg.

[0034] (b) an outer coating over said core, said outer coating comprising a water insoluble hydrophobic carrier and water-insoluble but hydrophilic particulate matter, contained in the carrier, that forms channels in the outer coating, upon contact with water or an aqueous medium wherein said channels imbibe liquid and cause said at least one burst controlling agent to burst said coating, thereby enabling the delayed burst release of venlafaxine through these channels after at least three hours followed by dispersion of venlafaxine into the blood stream mainly through the colon over a period extending over at least twenty-four hours.

[0058] According to still another embodiment of the present invention, there is provided a method for providing enhanced bioavailability of venlafaxine in a subject, comprising: administering to the subject a formulation having a therapeutically effective amount of venlafaxine or a pharmaceutically acceptable salt thereof, wherein the formulation provides a substantially sustained plateau of blood concentration level of venlafaxine in the subject, the combination of preferential release in the colon and substantially sustained plateau of blood concentration level resulting in enhanced bioavailability of venlafaxine.

Problems solved by technology

Currently, in therapeutic dosing with venlafaxine hydrochloride tablets, rapid dissolution results in a rapid increase in blood plasma levels of the active compound shortly after administration followed by a decrease in blood plasma levels over several hours as the active compound is eliminated or metabolized, until subtherapeutic plasma levels are approached after about twelve hours following administration, thus requiring additional dosing with the drug.

However, administration of this formulation results in blood concentration levels having a distinct peak 4-8 hours after administration.

In addition, the location of release of venlafaxine may also be problematic, as the above taught formulations clearly result in release occurring to a significant degree in the small intestine, and possibly also in the stomach.

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