The present invention relates to a pharmaceutical tablet that provides extended release of venlafaxine besylate.
Venlafaxine, or the compound 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-cyclohexanol, is an antidepressant that is sold, as the hydrochloride salt, under the brand name EFFEXOR® (Wyeth Ayerst). The compound is described in U.S. Pat. No. 4,535,186 and a further synthesis thereof is described in U.S. Pat. No. 5,043,466. Venlafaxine hydrochloride is available as an immediate release tablet and as an extended release capsule.
U.S. Pat. No. 6,274,171 and EP 0 797 991 relate to an extended release dosage form of venlafaxine hydrochloride. Specifically, an encapsulated dosage form is taught that comprises spheroids of venlafaxine hydrochloride, microcrystalline cellulose, and hydroxypropylmethylcellulose (HPMC). These spheroids are coated with a mixture of ethyl cellulose and HPMC. By providing an appropriate amount of the coating, the desired blood plasma profile can be obtained. An acceptable batch of coated spheroids meets the following in vitro dissolution profile:
Average % venlafaxineTime (hours)hydrochloride released2<30430-55855-801265-9024>80While the encapsulated dosage form disclosed in these patents appears to be suitable for making an extended release dosage form, the dosage form is somewhat complicated and must be an encapsulated form. A tablet would be desirable. However these patents disclose that “[n]umerous attempts to produce extended release tablets by hydrogel technology proved to be fruitless because the compressed tablets were either physically unstable (poor compressibility or capping problems) or dissolved too rapidly in dissolution studies.” See U.S. Pat. No. 6,274,171 at column 4, lines 60-65 and EP 0 797 991A1 at page 3 lines 35-37.
More recently, U.S. Pat. No. 6,717,015 describes venlafaxine besylate as having some advantages over venlafaxine hydrochloride, including lower water solubility. A variety of pharmaceutical compositions are described therein including extended release dosage forms.
It would be desirable to provide additional tablet designs that exhibit extended release of venlafaxine besylate, especially extended release of venlafaxine besylate that is bioequivalent to the commercial venlafaxine hydrochloride extended release capsules.