Controlled absorption pharmaceutical composition

Claim 1

A controlled absorption propranolol containing pellet for oral administration, said pellet comprising: (A) a core of (i) a powder mixture comprising propranolol or a pharmaceutically acceptable salt thereof and an organic acid selected from the group consisting of citric acid, tartaric acid, succinic acid, malic acid, ascorbic acid and fumaric acid or a mixture thereof, and (ii) a polymeric material comprising a major proportion of a pharmaceutically acceptable water-soluble polymer and a minor proportion of a pharmaceutically acceptable water-insoluble polymer, said core comprising layers of said powder mixture and said polymeric material superimposed one upon the other wherein said polymeric material is present in an amount sufficient to ensure that all of said powder mixture is coated into said core; and (B) a multi-layer membrane surrounding said core and containing a major proportion of a pharmaceutically acceptable film forming, water-insoluble polymer and a minor proportion of a pharmaceuticaly acceptable film forming, water-soluble polymer, the number of layers in said membrane and the ratio of said water-insoluble polymer to said water-soluble polymer being effective to permit release of said propranolol from said pellet at a rate allowing controlled absorption thereof over a twenty four hour period following oral administration, said rate being measured in vitro as a dissolution rate of said pellet in a buffer solution at pH 7.5 which, when measured in a basket assembly according to U.S. Pharmacopoeia XX at 37° C. and 75 r.p.m., substantially corresponds to the following dissolution pattern: (a) from 0 to 15% of the total propranolol is released after 2 hours of measurement in said assembly; (b) from 15 to 30% of the total propranolol is released after 4 hours of measurement in said assembly; (c) from 43 to 63% of the total propranolol is released after 6 hours of measurement in said assembly; (d) from 75 to 100% of the total propranolol is released after 8 hours of measurement in said assembly; (e) from 85 to 100% of the total propranolol is released after 10 hours of measurement in said assembly.