Controlled absorption pharmaceutical formulation

Claim 1

A controlled absorption quinidine pellet formulation for oral administration comprising: (i) a core of (a) a powder mixture comprising quinidine or a pharmaceutically acceptable salt thereof and an organic acid selected from the group consisting of adipic acid, ascorbic acid, citric acid, fumaric acid, malic acid, succinic acid and tartaric acid or a mixture thereof, and (b) 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 and said polymeric material being present in an amount effective to ensure that all of said powder mixture is coated into said core; and (ii) 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 pharmaceutically acceptable film-forming, water-soluble polymer, the number of layers in said membrane and the ratio of said water-soluble polymer to said water-insoluble polymer being effective to permit release of said quinidine 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 which is substantially pH independent and which, when measured in a Basket Assembly according to U.S. Pharmacopoeia XXI at 37° C. and 75 r.p.m., substantially corresponds to the following: (a) from 0 to 15% of the total quinidine is released after one hour of measurement in said assembly; (b) from 30 to 50% of the total quinidine is released after four hours of measurement in said assembly; (c) from 55 to 80% of the total quinidine is released after eight hours of measurement in said assembly; and (d) not less than 90% of the total quinidine is released after twenty-four hours of measurement in said assembly.