Ibuprofen Tablets Dissolution Versus Bioavailability

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Abstract
Dissolution studies and a 24 patient randomized double-blind crossover bioavailability study were performed using two commercially-sized batches of an ibuprofen 200 mg tablet formulation (sugar-coated). The batches were equivalent with respect to the USP dissolution test, but differed, particularly from tablet-to-tablet, when a paddle at 50 rpm was substituted, one batch consistently giving a high dissolution and the other consistently giving a low dissolution. The bioavailability study showed the batches to be bioequivalent, thus prompting an investigation as to why the substitution of a paddle at 50 rpm gave no correlation with bioavailability and should therefore be unsuitable as a standard dissolution test. It was found that soaking tablets in acid prior to using the paddle at 50 rpm (thus simulating more closely the in vivo pH sequence) increased the dissolution rate. The increase is such that the maximum dissolution rate, which also approximates that given by the USP method, is achievable within five minutes, even when the presoak medium is an unbuffered solution of hydrochloric acid at pH 4. A standard presoak procedure was then developed consisting of soaking each tablet for five minutes in 5 ml of USP gastric fluid without pepsin at room temperature and with no agitation. A comprehensive application of this procedure to both batches consistently produced results equivalent to those obtained by the USP method. In particular, there was very little tablet to tablet variation. Studies with formulations of varying bioavailability will be necessary before it can be determined whether this new acid presoak procedure will provide a more meaningful dissolution test compared with the current USP method.