Crystal suspensions of poorly soluble peptides for intra-articular application: a novel approach for biorelevant assessment of their in vitro release.

Crystal suspensions of 3 poorly soluble peptides (MSC1, 2 and 3), intended for intra-articular administration were prepared and in vitro release was tested by a modified USP IV apparatus, combined with a dialysis system. Half-lives of release profiles were ∼5 days for MSC1 and ∼0.5 days for MSC2 and MSC3, showing the potential to achieve sustained exposure from crystal suspensions after intra-articular administration. The in vitro release setup discriminated between (i) different formulations, (ii) different concentrations of API and (iii) different APIs. In addition it was shown that this method allows the modification of release conditions in order to gain more biorelevance for in vitro release testing in the field of intra-articular application: the influence of synovial fluid components hyaluronic acid and albumin was demonstrated, showing prolonged half-lives for suspensions containing 2.5% bovine serum albumin (5 days) and accelerated release rates for suspensions containing 1% sodium hyaluronate (2.5 days) in comparison to a suspension in phosphate buffered saline (4 days). Furthermore, it was demonstrated that release rates of a suspension containing an artificial synovial fluid were in accordance with suspensions containing bovine synovial fluid (t1/2∼4 days).