A sensitive in vitro performance assay reveals the in vivo drug release mechanisms of long-acting medroxyprogesterone acetate microparticles

In-Vitro Product Performance of Parenteral Drug Products: View of the USP Expert Panel

“…The stirrers of Apparatus 1 and Apparatus 2 have been used with the dispersion releaser, assessing release from liposomes, nanoparticles, microparticles, and nanocrystals (3,7,9,10,12). The set-up minimizes evaporation with an average weight loss per vessel of approximately 3.4% at 37° over 21 days.…”

“…For some dosage forms such as microspheres (10,21,28,31), manipulation of in vitro test parameters to decrease test run times can still lead to tests with definable correlations between in vitro and in vivo performance, or at least a secondary relationship between an accelerated and a non-accelerated (and more biorelevant) test. A correlation could be established due to having prior knowledge of the mechanisms of drug release, in vitro and in vivo release phases, and other physical properties of the dosage form.…”

“…Some biorelevance aspects of performance tests may be compromised with accelerated methods, such as differences in mechanism of release from the dosage form depending on testing (in vivo or in vitro) (21), microenvironment of the site of administration/media (10), and release phases of the dosage form (31). Dosage form attributes that should be considered with respect to biorelevance during test acceleration may include:…”

“…A study by Gao et al presented a novel Simulated Subcutaneous Interstitial Fluid (SSIF), which is a biorelevant medium designed to reflect major characteristics of the subcutaneous tissue (ionic composition, buffer capacity, and protein concentration) and was applied to a novel dispersion releaser set-up, which allowed discrimination between drug release of microparticles before and after storage (10). This medium can be considered as a first step towards a more biorelevant medium that could also be applied in quality control (45).…”

Development of an In Vitro System To Emulate an In Vivo Subcutaneous Environment: Small Molecule Drug Assessment

“…These systems include dispersion releaser (DR), SC injection site simulator (SCISSOR), shake-flask setup, flow-through cell, hydrogel assay in an IVIS system, UV imaging system, and so forth . It is noted that the dispersion releaser (DR), a modification of a USP apparatus 1 via replacing the basket with a vessel, has presented some capabilities in predicting the in vivo performance of SC formulations. − SCISSOR is the first commercialized instrument that aims to model the SC environment and simulate drug migration from the injection site to the absorption site. Our previous work developed a Monte Carlo method to simulate particle movement inside SCISSOR and identified a list of potential critical parameters .…”