Dissolution testing poorly soluble drugs

Hydrodynamics in the upper GI tract contribute to in vivo dissolution. Our ability to forecast dissolution of poorly soluble drugs in vitro depends on our knowledge of and ability to control hydrodynamics as well as other factors influencing dissolution. Provided suitable conditions (apparatus, hydrodynamics, media) are chosen for the dissolution test, it seems possible to predict dissolution limitations to the oral absorption of drugs and to reflect variations in hydrodynamic conditions in the upper GI tract. The fluid volume available for dissolution in the gut lumen, the contact time of the dissolved compound with the absorptive sites, and particle size have been identified as the main hydrodynamic determinants for the absorption of poorly soluble drugs in vivo. The influence of these factors is usually more pronounced than that of the motility pattern or the GI flow rates per se. 

The following steps are crucial fordesigning a dissolution test for poorly soluble drug products ... 

To compare the in vivo absorption profile as presented in Fig. 6 with in vitro data, an in vitro profile must be obtained. Various in vitro dissolution tests exist. Any method which can discriminate between the formulations can be used but certain techniques tend to be preferred, i.e., paddle, flow through cell, and basket (USPII, IV, I). In addition, aqueous media is preferred (pH not exceeding 6.8 or 7.2) the addition of surfactant is possible for poorly soluble drugs. Some media are... 

Van der Weerd J, Kazarian SG. Release of poorly soluble drugs from HPMC tablets studied by FITR imaging and flow-through dissolution tests. J Pharm Sci 2005 94(9) 2096-2109. 

Comparison of in vitro dissolution results with corresponding in vivo data for different formulations in order to verify that the in vitro methods predict the in vivo dissolution properties (see the section In Vitro/In Vivo Correlations ) is preferably used already in the design of the test method. However, if not so, the in vivo validity of the method should be investigated at a later stage, especially for modified release formulations and poorly soluble drugs. 

Almost half a century after the first attempts at dissolution testing, we are still grappling with the question of which media to use to run which dissolution tests. This is not a trivial question, since the outcome of a test can be greatly dependent on the dissolution medium, especially if the drug itself and/or key excipients are poorly soluble and/or ionizable. In addition, dissolution tests are run for different reasons at... 

Shaw, J.M. Sullivan, B.M. Bowen, W.E. Martin, G.P. Reed, R.A. Studies Directed Towards the Development of Enzymatic Dissolution Test Methods for Cross-Linked Hard Gelatin Capsule Formulations Containing Poorly Water-Soluble Drug Substances. Abstracts of the AAPS Annual Meeting, New Orleans, LA, Nov 14-18, 1999 American Association of Pharmaceutical Scientists Arlington, VA, 1999 Abstract No. 3358. 

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