Development of an automated flow-through dissolution system for poorly soluble drugs with poor chemical stability in dissolution media

A novel dissolution system, based on the principle of the flow-through cell s of Thoma and Zimmer, was designed to meet the special requirements of dru gs with pH-dependent poor solubility connected with poor chemical stability in dissolution media. The weakly basic compound fenoldopam mesylate was us ed as a model drug as it shows low solubility (0.06 mg/ml) in simulated int estinal fluid pH 7.5 and a degradation of approximately 5% per hour at that pH. Being an open flow-through system, the system ensures sink conditions over the complete testing time irrespective of the drug loading, the testin g time or the pH. Simple UV spectroscopic quantification could be used for quantification only because any interference in UV absorption could be elim inated in the absence of degradation products. Drug stability and thus abse nce of degradation product was ensured by the novel dissolution method. The automated version of the dissolution method allows the simple and reproduc ible dissolution testing of controlled release items, especially those cont aining drugs with poor solubility and stability in dissolution media. Testi ng times, pH-gradients and sampling intervals can be run automatically, as can the addition of acids, bases or buffers to ensure the stability of comp ounds in solution. The automated system was validated for a film coated pel let formulation containing the weakly basic drug fenoldopam mesylate in a s ustained release system, but could be used for any type of dosage form, rel ease system or drug compound with problems in dissolution media as to its s olubility or stability.