Conventional versus novel conditions for the in vitro dissolution testing of parenteral slow release formulations: application to doxepin parenteral dosage forms.

Parenteral slow release formulations of doxepin in lipid vehicles were prepared in the form of suspensions of doxepin hydrochloride, doxepin pamoate and of poly D,L-lactid and poly D,L-lactid-co-glycolide microspheres containing doxepin hydrochloride. The drug particles or the drug containing microspheres were suspended in the vehicles isopropylmyristate or Miglyol. The dissolution rate of the different doxepin formulations was investigated in two flow through cells, a membrane and a non-membrane system, using either plain buffer or human plasma containing buffer as dissolution media, in order to study the influence of dissolution conditions on dissolution rates. An attempt was made to obtain biorelevant dissolution data. In the membrane system a linear relationship between time and percent drug dissolved during the period of investigation was found. Drug release was very slow and incomplete, especially when buffer was used as dissolution medium. Dissolution data from the nonmembrane system were fitted to monoexponential and biexponential models, respectively. Significant differences were found using different modes of formulation positioning and using the two dissolution media. The most rapid release rates were found when the formulations were spread on glass carriers and plasma was used as dissolution medium. It is suggested that this dissolution procedure has physiological relevance.