Albendazole vs. albendazole sulphate in the fasted upper gastrointestinal lumen based on ex vivo and in vitro data

To evaluate the impact of salt form on solubility in upper gastrointestinal (GI) lumen and on concentrations of albendazole (ABZ) in upper small intestine following oral administration of simple aqueous suspensions in the fasted state, using ex vivo and in vitro data. A crystalline stable sulfate salt of albendazole (ABZ-S) was recrystallized from tetrahydrofuran. Differential scanning calorimetry and elemental analysis confirmed the salt formation. Solubility of ABZ and ABZ-S was measured in human aspirates and in fasted state simulating gastric and intestinal fluid. GI transfer of ABZ and ABZ-S suspensions (each at two dose levels, 200 mg and 50 mg) was simulated by using an optimized in vitro methodology which has been shown to be useful in evaluating luminal events relating to the GI transfer (Psachoulias et al. Pharm Res. 2012; Symillides et al. 5 th BBBB Int. Conference, 2013). The effect of precipitation inhibitors was evaluated by including HPMC E5 and PVP (Kollidon® 30) in the suspensions. ABZ was assayed with HPLC in all cases. Equilibrium solubility data in aspirates and simulated GI fluids indicated that, compared to base, ABZ-S is at least 3 times more soluble in stomach and at least two times more soluble in upper small intestine. The in vitro transfer data indicated extensive precipitation and limited supersaturation leading to similar duodenal compartment concentrations for both ABZ and ABZ-S. By decreasing the dose to 50 mg duodenal compartment concentrations were increased. In addition, concentrations in duodenal compartment were slightly increased when HPMC E5 was included in the gastric compartment. For ABZ, a weak base which is expected to precipitate extensively in the upper small intestine, the use of a salt with clearly improved solubility characteristics in the upper GI lumen does not seem to greatly increase the concentrations in simulations of the upper small intestine. The impact of precipitation inhibitors seems to be also small. Acknowledgement This work was performed within the OrBiTo project which is funded by the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No 115369. The authors would like to thank Biorelevant.com for providing SIF powder original.