Topography of Simulated Intestinal Equilibrium Solubility

Oral administration of a solid dosage form requires drug dissolution in the gastro-intestinal tract before absorption. Solubility is a key factor controlling dissolution and it is recognised that within the intestinal tract this is influenced by the luminal fluid pH, amphiphile content and composition. Various simulated intestinal fluid recipes have been introduced to mimic this behaviour and studied using a range of different experimental techniques. In this paper we have measured equilibrium solubility utilising a novel four component mixture design (4CMD) with biorelevant amphiphiles (bile salt, phospholipid, oleate and monoglyceride) within a matrix of three pH values (5, 6 and 7) and total amphiphile concentrations (11.7.mM, 30.6mM and 77.5mM) to provide a topographical and statistical overview. Three poorly soluble drugs representing acidic (indomethacin), basic (carvedilol) and neutral (fenofibrate) categories have been studied. The macroscopic solubility behaviour agrees with literature and exhibi...