Co-solvent systems in dissolution testing: Theoretical considerations

Abstract

The situation was considered where a co-solvent, added to enhance drug solubility and thus provide sink conditions for a drug, also resulted in a decrease in solubility and hence dissolution rate of a water soluble excipient present in the dosage form. Theory predicted that, in the absence of disintegration, at sufficiently high excipient content and or co-solvent concentration the drug dissolution rate may decrease, release becoming controlled by the now less soluble excipient. Solubility and dissolution studies using tolbutamide and lactose mixtures in water-ethanol mixtures provided results which were reasonably consistent with theory, indicating that the presence of the excipient may greatly reduce the drug dissolution rate below that expected for the drug alone.