Related Experiment Video
Updated: May 17, 2026

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid
Published on: September 20, 2017
Overcoming sink limitations in dissolution testing: a review of traditional methods and the potential utility of
Daniel J Phillips1, Samuel R Pygall, V Brett Cooper
1Department of Chemistry, University of Warwick, Coventry Development Laboratories, MSD, Hoddesdon, UK.
Objectives:
The conventional dissolution test, particularly the USP apparatus I and II, remains an important tool in the armory of the pharmaceutical development scientist. For realistic dissolution characterization, sink conditions, where saturation solubility of a drug in the dissolution medium is at least three times more than the drug concentration, are critical. These conditions can be problematic to maintain with formulations containing poorly-soluble actives. This review summarizes the role of the dissolution test in the pharmaceutical industry, together with some traditional techniques/additives used to enhance solubility and facilitate the achievement of sink conditions. The biphasic dissolution system, an innovative model for the treatment of poorly-soluble species, will also be discussed.
Key Findings:
The biphasic dissolution model utilizes media comprising immiscible aqueous and organic layers whereby the drug, following initial aqueous dissolution, partitions into the organic layer. This step, which acts to remove all dissolved species from the aqueous layer, enables further aqueous dissolution to occur and hence the dissolution-partition cycle continues. Crucially, the aqueous layer does not saturate allowing sink conditions to be maintained and hence the experiment will, in theory, yield complete dissolution.
Summary:
This review highlights important concepts regarding solubility/sink limitation and intends to provoke debate among analytical and formulation scientists as to the potential advantages, long-term development and widespread implementation of a biphasic dissolution system in drug development.
Related Concept Videos
In Vitro Drug Dissolution: Compendial Testing Models I
In Vitro Drug Dissolution: Alternative Methods
In Vitro Drug Dissolution: Compendial Testing Models II
Theories of Dissolution: Diffusion Layer Model
This process starts with a thin layer, saturated with the drug, forming at the interface between the solid and liquid. The solute then diffuses from this layer into the main solution. The Noyes-Whitney equation suggests that the rate of dissolution relies on the diffusion...
Drug Dissolution: Requirements and Profile Comparison
Theories of Dissolution: The Danckwerts' Model and Interfacial Barrier Model
