2012/04/26 by Daniel J. Phillips, Daniel J Phillips, Samuel R Pygall +4 · 1 citation
Chemistry · Materials Science · Pharmacology, Toxicology and Pharmaceutics · #Crystallization and Solubility Studies #Crystallography and molecular interactions #Drug Solubulity and Delivery Systems
paper · pdf · doi:10.1111/j.2042-7158.2012.01523.x
openalex publication_date 2012/04/26 · crossref created 2012/04/26 · crossref issued 2012/11/01 · crossref published 2012/11/01 · crossref published-online 2012/11/01 · crossref published-print 2012/11/01 · crossref deposited 2024/10/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30 · crossref indexed 2026/08/01
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.