title: Matching phosphate and maleate buffer systems for dissolution of weak acids: Equivalence in terms of buffer capacity of bulk solution or surface pH?
abstract: The development of in vitro dissolution tests able to anticipate the in vivo fate of drug products has challenged pharmaceutical scientists over time, especially in the case of ionizable compounds. In the seminal model proposed by Mooney et al. thirty-five years ago, the pH at the solid-liquid interface (pH0) was identified as a key parameter in predicting dissolution rate. In the current work it is demonstrated that the in vitro dissolution of the weak acid ibuprofen in maleate and phosphate buffer systems is a function of the pH0, which in turn is affected by properties of the drug and the medium. The reported pH0 for ibuprofen dissolution in bicarbonate buffer, the predominant buffer species in the human small intestine under fasting conditions, can be achieved by reducing the phosphate buffer concentration to 5.0mM or the maleate buffer concentration to 2.2mM. Using this approach to identify the appropriate buffer/buffer capacity combination for in vitro experiments in FaSSIF-type media, it would be possible to increase the physiological relevance of this important biopharmaceutics tool. However, the necessity of monitoring and adjusting the bulk pH during the experiments carried out in 5.0mM phosphate or 2.2mM maleate buffers must also be taken into consideration.
authors.affiliation: Brazilian Health Surveillance Agency (ANVISA), Division of Therapeutic Equivalence, Brasilia, Brazil; Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Cristofoletti
authors.affiliation: Institute of Pharmaceutical Technology, Goethe University, Frankfurt am Main, Germany. Electronic address: dressman@em.uni-frankfurt.de.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Dressman
mesh_terms: D002021:Buffers; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000032:analysis; D008298:Maleates / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D013499:Surface Properties
chemical_list: D002021:Buffers; D008298:Maleates; D010710:Phosphates; D012996:Solutions; D007052:Ibuprofen
keywords: Biorelevant media; Buffer capacity; Dissolution; Surface pH; Weak acids