Toward an Improved Understanding of the Precipitation Behavior of Weakly Basic Drugs from Oral Lipid-Based Formulations

The aim of the present study was to analyze the impact of lipid-based formulation (LBF) dispersion and digestion on the precipitation behavior of weakly basic drugs. Loratadine and carvedilol were formulated in a range of LBFs and drug solubilization was analyzed under simulated dispersive and digestive conditions (fasted state). The extent of supersaturation and drug precipitation as well as the solid-state properties and redissolution behavior of precipitated drugs were assessed. X-ray powder diffraction indicated that carvedilol precipitated in a crystalline form upon dispersion, but interestingly, this drug gave an amorphous precipitate during lipolysis. In contrast, loratadine precipitated as crystalline material during both formulation dispersion and digestion. No influence of the formulation composition on the type of precipitation was observed. These results suggested that in vitro conditions (dispersive versus digestive) largely influenced the solid-state properties of precipitating weak bases. Solid-state characterization of precipitated drugs under different experimental conditions should be routinely performed in formulation screening to better understand the biopharmaceutical behavior of LBFs. Hence, these findings are of high practical importance for the pharmaceutical development and in vitro assessment of LBFs using weakly basic drugs. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1194-1203, 2014