Evaluation of drug precipitation of solubility‐enhancing liquid formulations using milligram quantities of a new molecular entity (NME)

Predicting Intestinal Precipitation—A Case Example for a Basic BCS Class II Drug

“…This observation is in contrast to previous publications where relationships between in vitro and in vivo data have been claimed (4,5). However, the majority of literature data compares different formulations of the same dose, making it very difficult to distinguish between dissolution-enhancing properties and precipitation as underlying reasons for observations of differences in rate and extent of bioavailability (2,5,7). The present study included a more mechanistically based approach to elucidate the existence of in vivo precipitation based on human pharmacokinetic data, and no such analysis has, to our knowledge, been published in order to evaluate the accuracy of predictions of in vivo intestinal precipitation of drugs.…”

“…Dai et al have described 96-well plate experiments where precipitation has been measured over time in small volumes of various simulated gastrointestinal media, suitable for screening of different additives for prevention of precipitation (2). A number of different in vitro models using multi-compartment systems for detection of incomplete dissolution and precipitation have also been reported (3)(4)(5)(6)(7)(8).…”

“…Prediction of the extent and influence of intestinal precipitation of basic drugs after oral administration has previously been described in the literature (2)(3)(4)(5)(6)(7)(8). Dai et al have described 96-well plate experiments where precipitation has been measured over time in small volumes of various simulated gastrointestinal media, suitable for screening of different additives for prevention of precipitation (2).…”

In vitro methods to assess drug precipitation

“…Therefore, F1-250-1 denotes Formulation 1 at a 250-fold dilution for 1 h of incubation time. Reproduced with permission (Dai et al, 2007b). tion/solid dispersion, and complexation formulations (Dai et al, 2008a,b).…”

Instrumentation of Flow-Through USP IV Dissolution Apparatus to Assess Poorly Soluble Basic Drug Products: a Technical Note

“…One study has reported the use of a 96-well microtiter plate to study drug precipitation in different simulated GI fluids (5). Also, a United States Pharmacopoeia (USP) dissolution test with single medium for each test has been utilised (6).…”