A new dissolution test detects as little as 10% crystalline drug contamination in evacetrapib spray-dried dispersion tablets (J Pharm Biomed Anal 2017)

Original title: Development of an in vivo-relevant drug product performance method for an amorphous solid dispersion

J Pharm Biomed Anal · 17 May 2017 · 4

Pack BW, Babayan Y, Schrad MA, Stroud PA, Sperry DC, White KC, Aburub A

This work developed an in vitro dissolution method for evacetrapib spray-dried dispersion tablets designed to discriminate crystalline drug substance content, optimizing dissolution media, rotation speed, and surfactant conditions to achieve sink conditions. Spray-dried dispersion tablets spiked with 10%, 20%, and 30% crystalline drug substance showed corresponding 13%, 22%, and 32% drops in the dissolution endpoint relative to unspiked tablets, demonstrating the method's discriminating power. Using this method, spray-dried dispersion tablets showed a dissolution endpoint approximately 4-fold higher than tablets containing crystalline drug substance, closely matching a relative bioavailability study in which spray-dried dispersion tablets showed a 4.6-fold increase in exposure over crystalline tablets, validating the new dissolution method as a meaningful in vivo-relevant quality control tool for the amorphous formulation of evacetrapib.

Original abstract

The purpose of this work was to develop a meaningful in vitro dissolution method for evacetrapib spray-dried dispersion (SDD) tablets that is discriminating for crystalline drug substance (DS) content. Justification of the method conditions included evaluation of dissolution media, rotation speed, surfactant selection and level of surfactant to achieve sink conditions. Discrimination was illustrated by testing SDD tablets spiked with 10%, 20%, and 30% crystalline DS. The results demonstrated a 13%, 22% and 32% drop in the dissolution end point, respectively, as compared to unspiked SDD tablets. Additionally, tablets containing crystalline DS and tablets containing SDD were tested in a relative bioavailability (RBA) study. Utilizing the proposed dissolution method, the dissolution end point of SDD tablets was determined to be approximately 4 fold higher than that of the tablets containing crystalline DS. These results compare favourably to the in vivo RBA study results where SDD tablets had a 4.6 fold increase in exposure compared to tablets containing crystalline DS.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.