Applicability of the one-step XXXX method for the determination of amorphous amounts for further different hydrophilic and hydrophobic drugs.

@entity10924 @entity1044 @entity1042 @entity2421 @entity5723 @entity6094
UNASSIGNED: In a former publication the authors showed that low amounts of amorphous content (LOQ of 0.5%) in a hydrophobic model API ( @entity10924 ) can be measured with an individually adjusted one-step dynamic organic vapor sorption ( @entity6094 ). In this investigation the applicability is tested on various APIs which differ in @entity2421 (absorption of water). The vapor sorption method proved to be applicable in almost all cases. Moisture sorption isotherms were determined for all five investigated crystalline and amorphous APIs. However, it was necessary to select the parameters individually for each API. The used solvents (water, @entity1042 , @entity5723 and @entity1044 ) and the humidity-levels (0.05 p/p0 until 0.5 p/p0) were chosen carefully because otherwise the amorphous amounts switch to their crystalline counterparts and are not detectable. The production of fully amorphous samples (absence of crystalline material measured by DSC, mDSC and XRPD) was optimized over several trials. As successfully methods proved ball-milling, freeze-drying, spray-drying and/or quench cooling. In the next step these fully amorphous amounts were blended with crystalline starting material to calibration curves (Turbula blender, influence of electrostatic charge to homogeneity) for the calculation of amorphous content. In summary, the following presented methods were used to determine and quantify low amorphous amounts (between 1.5% and 17.0%) in jet-milled powders (grinding pressure of 8bar, 1-3 grinding cycles), respectively.
