Formation of lactose-mannitol molecular alloys by solid state vitrification

Transformation of Pharmaceutical Compounds upon Milling and Comilling: The Role of Tg

“…(ii) Milling crystalline compounds above T g may induce polymorphic transformations which generally place the system in a metastable states (cases of sorbitol, 21 mannitol, 24 sulfamerazine 11 ).…”

“…24 The X-ray diffraction patterns on Figure 5a,b show that upon milling, the stable crystalline form b of mannitol undergoes a polymorphic transformation toward the metastable form a. The X-ray diffraction patterns in Figure 5d,e reveal that the polymorphic form b of mannitol undergoes the same transformation upon milling.…”

Amorphous Solid Dispersions of Sulfonamide/Soluplus® and Sulfonamide/PVP Prepared by Ball Milling

“…It is clear from the FH parameters' values that the greater ability of SMZ (compared to STZ, SDM and SDZ) to form amorphous dispersions with PVP or Soluplus® is not due to a greater miscibility with these excipients compared to the other sulfonamides studied in this article. It has been shown that, the greater the glass transition temperature, the easier the amorphisation of a compound upon milling at a given temperature (19,21,22,32,40,41). However, this cannot explain the amorphisation of SMZ with lower excipient concentration compared to SDM as the Tg of SDM is higher than the Tg of SMZ, and therefore, one might expect that SDM/excipient systems should form amorphous dispersions over a wider concentration range than SMZ/excipient systems.…”

“…Milling is a technique widely used to reduce particle size (18) but is not commonly used for making amorphous dispersions, although it has been shown to be suitable to amorphise pharmaceutical compounds and to produce glassy solutions (10,(19)(20)(21)(22). Although milling presents some disadvantages compared to the more traditional techniques mentioned above, such as potential for material caking in the mill and challenges with scale-up, advantages associated with the process include the absence of thermal stress if the process is properly controlled (23) and the absence of solvent.…”

An investigation into the crystallisation behaviour of an amorphous cryomilled pharmaceutical material above and below the glass transition temperature

“…Others argue that the disordering process is best regarded as an accumulation of defects (or, viewed another way, a dramatic reduction in crystallite size) and hence may not necessarily be regarded as amorphisation in the traditional sense 12. A very significant contribution to the debate with regard to how these theories apply to organic crystalline materials is provided by the group of Descamps13–15 who have highlighted the relationship between the temperature of milling and the glass transition temperature of the corresponding material. In particular they have demonstrated that while cryomilling (well below T g ) results in amorphisation, milling above T g results in polymorphic transformation; this therefore contradicts the melt‐quench explanation.…”