Revealing Polymorphic Phase Transformations in Polymer-Based Hot Melt Extrusion Processes

Abstract

The inadvertent occurrence of polymorphic phase transformations in active pharmaceutical ingredients (APIs) during hot melt extrusion (HME) processes has been claimed to limit the application of this technique. Hence, the control of polymorphism would need to be addressed if there is any prospect of HME to be successfully implemented as an alternative solid dosage formulation strategy in integrated, continuous end-to-end pharmaceutical manufacturing settings. This work demonstrates that flufenamic acid (FFA), one of the most polymorphic APIs known, thus far, can be processed using temperature-simulated HME with polyethylene glycol (PEG) as polymeric carrier. At temperatures above the transition point of FFA forms III and I (42 °C), the induction time of the polymorphic phase transformation is longer than the average reported residence time in conventional HME processes (5 min). Moreover, it was demonstrated that thorough understanding of the thermodynamic and kinetic design space for the PEG-FFA system leads to polymorphic control in the produced crystalline solid dispersions. Ultimately, this investigation helps to gain fundamental understanding of the processing needs of crystalline solid dispersions, which will lead to the broader application of HME as a continuous manufacturing strategy for drug products containing APIs prone to polymorphism, representing about 80% of all APIs.

Coprocessing of Pharmaceutical Cocrystals for High Quality and Enhanced Physicochemical Stability

“…This can be attributed to the tendency for polyols to be inert during extrusion, and xylitol's low viscosity combined with is decreased miscibility allowing for increased molecular mobility and the rapid solidification. [17][18][19][20] However, a remaining barrier to the success of this method was the presence of amorphous IBU existing within the inert xylitol matrix, a trend which has been observed in previous studies. [16][17][18] A possible explanation for this is that the addition of any matrix, in high concentrations will hinder the interactions of the API-coformer pair at a molecular level.…”

Hydrogel with silver nanoparticles synthesized by Mimosa tenuiflora for second-degree burns treatment

“…Powder samples were mounted in MiTeGen microloops. Powder diffractograms were collected over an angular 2θ range between 35° and 90° with a step size 36 of 0.01°.…”

Pengaruh Komponen Hidrofobik Elastis terhadap Karakteristik Fisik dan Laju Disolusi Tablet Eritromisin Stearat

“…Campuran biner ERS-ASM 50:50 (% b/b) memiliki puncak endotermik pada 106,1; 169,8; dan 203,8 °C yang teramati sebagai titik lebur masing-masing ERS dan ASM yang mengalami pergeseran pada tingkat yang lebih ekstrim (Gambar 5). Keberadaan komponen kedua telah dipelajari dapat menyebabkan transformasi polimorfik dan pergeseran titik lebur komponen pertama [17]. Hasil karakterisasi dengan DTA mengindikasikan tidak ada interaksi yang terbentuk antara ERS-PRS maupun ERS-ASM.…”