Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

Abstract

Abstract. Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.

A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets

“…PVP is frequently used in HME to enhance the dissolution pattern of poorly soluble molecules (24)(25)(26)(27)(28). TGA thermographs ( Figs.…”

Improved Dissolution and Pharmacokinetics of Abiraterone through KinetiSol® Enabled Amorphous Solid Dispersions

“…The Lot 1 and Lot 2 KSDs showed slight discoloration and were yellowish in color, while the Lot 3 KSD also showed slight discoloration but was light brown in color. None of these KSDs showed high levels of discoloration consistent with polymer degradation, as was seen during HME of these polymers [42,43]. The Lot 4 KSD showed significant discoloration and was brown in color.…”

Application of Deep Learning Convolutional Neural Networks for Internal Tablet Defect Detection: High Accuracy, Throughput, and Adaptability

“…[3][4][5] In the realm of pharmaceutical sciences, XRCT is commonly used to identify and analyze dosage forms that have a different density between adjacent regions, such as tablet coating and its thickness 6 relative to the tablet core, porosity of granules, 7 and the structure of solid dispersions prepared by hotmelt extrusion. 8 Owing to the inherent density difference between internal tablet cracks and tablet matrices, XRCT is well suited for the identification of these internal tablet defects in a nondestructive fashion.…”