Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying

Abstract

The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression.

Vacuum drum drying – A novel solvent-evaporation based technology to manufacture amorphous solid dispersions in comparison to spray drying and hot melt extrusion

“…However, considering tabletability, there are more factors involved in influencing the mechanical strength of the tablets, such as particle morphology, as demonstrated in previous work [45]. It was shown that tabletability as such is mostly influenced by the particle morphology comparing ASDs with similar solid-state by hot-melt extrusion, spray-drying, or vacuum drum drying.…”

“…In addition, each manufacturing technology will potentially result in ASD intermediates with different properties such as solid-state or material/powder characteristics. Studies comparing hot-melt extruded and spray dried intermediates are described in literature [44][45][46][47]. Moreover, the physical and chemical stability of the intermediate might be affected by different factors depending on the ASD manufacturing technique used.…”

Compression Modulus and Apparent Density of Polymeric Excipients during Compression—Impact on Tabletability

“…In addition, the results offer the opportunity to rate the risk for tablet defects based on stored elastic energy depending on the required compaction pressure for a certain mechanical strength of the tablet. However, considering tabletability, there are more factors involved in influencing the mechanical strength of the tablets, such as particle morphology, as demonstrated in previous work [ 45 ]. It was shown that tabletability as such is mostly influenced by the particle morphology comparing ASDs with similar solid-state by hot-melt extrusion, spray-drying, or vacuum drum drying.…”

Formulation and In Vitro Characterization of a Vacuum-Dried Drug–Polymer Thin Film for Intranasal Application

“…Commonly utilized thermal processing methods for bulk and powder manufacturing include hot-melt extrusion (HME) [ 48 , 49 , 50 , 51 , 52 ] and spray drying (SD) [ 53 , 54 , 55 , 56 , 57 ]. In contrast, vacuum drying does not require a heating process [ 28 ], and offers many advantages such as applicability to APIs with a high melting point or low resistance against thermal and shear stress, and the potential for processing highly viscous solutions and those of high molecular weight, which are difficult to process using HME and SD [ 58 , 59 ]. Vacuum drying may thus be an optimal drying method for nasal formulations, which are suitable for various drug modalities such as peptides, proteins, nucleic acids, and antibodies.…”