Downstream processing of a ternary amorphous solid dispersion: The impacts of spray drying and hot melt extrusion on powder flow, compression and dissolution

Abstract

Downstream processing aspects of a stable form of amorphous itraconazole exhibiting enhanced dissolution properties were studied. Preparation of this ternary amorphous solid dispersion by either spray drying or hot melt extrusion led to significantly different powder processing properties. Particle size and morphology was analysed using scanning electron microscopy. Flow, compression, blending and dissolution were studied using rheometry, compaction simulation and a dissolution kit. The spray dried material exhibited poorer flow and reduced sensitivity to aeration relative to the milled extrudate. Good agreement was observed between differing forms of flow measurement, such as Flow Function, Relative flow function, Flow rate index, Aeration rate, the Hausner ratio and the Carr index. The stability index indicated that both powders were stable with respect to agglomeration, de-agglomeration and attrition. Tablet ability and compressibility studies showed that spray dried material could be compressed into stronger compacts than extruded material. Blending of the powders with low moisture, freely-flowing excipients was shown to influence both flow and compression. Porosity studies revealed that blending could influence the mechanism of densification in extrudate and blended extrudate formulations. Following blending, the powders were compressed into four 500 mg tablets, each containing a 100 mg dose of amorphous itraconazole. Dissolution studies revealed that the spray dried material released drug faster and more completely and that blending excipients could further influence the dissolution rate.

Assessment of the effect of Cellets’ particle size on the flow in a Wurster fluid-bed coater via powder rheology

“…The BFE is a measure of the resistance required by a twisted blade to displace a powder during non-gravitational, forced flow, i.e. its resistance to flow in a constrained environment, for example, feeding via flowing in a conveyer [15] or mixing [16]. Cellets without MgSt demonstrated an almost linear increase in BFE with decreasing size (Figure 10 A).…”

Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance

“…Finally, flowability can be influenced by adding extra excipients to the composition before the ASD preparation. Davis et al studied the impacts of spray drying and HME on powder flow, compression and dissolution in case of itraconazole-containing ASDs [117]. A ternary ratio of API-Soluplus ® -HPMCP 30-40-30 (w/w%) was selected for preparation of ASDs.…”

“…Different sugars turned out to possibly have an impact on the friability of polyvinyl alcoholnanofibers thus the application of extra excipients can help in case of electrospun materials as well [122]. Davis et al, studied the impacts of spray drying and HME on powder flow, compression and dissolution in case of itraconazole-containing ASDs [117]. A ternary ratio of API-Soluplus ® -HPMCP 30-40-30 (w/w%) was selected for preparation of ASDs.…”

Microwave-Induced In Situ Amorphization: A New Strategy for Tackling the Stability Issue of Amorphous Solid Dispersions

“…Despite the extensive in-depth studies carried out in ASDs, commercialization of ASDs is still very limited (approximately 30 marketed products since 1975) [9,[16][17][18]. This situation may stem from a range of problematic issues of ASDs, mainly including physical stability, downstream processing and scale-up difficulties [19][20][21]. In 2017, microwave-induced in situ amorphization was firstly proposed by Doreth et al as a promising approach to tackling these problems [22].…”