Comparison of Spray Congealing and Hot Melt Extrusion for the Taste Masking of Bitter Drugs

Purpose / Introduction

 

Taste masking of bitter drugs is critical for the successful development of solid oral dosage forms as it correlates with patient compliance. The increasing demand for new formulations as part of drug life cycle management or to address New Chemical Entities challenges is boosting the use of spray congealing, which can be described as a combination of spray drying and hot melt extrusion techniques. This platform can match many of the systems prepared by spray drying or hot melt extrusion but also enables the preparation of powders with unique properties and applications. In this work, the potential of spray congealing for taste masking was explored and compared to another commonly used technology, hot melt extrusion.

Spray congealing, also called spray chilling or spray cooling, is a unit operation in which a liquid melt is atomized into a cooling chamber. A sufficiently cold gas stream enters the chamber, typically in co-current configuration, contacting with the droplets and solidification takes place. This involves the transformation of molten droplets from liquid to solid state with removal of energy from the droplets. The transition of a melt from a soft or fluid state to a rigid or solid state by cooling is called congealing. Hence, the spray congealing process can be described by four events: i) atomization of the melt into droplets, ii) contact of the droplets with the cold congealing gas, iii) solidification of the droplets into particles and iv) separation of the particles from the congealing gas. A simplified scheme of the spray congealing process is shown in Figure 1.

Figure 1 – Standard spray congealing setup.

The ability to control the powder characteristics without the need of other downstream processing methods is a marked advantage of spray congealing over other “particle-engineering” technologies. Moreover, spray congealing is an environmentally friendly process where high throughputs can be achieved. This technology involves some critical stages that should be thoroughly evaluated when establishing the process, namely the atomization, cooling and feed stages. Spray congealing represents a very attractive and promising platform to address some of the challenges related to drug development and drug life cycle management.

Multiple spray congealing parameters were tested in the current work to assess their impact in the quality attributes of the formulation without compromising taste masking. The material produced with the best found conditions was compared with taste masked powders obtained using hot melt extrusion.

 

Methods

 

A modified lab scale spray dryer (Buchi, model B-290) was used to yield microparticles with high drug load. A bitter crystalline model drug, Quinine sulphate (Figure 2), was selected for its fluorescent characteristics and for having a sulfur element in its constitution which facilitates chemical mapping of the microparticles. The feed mixture was heated to 10ºC above the melting temperature of the excipient, where the drug was suspended. A structured Design of Experiments (DoE) with three parameters (atomization ratio, inlet temperature and drug content) was used to conduct the work (Figure 3). The characterization of the material involved the study of its surface by SEM-EDS and fluorescence microscopy. Finally, the material obtained by spray congealing was compared with those produced by hot melt extrusion (Thermo Scientific HAAKE MiniLab II) and subsequent milling.

 

Figure 2 – Crystalline model drug (SEM image with 1000x magnification).

 

 

 

Figure 3 – Design of Experiments with three parameters.

 

 

Results

 

Taste masking was achieved for all the materials obtained without modifying the crystalline structure of the drug, even for those materials with high drug content. No clear differences were observed between the spray congealing trials concerning morphology and encapsulation efficiency.

Figure 4 shows noticeable differences on the microparticles morphology (same starting formulation) obtained by spray congealing and hot melt extrusion, where roughness is indicative of drug crystals at the surface. Moreover, particles obtained by hot melt extrusion are not as smooth-surfaced as the spray congealed particles.

Figure 4 – SEM images produced by hot melt extrusion (HME) and spray congealing (SC).

The main disadvantage of hot melt extrusion, especially if the purpose is to mask the taste of the drug, is related to the downstream processing of this technology that by necessity includes the milling or pelletization of extrudates, which increases the probability of having drug molecules at the particle surface.

The higher taste masking efficiency of the material produced by spray congealing was confirmed by SEM-EDS with the absence of surface sulfur elements in the spray congealed samples whereas sulfur peaks were detected in the extruded materials (Figure 5). In addition, the images obtained by fluorescence microscopy also revealed a higher fluorescence intensity for the extruded material.

 

Figure 5 – SEM and fluorescence microscopy images of the materials produced by Hot Melt Extrusion (HME) and Spray Congealing (SC) and correspondent SEM-EDS spectra.

 

Conclusion

Taste masking is fundamental for the successful development of solid oral dosage forms as it correlates with patient compliance. Many drugs have a bitter or unpleasant taste and spray congealing can be used with success for taste masking purposes.

Spray congealing is an efficient technology for taste masking purposes and it may be considered an alternative to commonly used technologies, particularly when high drug loads are required. Additionally, spray congealing is an environmentally friendly process and high throughputs can be achieved. The ability to control powder characteristics (particle size, morphology, density) without the need of other downstream processing methods (e.g. secondary drying, granulation, milling, pelletization) is a marked advantage over other methods.

Spray congealing represents an attractive and promising platform to address some of the challenges related to drug life cycle management and development of certain New Chemical Entities, with expected growth in the number of approved products using this platform in the next few years.