(696e) Comparison of Spray Congealing and Hot Melt Extrusion for the Taste Masking of Bitter Drugs
AIChE Annual Meeting
2014
2014 AIChE Annual Meeting
Particle Technology Forum
Particle Engineering as Applied to Pharmaceutical Formulations
Thursday, November 20, 2014 - 1:46pm to 2:05pm
Hovione - Blank Template
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font-family:"Times New Roman","serif"'>Purpose / Introduction
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font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>Spray congealing, also called spray
chilling or spray cooling, is a unit operation in which a liquid melt is
atomized font-family:"Times New Roman","serif"'>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 150%;font-family:"Times New Roman","serif"'> 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. 10.0pt;line-height:150%;font-family:"Times New Roman","serif"'> A
simplified scheme of the spray congealing process is shown in Figure 1. line-height:150%"> font-family:"Times New Roman","serif"'> text-align:center;line-height:150%;text-autospace:none"> 150%;font-family:"Times New Roman","serif"'>
text-align:center;line-height:150%;text-autospace:none">Figure 1 ?
Standard spray congealing setup. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>Methods line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> 10.0pt;line-height:150%;font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'>
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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'>
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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'>
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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> line-height:150%;font-family:"Times New Roman","serif"'>
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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>Spray congealing, also called spray
chilling or spray cooling, is a unit operation in which a liquid melt is
atomized font-family:"Times New Roman","serif"'>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 150%;font-family:"Times New Roman","serif"'> 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. 10.0pt;line-height:150%;font-family:"Times New Roman","serif"'> A
simplified scheme of the spray congealing process is shown in Figure 1. line-height:150%"> font-family:"Times New Roman","serif"'> text-align:center;line-height:150%;text-autospace:none"> 150%;font-family:"Times New Roman","serif"'>
text-align:center;line-height:150%;text-autospace:none">Figure 1 ?Standard spray congealing setup. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>Methods line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> 10.0pt;line-height:150%;font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'>
Figure
2 ?
font-family:"Times New Roman","serif"'>Crystalline model drug (SEM image with
1000x magnification).
Figure
3 ?
font-family:"Times New Roman","serif"'>Design of Experiments with three
parameters.
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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'>
Figure
4 ? SEM images produced by hot melt extrusion (HME) and spray congealing (SC).
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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'>
Figure
5 ?
font-family:"Times New Roman","serif"'>SEM and fluorescence microscopy images
of the materials produced by Hot Melt Extrusion (HME) and Spray Congealing (SC)
and correspondent SEM-EDS spectra.
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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> font-family:"Times New Roman","serif"'> line-height:150%"> font-family:"Times New Roman","serif"'>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. line-height:150%"> line-height:150%;font-family:"Times New Roman","serif"'>