Spray Drying of Mannitol as a Drug Carrier—The Impact of Process Parameters on Product Properties

Abstract

Powders intended for the use in dry powder inhalers have to fulfill specific product properties, which must be closely controlled in order to ensure reproducible and efficient dosing. Spray drying is an ideal technique for the preparation of such powders for several reasons. The aim of this work was to investigate the influence of spray-drying process parameters on relevant product properties, namely, surface topography, size, breaking strength, and polymorphism of mannitol carrier particles intended for the use in dry powder inhalers. In order to address this question, a full-factorial design with four factors at two levels was used. The four factors were feed concentration (10 and 20% [w/w]), gas heater temperature (170 and 190 C), feed rate (10 and 20 L/h), and atomizer rotation speed (6,300 and 8,100 rpm). The liquid spray was carefully analyzed to better understand the dependence of the particle size of the final product on the former droplet size. High gas heater temperatures and low feed rates, corresponding to high outlet temperatures of the dryer (96-98 C), led to smoother particles with surfaces consisting of smaller crystals compared to those achieved at low outlet temperatures (74-75 C), due to lower gas heater temperatures and higher feed rates. A high solution concentration of the feed also resulted in the formation of comparably rougher surfaces than a low feed concentration. Spray-dried particles showed a volumeweighted mean particle size of 71.4-90.0 lm and narrow particle size distributions. The mean particle size was influenced by the atomizer rotation speed and feed concentration. Higher rotation speeds and lower feed concentrations resulted in smaller particles. Breaking strength of the dried particles was significantly influenced by gas heater temperature and feed rate. High gas heater temperatures increased the breaking strength, whereas high feed rates decreased it. No influence of the process parameters on the polymorphism was observed. All products were crystalline, consisting of at least 96.9% of mannitol crystal modification I.

A multivariate approach applied to quality on particle engineering of spray-dried mannitol

“…The great advantage of using mannitol in place of a-lactose is the possibility of using spray dryer to design particle without affecting product stability [11]. SDM particle sizes can be modified by changing the droplet size during atomization; the concentration of the feed solution or the solubility of the solute [12].…”

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“…Interestingly, Littringer et al found that influence of feed concentration on the droplet size at high atomizer revolution rates is less 48 . This is also an example of possible complex interaction between various process parameters (in this case between feed concentration and atomizer revolution rate).…”

“…This can affect the morphology of the dried particle. Temperature variation results in different surface properties and shape such as particle roughness 48,54 . Higher inlet temperature results in enlarged particle diameter 51 .…”

“…This is particularly relevant in the lab-scale equipment of non-continuous nature. Feed rate can impact the particle surface topography 48 . An increase in feed flow rate caused a reduction in particle size and crystallinity of the artemisininmaltodextrin microparticles 51 .…”

“…More than two factors can also be involved. For instance, particle size is result of feed concentration, droplet size, drying air temperature and feed rate 48 .…”