Combined control of morphology and polymorph in spray drying of mannitol for dry powder inhalation

Abstract

The morphology and polymorphism of mannitol particles were controlled during spray drying with the aim of improving the aerosolization properties of inhalable dry powders. The obtained microparticles were characterized using scanning electron microscopy, infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction and inhaler testing with a next generation impactor. Mannitol particles of varied -mannitol content and surface roughness were prepared via spray drying by manipulating the concentration of NH 4 HCO 3 in the feed solution. The bubbles produced by NH 4 HCO 3 led to the formation of spheroid particles with a rough surface. Further, the fine particle fraction was increased by the rough surface of carriers and the high -mannitol content.Inhalable dry powders with a 29.1 ± 2.4% fine particle fraction were obtained by spray-drying using 5% mannitol (w/v)/2% NH 4 HCO 3 (w/v) as the feed solution, proving that this technique is an effective method to engineer particles for dry powder inhalation.

Application of Spray Drying Technique for Flowability enhancement of Divalproex Sodium

“…It is generally accepted that the larger the particles, the better the flow. Typically, particles larger than 250 µm are free-flowing while for those smaller than 100 µm, powders turn out to be cohesive and lead to flow problems [14,15]. Spray drying technology is a particle production technique.…”

Characteristics and Analytical Methods of Mannitol: An Update

“…The α form shows the fastest growth rate and its seeds tend to form the same type of polymorph. Whereas, seeds of α or β form appears from β polymorph and α form forms δ polymorph [72][73][74]. Although the δ form is the least stable, its superior compaction properties increasingly increase its importance as an excipient, particularly for tablet manufacturing.…”

Drying kinetics and nucleation in evaporating sodium nitrate aerosols

“…The microphysics of the drying process also likely has an impact on the viability of bacteria in aerosols 3 . In spray drying the goal is to control the distribution of sizes, morphology and phase of the final droplets, which are very sensitive to processing conditions such as solvent 4,5 , temperature [6][7][8] , pH 9,10 and additional co-excipients [11][12][13] . Tailoring crystallisation is particularly important because crystal and amorphous states have fundamentally different properties: crystalline droplets are typically more stable and suitable for product storage 14,15 , whereas amorphous droplets are more easily re-dissolved into an aqueous solution droplet which is desirable for inhalable powders for respiratory drug delivery 16,17 .…”