(M1430-08-51) Co-processing PVP with Maltodextrin during Spay-Drying Reduces the Impact of Humid Weather on Product Attributes

Purpose: Spray-drying hygroscopic materials in uncontrolled humidity facilities can be problematic. When the relative humidity (%RH) >45%, particles may partially deliquesce after formation, making them sticky (1). Although the use of dehumidifiers can control the inlet air %RH to a certain extent, formulation approaches may be needed for spray-drying very hygroscopic polymers such as polyvinyl pyrrolidone (PVP; Kollidon 12 pf). The purpose of this study was to develop a formulation for spray-dried microparticles containing PVP, having improved physiochemical properties when processed in an uncontrolled %RH environment. Co-processing spray-dried PVP with maltodextrin as a formulation aid was explored to improve the spray-drying process and resulting microparticle size, morphology and flowability at high %RH ( >65%).

Methods: Spray-dried microparticles of PVP and PVP/maltodextrin (20:80 w/w) were prepared using a Yamato ADL 311S mini spray-dryer, equipped with a 0.7 mm spray nozzle. Feed solutions were prepared by dissolving components in deionized water at 58% w/v solids content. Dissolution was aided by sonication for up to 45 min. Solutions were spray-dried using an inlet air temperature of 180°C, atomization pressure of 0.05 MPa, exhaust speed of 0.41 m³/min, and feed solution flow rate of 8.2 mL/min. Microparticle size distributions (number distribution for approximately 5000 particles) were characterized using a BX-51 optical microscope by determining the Feret’s diameter from images obtained at 10X objective and processed using ImageJ software. The residual moisture content was analyzed using thermogravimetric analysis (TGA); approximately 15 mg of microparticles were heated from ambient to 150 °C at 10 °C/min in a platinum pan. Flow properties of the spray-dried microparticles were evaluated by calculating Carr’s index (CI) and Hausner ratio from the tapped and bulk density of the microparticles.

Results: Particle size characterization for spray-dried PVP microparticles could not be done when processed at 69 %RH, as their high hygroscopicity led to immediate moisture absorption after placement on the microscope, owing to high ambient %RH (Figure 1A). Microparticles prepared from maltodextrin and PVP (80:20), however, were easily characterized, and had a median particle size (d₅₀) ̴ 21 µm (Figure 2). Circularity and roundness were >0.8, demonstrating that co-processing PVP with maltodextrin resulted in spherical, smooth microparticles (Figure 1B). The residual moisture content of PVP microparticles was not evaluated due to their deliquescence. In contrast, the moisture content of PVP/maltodextrin microparticles was around 4% (w/w) (Figure 3). Spray-dried microparticles made using only PVP had poor flow (CI = 30, Hausner ratio =1.42), whereas PVP co-processed with maltodextrin led to better flow with CI = 18 and Hausner ratio =1.22 (fair flow).

Conclusion: Owing to high hygroscopicity, spray-drying PVP alone at high %RH resulted in non-viable product. In contrast, co-processing PVP with maltodextrin produced dry powders with much less microparticle adhesion inside the equipment drying chamber. Furthermore, the co-processed microparticles were amenable to characterization, had a low residual moisture content (around 4%), and better flow properties compared to PVP alone. These findings suggest that addition of 80% w/w maltodextrin to the formulation mitigated the hygroscopicity of the PVP, allowing production of solid microparticles having significantly improved size, shape, moisture content and flow properties. Moreover, this formulation approach enabled year-round spray-drying of PVP in an uncontrolled humidity environment.

References: 1. Boel E, Koekoekx R, Dedroog S, Babkin I, Vetrano MR, Clasen C, Van den Mooter G. Unraveling particle formation: From single droplet drying to spray drying and electrospraying. Pharmaceutics. 2020 Jul 4;12(7):625.

Figure 1: (A) Optical photomicrographs showing deliquescence of spray-dried PVP microparticles in atmospheric moisture on microscope slide within 5 minutes (Room temp. 21°C and RH 69%). (B) Photomicrographs of microparticles of PVP co-processed with maltodextrin (Room temp. 21°C and RH 65%).

Figure 2: Number distribution of PVP/maltodextrin microparticles, median particle size d50 of around 21 µm and approximately 5000 microparticles were inspected to fully define the distribution.

Figure 3: TGA curve showing the residual moisture content of spray-dried PVP/maltodextrin (20:80 w/w) microparticles.