(T1230-01-03) Identification of Critical Spray-Drying Process Parameters for Preparing Size Tunable Microparticles using Polyvinyl Pyrrolidone and Sodium Alginate

Purpose: Spray-drying is a reliable and reproducible method used to design and produce microparticles. Intranasal delivery of spray-dried solid microparticles formed from bioadhesive polymers can allow for prolonged residence time on the nasal epithelium, resulting in reduced mucociliary clearance. The objective of the present study was to identify critical spray-drying process parameters for manufacturing solid microparticles having a target median particle size of 30 µm.

Methods: Preparation of Spray Dried Microparticles: Two polymers, polyvinyl pyrrolidone (PVP; Kollidon 12 pf) and sodium alginate (Manucol LKX) were separately dispersed in deionized water at different %w/v concentrations. PVP was dissolved by stirring while samples were immersed in a room temperature ultrasonic bath for 3 hr. Sodium alginate solutions were prepared by dissolving the polymer in deionized water with gentle agitation using a magnetic stirrer for 24 h. Spray-drying was accomplished using a Yamato ADL 311S mini spray-dryer, equipped with a 0.7 mm spray nozzle. Polymer solutions were fed into the spray-dryer at feed rates between 5-11 mL/min; spraying was done using atomization air pressures between 0.03-0.1 MPa, while drying was accomplished using inlet air temperatures ranging from 150–180 °C. Microparticles were sized using an Olympus light microscope to determine the Feret’s diameter from images obtained at 10× and 50× magnification and processed using ImageJ software(ij153-win-java8).

Results: Spray-drying process parameters were optimized for PVP solutions to produce microparticles with the target median particle size. Attempts to influence the diameters of spray-dried particles was done by varying inlet air temperature, atomization pressure, and feed flow rate. These changes had limited effect on the resulting size and distribution of microparticles, relative to variation of % w/v solids content of the polymer. Ultimately, PVP solutions were fed into the nozzle at 8.2 mL/min, and spray-dried at an atomization pressure of 0.05 MPa and an inlet temperature of 170 ^oC. The 5% w/v PVP solutions resulted in microparticles having a D₅₀ = 10.77 µm, while the 30% w/v and 58% w/v PVP solutions yielded microparticles with D₅₀ of 16.34 µm and 29.69 µm, respectively (Table 1). A photomicrograph of the 58% w/v PVP spray-dried particles is shown in Figure 1. Variation of spray-dryer parameters also resulted in little change to the D₅₀ for microparticles prepared from the 5% w/v sodium alginate solutions, yielding particles with D₅₀ = 10.19 µm when processed at 8.2 mL/min feed rate, 0.05 MPa atomization and an inlet temperature of 170 ^oC (Table 1). Attempts to vary sodium alginate microparticle diameter using similar % w/v solids concentration failed, as higher concentrations of this polymer resulted in a highly viscous gel that could not be sprayed. A photomicrograph of the 5% w/v sodium alginate spray-dried particles is shown in Figure 1.

Conclusion: Spray-drying aqueous solutions of two bioadhesive polymers resulted in microparticles whose median diameters were suitable for intranasal deposition. Process parameters such as feed rate, atomization pressure, and inlet air temperature had minimal influence over the particle size and distribution for both PVP and sodium alginate. The D₅₀ of PVP solutions could be controlled by changing the solids content of the spray-drying solution, with 5% w/v aqueous solutions resulting in smaller particles (D₅₀≈10 mm) and 58% w/v aqueous solutions resulting in larger particles (D₅₀≈30 mm). Although 5% w/v aqueous sodium alginate solutions yielded particle size distributions comparable to PVP at the same concentration (D₅₀≈10 mm), higher concentrations of sodium alginate resulted in gels that were too viscous to spray-dry. These data suggest that transfer of processing conditions between polymers may be limited by the material itself, as evidenced by the sodium alginate.


Table 1: Particle size distributions of sodium alginate and PVP


Figure 1: Photomicrographs of spray dried microparticles of a) PVP (58% w/v solution) and b) sodium alginate (5% w/v solution)