Track: Manufacturing and Analytical Characterization - Biomolecular - Process Design and Controls - QbD and Assessment of Process Parameters
Category: Poster Abstract
Optimization of Spray Drying of Mucoadhesive Microparticles Using Design of Experiments (DoE)
Purpose: Mucoadhesive microparticles adhere to the mucosal surface of many biological tissues resulting in longer residence times leading to enhanced bioavailability. Spray drying is an efficient approach to manufacture mucoadhesive microparticles directly from solution by rapid solvent removal in a single step. However, the yield varies significantly in literature reports, and a low yield presents difficulties in formulating drug molecules when limited supplies are available. In order to maximize yield of mucoadhesive microparticles, it is necessary to understand how the various spray drying process parameters affect yield. The objective of this study was to identify the critical spray drying parameters affecting mucoadhesive microparticle yield, and then to optimize the spray drying process for mucoadhesive microparticles to maximize yield. Methods: Pectin was used as a mucoadhesive polymer and was dissolved in water prior to spray drying. Microparticles were prepared using a Buchi B-290 Spray Dryer. Optimization of the spray drying process was performed using a DoE approach. A central composite design was used. Five factors (input temperature, aspirator rate, feed flow rate, pectin concentration, and pectin feed amount) with three levels were selected. Yield as well as particle size (D10, D50, D90 and span value) were tested as responses. The particle size was analyzed using a Malvern MasterSizer. The yield and span value were calculated using the equations: Yield (%) = Total amount of particles collected/Total amount of solid sprayed and span = (D90 - D10)/D50. The experimental design is shown in Table 1. The data were analyzed using least squares fitting on JMP® software. The morphology of the microparticles was observed using a FlowCam Nano. Results: The yield and particle size of the pectin microparticles are shown in Table 1. The yield was analyzed using a quadratic model. The model was valid with R2, root mean square error and p-value of 0.98, 0.021 and < 0.0001, respectively. As shown in Figure 1A, the most significant factor affecting spray drying yield was pectin concentration, followed by aspirator rate and pectin feed, with p-values less than 0.0001. The optimized conditions for a maximum yield of 76.9% were as follows: input temperature 118.8°C, aspirator rate 94.7%, feed flow 8% (~2.4 mL/min), pectin concentration 0.5% (w/v) and pectin feed amount 5 g (Figure 1B). The particle size was not markedly affected by the selected spray drying parameters (Table 1). The microparticles were close to spherical in shape with uneven surfaces (Figure 1C). Conclusion: This study demonstrates the usefulness of applying DoE to identify the critical spray drying parameters for mucoadhesive microparticle yield using the Buchi B-290 spray drier. Furthermore, DoE is a helpful tool to optimize spray drying conditions to obtain maximized yield of mucoadhesive microparticles.