The Impact of Particle Properties on High Concentration Suspension Performance and Stability of Spray-Dried Monoclonal Antibodies.

Subcutaneous (subQ) administration of biologic drug products is increasingly preferred to enable patient self-administration and reduce healthcare burden. However, the small dosing volume for subQ delivery necessitates high-concentration formulations, which often suffer from elevated viscosity and physical instability, creating challenges in manufacturing, injectability, and storage. Spray drying has emerged as a versatile particle engineering technique to produce solid biologic powders that can be redispersed into suspensions. While suspensions of spray-dried particles have shown promise in reducing viscosity compared to liquid solutions, the influence of biologic particle properties on suspension performance remains poorly understood. This study aimed to elucidate how particle size and surface characteristics affect viscosity and stability of high-concentration monoclonal antibody (mAb) suspensions. Spray-dried mAb particles were prepared with varied sizes and leucine addition. Suspensions were evaluated for viscosity, injectability through 27G needles, sedimentation, physical, chemical and structural stability during storage at 5°C and 25°C for 3 months and at 40°C for 1 month. Larger particle size, less surface dimpling and leucine addition significantly reduced viscosity without compromising physical and chemical stability; no sedimentation was observed. All suspensions were injectable via 27G needles. No notable aggregation or fragmentation occurred under tested conditions. Particle size and surface properties modulate suspension viscosity but do not impact stability. Particle engineering through spray drying represents an effective approach to enable high-concentration biologic suspensions for subQ delivery.

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Background Subcutaneous (subQ) administration of biologic drug products is increasingly preferred to enable patient self-administration and reduce healthcare burden. However, the small dosing volume for subQ delivery necessitates high-concentration formulations, which often suffer from elevated viscosity and physical instability, creating challenges in manufacturing, injectability, and storage. Spray drying has emerged as a versatile particle engineering technique to produce solid biologic powders that can be redispersed into suspensions. While suspensions of spray-dried particles have shown promise in reducing viscosity compared to liquid solutions, the influence of biologic particle properties on suspension performance remains poorly understood.

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Methods Spray-dried mAb particles were prepared with varied sizes and leucine addition. Suspensions were evaluated for viscosity, injectability through 27G needles, sedimentation, physical, chemical and structural stability during storage at 5°C and 25°C for 3 months and at 40°C for 1 month.

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Results Larger particle size, less surface dimpling and leucine addition significantly reduced viscosity without compromising physical and chemical stability; no sedimentation was observed. All suspensions were injectable via 27G needles. No notable aggregation or fragmentation occurred under tested conditions. Particle size and surface properties modulate suspension viscosity but do not impact stability.

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Data Summary Larger particle size, less surface dimpling and leucine addition significantly reduced viscosity; no sedimentation was observed. All suspensions were injectable via 27G needles. No notable aggregation or fragmentation occurred under tested conditions.

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Conclusions Particle size and surface properties modulate suspension viscosity but do not impact stability. Particle engineering through spray drying represents an effective approach to enable high-concentration biologic suspensions for subQ delivery.

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Practical Significance Subcutaneous (subQ) administration of biologic drug products is increasingly preferred to enable patient self-administration and reduce healthcare burden. Spray drying has emerged as a versatile particle engineering technique to produce solid biologic powders that can be redispersed into suspensions, showing promise in reducing viscosity compared to liquid solutions.