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Spray-Coating for Biopharmaceutical Powder Formulations: Beyond the Conventional Scale and Its Application

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Abstract

Purpose: Fluid-bed spray-coating process is widely used to prepare non-protein pharmaceutical solid dosage forms using macro-size seed particles (200-1000 μm) at kilogram batch sizes. In this study we developed a small-scale fluid-bed spray-coating process (20 g) to produce micro-sized vaccine powder formulations (40-60 μm) for epidermal powder immunization (EPI)

Methods: A bench-top spray coater was used to spray two vaccines, diphtheria toxoid (dT) and alum-adsorbed hepatitis-B surface antigen (Alum-HBsAg), onto crystalline lactose particles of 40-60 μm in diameter. Particle properties such as particle size, surface morphology, and degree of particle agglomeration were determined. Protein stability was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The immunogenicity of the vaccine was evaluated in vivo by needle injection and epidermal powder immunization (EPI) of mice or guinea pigs.

Results: Coating feasibility was demonstrated for both vaccine formulations containing different excipients. However, the nature of the vaccine antigen appeared to affect coating feasibility in terms of particle agglomeration considerably. Delivery of spray-coated dT and alum-HBsAg through EPI to mice and guinea pigs, respectively, generated significant antibody responses, at a level comparable to liquid formulation delivered subcutaneously through needle/syringe injection.

Conclusions: The new spray-coating process represents an important technical advance and may provide a useful tool for developing high-valued biopharmaceutical powder formulations for novel applications. The strong in vivo performance of the coated dT and alum-HBsAg powders by EPI further demonstrated that spray-coating is a viable dry powder formulation process and the skin's epidermal layer presents an efficient vaccine delivery route.

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Author notes

  1. Yuh-Fun Maa & Mahmoud Ameri

    Present address: Alza Corporation, 1900 Charleston Road, Mountain View, California, 94043

Authors and Affiliations

  1. PowderJect Vaccines, Inc, 585 Science Drive, Madison, Wisconsin, 53711

    Yuh-Fun Maa, Mahmoud Ameri, Lendon G. Payne & Dexiang Chen

  2. Fluid Air, Inc., 2550 White Oak Circle, Aurora, Illinois, 60504-9678

    Robert Rigney

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  1. Yuh-Fun Maa
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  2. Mahmoud Ameri
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  4. Lendon G. Payne
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  5. Dexiang Chen
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Maa, YF., Ameri, M., Rigney, R. et al. Spray-Coating for Biopharmaceutical Powder Formulations: Beyond the Conventional Scale and Its Application. Pharm Res 21, 515–523 (2004). https://doi.org/10.1023/B:PHAM.0000019307.27058.a1

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