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A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein

Theme: Formulation and Manufacturing of Solid Dosage Forms Guest Editors: Tony Zhou and Tonglei Li

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Abstract

Purpose

There are many important diseases whose treatment could be improved by delivering a therapeutic protein to the colon, for example, Clostridium difficile infection, ulcerative colitis and Crohn’s Disease. The goal of this project was to investigate the feasibility of colonic delivery of proteins using multiparticulate beads.

Methods

In this work, bovine serum albumin (BSA) was adopted as a model protein. BSA was spray layered onto beads, followed by coating of an enteric polymer EUDRAGIT® FS 30 D to develop a colonic delivery system. The secondary and tertiary structure change and aggregation of BSA during spray layering process was examined. The BSA layered beads were then challenged in an accelerated stability study using International Council for Harmonization (ICH) conditions. The in vitro release of BSA from enteric coated beads was examined using United States Pharmacopeia (USP) dissolution apparatus 1.

Results

No significant changes in the secondary and tertiary structure or aggregation profile of BSA were observed after the spray layering process. Degradation of BSA to different extents was detected after storing at 25°C and 40°C for 38 days. Enteric coated BSA beads were intact in acidic media while released BSA in pH 7.4 phosphate buffer.

Conclusion

We showed the feasibility of delivering proteins to colon in vitro using multiparticulate system.

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Abbreviations

BSA:

Bovine serum albumin

CD:

Circular dichroism

CDI:

Clostridium difficile infection

CQA:

Critical Quality Attributes

GI:

Gastrointestinal

ICH:

International Council for Harmonization

MCC:

Microcrystalline cellulose

RH:

Relative humidity

rhDNase:

Recombinant human deoxyribonuclease

SEM:

Scanning electron microscope

USP:

United States Pharmacopeia

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Correspondence to Stephen W. Hoag.

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Jiang, B., Yu, H., Zhang, Y. et al. A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein. Pharm Res 34, 2663–2674 (2017). https://doi.org/10.1007/s11095-017-2237-9

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  • DOI: https://doi.org/10.1007/s11095-017-2237-9

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