Journal of Pharmaceutical Sciences 2014-11-01

On prilling of hydrophilic microgels in lipid dispersions using mono-N-carboxymethyl chitosan for oral biologicals delivery.

Jan Kendall De Kruif, Elizaveta Fasler-Kan, Felipe Varum, Roberto Bravo, Martin Kuentz

文献索引：J. Pharm. Sci. 103(11) , 3675-87, (2014)

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摘要

Oral delivery of biologicals is a thriving field in pharmaceutics and the first challenge is to achieve a stable drug product. Interesting is prilling of a drug-containing polymeric solution as microgel into an aqueous hardening bath where crosslinking occurs. However, to deliver a final dosage form, for example, soft gelatin capsules, the aqueous hardening bath must be removed, thus leading to manufacturing processes that are potentially harmful for the active. The current work introduces a prilling method with a lipid-based hardening bath, which could theoretically be filled directly into capsules. Bovine serum albumin (BSA) and mono-N-carboxymethyl chitosan (MCC) were selected as model biological and encapsulating polymer, respectively. Several nonaqueous formulations of the receiving bath were investigated; calcium chloride was added to these formulations to allow the MCC gelling. The obtained microgels had average diameters of ∼300 μm and spherical to toroidal shapes, according to the hardening bath composition. Along with a high encapsulation efficiency (>85%), the microgels protected the BSA from any denaturing effect of the hardening bath. The release study showed a rather fast BSA release within the first 10 min from most microgels. This novel approach demonstrated technical viability for encapsulation of biologicals using lipid formulations regarding oral delivery.© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.