Hosokawa Powder Technology Foundation ANNUAL REPORT
Online ISSN : 2189-4663
ISSN-L : 2189-4663
Research Grant Report
Less Invasive, Locally Injectable Drug Delivery Systems Fabricated by Nanodispersion Spray-Coating Technology
Hideki Ichikawa
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2007 Volume 15 Pages 101-108


The ultimate goal of the present study is to develop less invasive, locally injectable microdevices as a prolonged-release depot for peptide- or protein-based drugs. In order to fabricate such devices, a biodegradable coating material and nanoporous spherical core particles with high density and biocompatibility applicable for spouted bed spray coating were prepared; hydroxyapatite (HAp) and chitosan were selected for the sources of those materials.

HAp slurry was prepared by ball-milling of HAp powders with distilled water and dispersant for 4h. The slurry was spray-dried and the resultant products were sintered at various temperature. The spray-dried HAp microparticles showed porous and spherical shape. The pore size was dependent on the sintering temperature. The protein absorption study of HAp microparticles was carried out using bovine serum albumin (BSA) as a model protein-drug. The results demonstrated that The Hap microparticles possessed the adsorption capacity of BSA around 6 mass% at least.

Chitosan nanoparticles (CNPs) were prepared by a novel aqueous neutralization-precipitation technique as a biodegradable coating material. In a typical formulation, the CNPs with 300-400 nm in size were obtained. Using the CNPs thus prepared, microencapsulation of BSA-layered CaCO3 core particles (63-75μm) was carried out using a spouted-bed spray-coating process to evaluate the coating performance of the CNPs. The mass median diameter of microcapsules and the %fraction of agglomerates were 96μm and below 5%, respectively, indicating that the CNPs have a low agglomeration tendency. It was found on the SEM observation that the microcapsules had a smooth surface without any post-thermal curing, indicating a good film-formability. In vitro release studies revealed that BSA was released from the microcapsules in a prolonged manner over a week in phosphate buffered saline (pH 7.4); no burst effect in the initial release period was observed when the feed weight percent of CNPs was 50 wt%.

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