Formulating food protein-stabilized indomethacin nanosuspensions into pellets by fluid-bed coating technology: physical characterization, redispersibility, and dissolution

Wei He,^1,2 Yi Lu,¹ Jianping Qi,¹ Lingyun Chen,³ Lifang Yin,² Wei Wu<sup>1

1</sup>School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery of Ministry of Education and PLA, Shanghai, ²Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People's Republic of China; ³Department of Agricultural, Food and Nutritional Sciences, University of Alberta, Edmonton, AB, Canada

Background: Drug nanosuspensions are very promising for enhancing the dissolution and bioavailability of drugs that are poorly soluble in water. However, the poor stability of nanosuspensions, reflected in particle growth, aggregation/agglomeration, and change in crystallinity state greatly limits their applications. Solidification of nanosuspensions is an ideal strategy for addressing this problem. Hence, the present work aimed to convert drug nanosuspensions into pellets using fluid-bed coating technology.
Methods: Indomethacin nanosuspensions were prepared by the precipitation-ultrasonication method using food proteins (soybean protein isolate, whey protein isolate, ß-lactoglobulin) as stabilizers. Dried nanosuspensions were prepared by coating the nanosuspensions onto pellets. The redispersibility, drug dissolution, solid-state forms, and morphology of the dried nanosuspensions were evaluated.
Results: The mean particle size for the nanosuspensions stabilized using soybean protein isolate, whey protein isolate, and β-lactoglobulin was 588 nm, 320 nm, and 243 nm, respectively. The nanosuspensions could be successfully layered onto pellets with high coating efficiency. Both the dried nanosuspensions and nanosuspensions in their original amorphous state and not influenced by the fluid-bed coating drying process could be redispersed in water, maintaining their original particle size and size distribution. Both the dried nanosuspensions and the original drug nanosuspensions showed similar dissolution profiles, which were both much faster than that of the raw crystals.
Conclusion: Fluid-bed coating technology has potential for use in the solidification of drug nanosuspensions.

Keywords: nanocrystals, nanosuspensions, food proteins, poorly water-soluble drugs, indomethacin, fluid-bed coating