Preserving the supersaturation generation capability of amorphous drug-polysaccharide nanoparticle complex after freeze drying

International Journal of Pharmaceutics
Tie Yi KiewKunn Hadinoto

Abstract

While the supersaturation generation capability of amorphous nanopharmaceuticals (NPs) in their aqueous suspension form has been well established, their supersaturation generation is adversely affected after drying. Herein we investigated the effects of freeze drying on the supersaturation generation capability of a new class of amorphous NPs referred to as drug nanoplex prepared and stabilized by electrostatic complexation of drug molecules with polysaccharides (dextran sulfate). Using ciprofloxacin as the model drug, two types of freeze-drying adjuvants were investigated, i.e., (1) highly water-soluble excipient (trehalose, mannitol), whose role was to prevent irreversible NPs aggregations upon drying, and (2) crystallization inhibitor (hydroxypropylmethylcellulose (HPMC)), whose role was to suppress crystallization of the dissolved drug and the remaining solid phase. The results showed that dual-adjuvant formulations (i.e. trehalose-HPMC and mannitol-HPMC) were required to preserve the supersaturation generation capability of the drug nanoplex suspension after drying. Freeze drying with only one adjuvant type, or incorporating HPMC as physical mixtures with the freeze-dried nanoplex, were ineffective in preserving the supers...Continue Reading

References

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Citations

May 18, 2016·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Minh-Hiep NguyenKunn Hadinoto
Jun 24, 2021·Pharmaceutical Development and Technology·Maryam MaghsoodiHadi Pourasghari Azar

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