Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q₁₀ as naked nanocrystals

Jiao Sun,¹ Fan Wang,^1,2 Yue Sui,¹ Zhennan She,¹ Wenjun Zhai,¹ Chunling Wang,¹ Yihui Deng<sup>1

1</sup>College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; ²Beijing Zhijianjinrui Applied Pharmaceutical Science Inc, Beijing, China

Abstract: In this paper work, four naked nanocrystals (size range 80–700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q₁₀ nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q₁₀ increased as particle size decreased. The bioavailability of coenzyme Q₁₀ after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC_0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold.

Keywords: particle size, solubility, dissolution, nanocrystal, bioavailability, coenzyme Q₁₀

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