期刊
INTERNATIONAL JOURNAL OF NANOMEDICINE
卷 13, 期 -, 页码 3763-3779出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S164228
关键词
nanocrystal-based solid dispersion; nanocrystals; andrographolide; superdisintegrant; dissolution; bioavailability
资金
- Scientific Research Foundation for the National Natural Science Foundation of China [81560656, 81760715]
- Fund of Distinguished Young Scientists of Jiangxi Province [20162BCB23033]
- Natural Science Fund of Jiangxi Province [20161BAB205221]
Objective: The current study sought to design a quickly dissolving, high drug loading nanocrystal-based solid dispersion (NC-SD) in order to improve the dissolution of poorly soluble drugs. Methods: The NC-SD was prepared by means of combination of homogenization and spray-drying. Polymer hydroxypropylmethylcellulose (HPMC) was used as baseline dispersant for NC-SD of the model drug-andrographolide (AG). Three superdisintegrants cohomogenized with HPMC were used as codispersant for AG-NC-SD and compared to common water-soluble dispersants-mannitol and lactose. The dissolution characterization and oral bioavailability of AG-NC-SD were evaluated. Results: The AG-NC-SD with the higher concentration of HPMC exhibited fast dissolution due to the enhanced wettability of HPMC. The water-soluble codispersants (mannitol and lactose) did not completely prevent AG-NC from aggregation during spray-drying. To achieve much faster AG release, cohomogenized superdisintegrants at a level of 20% must be used along with 25% HPMC. Compared with water-soluble dispersants like mannitol and lactose, superdisintegrants with high swelling capacity were much more effective dispersants for enhancing fast redispersion/ dissolution of AG-NC-SD via a swelling-triggered erosion/disintegration mechanism. Surfactant-free AG-NC-SD with 15% cohomogenized sodium carboxymethyl starch combined with 15% HPMC and 10% lactose enhanced the dissolution further, without comprising drug loading, exhibited a barely compromised dissolution rate compared to precursor NC suspensions (f2.50), and possessed drug loading up to 67.83%+/- 1.26%. The pharmacokinetics results also demonstrated that the AG-NC-SD significantly improved the bioavailability in vivo of AG (P, 0.05), compared with to the coarse AG. Conclusion: This study illustrates that a quickly dissolving, high drug load, surfactant-free NC-SD can be prepared by using a superdisintegrant as codispersant, and provides a feasible strategy to improve the oral bioavailability of poorly soluble drugs.
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