Preparation of Nanocrystals for Insoluble Drugs by Top-Down Nanotechnology with Improved Solubility and Bioavailability

Abstract

Midazolam is a rapidly effective benzodiazepine drug that is widely used as a sedative worldwide. Due to its poor solubility in a neutral aqueous solution, the clinical use of midazolam is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have drawn worldwide attention. We prepared a stable nanosuspension system that causes little muscle irritation. The particle size of the midazolam nanocrystals (MDZ/NCs) was 286.6 ± 2.19 nm, and the crystalline state of midazolam did not change in the size reduction process. The dissolution velocity of midazolam was accelerated by the nanocrystals. The pharmacokinetics study showed that the AUC0–t of the MDZ/NCs was 2.72-fold (p < 0.05) higher than that of the midazolam solution (MDZ/S), demonstrating that the bioavailability of the MDZ/NC injection was greater than that of MDZ/S. When midazolam was given immediately after the onset of convulsions, the ED50 for MDZ/NCs was significantly more potent than that for MDZ/S and DZP/S. The MDZ/NCs significantly reduced the malondialdehyde content in the hippocampus of the seizures model rats and significantly increased the glutathione and superoxide dismutase levels. These results suggest that nanocrystals significantly influenced the dissolution behavior, pharmacokinetic properties, anticonvulsant effects, and neuroprotective effects of midazolam and ultimately enhanced their efficacy in vitro and in vivo.

Lipid-based nanoparticles for psoriasis treatment: a review on conventional treatments, recent works, and future prospects

“…22,27,28 Poorly soluble active pharmaceutical ingredients (API) can be improved through the use of nanotechnology whilst increasing their bioavailability and physicochemical stability. [28][29][30][31][32] It is presumed that ineffective APIs have low pharmacokinetic proles, lack of stability and Norazlinaliza Salim received her PhD (2013) in Oleochemistry from the Universiti Putra Malaysia and went for a research attachment at the IQAC-CSIC, Barcelona, Spain (2010). In 2014, she was a postdoctoral research fellow at Centre for Fundamental and Frontier Sciences in Nanostructure Self-Assembly, Universiti Malaya and thereaer, was appointed as a senior lecturer at the Centre of Foundation Studies for Agricultural Science, Universiti Putra Malaysia.…”

“…22,27,28 Poorly soluble active pharmaceutical ingredients (API) can be improved through the use of nanotechnology whilst increasing their bioavailability and physicochemical stability. 28–32 It is presumed that ineffective APIs have low pharmacokinetic profiles, lack of stability and solubility, or ones with limited dose toxicity. 33 Therefore, by employing novel drug delivery systems, these drawbacks can be overcome and thus improve the therapeutic actions.…”

Preparation and optimization of surface stabilized cryptotanshinone nanocrystals with enhanced bioavailability

“…The transformation of crystallinity to amorphous states, as we presented above in the PXRD and DSC spectra, contributed to rapid drug dissolution as well. Additionally, the surfactant poloxamer 407 not only acts as the crystal stabilizer, but also has low surface tension and small contact angle to promote the interaction of drug nanocrystals with the aqueous phase by wetting and dispersibility resulting in a quick dissolution profile (Meruva et al, 2020;Zhang et al, 2020). On the contrary, bulk CTS is hard to wetting because of its hydrophobicity.…”

Preparation of ICA-loaded mPEG-ICA nanoparticles and their application in the treatment of LPS-induced H9c2 cell damage

“…Nanoparticles have unique advantages in the drug delivery of insoluble drugs [19], polymer drugs [20] and gene therapy [21]. Similar to tumor tissue, myocardial inflammatory sites have similar permeability and retention functions (EPRs) [22].…”