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Application of Drug Nanocrystal Technologies on Oral Drug Delivery of Poorly Soluble Drugs

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Abstract

The limited solubility and dissolution rate exhibited by poorly soluble drugs is major challenges in the pharmaceutical process. Following oral administration, the poorly soluble drugs generally show a low and erratic bioavailability which may lead to therapeutic failure. Pure drug nanocrystals, generated by “bottom up” or “top down” technologies, facilitate a significant improvement on dissolution behavior of poorly soluble drugs due to their enormous surface area, which in turn lead to substantial improvement in oral absorption. This is the most distinguished achievement of drug nanocrystals among their performances in various administration routes, reflected by the fact that most of the marketed products based on the nanocrystals technology are for oral application. After detailed investigations on various technologies associated with production of drug nanocrystals and their in vitro physicochemical properties, during the last decade more attentions have been paid into their in vivo behaviors. This review mainly describes the in vivo performances of oral drug nanocrystals exhibited in animals related to the pharmacokinetic, efficacy and safety characteristics. The technologies and evaluation associated with the solidification process of the drug nanocrystals suspensions were also discussed in detail.

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Abbreviations

AN:

aqueous nanosuspension

AUC:

area under the blood concentration–time curve

BCS:

biopharmaceutics classification system

CL:

clearance rate

Cmax :

maximum plasma concentration

DDSs:

drug delivery systems

EPAS:

evaporative precipitation into aqueous solution

GIT:

gastrointestinal tract

IVIVC:

in vitro–in vivo correlation

MCC:

microcrystalline cellulose

MRT:

mean residence time

NSAIDs:

non-steroidal anti-inflammatory drugs

P-gp:

p-glycoprotein

Tmax :

time to maximum plasma concentration

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Acknowledgments and Disclosures

This work was partially supported by Scientific Foundation of the First Affiliated Hospital of General Hospital of PLA, the project number is QN201105.

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  1. Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing, 100048, China

    Lei Gao, Guiyang Liu, Jianli Ma, Xiaoqing Wang, Liang Zhou, Xiang Li & Fang Wang

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  1. Lei Gao
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Correspondence to Lei Gao.

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Lei Gao and Guiyang Liu contributed equally to this paper.

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Gao, L., Liu, G., Ma, J. et al. Application of Drug Nanocrystal Technologies on Oral Drug Delivery of Poorly Soluble Drugs. Pharm Res 30, 307–324 (2013). https://doi.org/10.1007/s11095-012-0889-z

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