Drug Nanocrystals: A Comprehensive Review with Current Regulatory Guidelines

Abstract

: Drug nanocrystals offer an attractive approach for improving the solubility and dissolution rate of poorly soluble drugs which accounts for nearly 40 % newly discovered drug molecules. Both methods for manufacturing drug nanocrystals have high industrial acceptability for being simple and easy to scale which is evident from the number of approved products available in the market. Ability to modify multiple aspects of dosage form like bioavailability, release pattern and dosage form requirement along with flexibility in choosing final dosage form starting from the tablet, capsule, suspension to parenteral one, have made nanocrystal technology one of the very promising and adaptable technology for dosage form design.

Fabrication and in vitro/vivo evaluation of quercetin nanocrystals stabilized by glycyrrhizic acid for liver targeted drug delivery

“…The solubility of QT-NCs/P188 and QT-NCs/GL was increased by about 67 and 160 times, respectively, as compared to raw QT, but only a slight solubility increase was observed for their physical mixture (1.25 ± 0.17 μg/mL for the physical mixture of QT and GL, 0.41 ± 0.07 μg/mL for the physical mixture of QT and P188). Therefore, the reduction of the particle size into the nanosize range is the main contribution for QT solubility increase ( Dhaval et al, 2020 ).…”

“…Only 31.22% of QT was released form raw QT within 60 min, while the cumulative release of QT from QT-NCs/GL and QT-NCs/P188 were 74.27% and 68.31%, respectively. According to the Noyes–Whitney equation and the Prandtl equation, the improvement of QT release achieved by NCs formulations could be explained as follows: the significant particle size reduction of drug NCs creates high surface area in contact with the dissolution medium and simultaneously decrease the distance of diffusion layer around the drug particles, thereby resulting in high drug release ( Dhaval et al, 2020 ; Junyaprasert and Morakul, 2015 ).

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Design Space and Control Strategy for the Manufacturing of Wet Media Milled Drug Nanocrystal Suspensions by Adopting Mechanistic Process Modeling

“…Over the last three decades, nanocrystals have emerged as a formulation strategy to improve bioavailability-related problems of poorly soluble drugs, enhance clinical convenience, and enable specific therapeutic benefits [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Until now, several commercialized nanocrystalline drug products have reached the market for oral, ocular, subcutaneous, intramuscular and intravenous routes of administration [ 8 , 9 ]. The manufacturing of drug nanocrystals for industrial applications can be accomplished by wet stirred media milling technology [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

“…Until now, several commercialized nanocrystalline drug products have reached the market for oral, ocular, subcutaneous, intramuscular and intravenous routes of administration [ 8 , 9 ]. The manufacturing of drug nanocrystals for industrial applications can be accomplished by wet stirred media milling technology [ 9 , 10 , 11 , 12 , 13 , 14 , 15 ]. In essence, a size reduction of drug particles takes place in an aqueous suspension in the presence of stabilizers between colliding grinding media.…”

Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation

“…The FDA defines a substance or finished product of nanosize dimensions with certain biological, physical, or chemical properties as a nanomaterial (up to 1000 nm). Substances in the nanoscale range may differ from their microsize or coarse-size equivalents in their biological, physical, and chemical characteristics, such as the ability to identify infections, bioavailability, dosage required, potency, and toxicity [ 10 ].…”