Pharmaceutical nanocrystals: production by wet milling and applications

Abstract

Nanocrystals are regarded as an important nanoformulation approach exhibiting advantages of increased dissolution and saturation solubility with chemical stability and low toxicity. Nanocrystals are produced in the form of nanosuspensions using top-down (e.g., wet milling or high pressure homogenization) and bottom-up methods (e.g., antisolvent precipitation). Wet milling is a scalable method applicable to drugs with different physicochemical and mechanical properties. Nanocrystalline-based formulations, either as liquid nanosuspensions or after downstream processing to solid dosage forms, have been developed as drug delivery systems for various routes of administration (i.e., oral, parenteral, pulmonary, ocular, and dermal). In this review, we summarize and discuss the features, preparation methods, and therapeutic applications of pharmaceutical nanocrystals, highlighting their universality as a formulation approach for poorly soluble drugs.

Nanocrystals: A perspective on translational research and clinical studies

“…This highlights the versatility of a nanocrystal drug platform. Pharmacokinetic, biodistribution, and bioavailability data for organs involved in delivery routes tested using nanocrystal technology have been addressed at length previously . Specifically, the reviews of Lu et al 2016 and 2017 delve into the biodistribution pattern of nanocrystal drugs in the blood, heart, liver, spleen, lung, kidney, tumor, and thymus (i.e., the organs involved in clearance/circulation and host immune responses) …”

“…10,11 Commonly used synthesis techniques include the use of microfluidic based platforms or the milling method, which, among others, is both flexible and tunable. 7,[12][13][14][15][16][17] Taken together, the nanocrystal drug technology has been studied extensively and is well positioned for further exploration in the field of drug delivery.…”

Harnessing nanostructured systems for improved treatment and prevention of HIV disease

“…Because the NPs are pure drug, nanosuspensions have highly efficient drug loading capabilities . Nanosuspensions are also simple to manufacture in comparison to other nanoscale delivery systems and thus are easy to scale up for mass production . However, drugs must display the necessary hydrophobicity to be suitable for nanoformulation …”

“…96 Nanosuspensions are also simple to manufacture in comparison to other nanoscale delivery systems and thus are easy to scale up for mass production. 97 However, drugs must display the necessary hydrophobicity to be suitable for nanoformulation. 96,97 Tibotec Pharmaceuticals, in partnership with Johnson & Johnson, developed NPs of varying size of crystalline, free base rilpivirine (RPV) stabilized with different surfactants.…”

“…97 However, drugs must display the necessary hydrophobicity to be suitable for nanoformulation. 96,97 Tibotec Pharmaceuticals, in partnership with Johnson & Johnson, developed NPs of varying size of crystalline, free base rilpivirine (RPV) stabilized with different surfactants. 98 Subcutaneous injection of the 200 nm particles at a dose of 5 mg/kg resulted in constant plasma concentrations of 25 ng/mL for 20 days in dogs with a slow decline to 1-3 ng/mL 3 months after injection.…”