Parenteral nanosuspensions: a brief review from solubility enhancement to more novel and specific applications

Abstract

Advancements in in silico techniques of lead molecule selection have resulted in the failure of around 70% of new chemical entities (NCEs). Some of these molecules are getting rejected at final developmental stage resulting in wastage of money and resources. Unfavourable physicochemical properties affect ADME profile of any efficacious and potent molecule, which may ultimately lead to killing of NCE at final stage. Numerous techniques are being explored including nanocrystals for solubility enhancement purposes. Nanocrystals are the most successful and the ones which had a shorter gap between invention and subsequent commercialization of the first marketed product. Several nanocrystal-based products are commercially available and there is a paradigm shift in using approach from simply being solubility enhancement technique to more novel and specific applications. Some other aspects in relation to parenteral nanosuspensions are concentrations of surfactant to be used, scalability and in vivo fate. At present, there exists a wide gap due to poor understanding of these critical factors, which we have tried to address in this review. This review will focus on parenteral nanosuspensions, covering varied aspects especially stabilizers used, GRAS (Generally Recognized as Safe) status of stabilizers, scalability challenges, issues of physical and chemical stability, solidification techniques to combat stability problems and in vivo fate.

Application of flash nanoprecipitation to fabricate poorly water-soluble drug nanoparticles

“…The fabrication techniques of drug nanoparticles are mainly divided into top-down and bottom-up methods 15 . The top-down methods start with large drug solid crystals, which will be mechanically broken down into nanometer scaled drug particles by media milling or high-pressure homogenization.…”

Thymoquinone-Loaded Soluplus®-Solutol® HS15 Mixed Micelles: Preparation, In Vitro Characterization, and Effect on the SH-SY5Y Cell Migration

“…It has a low critical micelle concentration (CMC) and its micelles are highly stable after dilution [ 34 , 35 ]. It is an innovative excipient that gives new levels of solubility and bioavailability of poorly water-soluble drugs and natural compounds both for oral and parenteral administration [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Solutol ® HS15 (polyoxyethylene esters of 12-hydroxystearic acid, Figure 2 ) is a known non-ionic surfactant with high solubility and stability and low toxicity in vivo.…”

HPMC- and PLGA-Based Nanoparticles for the Mucoadhesive Delivery of Sitagliptin: Optimization and In Vivo Evaluation in Rats

“…Currently, there are a number of techniques to prepare nanosized particles, i.e., wet-mills, high-gravity controlled precipitation reactors, and homogenizers [15,16]. However, none of these methods produce free-flowing powder, and the final product is still in a suspension form with a wide size distribution.…”