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Poor aqueous solubility drugs are a concern of pharmaceutical industries due to low dissolution rates and low bioavailability. Various approaches and techniques address these issues by customizing drug micro–nanonization, as investigated by many researchers. Establishing a compelling synthesis of tailored nanoparticles with highly variable qualities intended for therapeutic applications needs the flexibility to vary particle size, content, crystallinity, and shape. Such an approach necessitates getting to the desired yield and developing a synthetic process that is durable, reproducible, and scalable. However, precipitation techniques to produce nanoparticles are more convenient than other approaches. Liquid antisolvent precipitation is one of the robust crystal manipulation approaches extensively used for producing nanoparticles, where mixing sets the basis to create supersaturation followed by corresponding quality precipitation. Various process intensification equipments are in use for adequate mixing‐based precipitation. Nowadays, microfluidic precipitation system is gaining interest in the production of nanodrugs. Further, the use of ultrasound in a microfluidic system improves the mixing quality by cavitation phenomena. This review focuses on the transport phenomena and hydrodynamics involved in mixing to enhance the mass transfer during antisolvent precipitation of synthesized nanodrugs in the microfluidic system. [ABSTRACT FROM AUTHOR]

• Ultrasonic microfluidics under continuous cooling crystallization was introduced as a process intensification approach. • The process was intensified by precipitating an average ezetimibe 101 ± 1.1 nm nano-drugs under best parametric condition. • Ultrasonic frequency, flow rate ratio, and bath temperature were the significant factors for the response EZB PS using PBD. The current research focuses on the antisolvent precipitation of Ezetimibe (EZB) via microfluidics under continuous ultrasonic cooling crystallization. One factor at a time was applied to study the effect of parameters: organic-aqueous flow rate ratio (1:2–1:5), EZB concentration (2.5–12.5, mg/mL), polymer concentration (0.025–0.3, % w/v), ultrasonic frequency (22–42, kHz), ultrasonic bath temperature (10–25, °C), ultrasonic amplitude (20–100, %), confluence angle of micromixer inlet (90°–180°) on the particle size (PS, nm), % yield, % encapsulation efficiency (% EE), and % dissolution rate (% DR). A PBD (Plackett–Burman design) was also employed for the screening studies of influencing factors for aforementioned responses. PS, Zeta potential (ZP, mv), Field Emission Gun Transmission Electron microscope (FEG-TEM), and X-ray diffraction (XRD) were analyzed for raw EZB and nano-precipitated EZB. An average EZB PS of 101 ± 1.1 nm, PDI of 0.027 ± 0.01, 80 ± 1.7 % yield, 78.83 ± 0.5 % DR, 90.67 ± 0.1 % EE, and −20 mV ZP were obtained under best parametric condition. FEG-TEM revealed the final nano EZB morphology was likely to be elongated cuboidal or rod-shaped. An approximately 5-fold increase in %DR was observed for the confluence angle of 90° (├ shaped) micromixer as compared to raw EZB. However, 94.14 % decreament in avg EZB PS was achieved for the confluence angle of 90° (├ shaped) micromixer and utilizing ultrasonic microfluidic system (USMS) under cooling crystallization as a process intesification approach. [Display omitted] [ABSTRACT FROM AUTHOR]

• Challenges in drug delivery and their solution through microfluidics is presented. • Microfluidics enables nano-size drug with reproducible physicochemical properties. • Scope for drug encapsulation by ultrasound enhanced microfluidics is highlighted. The intrinsic limitations of conventional dosages have facilitated the emergence of novel drug delivery methodologies. Drug nanonization and encapsulation in polymeric biomaterials offers a new platform to enhance therapeutic efficiency and patient compliance. The two most basic approaches for drug size reduction are top-down, bottom-up, or a combination of these methods. This review analyzes three widely investigated techniques (viz. spray drying, high pressure homogenization, and ultrasonication) along with microfluidics for drug nanonization and encapsulation in past few years. Also, the existing challenges of aforesaid methodologies and their solution through microfluidics are highlighted. Microfluidics has brought unique opportunities towards complete control over process parameters, owing to miniaturization of fluidic environment. Overall, the emergence of microfluidic technology has created exciting possibilities in the field of controlled drug delivery and has paved a way for clinical translation of nanomedicines. [ABSTRACT FROM AUTHOR]