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Microfluidic Technologies for Accelerating the Clinical Translation of Nanoparticles
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Pedro M. Valencia, Omid C. Farokhzad, Rohit Karnik, Robert Langer
In recent years, several microfluidic systems that enable rapid mixing without the need of external actuators, such as stirrers or electric fields, have been developed [19]. The most widely used include flow-focusing mixers [20], droplet mixers [21] and those with micromixing structures embedded inside the channel [22]. Flow focusing squeezes the solvent stream between two anti-solvent streams, resulting in rapid solvent exchange via diffusion (Fig. 3.2b). Droplets and three-dimensional microchannel geometries result in complex folding of fluid flows, which can completely mix two or more streams in milliseconds (Fig. 3.2b). The implementation of these mixing techniques for the formation of organic nanoparticles in continuous flow has resulted in polymeric and lipid nanoparticles with tunable nanoparticle size, narrower size distribution, higher drug loadings and greater batch-to-batch reproducibility relative to those made with conventional bulk techniques [23] (Fig. 3.2c).
Nanosuspensions as Nanomedicine: Current Status and Future Prospects
Published in Debarshi Kar Mahapatra, Sanjay Kumar Bharti, Medicinal Chemistry with Pharmaceutical Product Development, 2019
Shobha Ubgade, Vaishali Kilor, Abhay Ittadwar, Alok Ubgade
It represents an innovative methodology employed for the generation of nanoparticles. Its utility for the generation of inorganic nanomaterials like CaCO3 (15–40 nm) [44], Al(OH)3 (1–10 nm), and SrCO3 (40 nm) has been very well established. This process yields nanoparticles at significantly lower production costs than conventional production methods for nanomaterials. The method is based on the reactive precipitation method and is tailored to generate nanomaterials by employing high gravity micromixing of reactants with the help of rotating packed bed (RPB). The high gravity micromixing helps in enhancing the mass transfer and heat transfer between the reactants, thus inducing the rapid nucleation of the final product while suppressing the crystal growth. When the reactants enter the rotating packed bed, they are spread or split into very thin films or nanodroplets under the high shear created by high gravity. An intense micromixing and centrifugal force together help in enhanced mass transfer resulting in the production of nanoparticles [45].
Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects
Published in Drug Delivery, 2022
Amr Maged, Reda Abdelbaset, Azza A. Mahmoud, Nermeen A. Elkasabgy
Micromixing in microfluidics platforms has been applied in several fields like nanoparticles production, tissue engineering, and pathogen identification (Damiati et al., 2018; Hamblin & Karimi, 2020). The general structure of micromixer includes many inlets, one outlet, and main mixing channel. Many researchers compete in the development of microfluidic designs to achieve high mixing efficiency. When developing microfluidic devices, several elements should be considered, including flow rates (FRs), inlets channels, and the shape of the main channel. Microfluidic parameters like FR as well as total flow rate (TFR) and flow rate ratio (FRR), which are the combined FRs of both phases (organic and aqueous) in the main mixing channel and the ratio between the flow of the two phases, correspondingly are considered the most important specific parameters (Zhigaltsev et al., 2012). Micromixers can be categorized based on the nature of fluid flow in the main mixing channel into two main catalogs, continuous flow (single-phase) and segmented flow (multiphase), as described briefly in Table 1 (Gonidec & Puigmartí-Luis 2018).
Exploring microfluidics and membrane extrusion for the formulation of temozolomide-loaded liposomes: investigating the effect of formulation and process variables
Published in Journal of Liposome Research, 2023
Tejashree Waghule, Ranendra Narayan Saha, Gautam Singhvi
Liposomes are traditionally prepared using the thin film hydration technique. However, mostly multilamellar liposomes with broad particle sizes are formed using this technique. It is difficult to produce liposomes in a reproducible manner. Other methods of preparation include reverse-phase evaporation, solvent injection method, detergent removal method, dialysis method, and freeze-thaw method. The membrane extrusion technique, microfluidization technique, and proliposome technique can be used for large-scale industrial production of liposomes (Bhupendra Pradhan et al.2015). The membrane extrusion technique is most commonly used for the down-sizing of liposomes by passing them through a membrane of defined pore size. Microfluidics involves the self-assembly of liposomes through micromixing and diffusion between two phases inside small channels. Both these techniques have high scope for industrial application. They produce small size liposomes with high reproducibility following different principles. Several material and process parameters can significantly affect the final product characteristics of liposomes. A detailed evaluation of each variable is crucial to ease the process of scale-up (Mishra et al. 2018, Dormont et al.2019). This can be easily evaluated using the principles of Quality by Design (QbD). Various critical and non-critical parameters affecting the critical quality attributes can be systematically identified and studied using risk-based assessment. With the help of QbD, quality can be built into the product from the early development stages itself. A manufacturing process that is robust and consistently produces the intended product can be designed (Sangshetti et al.2017, Zhang and Mao 2017).
Intrathecal drug delivery for pain management: recent advances and future developments
Published in Expert Opinion on Drug Delivery, 2019
Sameer Jain, Mark Malinowski, Pooja Chopra, Vishal Varshney, Timothy R. Deer
In 1926, Cushing first introduced the concept of CSF flow as a ‘third circulation’, where CSF flows from ventricles, cisterns, and subarachnoid space (SAS) and is reabsorbed in blood at the arachnoid villi [20]. However, in recent years a pulsatile bidirectional model of CSF flow has been favored where CSF flow is influenced by multiple physiological factors. Imaging studies have confirmed the influence of the cardiac cycle on the CSF flow resulting in its pulsatile flow pattern [21]. CSF flows from cranial to the spinal SAS in systole and vice versa in diastole. Friese et al. proposed that cardiac pulsations were the main driver of CSF flow, but respiration plays a dominant role in the thoracolumbar regions [22]. A study by Dreha-Kulacewski found high CSF flow during inspiration phases [23]. Another study by Yildiz et al. employed real-time PC MRI to evaluate the relative impact of cardiac cycle and respiration on CSF flow [24]. They found that while deep inspiration forced CSF cephalad and deep expiration forced CSF caudad, CSF flow during natural breathing was more influenced by cardiac pulsations. However, the relative strength of cardiac versus respiratory influence on CSF flow is still questionable and further studies are needed. Intracranial pulsations are also transmitted caudally which may be interrupted by curvatures of the spine at cervical, thoracic, and lumbar regions [25,26]. Microanatomical structures, such as nerve rootlets, epidural fat, and venous plexuses, present in the subarachnoid space also create barriers to bidirectional CSF flow resulting in complex local mixing [27]. Micromixing patterns associated with geometry-induced flow regimes, also known as chaotic advection, can have a significant impact on intrathecal drug distribution [28].