Calcium Phosphate Nanoparticle Precipitation by a Continuous Flow Process: A Design of Experiment Approach

Abstract

Calcium phosphate nanoparticles (CaP NPs) are an efficient class of nanomaterials mainly used for biomedical applications but also very promising in other sectors such as cosmetics, catalysis, water remediation, and agriculture. Unfortunately, as in the case of other nanomaterials, their wide application is hindered by the difficulty to control size, morphology, purity and degree of particle aggregation in the translation from laboratory to industrial scale production that is usually carried out in batch or semi-batch systems. In this regard, the use of continuous flow synthesis can help to solve this problem, providing more homogenous reaction conditions and highly reproducible synthesis. In this paper, we have studied with a design of experiment approach the precipitation of citrate functionalized CaP NPs aided by sonication using a continuous flow wet chemical precipitation, and the effect of some of the most relevant process factors (i.e., reactant flow rate, sonication amplitude, and maturation time) on the physico-chemical properties of the NPs were evaluated. From the statistical data analysis, we have found that CaP NP dimensions are influenced by the reactor flow rate, while the crystalline domain dimensions and product purity are influenced by the maturation process. This work provides a deeper understanding of the relationships between reaction process factors and CaP NP properties, and is a relevant contribution for the scale-up production of CaP NPs for nanomedical or other applications.

Inhalable Microparticles Embedding Calcium Phosphate Nanoparticles for Heart Targeting: The Formulation Experimental Design

“…CaP nanoparticles in water dispersion were prepared by a continuous flow process as reported in the paper of Degli Esposti et al [6]. A pilot scale batch of three litres of unloaded CaPs was manufactured.…”

Scaled-Up 3D-Printed Reactor for Precipitation of Lecithin-Modified Hydroxyapatite Nanoparticles

“…The way of conducting the HAp precipitation and the solution composition for the process have a crucial influence on its properties. HAp synthesized in the single-channel continuous micro- and millifluidic devices (with characteristic size ranging from 10 μm to 5 mm) exhibits desired properties for medical application. − There is a need for the improvement of the productivity of the precipitation of HAp under microfluidic conditions.…”

“…They incorporated a novel drainage design into the microreactor channel network, which successfully eliminated the commonly encountered problem of clogging and coalescence of microdroplets containing nanoparticles in the microchannel. Another approach to take advantage of microreactors’ benefits and conduct the precipitation process is to use channels with size at the micro- and, in some cases, milliscale. − This is how we investigated the wet preparation of HAp in our previous work . We used a single channel with square cross-section dimensions of 1 mm × 1 mm, and we conducted the process successfully.…”

Flow synthesis of photocatalytic semiconductor–metal hybrid nanocrystals

“…Such reactions were utilized to synthesize different semiconductor and metal nanocrystals and were suggested to offer larger-scale production, as well as maintain high purity products with well-defined physical and chemical properties. [30][31][32][33][34][35][36] However, they have not yet been developed for the synthesis of hybrid semiconductor-metal nanoparticles.…”