Abstract
Hydrocortisone (HC) nanocrystals intended for parenteral administration of HC were produced by anti-solvent crystallisation within coaxial assemblies of pulled borosilicate glass capillaries using either co-current flow of aqueous and organic phases or counter-current flow focusing. The organic phase was composed of 7 mg/mL of HC in a 60:40 (v/v) mixture of ethanol and water and the anti-solvent was milli-Q water. The microfluidic mixers were fabricated with an orifice diameter of the inner capillary ranging from 50 µm to 400 µm and operated at the aqueous to organic phase flow rate ratio ranging from 5 to 25. The size of the nanocrystals decreased with increasing aqueous to organic flow rate ratio. The counter-current flow microfluidic mixers provided smaller nanocrystals than the co-current flow devices under the same conditions and for the same geometry, due to smaller diameter of the organic phase stream in the mixing zone. The Z-average particle size of the drug nanocrystals increased from 210–280 nm to 320–400 nm after coating the nanocrystals with 0.2 wt % aqueous solution of hydroxypropyl methylcellulose (HPMC) in a stirred vial. The differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analyses carried out on the dried nanocrystals stabilized with HPMC, polyvinyl pyrrolidone (PVP), and sodium lauryl sulfate (SLS) were investigated and reported. The degree of crystallinity for the processed sample was lowest for the sample stabilised with HPMC and the highest for the raw HC powder.
Highlights
Microfluidic routes have been shown to be highly effective ways of producing nano- and micro-materials, with reduced production costs when compared to previous methods of industrial approach of production of materials, which normally involve the use of large robotic fluidic workstations
Based on channel geometry and flow patterns, microfluidic systems can be divided into co-flow [9], flow focusing [10], terrace-based [11], junction-based [12] and those combining two or more different geometries, such as co-flow and flow focusing [13]
Microfluidic devices can be constructed from different materials, such as polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), glass, single crystal silicon, piezoelectric materials, e.g., lithium niobate, etc
Summary
Microfluidic routes have been shown to be highly effective ways of producing nano- and micro-materials, with reduced production costs when compared to previous methods of industrial approach of production of materials, which normally involve the use of large robotic fluidic workstations (often with large space requirements, high cost of labour, high expenses in the final production process, and even right from the research phase). The high surface area-to-volume ratio of microfluidic channels is highly attractive in many applications, as it offers higher heat and mass transfer rates, reduced residence times [3], and well-controlled and defined process conditions [2,4,5]. Nanocrystals have been shown to be effective forms of drugs because the decrease in the crystal size leads to increase in the surface area-to-volume ratio, which increases the dissolution rate and saturated solubility of the drug [31], as well as its adhesiveness to cell membranes They can be produced on a large scale using a variety of top-down or bottom-up methods [32,33], but many of them lack control over the size of nanocrystals. Polymer coating was achieved after collection of the nanocrystals
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