Microfluidic-based high-flux crystallization condition screening method

Abstract

The invention discloses a microfluidic-based high-flux crystallization condition screening method. The method comprises the following steps of S1, pouring a mixture of PDMS and a cross-linking agent into a cleaned mold, vacuumizing, heating for curing, stripping the cured PDMS from the mold, pasting the PDMS to a substrate, and heating for curing to obtain a microfluidic chip; S2, uniformly mixinga substance to be crystallized, a solvent and an anti-solvent to output a dispersed phase, pouring a continuous phase and the dispersed phase into a channel of the microfluidic chip, and generating liquid drops containing crystals under several crystallization conditions; S3, collecting the liquid drops containing the crystals; and S4, identifying a crystal morphology, and screening a corresponding crystallization condition according to the crystal morphology. The microfluidic chip can be used as a micro-reactor, and has advantages of high-flux treatment, rapid reaction, low reagent consumption, flexible operation, automation, integration and the like.

Description

technical field [0001] The invention relates to the technical field of crystallization, and more specifically, to a method for screening high-throughput crystallization conditions based on microfluidics. Background technique [0002] Drug crystals are drugs that are affected by various factors during the crystallization of the drug, which changes the way of intramolecular or intermolecular bonds, resulting in different arrangements of molecules or atoms in the lattice space, forming different crystal structures; different crystal forms of the same drug There may be significant differences in solubility, dissolution rate, stability, bioavailability, etc., thereby affecting the bioavailability and curative effect of the drug; this phenomenon is particularly evident in oral solid preparations; at the same time, in the pharmaceutical industry, efficient production In the process, drug crystallization plays a crucial role in purification. Therefore, it is very necessary to explor...

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Problems solved by technology

[0003] However, due to the diversity of drug types, the flexibility of the arrangement of drug organic molecules in two-dimensional / three-dimensional space, and the complexity of crystal formation conditions, the traditional drug crystal screening method not only consumes a lot of manpower, material and time costs, but also requires a huge amount of time. Reagent consumption and complex screening process

[0004] Microfluidic technology has been widely recognized and applied for its characteristics of less sample and reagent consumption, high integration, low energy consumption, fast reaction speed, low cost and large-scale reaction; the introduction of high-throughput screening technology Microfluidic technology can play an important role in exploring the formation of drug crystals under different influence conditions. However, when traditional microfluidic technology introduces drug crystal characterization methods, it needs to manually process a large amount of characterization data, which will undoubtedly increase the result analysis. difficulty

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