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A facile way to continuously coat drug crystals with a polymer is needed in controlled drug release. Conventional polymer coating methods have disadvantages: high energy consumption, low productivity, batch processing. A novel method for continuous polymer coating of drug crystals based on solid hollow fiber cooling crystallization (SHFCC) is introduced here. The drug acting as the host particle and the polymer for coating are Griseofulvin (GF) and Eudragit RL100, respectively. The polymer's cloud point temperature in its acetone solution was determined by UV spectrophotometry. An acetone solution of the polymer containing the drug in solution as well as undissolved drug crystals in suspension were pumped through the tube side of the SHFCC device; a cold liquid was circulated in the shell side to rapidly cool down the feed solution-suspension in the hollow-fiber lumen. The polymer precipitated from the solution and coated the suspended crystals due to rapid temperature reduction and heterogeneous nucleation; crystals formed from the solution were also coated by the polymer. Characterizations by scanning electron microscopy, thermogravimetric analysis, laser diffraction spectroscopy, X-ray diffraction, Raman spectroscopy, and dissolution tests show that a uniformly coated, free-flowing drug/product can be obtained under appropriate operating conditions without losing the drug's pharmaceutical properties and controlled release characteristics., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Using porous hollow fiber membranes, this study illustrates a novel technique to continuously synthesize polymer-coated drug crystals by antisolvent crystallization. The synthesized polymer-coated drug crystals involve crystals of the drug Griseofulvin (GF) coated by a thin layer of the polymer Eudragit RL100. The process feed, an acetone solution of the drug GF containing the dissolved polymer, was passed through the shell side of a membrane module containing many porous hollow fibers of Nylon-6. Through the lumen of the hollow fibers, the antisolvent water was passed at a higher pressure to inject water jets through every pore in the fiber wall into the shell-side acetone feed solution, creating an extremely high level of supersaturation and immediate crystallization. It appears that the GF crystals are formed first and serve as nuclei for the precipitation of the polymer Eudragit, which forms a thin coating around the GF crystals. The polymer-coated drug crystals were collected by a filtration device at the shell-side outlet of the membrane module, and the surface morphology, particle size distribution, and the polymer coating thickness were then characterized by scanning electron microscopy (SEM), scanning transmission electron microscopy (STEM), laser diffraction spectroscopy (LDS), and thermogravimetric analysis (TGA). To study the properties of the coated drug crystals, X-ray diffraction (XRD), Raman spectroscopy, and dissolution tests were implemented. These results indicate that a polymer-coated, free-flowing product was successfully developed under appropriate conditions in this novel porous hollow fiber antisolvent crystallization (PHFAC) method. The coated drug particles can be potentially used for controlled release. The molecular and the crystal structures of GF were not affected by the PHFAC method, which may be easily scaled up.

Nanotechnology is being utilized to develop advanced concepts in drug delivery systems including production of nanodrugs such as, nanocrystals and nanosuspensions. Continuous crystallization methods are of increasing interest and porous hollow fiber membrane (HFM) based modules have been recently utilized as an anti-solvent crystallizer. The porous hollow fiber anti-solvent crystallizer (PHFAC) based method has been modified here to produce continuously nanocrystals of Griseofulvin (GF). In the PHFAC device, deionized water introduced from the HFM bore into the shell side is used as the anti-solvent; acetone containing dissolved GF is introduced into the shell side of the HFM module as the drug solution. Water, the anti-solvent, mixed vigorously with the drug solution leading to drug crystallization and the drug crystals were separated by vacuum filtration and freeze-dried. The experimental conditions were varied to control the particle size, size distribution and the appearance of the nanoparticles. The properties of the drug nanocrystals were characterized via Transmission Electron Microscopy (TEM), Scanning Electron Microscope (SEM), Dynamic Light Scattering (DLS), Raman Spectroscopy, Energy Dispersive X-rays Spectroscopy (EDX), Differential Scanning Calorimetry (DSC), FT-IR Spectrometer, X-ray Diffraction (XRD); drug dissolution tests were also implemented. Drug nanocrystals as small as 86.4 nm were produced under modest pressure and temperature conditions in a controllable and continuous manner. [ABSTRACT FROM AUTHOR]

Size reduction of drug with poor water solubility to nanoscale is an effective way to help improve the efficacy of drug delivery to the human body. A solid hollow fiber cooling crystallization technique has been adopted to continuously produce griseofulvin drug nanoparticles under modest conditions with accurate controllability. In the solid hollow fiber cooling crystallization device, drug solution flowed through the bores of solid hollow fibers while the cooling liquid was circulated counter-currently in the shell side of the device to cool down the drug solution in the tube side. Due to intense heat exchange between the cooling liquid and the drug solution through the thin fiber walls, the temperature of drug solution decreased rapidly so that drug nanoparticles were precipitated out from the solution by sudden reduction of solubility. Through variation of the experimental conditions and parameters, the mean size of the produced nanoparticles was regulated and controlled. The nanoparticles were dispersed uniformly, the chemical structure and bonds of prepared nanoparticles was the same with as-received griseofulvin. Both raw material and NPs the polymorph(s) present form I, the melting point was 220 °C. Drug dissolution testing was also executed to verify that nanocrystals have a higher dissolution profile. [ABSTRACT FROM AUTHOR]