Continuous preparation of polymer coated drug crystals by solid hollow fiber membrane-based cooling crystallization

Abstract

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.

Cooling Crystallization of Sodium Chloride via Hollow Fiber Devices to Convert Waste Concentrated Brines to Useful Products

“…Among them, cooling crystallization by means of nonporous hollow fibers (or solid hollow fiber cooling crystallization, termed SHFCC) has received our attention because of its unique advantages such as uniform cooling of the feed solution, high efficiency, small footprint, and the potential use of cold energy. As proposed by Prof. Sirkar and co-workers, the basic concept of SHFCC involves polymeric hollow fibers serving as heat-exchanging tubes, but the hollow fiber dimensions are orders of magnitude smaller than those of conventional metal tubes for heat exchange. − As illustrated in Figure , the hot concentrated brine solution is pumped through the lumen side of hollow fibers, where rapid cooling takes place by the coolant circulating on the shell side. The brine temperature exiting from the hollow fiber becomes much lower than its initial temperature so that supersaturation occurs.…”

Enhanced Dissolution Efficiency of Tamoxifen Combined with Methacrylate Copolymers in Amorphous Solid Dispersions

“…As expected from a crystalline-organized structure, TMX showed distinct intense peaks corresponding to the polymorph II of the drug [32]. These peaks also appeared in the diffractogram of PM 30%, although with lower intensity, indicating that the components of the amorphous polymer blend were present but not capable of preventing drug crystallites to co-exist, which is due to the thick polymer coating around the coated particles, which could weaken the signals, as these polymers have amorphous characteristics [33,34].…”

Application of Polymers as a Tool in Crystallization—A Review

“…Atorvastatin calcium [82] Eudragit RL100 Griseofulvin [85] Poly(aspartic acid-citric acid) copolymer, polymaleic acid Ca 3 (PO4) 2 [91] Poly(citric acid) CaSO 4 [92] Polyaspartic acid/furfurylamine graft copolymer CaCO 3 , Ca 3 (PO4) 2 [93] Acrylic acid-allyloxy polyethoxy glutamate copolymer CaCO 3 [94] Starch-graft-poly(acrylic acid) CaCO 3 [95] Epoxysuccinic acid derivative CaCO 3 [97] Epoxysuccinic acid derivative CaCO 3 , CaSO 4 , Ca 3 (PO 4 ) 2 [98] Table 3. Cont.…”

“…Chen et al presented a novel method for continuous polymer coating of griseofulvin crystals based on solid hollow fiber cooling crystallization [ 85 ]. The Eudragit RL100 polymer precipitated from the solution and coated the suspended crystals due to rapid temperature reduction and heterogeneous nucleation.…”