title: Continuous API-crystal coating via coacervation in a tubular reactor.
abstract: We present a proof-of-concept study of a continuous coating process of single API crystals in a tubular reactor using coacervation as a microencapsulation technique. Continuous API crystal coating can have several advantages, as in a single step (following crystallization) individual crystals can be prepared with a functional coating, either to change the release behavior, to protect the API from gastric juice or to modify the surface energetics of the API (i.e., to tailor the hydrophobic/hydrophilic characteristics, flowability or agglomeration tendency, etc.). The coating process was developed for the microencapsulation of a lipophilic core material (ibuprofen crystals of 20 μm- to 100 μm-size), with either hypromellose phthalate (HPMCP) or Eudragit L100-55. The core material was suspended in an aqueous solution containing one of these enteric polymers, fed into the tubing and mixed continuously with a sodium sulfate solution as an antisolvent to induce coacervation. A subsequent temperature treatment was applied to optimize the microencapsulation of crystals via the polymer-rich coacervate phase. Cross-linking of the coating shell was achieved by mixing the processed material with an acidic solution (pH<3). Flow rates, temperature profiles and polymer-to-antisolvent ratios had to be tightly controlled to avoid excessive aggregation, leading to pipe plugging. This work demonstrates the potential of a tubular reactor design for continuous coating applications and is the basis for future work, combining continuous crystallization and coating.
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz 8010, Austria; Siemens AG, Corporate Technology, Graz 8054, Austria.
authors.forename: M O
authors.initials: MO
authors.lastname: Besenhard
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz 8010, Austria; Microinnova Engineering GmbH, Allerheiligen/Wildon 8412, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Thurnberger
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz 8010, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Hohl
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz 8010, Austria.
authors.forename: E
authors.initials: E
authors.lastname: Faulhammer
authors.affiliation: Graz University of Technology, Institute for Electron Microscopy and Nanoanalysis, Graz 8010, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Rattenberger
authors.affiliation: Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz 8010, Austria; Graz University of Technology, Institute for Process and Particle Engineering, Graz 8010, Austria. Electronic address: khinast@tugraz.at.
authors.forename: J G
authors.initials: JG
authors.lastname: Khinast
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D003460:Crystallization / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013696:Temperature
chemical_list: D000180:Acrylic Resins; C446821:Eudragit L100-55; D005079:Excipients; D011108:Polymers; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D007052:Ibuprofen
keywords: Coacervation; Continuous coating; Enteric coating; Eudragit; HPMCP; Tubular reactor