title: Antisolvent precipitation of novel xylitol-additive crystals to engineer tablets with improved pharmaceutical performance.
abstract: The purpose of this work was to develop stable xylitol particles with modified physical properties, improved compactibility and enhanced pharmaceutical performance without altering polymorphic form of xylitol. Xylitol was crystallized using antisolvent crystallization technique in the presence of various hydrophilic polymer additives, i.e., polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) at a range of concentrations. The crystallization process did not influence the stable polymorphic form or true density of xylitol. However, botryoidal-shaped crystallized xylitols demonstrated different particle morphologies and lower powder bulk and tap densities in comparison to subangular-shaped commercial xylitol. Xylitol crystallized without additive and xylitol crystallized in the presence of PVP or PVA demonstrated significant improvement in hardness of directly compressed tablets; however, such improvement was observed to lesser extent for xylitol crystallized in the presence of PEG. Crystallized xylitols produced enhanced dissolution profiles for indomethacin in comparison to original xylitol. The influence of additive concentration on tablet hardness was dependent on the type of additive, whereas an increased concentration of all additives provided an improvement in the dissolution behavior of indomethacin. Antisolvent crystallization using judiciously selected type and concentration of additive can be a potential approach to prepare xylitol powders with promising physicomechanical and pharmaceutical properties.
authors.affiliation: School of Pharmacy, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK. Electronic address: w.kaialy@wlv.ac.uk.
authors.forename: Waseem
authors.initials: W
authors.lastname: Kaialy
authors.affiliation: Department of Pharmaceutical Sciences, School of Science, University of Greenwich, ME4 4TB Kent, UK.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Maniruzzaman
authors.affiliation: Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, Kent ME4 4TB, UK.
authors.forename: Saeed
authors.initials: S
authors.lastname: Shojaee
authors.affiliation: School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RH, UK; (e)Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: a.nokhodchi@sussex.ac.uk.
authors.forename: Ali
authors.initials: A
authors.lastname: Nokhodchi
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D005079:Excipients / Q000737:chemistry* / Q000494:pharmacology; D006244:Hardness; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D014993:Xylitol / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D005079:Excipients; D013607:Tablets; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; D011205:Povidone; D014993:Xylitol; D007213:Indomethacin
keywords: Additives; Crystallization; Engineered xylitol; Indomethacin; Tableting