title: Dissolution Performance of High Drug Loading Celecoxib Amorphous Solid Dispersions Formulated with Polymer Combinations.
abstract: OBJECTIVE
  The aims of this study were twofold. First, to evaluate the effectiveness of selected polymers in inhibiting solution crystallization of celecoxib. Second, to compare the release rate and crystallization tendency of celecoxib amorphous solid dispersions (ASDs) formulated with a single polymer, or binary polymer combinations.
  
  
  METHODS
  The effectiveness of polymers, polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC) or HPMC acetate succinate (HPMCAS), in maintaining supersaturation of celecoxib solutions was evaluated by performing nucleation induction time measurements. Crystallization kinetics of ASD suspensions were monitored using Raman spectroscopy. Dissolution experiments were carried out under non-sink conditions.
  
  
  RESULTS
  Pure amorphous celecoxib crystallized rapidly through both matrix and solution pathways. Matrix and solution crystallization was inhibited when celecoxib was molecularly mixed with a polymer, resulting in release of the drug to form supersaturated solutions. Cellulosic polymers were more effective than PVP in maintaining supersaturation. Combining a cellulosic polymer and PVP enabled improved drug release and stability to crystallization.
  
  
  CONCLUSIONS
  Inclusion of an effective solution crystallization inhibitor as a minor component in ternary dispersions resulted in prolonged supersaturation following dissolution. This study shows the feasibility of formulation strategies for ASDs where a major polymer component is used to achieve one key property e.g. release, while a minor polymer component is added to prevent crystallization.
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA. lstaylor@purdue.edu.
authors.forename: Lynne S
authors.initials: LS
authors.lastname: Taylor
mesh_terms: D000068579:Celecoxib / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004355:Drug Stability; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013059:Spectrum Analysis, Raman / Q000379:methods
chemical_list: D011108:Polymers; D012996:Solutions; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D011205:Povidone; D000068579:Celecoxib
keywords: amorphous solid dispersion; crystallization; dissolution; supersaturation