title: The influence of polymorphism on the manufacturability and in vitro dissolution of sulindac-containing hard gelatin capsules.
abstract: BACKGROUND
  Drug polymorphism could affect drug product dissolution, manufacturability, stability and bioavailability/bioequivalence. The impact of polymorphism on the manufacturability and in vitro dissolution profiles of sulindac capsules has not been studied yet.
  
  
  OBJECTIVE
  To evaluate the impact of polymorphism on the manufacturability and in vitro dissolution of sulindac hard gelatin capsules.
  
  
  METHODS
  Sulindac crystal forms I and II (SLDI and SLDII, respectively) were prepared and characterized. Powder formulations containing one of the polymorphs, lactose and magnesium stearate (at three different levels) were prepared and their flow properties determined. Hard gelatin capsules were filled with the formulations and tested for fill-weight variations. Drug dissolution for SLDI- and SLDII-containing hard gelatin capsules was determined.
  
  
  RESULTS
  Differences in flow properties for each polymorph were observed, as well as for their formulations, which in turn affected capsule weight homogeneity. Statistically significant differences in the rate and extent of drug release were observed between SLDI- and SLDII-containing capsules.
  
  
  CONCLUSIONS
  Formulations containing SLDI showed a better manufacturability and a better dissolution profile than those with SLDII.
  
  
  CONCLUSIONS
  Sulindac crystalline form I was the best candidate for hard gelatin capsule formulation because of its technological and in vitro dissolution properties.
authors.affiliation: Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria , Mexico City , Mexico .
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Guadalupe Sánchez-González
authors.forename: Lilian
authors.initials: L
authors.lastname: Yépez-Mulia
authors.forename: Vicente
authors.initials: V
authors.lastname: Jesús Hernández-Abad
authors.forename: Helgi
authors.initials: H
authors.lastname: Jung Cook
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003460:Crystallization; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D005780:Gelatin; D007785:Lactose / Q000737:chemistry; D011208:Powders; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013467:Sulindac / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D005079:Excipients; D011208:Powders; D013229:Stearic Acids; D013467:Sulindac; C031183:stearic acid; D005780:Gelatin; D007785:Lactose
keywords: Formulation; manufacturability; mechanical properties; physical characterization; polymorphs