title: New conformational polymorph of hydrochlorothiazide with improved solubility.
abstract: BACKGROUND
  To characterize a new conformation of hydrochlorothiazide (HCT) with better solubility and establishing its relationship with previously reported form I, obtained during attempted crystallization experiments.
  
  
  OBJECTIVE
  The aim of present investigation is to unveil a new conformational polymorph (form IA) having a higher solubility compared to commercially available form I.
  
  
  METHODS
  New form (IA) was obtained from slow evaporation as well as by solvent-antisolvent method and was then characterized by DSC, FTIR, PXRD and SCXRD. Equilibrium solubility profile shows that it is more soluble than form I.
  
  
  RESULTS
  Appearance of phase transition endotherm at 215.87 °C in DSC spectra indicated the existence of new polymorph which was further confirmed by FTIR and PXRD. Single crystal study showed significant difference in various bond angles and torsion angles of the two forms. The solubility exhibited by form IA was (938 µg/mL) compared to form I (791 µg/mL) in water.
  
  
  CONCLUSIONS
  Complete structural analysis and molecular arrangements in the unit cell along with the DSC and FTIR data confirm the existence of new conformer of HCT.
  
  
  CONCLUSIONS
  This study reveals the existence of a new conformational polymorph of HCT molecule having higher solubility could prove to be promising in pre-formulation.
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , Punjab , India .
authors.forename: Anupam
authors.initials: A
authors.lastname: Saini
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , Punjab , India .
authors.forename: Renu
authors.initials: R
authors.lastname: Chadha
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , Punjab , India .
authors.forename: Ashish
authors.initials: A
authors.lastname: Gupta
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , Punjab , India .
authors.forename: Pawanpreet
authors.initials: P
authors.lastname: Singh
authors.affiliation: a University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , Punjab , India .
authors.forename: Swati
authors.initials: S
authors.lastname: Bhandari
authors.affiliation: b Department of Chemical Sciences , Indian Institute of Science Education and Research , Mohali , Punjab , India , and.
authors.forename: Sadhika
authors.initials: S
authors.lastname: Khullar
authors.affiliation: b Department of Chemical Sciences , Indian Institute of Science Education and Research , Mohali , Punjab , India , and.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mandal
authors.affiliation: c Department of Chemistry , Panjab University , Chandigarh , Punjab , India.
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Jain
mesh_terms: D002152:Calorimetry, Differential Scanning / Q000379:methods; D006852:Hydrochlorothiazide / Q000032:analysis* / Q000737:chemistry*; D008968:Molecular Conformation; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D006852:Hydrochlorothiazide
keywords: Conformation; FT-IR; crystal energy landscape; crystal structure; differential scanning calorimetry