title: Multicomponent solid forms of felodipine: preparation, characterisation, physicochemical and in-vivo studies.
abstract: OBJECTIVE
  This study aimed to improve biopharmaceutical parameters of the poorly soluble antihypertensive drug, felodipine, by preparing multicomponent solid forms using three coformers, viz. imidazole, nicotinamide and malonic acid.
  
  
  METHODS
  The multicomponent solid forms were prepared by mechanochemical synthesis and characterised by various analytical techniques. These solid forms were further assessed for their physicochemical parameters. Pharmacokinetic and in-vivo antihypertensive activity was performed in rats.
  
  
  RESULTS
  Felodipine (FEL) was found to be cocrystallised with imidazole (FEL-IM) while it formed eutectic with nicotinamide (FEL-NCT) and malonic acid (FEL-MA). Cocrystal was sustained by NH…N and NH….O hydrogen-bonded network. Solubility and intrinsic dissolution studies in 0.1 N HCl (pH 1.2) revealed that eutectics exhibited higher solubility and release rate than cocrystal vis-a-vis pure drug and were found to be stable under accelerated storage condition. Significant enhancement of bioavailability was observed in eutectics (3.5- to twofold) and cocrystal (1.3-fold) compared with the pure drug. Antihypertensive activity of new solid forms in an animal model showed a marked decrease in systolic blood pressure.
  
  
  CONCLUSIONS
  Mechanochemical approach was successful to prepare multicomponent solid forms that have the potential to improve biopharmaceutical parameters of the poorly soluble drug, FEL.
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh, India.
authors.forename: Renu
authors.initials: R
authors.lastname: Chadha
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh, India.
authors.forename: Mohit
authors.initials: M
authors.lastname: Sharma
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Studies, Panjab University, Chandigarh, India.
authors.forename: Jamshed
authors.initials: J
authors.lastname: Haneef
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D004355:Drug Stability; D015736:Felodipine / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008314:Malonates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000959:Antihypertensive Agents; D008314:Malonates; C030290:malonic acid; D015736:Felodipine
keywords: bioavailability; cocrystal; eutectics; mechanochemical synthesis; multicomponent solid forms