title: Nanomechanical properties of selected single pharmaceutical crystals as a predictor of their bulk behaviour.
abstract: OBJECTIVE
  The main goal of this research was to assess the mechanical properties of APIs' polymorphic forms at the single-crystal level (piroxicam, famotidine, nifedipine, olanzapine) in order to predict their bulk deformational attributes, which are critical for some pharmaceutical technology processes.
  
  
  METHODS
  The mechanical properties of oriented single crystals were determined using instrumented nanoindentation (continuous stiffness measurement). All polymorphic forms investigated were previously identified using a combination of calorimetric and spectroscopic techniques.
  
  
  RESULTS
  Mechanical properties such as Young's modulus and indentation hardness were consistent with the molecular packing of the polymorphic forms investigated with respect to crystal orientation. For mechanically interlocked structures, characteristic of most polymorphic forms, response of single crystals to indentation was isotropic. The material's bulk elastic properties can be successfully predicted by measuring Young's modulus of single crystals because a good linear correlation with a bulk parameter such as the tablets' elastic relaxation index was determined.
  
  
  CONCLUSIONS
  The results confirm the idea that the intrinsic mechanical properties of pharmaceutical crystals (Young's modulus) largely control and anticipate their deformational behavior during tablet compression. Young's modulus and indentation hardness represent a very valuable and effective tool in preformulation studies for describing materials' mechanical attributes, which are important for technological processes in which materials are exposed to deformation.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Aškerčeva 7, 1000, Ljubljana, Slovenia.
authors.forename: Mateja
authors.initials: M
authors.lastname: Egart
authors.forename: Biljana
authors.initials: B
authors.lastname: Janković
authors.forename: Nina
authors.initials: N
authors.lastname: Lah
authors.forename: Ilija
authors.initials: I
authors.lastname: Ilić
authors.forename: Stanko
authors.initials: S
authors.lastname: Srčič
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry; D019245:Compressive Strength; D003460:Crystallization; D055119:Elastic Modulus; D005544:Forecasting; D006244:Hardness; D049329:Nanostructures / Q000737:chemistry*; D009543:Nifedipine / Q000737:chemistry; D000077152:Olanzapine; D013314:Stress, Mechanical; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D001569:Benzodiazepines; D009543:Nifedipine; D000077152:Olanzapine
references.citation: J Am Chem Soc. 2009 Oct 14;131(40):14252-4
references.pmid: 19757791
references.citation: Int J Pharm. 2013 Mar 25;446(1-2):6-15
references.pmid: 23402976
references.citation: J Pharm Sci. 2007 Sep;96(9):2457-68
references.pmid: 17518361
references.citation: Int J Pharm. 2006 Aug 2;318(1-2):86-91
references.pmid: 16647827
references.citation: Int J Pharm. 2003 Apr 30;256(1-2):3-15
references.pmid: 12695006
references.citation: Eur J Pharm Biopharm. 2006 Feb;62(2):194-201
references.pmid: 16202574
references.citation: Pharm Res. 2012 Jan;29(1):319-31
references.pmid: 21845506
references.citation: J Pharm Sci. 2003 Dec;92(12):2519-33
references.pmid: 14603498
references.citation: J Med Chem. 1980 Dec;23(12):1442-5
references.pmid: 6256552
references.citation: Acta Crystallogr B. 2000 Apr;56 ( Pt 2):299-309
references.pmid: 10794283
references.citation: Pharm Res. 2011 Dec;28(12):3116-27
references.pmid: 21671136
references.citation: Pharm Res. 2006 Jul;23(7):1608-16
references.pmid: 16783478
references.citation: Acta Crystallogr A. 2004 Sep;60(Pt 5):480-7
references.pmid: 15477688
references.citation: Chem Commun (Camb). 2005 May 21;(19):2439-41
references.pmid: 15886763
references.citation: J Pharm Pharmacol. 1972 Dec;24:Suppl:135P-136
references.pmid: 4144857
references.citation: J Pharm Sci. 2010 Nov;99(11):4458-62
references.pmid: 20845444