Skip to main content

Advertisement

SpringerLink
Log in

Polymorphs and Cocrystals: A Comparative Analysis

  • Review Article
  • Published:
Journal of the Indian Institute of Science Aims and scope

Abstract

Controlling polymorphism has been the subject of vigorous research in the recent past in the pharmaceutical industry due to the distinct physicochemical properties associated with each solid form. Developing cocrystals/salts of active pharmaceutical ingredients (APIs) has gained tremendous research interest in recent years owing to their potential to improve pharmaceutically relevant properties without affecting therapeutic efficacy. It is observed that compounds that exhibit polymorphism and also contain several H bond donor/acceptor groups have a tendency to form cocrystals and sometime even display cocrystal polymorphism, although this tendency cannot be generalized. The aim of this contribution is to correlate crystal structures of some polymorphic APIs and their respective cocrystals to understand the rationale behind a polymorphic compound generating cocrystals. Here, we make an attempt to compare how the conformation of the molecule observed in its polymorphs support the generation of cocrystals/salts. We understand that it is impossible to cover all the polymorphs and their cocrystals/salts available in the CSD; the comparative study has been carried out with a few case studies, wherein APIs displayed polymorphism (conformation) and also formed cocrystals/salts.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure. 1:
Figure 2:
Figure 3:
Figure 4:
Figure 5:
Figure 6:
Figure 7:
Figure 8:
Figure 9:
Figure 10:
Figure 11:
Figure 12:
Figure 13:
Figure 14:
Figure 15:
Figure 16:
Figure 17:
Figure 18:
Figure 19:
Figure 20:
Figure 21:
Figure 22:
Figure 23:
Figure 24:
Figure 25:
Figure 26:
Figure 27:
Figure 28:
Figure 29:
Figure 30:
Figure 31:

Similar content being viewed by others

References

  1. Bernstein J (2002) Polymorphism in molecular crystals. Clarendon, Oxford

    Google Scholar 

  2. McCrone WC (1965) Physics and chemistry of the organic solid state, vol 2. In: Fox D, Labes MM, Weissberger A (eds) Wiley Interscience Publishers, New York, pp 725–767

  3. Kitaigorodskii AI (1970) Advances in structure research by diffraction methods, vol 3. In: Brill R, Mason R (eds) Pergamon Press, Oxford, pp 173–247

  4. Brittain HG (1999) Polymorphism in pharmaceutical solids. Marcel Dekker, New York

    Google Scholar 

  5. Hilfiker R (2006) Polymorphism in the pharmaceutical industry. Wiley, Weinheim

    Book  Google Scholar 

  6. Berstein J (1987) Organic solid state chemistry. Elsevier, Amsterdam, pp 471–518

    Google Scholar 

  7. Byrn SR, Pfeiffer RR, Stowell JG (1999) Solid-state chemistry of drugs, 2nd edn. SSCI, West Lafayette

    Google Scholar 

  8. Vishweshwar P, McMahon JA, Peterson ML, Hickey MB, Shattock TR, Zaworotko MJ (2005) Crystal engineering of pharmaceutical co-crystals from polymorphic active pharmaceutical ingredients. J Chem Commun 4601–4603

  9. US Food and Drug Administration. FDA approves new drug to treat heart failure. Press release—July 7, 2015. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm453845.htm

  10. Reddy LS, Babu NJ, Nangia A (2006) Carboxamide–pyridine N-oxide heterosynthon for crystal engineering and pharmaceutical cocrystals. Chem Commun 1369–1371

  11. Sarkar A, Rohani S (2014) Cocrystals of acyclovir with promising physicochemical properties. J Pharm Sci 104:98–105

    Article  Google Scholar 

  12. Aitipamula S, Vangala VR, Chow PS, Tan RBH (2012) Cocrystal hydrate of an antifungal drug, griseofulvin, with promising physicochemical properties. Cryst Growth Des 2:5858–5863

    Article  Google Scholar 

  13. Good D, Rodriguez-Hornedo N (2009) Solubility advantage of pharmaceutical cocrystals. Cryst Growth Des 9:2252–2264

    Article  Google Scholar 

  14. Remenar JF, Morissette SL, Peterson ML, Moulton B, MacPhee JM, Guzman HR, Almarsson O (2003) Crystal engineering of novel cocrystals of a triazole drug with 1,4-dicarboxylic acids. J Am Chem Soc 125:8456–8457

    Article  Google Scholar 

  15. Gonnade RG (2015) Pharmaceutical cocrystals of gefitinib. WO2015170345 A1

  16. Duggirala NK, Smith AJ, Wojtas L, Shytle RD, Zaworotko MJ (2014) Physical stability enhancement and pharmacokinetics of a lithium ionic cocrystal with glucose. Cryst Growth Des 14:6135–6142

    Article  Google Scholar 

  17. Jung MS, Kim JS, Kim MS, Alhalaweh A, Cho W, Hwang SJ, Velaga SP (2010) Bioavailability of indomethacin-saccharin cocrystals. J Pharm Pharmacol 62:1560–1568

    Article  Google Scholar 

  18. Variankaval N, Wenslow R, Murry J, Hartman R, Helmy R, Kwong E, Clas SD, Dalton C, Santos I (2006) Preparation and solid-state characterization of nonstoichiometric cocrystals of a phosphodiesterase-IV inhibitor and L-tartaric acid. Cryst Growth Des 6:690–700

    Article  Google Scholar 

  19. McNamara DP, Childs SL, Giordano J, Iarriccio A, Cassidy J, Shet MS, Mannion R, O’Donnell E, Park A (2006) Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API. Pharm Res 23:1888–1897

    Article  Google Scholar 

  20. Sun C (2013) Cocrystallization for successful drug delivery. Expert Opin Drug Deliv 10:201–213

    Article  Google Scholar 

  21. Karki S, Friščić T, Fabian L, Laity PR, Day GM, Jones W (2009) Improving mechanical properties of crystalline solids by cocrystal formation: new compressible forms of paracetamol. Adv Mater 21:3905–3909

    Article  Google Scholar 

  22. Vangala VR, Chow PS, Tan RBH (2012) Co-crystals and co-crystal hydrates of the antibiotic nitrofurantoin: structural studies and physicochemical properties. Cryst Growth Des 12:5925–5938

    Article  Google Scholar 

  23. Azizi A, Ebrahimi A, Habibi-Khorassani M, Rezazade S, Behazain R (2014) The effects of interactions of dicarboxylic acids on the stability of the caffeine molecule: a theoretical study. Bull Chem Soc Jpn 87:1116–1123

    Article  Google Scholar 

  24. Cassidy A, Gardner C, Jones W (2009) Following the surface response of caffeine cocrystals to controlled humidity storage by atomic force microscopy. Int J Pharm 379:59–66

    Article  Google Scholar 

  25. Trask AV, Motherwell WDS, Jones W (2006) Physical stability enhancement of theophylline via cocrystallization. Int J Pharm 320:114–123

    Article  Google Scholar 

  26. Trask AV, Motherwell WD, Jones W (2005) Pharmaceutical cocrystallization: engineering a remedy for caffeine hydration. Cryst Growth Des 5:1013–1021

    Article  Google Scholar 

  27. Vangala VR, Chow PS, Tan RBH (2011) Characterization, physicochemical and photo-stability of a co-crystal involving an antibiotic drug, nitrofurantoin, and 4-hydroxybenzoic acid. CrystEngComm 13:759–762

    Article  Google Scholar 

  28. Sanphui P, Bolla G, Nangia A, Chernyshev V (2014) Acemetacin cocrystals and salts: structure solution from powder X-ray data and form selection of the piperazine salt. IUCrJ 1:136–150

    Article  Google Scholar 

  29. Mittapalli S, Bolla G, Perumalla S, Nangia A (2016) Can we exchange water in a hydrate structure: a case study of etoricoxib. CrystEngComm 18:2825–2829

    Article  Google Scholar 

  30. McKellar SC, Kennedy AR, McCloy NC, McBride E, Florence AJ (2014) Formulation of liquid propofol as a cocrystalline solid. Cryst Growth Des 14:2422–2430

    Article  Google Scholar 

  31. Hong C, Xie Y, Yao Y, Li G, Yuan X, Shen H (2015) A novel strategy for pharmaceutical cocrystal generation without knowledge of stoichiometric ratio: myricetin cocrystals and a ternary phase diagram. Pharm Res 32:47–60

    Article  Google Scholar 

  32. Chow S, Shi L, Ng WW, Leung K, Nagapudi K, Sun C, Chow A (2014) Kinetic entrapment of a hidden curcumin cocrystal with phloroglucinol. Cryst Growth Des 14:5079–5089

    Article  Google Scholar 

  33. Maeno Y, Fukami T, Kawahata M, Yamaguchi K, Tagami T, Ozeki T, Suzuki T, Tomono K (2014) Novel pharmaceutical cocrystal consisting of paracetamol and trimethylglycine, a new promising cocrystal former. Int J Pharm 473:179–186

    Article  Google Scholar 

  34. Dhumal RS, Kelly AL, York P, Coates PD, Paradkar A (2010) Cocrystalization and simultaneous agglomeration using hot melt extrusion. Pharm Res 27:2725–2733

    Article  Google Scholar 

  35. Sheikh AY, Rahim SA, Hammond RB, Roberts KJ (2009) Scalable solution cocrystallization: case of carbamazepine-nicotinamide I. CrystEngComm 11:501–509

    Article  Google Scholar 

  36. Qiu S, Li M (2015) Effects of coformers on phase transformation and release profiles of carbamazepine cocrystals in hydroxypropyl methylcellulose based matrix tablets. Int J Pharm 479:118–128

    Article  Google Scholar 

  37. Li M, Qiu S, Lu Y, Wang K, Lai X, Rehan M (2014) Investigation of the effect of hydroxypropyl methylcellulose on the phase transformation and release profiles of carbamazepine-nicotinamide cocrystal. Pharm Res 31:2312–2325

    Article  Google Scholar 

  38. Stahly GP (2009) A survey of cocrystals reported prior to 2000. Cryst Growth Des 9:4212–4229

    Article  Google Scholar 

  39. Trask AV (2007) An overview of pharmaceutical cocrystals as intellectual property. Mol Pharm 4:301–309

    Article  Google Scholar 

  40. Aitipamula S, Banerjee R, Bansal AK, Biradha K, Cheney ML, Choudhury AR, Desiraju GR, Dikundwar AG, Dubey R, Duggirala N, Ghogale PP, Ghosh S, Goswami PK, Goud NR, Jetti RRKR, Karpinski P, Kaushik P, Kumar D, Kumar V, Moulton B, Mukherjee A, Mukherjee G, Myerson AS, Puri V, Ramanan A, Rajamannar T, Reddy CM, Rodriguez-Hornedo N, Rogers RD, Row TNG, Sanphui P, Shan N, Shete G, Singh A, Sun CC, Swift JA, Thaimattam R, Thakur TS, Thaper RK, Thomas SP, Tothadi S, Vangala VR, Variankaval N, Vishweshwar P, Weyna DR, Zaworotko MJ (2012) Polymorphs, salts, and cocrystals: what's in a name? Cryst Growth Des 12:2147–2152

    Article  Google Scholar 

  41. Lide DR (2000) CRC handbook of chemistry and physics, 81st edn. CRC Press, Boca Raton, pp 2–55

    Google Scholar 

  42. Childs SL, Stahly GP, Park A (2007) The salt−cocrystal continuum:  the influence of crystal structure on ionization state. Mol Pharm 4:323–338

    Article  Google Scholar 

  43. Bhogala BR, Basavoju S, Nangia A (2005) Tape and layer structures in cocrystals of some di- and tricarboxylic acids with 4,4′-bipyridines and isonicotinamide. From binary to ternary cocrystals. CrystEngComm 7:551–562

    Article  Google Scholar 

  44. Desiraju GR (1989) Crystal engineering: the design of organic solids. Elsevier, Amsterdam

    Google Scholar 

  45. Desiraju GR, Vittal JJ, Ramanan A (2011) Crystal engineering. A textbook. World Scientific, Singapore

  46. Aitipamula S, Chow PS, Tan RBH (2014) Polymorphism in cocrystals: a review and assessment of its significance. CrystEngComm 16:3451–3465

    Article  Google Scholar 

  47. Aitipamula S, Chow PS, Tan RBH (2010) Polymorphs and solvates of a cocrystal involving an analgesic drug, ethenzamide, and 3, 5-dinitrobenzoic acid. Cryst Growth Des 10:2229–2238

    Article  Google Scholar 

  48. Sangtani E, Sahu SK, Thorat SH, Gawade RL, Jha KK, Munshi P, Gonnade RG (2015) Furosemide cocrystals with pyridines: an interesting case of color cocrystal polymorphism. Cryst Growth Des 15:5858–5872

    Article  Google Scholar 

  49. Allen FH (2002) The Cambridge structural database: a quarter of a million crystal structures and rising. Acta Cryst B58:380–388

    Article  Google Scholar 

  50. The American Society of Health-System Pharmacists. Retrieved 3 Apr 2011

  51. DrugBank. http://www.drugbank.ca/drugs/DB00695

  52. Babu NJ, Cherukuvada S, Thakuria R, Nangia A (2010) Conformational and synthon polymorphism in furosemide (Lasix). Cryst Growth Des 10:1979–1989

    Article  Google Scholar 

  53. BCS Classification. http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm128219.htm

  54. Ueto T, Takata N, Muroyama N, Nedu A, Sasaki A, Tanida S, Terada K (2012) Polymorphs and a hydrate of furosemide–nicotinamide 1:1 cocrystal. Cryst Growth Des 12:485–495

    Article  Google Scholar 

  55. Harriss BI, Vella-Zarb L, Wilson C, Evans IR (2014) Furosemide cocrystals: structures, hydrogen bonding, and implications for properties. Cryst Growth Des 12:783–791

    Article  Google Scholar 

  56. https://www.drugbank.ca/drugs/DB02266

  57. Lόpez-Mejías V, Kampf JW, Matzger AJ (2012) Nonamorphism in flufenamic acid and a new record for a polymorphic compound with solved structures. J Am Chem Soc 134:9872–9875

    Article  Google Scholar 

  58. McConnell JF (1973) 3’-Trifluoromethyldiphenylamine-2-carboxylic acid, C14H10F3NO2 flufenamic acid. Cryst Struct Commun 3:459–461

    Google Scholar 

  59. Kirshna Murthy HM, Bhat TN, Vijayan M (1982) Structure of a new crystal form of 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid (flufenamic acid). Acta Cryst B38:315–317

    Article  Google Scholar 

  60. Sugar AM (1990) Treatment of fungal infections in patients infected with the human immunodeficiency virus. Pharmacotherapy 10:154S–158S

    Google Scholar 

  61. Proposal to waive In vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms. http://www.who.int/medicines/services/expertcommittees/pharmprep/QAS04_109Rev1_Waive_invivo_bioequiv.pdf

  62. Karanam M, Dev S, Choudhury AR (2012) New polymorphs of fluconazole: results from cocrystallization experiments. Cryst Growth Des 12:240–252

    Article  Google Scholar 

  63. Mirza S, Miroshnyk I, Habib MJ, Brausch JF, Hussain MD (2010) Enhanced dissolution and oral bioavailability of piroxicam formulations: modulating effect of phospholipids. Pharmaceutics 2:339–350

    Article  Google Scholar 

  64. Kojić-Prodić B, Ružić-Toroš Ž (1982) Structure of the anti-inflammatory drug 4-hydroxy-2-methyl-N-2-pyridyl-2H-1λ6, 2-benzothiazine-3-carboxamide 1, 1-dioxide (piroxicam). Acta Cryst B38:2948–2951

    Article  Google Scholar 

  65. Vrečer F, Vrbinc M, Meden A (2003) Characterization of piroxicam crystal modifications. Int J Pharm 256:3–15

    Article  Google Scholar 

  66. Naelapää K, van de Streek J, Rantanen J, Bond AD (2012) Complementing high‐throughput X‐ray powder diffraction data with quantum–chemical calculations: application to piroxicam form III. J Pharm Sci 101:4214–4219

    Article  Google Scholar 

  67. Thomas LH, Walesa C, Wilson CC (2016) Selective preparation of elusive and alternative single component polymorphic solid forms through multi-component crystallization routes. Chem Commun 52:7372–7375

    Article  Google Scholar 

  68. Reck G, Dietz G, Laban G, Günther W, Bannier G, Höhne E (1988) X-ray studies on piroxicam modifications. Pharmazie 43:477–481

    Google Scholar 

  69. International Union of Crystallography, Online Dictionary of Crystallography. http://reference.iucr.org/dictionary/Polytypism

  70. Scheuer K, Rostock A, Bartsch R, Müller WE (1999) Piracetam improves cognitive performance by restoring neurochemical deficits of the aged rat brain. Pharmacopsychiatry 32:10–16

    Article  Google Scholar 

  71. Fabbiani FPA, Allan DR, David WIF, Davidson AJ, Lennie AR, Parsons S, Pulham CR, Warren JE (2007) High-pressure studies of pharmaceuticals: an exploration of the behavior of piracetam. Cryst Growth Des 7:1115–1124

    Article  Google Scholar 

  72. Fabbiani FPA, Allan DR, Parsons S, Pulham CR (2005) An exploration of the polymorphism of piracetam using high pressure. CrystEngComm 7:179–186

    Article  Google Scholar 

  73. Bandoli G, Clemente DA, Grassi A, Pappalardo GC (1981) Molecular determinants for drug-receptor interactions. Mol Pharmcol 20:558–564

    Google Scholar 

  74. Admiraal G, Eikelenboom JC, Vos A (1982) Structures of the triclinic and monoclinic modifications of (2-oxo-1-pyrrolidinyl) acetamide. Acta Cryst B38:2600–2605

    Article  Google Scholar 

  75. Louër D, Louër M, Dzyabchenko VA, Agafonov V, Céolin R (1995) Structure of a metastable phase of piracetami from X-ray powder diffraction using the atom–atom potential method. Acta Cryst B51:182–187

    Article  Google Scholar 

  76. Kühnert-Brandstätter M, Bürger A, Völlenkee R (1994) Stability behaviour of piracetam polymorphs. Sci Pharm 62:307–316

    Google Scholar 

  77. Hagles AT, Leiserowitz L (1978) The amide hydrogen bond and the anomalous packing of adipamide. J Am Chem Soc 100:5879–5887

    Article  Google Scholar 

  78. Acharya KR, Kuchela KN, Kartha G (1982) Crystal structure of sulfamerazine. J Crystallogr Spectrosc Res 12:369

    Article  Google Scholar 

  79. Caira MR, Mohamed R (1992) Positive identification of two orthorhombic polymorphs of sulfamerazine (C11H12N4O2S), their thermal analyses and structural comparison. Acta Cryst B48:492–498

    Article  Google Scholar 

  80. Hossain GMG (2006) A new polymorph of sulfamerazine. Acta Cryst E62:o2166–o2167

    Google Scholar 

  81. Brogden RN, Heel RC, Pakes GE, Speight TM, Avery GS (1980) Diflunisal: a review of its pharmacological properties and therapeutic use in pain and musculoskeletal strains and sprains and pain in osteoarthritis. Drugs 19:84–106

    Article  Google Scholar 

  82. Berry H, Bloom B, Hamilton EB, Swinson DR (1982) Naproxen sodium, diflunisal, and placebo in the treatment of chronic back pain. Ann Rheum Dis 41:129–132

    Article  Google Scholar 

  83. Cross WI, Blagden N, Davey RJ (2003) A whole output strategy for polymorph screening:  combining crystal structure prediction, graph set analysis, and targeted crystallization experiments in the case of diflunisal. Cryst Growth Des 2:151–158

    Article  Google Scholar 

  84. Flower RJ (1974) Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev 26:33–67

    Google Scholar 

  85. McConnell JF, Company FZ (1976) N-(2, 3-Xylyl) anthranilic acid, C15H15NO2. Mefenamic acid. Cryst Struct Commun 5:861–864

    Google Scholar 

  86. SeethaLekshmi S, Guru Row TN (2012) Conformational polymorphism in a non-steroidal anti-inflammatory drug, mefenamic acid. Cryst Growth Des 12:4283–4289

    Article  Google Scholar 

  87. Munroe A, Rasmuson AC, Hodnett BK, Croker DM (2012) Relative stabilities of the five polymorphs of sulfathiazole. Growth Des 12:2825–2835

    Article  Google Scholar 

  88. Hu Y, Erxleben A, Hodnett BK, Li B, McArdle P, Rasmuson AC, Ryder AG (2013) Solid-state transformations of sulfathiazole polymorphs: the effects of milling and humidity. Cryst Growth Des 13:3404–3413

    Article  Google Scholar 

  89. Perlovich GL, Surov AO, Hansen LK, Bauer-Brandl A (2007) Energetic aspects of diclofenac acid in crystal modifications and in solutions—mechanism of solvation, partitioning and distribution. J Pharm Sci 96:1031–1042

    Article  Google Scholar 

  90. Moser P, Sallmann A, Wiesenberg I (1990) Synthesis and quantitative structure-activity relationships of diclofenac analogs. J Med Chem 33:2358–2368

    Article  Google Scholar 

  91. Castellari C, Ottani S (1997) Two monoclinic forms of diclofenac acid. Acta Cryst C53:794–797

    Google Scholar 

  92. Jaiboon N, Yos-in K, Ruangchaithaweesuk S, Chaichit N, Thutivoranath R, Siritaedmukul K, Hannongbua S (2001) New orthorhombic form of 2-[(2, 6-dichlorophenyl) amino] benzeneacetic acid (diclofenac acid). Anal Sci 17:1465–1466

    Article  Google Scholar 

  93. Jones W, Motherwell WDS, Trask AV (2009) Pharmaceutical cocrystals: an emerging approach to physical property enhancement. MRS Bull 31:875–879

    Article  Google Scholar 

  94. Bolla G, Nangia A (2016) Pharmaceutical cocrystals: walking the talk. Chem Commun 52:8342–8360

    Article  Google Scholar 

  95. Bolton O, Simke LR, Pagoria PF, Matzger AJ (2012) High power explosive with good sensitivity: a 2: 1 cocrystal of CL-20: HMX. Growth Des 12:4311–4314

    Article  Google Scholar 

  96. Millar DIA, Maynard-Casely HE, Allan DR, Cumming AS, Lennie AR, Mackay AJ, Oswald IDH, Tang CC, Pulham CR (2012) Crystal engineering of energetic materials: co-crystals of CL-20. CrystEngComm 14:3742–3749

    Article  Google Scholar 

  97. Bolton O, Matzger A (2011) Improved stability and smart-material functionality realized in an energetic cocrystal. J Angew Chem Int Ed 50:8960–8963

    Article  Google Scholar 

  98. Zhangab J, Shreeve JM (2016) Time for pairing: cocrystals as advanced energetic materials. CrystEngComm 18:6124–6133

    Article  Google Scholar 

Download references

Acknowledgements

E.S. thanks the Council of Scientific and Industrial Research (CSIR) for Senior Research fellowship. We thank CSIR for financial support under the ORIGIN program of 12FYP.

Author information

Authors and Affiliations

  1. Center for Materials Characterization, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pashan, Pune, 411008, India

    Rajesh G. Gonnade & Ekta Sangtani

  2. Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi, 110001, India

    Rajesh G. Gonnade & Ekta Sangtani

Authors
  1. Rajesh G. Gonnade
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ekta Sangtani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajesh G. Gonnade.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gonnade, R.G., Sangtani, E. Polymorphs and Cocrystals: A Comparative Analysis. J Indian Inst Sci 97, 193–226 (2017). https://doi.org/10.1007/s41745-017-0028-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41745-017-0028-2

Keywords

Search

Navigation