Abstract
Rheology is the science of flow and deformation of matter. Particularly gels and non-Newtonian fluids, which exhibit complex flow behavior, are frequently encountered in pharmaceutical engineering and manufacturing, or when dealing with various in vivo fluids. Therefore understanding rheology is important, and the ability to use rheological characterization tools is of great importance for any pharmaceutical scientist involved in the field. Flow can be generated by shear or extensional deformations, or a combination of both. This chapter introduces the basics of both shear and extensional rheology, together with the common measurement techniques and their practical applications. Examples of the use of rheological techniques in the pharmaceutical field, as well as other closely related fields such as food and polymer science, are also given.
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References
Aho J, Rolon-Garrido VH, Syrjala S, Wagner MH (2010) Measurement technique and data analysis of extensional viscosity for polymer melts by Sentmanat extensional rheometer (SER). Rheol Acta 49(4):359–370. doi:10.1007/s00397-010-0439-8
Allen A, Cunliffe WJ, Pearson JP, Sellers LA, Ward R (1984) Studies on gastrointestinal mucus. Scand J Gastroenterol Suppl 93:101–113
Alvarez NJ, Marin JMR, Huang Q, Michelsen ML, Hassager O (2013) Creep measurements confirm steady flow after stress maximum in extension of branched polymer melts. Phys Rev Lett 110(16):168301. doi:10.1103/Physrevlett.110.168301
Anna SL, McKinley GH (2001) Elasto-capillary thinning and breakup of model elastic liquids. J Rheol 45(1):115–138. doi:10.1122/1.1332389
Antoniou E, Alexandridis P (2010) Polymer conformation in mixed aqueous-polar organic solvents. Eur Polym J 46(2):324–335. doi:10.1016/j.eurpolymj.2009.10.005
Anwar S, Fell JT, Dickinson PA (2005) An investigation of the disintegration of tablets in biorelevant media. Int J Pharm 290(1–2):121–127. doi:10.1016/j.ijpharm.2004.11.023
Atuma C, Strugala V, Allen A, Holm L (2001) The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol 280(5):G922–G929
Auhl D, Hoyle DM, Hassell D, Lord TD, Harlen OG, Mackley MR, McLeish TCB (2011) Cross-slot extensional rheometry and the steady-state extensional response of long chain branched polymer melts. J Rheol 55(4):875–900. doi:10.1122/1.3589972
Bach A, Rasmussen HK, Hassager O (2003) Extensional viscosity for polymer melts measured in the filament stretching rheometer. J Rheol 47(2):429–441. doi:10.1122/1.1545072
Bagley EB (1957) End corrections in the capillary flow of polyethylene. J Appl Phys 28(5):624–627. doi:10.1063/1.1722814
Bain MK, Maity D, Bhowmick B, Mondal D, Mollick MMR, Sarkar G, Bhowmik M, Rana D, Chattopadhyay D (2013) Effect of PEG–salt mixture on the gelation temperature and morphology of MC gel for sustained delivery of drug. Carbohydr Polym 91(2):529–536. doi:10.1016/j.carbpol.2012.08.040
Baldursdottir S, Kjoniksen A-L (2005) Rheological characterization and turbidity of riboflavin-photosensitized changes in alginate/GDL systems. Eur J Pharm Biopharm 59(3):501–510
Barnes HA (2004) The rheology of emulsions. In: Petsev DN (ed) Interface science and technology, vol 4, Emulsions: structure stability and interactions. Elsevier, London
Barry BW, Meyer MC (1979a) The rheological properties of carbopol gels. I. Continuous shear and creep properties of carbopol gels. Int J Pharm 2(1):1–25. doi:10.1016/0378-5173(79)90025-5
Barry BW, Meyer MC (1979b) The rheological properties of carbopol gels II. Oscillatory properties of carbopol gels. Int J Pharm 2(1):27–40. doi:10.1016/0378-5173(79)90026-7
Bhaskar KR, Gong D, Bansil R, Pajevic S, Hamilton JA, Turner BS, LaMont JT (1991) Profound increase in viscosity and aggregation of pig gastric mucin at low pH. Am J Physiol 261(5):G827–G832
Bhowmik M, Kumari P, Sarkar G, Bain MK, Bhowmick B, Mollick MMR, Mondal D, Maity D, Rana D, Bhattacharjee D, Chattopadhyay D (2013) Effect of xanthan gum and guar gum on in situ gelling ophthalmic drug delivery system based on poloxamer-407. Int J Biol Macromol 62:117–123. doi:10.1016/j.ijbiomac.2013.08.024
Binding DM (1988) An approximate analysis for contraction and converging flows. J Nonnewton Fluid Mech 27(2):173–189. doi:10.1016/0377-0257(88)85012-2
Boegh M, Baldursdóttir SG, Müllertz A, Nielsen HM (2014) Property profiling of biosimilar mucus in a novel mucus-containing in vitro model for assessment of intestinal drug absorption. Eur J Pharm Biopharm 87(2):227–35. doi:10.1016/j.ejpb.2014.01.001
Bohr A, Yang M, Baldursdottir S, Kristensen J, Dyas M, Stride E, Edirisinghe M (2012) Particle formation and characteristics of Celecoxib-loaded poly(lactic-co-glycolic acid) microparticles prepared in different solvents using electrospraying. Polymer 53(15):3220–3229. doi:10.1016/j.polymer.2012.05.002
Bollaın C, Collar C (2004) Dough viscoelastic response of hydrocolloid/enzyme/surfactant blends assessed by uni- and bi-axial extension measurements. Food Hydrocolloids 18(3):499–507. doi:10.1016/j.foodhyd.2003.08.007
Bourbon AI, Pinheiro AC, Ribeiro C, Miranda C, Maia JM, Teixeira JA, Vicente AA (2010) Characterization of galactomannans extracted from seeds of Gleditsia triacanthos and Sophora japonica through shear and extensional rheology: comparison with guar gum and locust bean gum. Food Hydrocolloids 24(2–3):184–192. doi:10.1016/j.foodhyd.2009.09.004
Brandsma RL, Rizvi SSH (2001) Effect of manufacturing treatments on the rheological character of Mozzarella cheese made from microfiltration retentate depleted of whey proteins1. Int J Food Sci Technol 36(6):601–610. doi:10.1046/j.1365-2621.2001.00506.x
Broughton-Head VJ, Shur J, Carroll MP, Smith JR, Shute JK (2007) Unfractionated heparin reduces the elasticity of sputum from patients with cystic fibrosis. Am J Physiol 293(5):L1240–L1249. doi:10.1152/ajplung.00206.2007
Cao X, Bansil R, Bhaskar KR, Turner BS, LaMont JT, Niu N, Afdhal NH (1999) pH-dependent conformational change of gastric mucin leads to sol-gel transition. Biophys J 76(3):1250–1258. doi:10.1016/S0006-3495(99)77288-7
Celli JP, Turner BS, Afdhal NH, Ewoldt RH, McKinley GH, Bansil R, Erramilli S (2007) Rheology of gastric mucin exhibits a pH-dependent sol-gel transition. Biomacromolecules 8(5):1580–1586. doi:10.1021/bm0609691
Chatraei S, Macosko CW, Winter HH (1981) Lubricated squeezing flow–a new biaxial extensional rheometer. J Rheol 25(4):433–443. doi:10.1122/1.549648
Cogswell FN (1972) Converging flow of polymer melts in extrusion dies. Polym Eng Sci 12(1):64. doi:10.1002/pen.760120111
Cone RA (2009) Barrier properties of mucus. Adv Drug Delivery Rev 61(2):75–85. doi:10.1016/j.addr.2008.09.008
Critchfield AS, Yao G, Jaishankar A, Friedlander RS, Lieleg O, Doyle PS, McKinley G, House M, Ribbeck K (2013) Cervical mucus properties stratify risk for Preterm birth. PLoS One 8(8), e69528. doi:10.1371/journal.pone.0069528
Cu Y, Saltzman WM (2009) Mathematical modeling of molecular diffusion through mucus. Adv Drug Delivery Rev 61(2):101–114. doi:10.1016/j.addr.2008.09.006
Dealy JM, Larson RG (2006) Structure and rheology of molten polymers—from structure to flow behavior and back again. Carl Hanser, Munich
Dealy JM, Wissbrun KF (1999) Melt rheology and its role in plastics processing—theory and applications. Kluwer Academic, Dordrecht
Denson CD, Gallo RJ (1971) Measurements on the biaxial extension viscosity of bulk polymers: the inflation of a thin polymer sheet. Polym Eng Sci 11(2):174–176. doi:10.1002/pen.760110213
Dott C, Tyagi C, Tomar LK, Choonara YE, Kumar P, du Toit LC, Pillay V (2013) A mucoadhesive electrospun nanofibrous matrix for rapid oramucosal drug delivery. J Nanomater 2013:924947. doi:10.1155/2013/924947
Eccleston GM, Hudson NE (2000) The use of a capillary rheometer to determine the shear and extensional flow behaviour of nasal spray suspensions. J Pharm Pharmacol 52(10):1223–1232. doi:10.1211/0022357001777351
Ferry JD (1980) Viscoelastic properties of polymers, 3rd edn. Wiley, New York
Franck A. 2007. The ARES-EVF: Option for measuring extensional viscosity of polymer melts. http://www.tainstruments.com/pdf/literature/APN002_V2_ARES_EVF_to_measure_elongation_viscosity.pdf
Haghighi M, Rezaei K, Labbafi M, Khodaiyan F (2011) On the formulation design and rheological evaluations of pectin-based functional gels. J Food Sci 76(1):E15–E22. doi:10.1111/j.1750-3841.2010.01876.x
Haward SJ (2014) Characterization of hyaluronic acid and synovial fluid in stagnation point elongational flow. Biopolymers 101(3):287–305. doi:10.1002/Bip.22357
Haward S, Odell J, Berry M, Hall T (2011) Extensional rheology of human saliva. Rheol Acta 50(11–12):869–879. doi:10.1007/s00397-010-0494-1
Haward SJ, Ober TJ, Oliveira MSN, Alves MA, McKinley GH (2012) Extensional rheology and elastic instabilities of a wormlike micellar solution in a microfluidic cross-slot device. Soft Matter 8(2):536–555. doi:10.1039/C1sm06494k
Horter D, Dressman JB (2001) Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Delivery Rev 46(1–3):75–87. doi:10.1016/S0169-409X(00)00130-7
Humphrey SP, Williamson RT (2001) A review of saliva: normal composition, flow, and function. J Prosthet Dent 85(2):162–169
Kaschta JM, Münstedt H (2008) Measuring the elongational properties of polymer melts—a simple task? Paper presented at The XVth International Congress on Rheology August 3–8, 2008—Monterey, California
Kirkham S, Kolsum U, Rousseau K, Singh D, Vestbo J, Thornton DJ (2008) MUC5B Is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 178(10):1033–1039. doi:10.1164/rccm.200803-391OC
Kocevar-Nared J, Kristl J, Smid-Korbar J (1997) Comparative rheological investigation of crude gastric mucin and natural gastric mucus. Biomaterials 18(9):677–681. doi:10.1016/S0142-9612(96)00180-9
Kojarunchitt T, Hook S, Rizwan S, Rades T, Baldursdottir S (2011) Development and characterization of modified poloxamer 407 thermoresponsive depot systems containing cubosomes. Int J Pharm 408(1–2):20–26. doi:10.1016/j.ijpharm.2011.01.037
Kompani M, Venerus DC (2000) Equibiaxial extensional flow of polymer melts via lubricated squeezing flow. I. Experimental analysis. Rheol Acta 39(5):444–451. doi:10.1007/s003970000106
Korhonen M, Hellen L, Hirvonen J, Yliruusi J (2001) Rheological properties of creams with four different surfactant combinations - effect of storage time and conditions. Int J Pharm 221(1–2):187–196. doi:10.1016/S0378-5173(01)00675-5
Lazaridou A, Duta D, Papageorgiou M, Belc N, Biliaderis CG (2007) Effects of hydrocolloids on dough rheology and bread quality parameters in gluten-free formulations. J Food Eng 79(3):1033–1047. doi:10.1016/j.jfoodeng.2006.03.032
Mackley MR, Tock C, Anthony R, Butler SA, Chapman G, Vadillo DC (2013) The rheology and processing behavior of starch and gum-based dysphagia thickeners. J Rheol 57(6):1533–1553. doi:10.1122/1.4820494
Macosko CW, Ocansey MA, Winter HH (1982) Steady planar extension with lubricated dies. J Nonnewton Fluid Mech 11(3–4):301–316. doi:10.1016/0377-0257(82)80037-2
Mao Y, McClements DJ (2011) Modulation of bulk physicochemical properties of emulsions by hetero-aggregation of oppositely charged protein-coated lipid droplets. Food Hydrocolloids 25(5):1201–1209. doi:10.1016/j.foodhyd.2010.11.007
Mao Y, McClements DJ (2012a) Fabrication of functional micro-clusters by heteroaggregation of oppositely charged protein-coated lipid droplets. Food Hydrocolloids 27(1):80–90. doi:10.1016/j.foodhyd.2011.08.013
Mao Y, McClements DJ (2012b) Modulation of emulsion rheology through electrostatic heteroaggregation of oppositely charged lipid droplets: influence of particle size and emulsifier content. J Colloid Interface Sci 380(1):60–66. doi:10.1016/j.jcis.2012.05.007
Morrison FA (2001) Understanding rheology. Oxford University Press, New York
Munstedt H, Stary Z (2013) Steady states in extensional flow of strain hardening polymer melts and the uncertainties of their determination. J Rheol 57(4):1065–1077. doi:10.1122/1.4803932
Nelson B (2003) Capillary rheometry. In: Lobo HB, Bonilla JV (eds) Handbook in plastics analysis. Marcel Dekker, New York
Ober TJ, Haward SJ, Pipe CJ, Soulages J, McKinley GH (2013) Microfluidic extensional rheometry using a hyperbolic contraction geometry. Rheol Acta 52(6):529–546. doi:10.1007/s00397-013-0701-y
Olmsted SS, Meyn LA, Rohan LC, Hillier SL (2003) Glycosidase and proteinase activity of anaerobic gram-negative bacteria isolated from women with bacterial vaginosis. Sex Transm Dis 30(3):257–261
Padmanabhan M, Kasehagen LJ, Macosko C (1996) Transient extensional viscosity from a rotational shear rheometer using fiber-windup technique. J Rheol 40(4):473–481. doi:10.1122/1.550792
Parojcic J, Vasiljevic D, Ibric S, Djuric Z (2008) Tablet disintegration and drug dissolution in viscous media: paracetamol IR tablets. Int J Pharm 355(1–2):93–99
Pedersen PB, Vilmann P, Bar-Shalom D, Müllertz A, Baldursdottir S (2013) Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities. Eur J Pharm Biopharm 85(3):958–965. doi:10.1016/j.ejpb.2013.05.007
Pipe CJ, Majmudar TS, McKinley GH (2008) High shear rate viscometry. Rheol Acta 47(5–6):621–642. doi:10.1007/s00397-008-0268-1
Radwan A, Amidon GL, Langguth P (2012) Mechanistic investigation of food effect on disintegration and dissolution of BCS class III compound solid formulations: the importance of viscosity. Biopharm Drug Dispos 33(7):403–416. doi:10.1002/bdd.1798
Raphaelides SN, Gioldasi A (2005) Elongational flow studies of set yogurt. J Food Eng 70(4):538–545. doi:10.1016/j.jfoodeng.2004.10.008
Rubin BK (2007) Mucus structure and properties in cystic fibrosis. Paediatr Respir Rev 8(1):4–7. doi:10.1016/j.prrv.2007.02.004
Saiki Y, Prestidge CA, Horn RG (2007) Effects of droplet deformability on emulsion rheology. Colloids Surfaces A 299 (1–3):65-72. doi:http://dx.doi.org/10.1016/j.colsurfa.2006.11.022
Schmitt C, Kolodziejczyk E (2009) Gums and stabilizers for the food industry, vol 15. Royal Society of Chemistry, Cambridge, UK
Sentmanat ML (2004) Miniature universal testing platform: from extensional melt rheology to solid-state deformation behavior. Rheol Acta 43(6):657–669. doi:10.1007/s00397-004-0405-4
Sokolovskaya E, Barner L, Braese S (2014) Lahann J (2014) Synthesis and On-Demand Gelation of Multifunctional Poly(ethylene glycol)-Based Polymers. Macromol Rapid Commun Macromol Rapid Commun 35(8):780–786
Son WK, Youk JH, Lee TS, Park WH (2004) The effects of solution properties and polyelectrolyte on electrospinning of ultrafine poly(ethylene oxide) fibers. Polymer 45(9):2959–2966. doi:10.1016/j.polymer.2004.03.006
Sridhar T, Tirtaatmadja V, Nguyen DA, Gupta RK (1991) Measurement of extensional viscosity of polymer-solutions. J Nonnewton Fluid Mech 40(3):271–280. doi:10.1016/0377-0257(91)87012-M
Stadler FJ, Friedrich T, Kraus K, Tieke B, Bailly C (2013) Elongational rheology of NIPAM-based hydrogels. Rheol Acta 52(5):413–423. doi:10.1007/s00397-013-0690-x
Stokes JR, Davies GA (2007) Viscoelasticity of human whole saliva collected after acid and mechanical stimulation. Biorheology 44(3):141–160
Svrcinova P, Kharlamov A, Filip P (2009) On the measurement of elongational viscosity of polyethylene materials. Acta Technica 54:49–57
Venerus DC, Kompani M, Bernstein B (2000) Equibiaxial extensional flow of polymer melts via lubricated squeezing flow. II. Flow modeling. Rheol Acta 39(6):574–582. doi:10.1007/s003970000107
Vinod KR, Vasa S, Sandhya S (2010) Emerging trends in pharmaceutical polymers. Pharm Lett 2(1):172–180
Vlachopoulos J, Strutt D (2003) The role of rheology in polymer extrusion. Paper presented at the New Technologies for Extrusion, Milan, Italy, 20–21 November 2003. http://www.polydynamics.com/Rheology.pdf
Wagner MH, Rolón-Garrido VH (2012) Constant force elongational flow of polymer melts: Experiment and modelling (1978-present). J Rheol 56(5):1279. doi:10.1122/1.4732157
Wang Y-Y, Lai SK, Ensign LM, Zhong W, Cone R, Hanes J (2013) The microstructure and bulk rheology of human cervicovaginal mucus are remarkably resistant to changes in pH. Biomacromolecules 14(12):4429–4435. doi:10.1021/bm401356q
Warburton B, Davis SS (1969) The oscillatory testing of pharmaceutical semi-solids using a transfer function analyser. Rheol Acta 8(2):205–214. doi:10.1007/BF01984660
Wine JJ, Joo NS (2004) Submucosal glands and airway defense. Proc Am Thorac Soc 1(1):47–53. doi:10.1513/pats.2306015
Yovanoudi M, Dimitreli G, Raphaelides SN, Antoniou KD (2013) Flow behavior studies of kefir type systems. J Food Eng 118(1):41–48. doi:10.1016/j.jfoodeng.2013.03.036
Yu T, Malcolm K, Woolfson D, Jones DS, Andrews GP (2011) Vaginal gel drug delivery systems: understanding rheological characteristics and performance. Expert Opin Drug Delivery 8(10):1309–1322. doi:10.1517/17425247.2011.600119
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Aho, J., Hvidt, S., Baldursdottir, S. (2016). Rheology in Pharmaceutical Sciences. In: Müllertz, A., Perrie, Y., Rades, T. (eds) Analytical Techniques in the Pharmaceutical Sciences. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-4029-5_23
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