Mucoadhesion and Characterization of Mucoadhesive Properties



Mucoadhesive dosage forms may improve both in vitro and in vivo performance of products due to their propensity to enhance the retention of the dosage form at the site of application. The appropriate and reliable characterization of mucoadhesive systems is crucial to enable the identification of the appropriate formulations for in vivo use. In this chapter, the basic concepts of mucoadhesion and mucin structure are introduced. In addition, we present both in vitro and in vivo methods utilized for measurement of mucoadhesion including tensile and flow techniques. Despite the availability of several reported methods to characterize mucoadhesion, the mechanism of mucoadhesion is still insufficiently understood, and a universal technique for the measurement of mucoadhesion of dosage forms has not, as yet, been developed.


Mucin Mucoadhesion Mucoadhesive characterization Tensile Flow 


  1. 1.
    Kinloch A. The science of adhesion. J Mater Sci. 1982;17(3):617–51.Google Scholar
  2. 2.
    Park K, Robinson JR. Bioadhesive polymers as platforms for oral-controlled drug delivery: method to study bioadhesion. Int J Pharm. 1984;19(2):107–27.Google Scholar
  3. 3.
    Leung S-HS, Robinson JR. The contribution of anionic polymer structural features to mucoadhesion. J Control Release. 1988;5(3):223–31.Google Scholar
  4. 4.
    Smart JD. The basics and underlying mechanisms of mucoadhesion. Adv Drug Deliv Rev. 2005;57(11):1556–68.PubMedGoogle Scholar
  5. 5.
    Andrews GP, Laverty TP, Jones DS. Mucoadhesive polymeric platforms for controlled drug delivery. Eur J Pharm Biopharm. 2009;71(3):505–18.PubMedGoogle Scholar
  6. 6.
    Park K. A new approach to study mucoadhesion: colloidal gold staining. Int J Pharm. 1989;53(3):209–17.Google Scholar
  7. 7.
    Bernkop-Schnürch A, Steininger S. Synthesis and characterisation of mucoadhesive thiolated polymers. Int J Pharm. 2000;194(2):239–47.PubMedGoogle Scholar
  8. 8.
    Khutoryanskiy VV. Advances in mucoadhesion and mucoadhesive polymers. Macromol Biosci. 2011;11(6):748–64.PubMedGoogle Scholar
  9. 9.
    Scrivener CA, Schantz CW. Penicillin; new methods for its use in dentistry. J Am Dent Assoc. 1947;35(9):644–7.PubMedGoogle Scholar
  10. 10.
    Baloglu E, Senyigit ZA, Karavana SY, Bernkop-Schnürch A. Strategies to prolong the intravaginal residence time of drug delivery systems. J Pharm Pharm Sci. 2009;12(3):312–36.PubMedGoogle Scholar
  11. 11.
    Allen A. Structure and function of gastrointestinal mucus. In: Johnson L, editor. Physiology of the gastroenterology tract. New York: Raven; 1981. pp. 617–39.Google Scholar
  12. 12.
    Moran DT, Rowley JC 3rd, Jafek BW, Lovell MA. The fine structure of the olfactory mucosa in man. J Neurocytol. 1982;11(5):721–46.PubMedGoogle Scholar
  13. 13.
    Burkitt HG, Young B, Heath JW. Histologia Funcional. 3rd ed. Rio de Janeiro: Guanabara Koogan; 1994.Google Scholar
  14. 14.
    Neutra M, Forstner J. Gastrointestinal mucus: synthesis, secretion, and function. In: Johnson L, editor. Physiology of the gastrointestinal tract. New York: Raven; 1987. pp. 975–1009.Google Scholar
  15. 15.
    Bansil R, Turner BS. Mucin structure, aggregation, physiological functions and biomedical applications. Curr Opin Colloid Interface Sci. 2006;11(2):164–70.Google Scholar
  16. 16.
    Stefan R-I, Draghici I, Baiulescu G-E. Determination of urinary oxalate using oxalate-selective membrane electrodes. Sens Actuators B Chem. 2000;65(1):250–2.Google Scholar
  17. 17.
    Gipson IK, Ho SB, Spurr-Michaud SJ, Tisdale AS, Zhan Q, Torlakovic E, Pudney J, Anderson DJ, Toribara NW, Hill J. Mucin genes expressed by human female reproductive tract epithelia. Biol Reprod. 1997;56(4):999–1011.PubMedGoogle Scholar
  18. 18.
    Dasari S, Pereira L, Reddy AP, Michaels JE, Lu X, Jacob T, Thomas A, Rodland M, Roberts CT Jr, Gravett MG, Nagalla SR. Comprehensive proteomic analysis of human cervical-vaginal fluid. J Proteome Res. 2007;6(4):1258–68.PubMedGoogle Scholar
  19. 19.
    Chiappin S, Antonelli G, Gatti R, De Palo EF. Saliva specimen: a new laboratory tool for diagnostic and basic investigation. Clin Chim Acta. 2007;383(1–2):30–40.PubMedGoogle Scholar
  20. 20.
    Spurr-Michaud S, Argueso P, Gipson I. Assay of mucins in human tear fluid. Exp Eye Res. 2007;84(5):939–50.PubMedCentralPubMedGoogle Scholar
  21. 21.
    Toribara NW, Roberton AM, Ho SB, Kuo WL, Gum E, Hicks JW, Gum JR Jr, Byrd JC, Siddiki B, Kim YS. Human gastric mucin. Identification of a unique species by expression cloning. J Biol Chem. 1993;268(8):5879–85.PubMedGoogle Scholar
  22. 22.
    Marriot C, Gregory N. Mucus physiology and pathology. In: Lenaerts V, Gurny R, editor. Bioadhesive drug delivery systems. Boca Raton: CRC; 1990. pp. 1–24.Google Scholar
  23. 23.
    Mortazavi S, Carpenter B, Smart J. A comparative study on the role played by mucus glycoproteins in the rheological behaviour of the mucoadhesive/mucosal interface. Int J Pharm. 1993;94(1):195–201.Google Scholar
  24. 24.
    Mortazavi SA, Smart JD. An investigation into the role of water movement and mucus gel dehydration in mucoadhesion. J Control Release. 1993;25(3):197–203.Google Scholar
  25. 25.
    Rossi S, Bonferoni M, Ferrari F, Bertoni M, Caramella C. Characterization of mucin interaction with three viscosity grades of sodium carboxymethylcellulose. Comparison between rheological and tensile testing. Eur J Pharm Sci. 1996;4(3):189–96.Google Scholar
  26. 26.
    Edsman K, Hägerström H. Pharmaceutical applications of mucoadhesion for the non-oral routes. J Pharm Pharmacol. 2005;57(1):3–22.PubMedGoogle Scholar
  27. 27.
    Capra RH, Baruzzi AM, Quinzani LM, Strumia MC. Rheological, dielectric and diffusion analysis of mucin/carbopol matrices used in amperometric biosensors. Sens Actuators B Chem. 2007;124(2):466–76.Google Scholar
  28. 28.
    Yang X, Robinson JR. Bioadhesion in mucosal drug delivery. In: Okano T, editor. Biorelated polymers and gels: controlled release and applications in biomedical engineering. San Diego: Academic;1998. pp. 135–192.Google Scholar
  29. 29.
    Riley RG, Smart JD, Tsibouklis J, Dettmar PW, Hampson F, Davis JA, Kelly G, Wilber WR. An investigation of mucus/polymer rheological synergism using synthesised and characterised poly(acrylic acid)s. Int J Pharm. 2001;217(1–2):87–100.PubMedGoogle Scholar
  30. 30.
    Fiebrig I, Harding SE, Rowe AJ, Hyman SC, Davis SS. Transmission electron microscopy studies on pig gastric mucin and its interactions with chitosan. Carbohydr Polym. 1995;28(3):239–44.Google Scholar
  31. 31.
    Van Klinken BJ, Dekker J, Büller HA, Einerhand AW. Mucin gene structure and expression: protection vs. adhesion. Am J Physiol. 1995;269(5 Pt 1):G613–27.Google Scholar
  32. 32.
    Bell S, Xu G, Khatri I, Wang R, Rahman S, Forstner J. N-linked. oligosaccharides play a role in disulphide-dependent dimerization of intestinal mucin Muc2. Biochem J. 2003;373:893–900.PubMedGoogle Scholar
  33. 33.
    Davies JM, Viney C. Water-mucin phases: conditions for mucus liquid crystallinity. Thermochim Acta. 1998;315(1):39–49.Google Scholar
  34. 34.
    Perez-Vilar J, Hill RL. Mucin family of glycoproteins. In: Lennarz WJ, Lane MD, editors. Encyclopedia of biological chemistry. Oxford: Academic/Elsevier; 2004. pp. 758–764.Google Scholar
  35. 35.
    Bettelheim FA, Hashimoto Y, Pigman W. Light-scattering studies of bovine submaxillary mucin. Biochim Biophys Acta. 1962;63:235–42.PubMedGoogle Scholar
  36. 36.
    Bettelheim F, Scheinthal B. Light scattering of mucins in concentrated solutions. J Polym Sci C Polym Symp. 1970;30:117–24Google Scholar
  37. 37.
    Harding SE. The macrostructure of mucus glycoproteins in solution. Adv Carbohydr Chem Biochem. 1989;47:345–81.PubMedGoogle Scholar
  38. 38.
    Bansil R, Stanley E, LaMont JT. Mucin biophysics. Annu Rev Physiol. 1995;57:635–57.PubMedGoogle Scholar
  39. 39.
    Bastardo L, Claesson P, Brown W. Interactions between mucin and alkyl sodium sulfates in solution. A light scattering study. Langmuir. 2002;18(10):3848–53.Google Scholar
  40. 40.
    Dua VK, Rao BN, Wu SS, Dube VE, Bush CA. Characterization of the oligosaccharide alditols from ovarian cyst mucin glycoproteins of blood group A using high pressure liquid chromatography (HPLC) and high field 1H NMR spectroscopy. J Biol Chem. 1986;261(4):1599–1608.PubMedGoogle Scholar
  41. 41.
    Naganagowda G, Gururaja T, Satyanarayana J, Levine M. NMR analysis of human salivary mucin (MUC7) derived O-linked model glycopeptides: comparison of structural features and carbohydrate-peptide interactions. J Peptide Res. 1999;54(4):290–310.Google Scholar
  42. 42.
    Thomsson KA, Prakobphol A, Leffler H, Reddy MS, Levine MJ, Fisher SJ, Hansson GC. The salivary mucin MG1 (MUC5B) carries a repertoire of unique oligosaccharides that is large and diverse. Glycobiology. 2002;12(1):1–14.PubMedGoogle Scholar
  43. 43.
    Kinarsky L, Suryanarayanan G, Prakash O, Paulsen H, Clausen H, Hanisch FG, Hollingsworth MA, Sherman S. Conformational studies on the MUC1 tandem repeat glycopeptides. implication for the enzymatic O-glycosylation of the mucin protein core. Glycobiology. 2003;13(12):929–39.PubMedGoogle Scholar
  44. 44.
    Paz HB, Tisdale AS, Danjo Y, Spurr-Michaud SJ, Argueso P, Gipson IK. The role of calcium in mucin packaging within goblet cells. Exp Eye Res. 2003;77(1):69–75.PubMedGoogle Scholar
  45. 45.
    McMaster TJ, Berry M, Corfield AP, Miles MJ. Atomic force microscopy of the submolecular architecture of hydrated ocular mucins. Biophys J. 1999;77(1):533–41.PubMedCentralPubMedGoogle Scholar
  46. 46.
    Hong Z, Chasan B, Bansil R, Turner BS, Bhaskar KR, Afdhal NH. Atomic force microscopy reveals aggregation of gastric mucin at low pH. Biomacromolecules. 2005;6(6):3458–66.PubMedGoogle Scholar
  47. 47.
    Round AN, McMaster TJ, Miles MJ, Corfield AP, Berry M. The isolated MUC5AC gene product from human ocular mucin displays intramolecular conformational heterogeneity. Glycobiology. 2007;17(6):578–85.PubMedGoogle Scholar
  48. 48.
    Haugstad KE, Gerken TA, Stokke BT, Dam TK, Brewer CF, Sletmoen M. Enhanced self-association of mucins possessing the T and Tn carbohydrate cancer antigens at the single-molecule level. Biomacromolecules. 2012;13(5):1400–9.PubMedCentralPubMedGoogle Scholar
  49. 49.
    Young T. An essay on the cohesion of fluids. Philos Trans R Soc Lond. 1805;95:65–87.Google Scholar
  50. 50.
    Mikos A, Peppas N. Systems for controlled release of drugs. V: bioadhesive systems. STP Pharma Sci. 1986;2(19):705–15.Google Scholar
  51. 51.
    Gandhi R, Robinson JR. Bioadhesion in drug delivery. Indian J Pharm Sci. 1988;50(3):145–52.Google Scholar
  52. 52.
    Gu JM, Robinson JR, Leung SH. Binding of acrylic polymers to mucin/epithelial surfaces: structure-property relationships. Crit Rev Ther Drug Carrier Syst. 1988;5(1):21–67.PubMedGoogle Scholar
  53. 53.
    Jiménez-Castellanos MR, Zia H, Rhodes C. Mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 1993;19(1–2):143–94.Google Scholar
  54. 54.
    Shaikh R, Raj Singh TR, Garland MJ, Woolfson AD, Donnelly RF. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011;3(1):89–100.PubMedCentralPubMedGoogle Scholar
  55. 55.
    Shafrin EG, Zisman WA. Constitutive relations in the wetting of low energy surfaces and the theory of the retraction method of preparing monolayers1. J Phys Chem. 1960;64(5):519–24.Google Scholar
  56. 56.
    Pritchard WH. The role of hydrogen bonding in adhesion. In: Alder D, editor. Aspects of adhesion. London: London University Press; 1970. pp. 11–23.Google Scholar
  57. 57.
    Krishnakumar P. Wetting and spreading phenomena, physics 563 Phase Transitions and the Renormalization Group. Urbana-Champaign: University of Illinois; 2010.Google Scholar
  58. 58.
    Peppas NA, Sahlin JJ. Hydrogels as mucoadhesive and bioadhesive materials: a review. Biomaterials. 1996;17(16):1553–61.PubMedGoogle Scholar
  59. 59.
    Packham DE. The mechanical theory of adhesion—a seventy year perspective and its current status. In: Van Ooij WJ, Anderson JHR, editors. First international congress on adhesion science and technology. The Netherlands: VSP BV; 1998. pp. 81–108.Google Scholar
  60. 60.
    Carvalho FC, Bruschi ML, Evangelista RC, Gremião MPD. Mucoadhesive drug delivery systems. Braz J Pharm Sci. 2010;46(1):1–17.Google Scholar
  61. 61.
    Lee JW, Park JH, Robinson JR. Bioadhesive-based dosage forms: the next generation. J Pharm Sci. 2000;89(7):850–66.PubMedGoogle Scholar
  62. 62.
    Derjaguin B, Aleinikova I, Toporov YP. On the role of electrostatic forces in the adhesion of polymer particles to solid surfaces. Powder Technol. 1969;2(3):154–8.Google Scholar
  63. 63.
    Derjaguin B, Toporov YP, Muller V, Aleinikova I. On the relationship between the electrostatic and the molecular component of the adhesion of elastic particles to a solid surface. J Colloid Interface Sci. 1977;58(3):528–33.Google Scholar
  64. 64.
    Chickering DE 3rd, Mathiowitz E. Definitions, mechanisms, and theories of bioadhesion. In: Mathiowitz E, Chickering DEIII, Lehr C-M, editors. Bioadhesive drug delivery systems: fundamentals, novel approaches, and development. New York: Dekker; 1999. pp. 1–10.Google Scholar
  65. 65.
    Dodou D, Breedveld P, Wieringa PA. Mucoadhesives in the gastrointestinal tract: revisiting the literature for novel applications. Eur J Pharm Biopharm. 2005;60(1):1–16.PubMedGoogle Scholar
  66. 66.
    Ahagon A, Gent A. Effect of interfacial bonding on the strength of adhesion. J Polym Sci Polym Phys Ed. 1975;13(7):1285–300.Google Scholar
  67. 67.
    Vasir JK, Tambwekar K, Garg S. Bioadhesive microspheres as a controlled drug delivery system. Int J Pharm. 2003;255(1–2):13–32.PubMedGoogle Scholar
  68. 68.
    Huang Y, Leobandung W, Foss A, Peppas NA. Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces. J Control Release. 2000;65(1–2):63–71.PubMedGoogle Scholar
  69. 69.
    Hägerström H, Edsman K, Strømme M. Low-frequency dielectric spectroscopy as a tool for studying the compatibility between pharmaceutical gels and mucous tissue. J Pharm Sci. 2003;92(9):1869–81.PubMedGoogle Scholar
  70. 70.
    Madsen F, Eberth K, Smart JD. A rheological assessment of the nature of interactions between mucoadhesive polymers and a homogenised mucus gel. Biomaterials. 1998;19(11–12):1083–92.Google Scholar
  71. 71.
    Hagesaether E, Sande SA. In vitro measurements of mucoadhesive properties of six types of pectin. Drug Dev Ind Pharm. 2007;33(4):417–25.PubMedGoogle Scholar
  72. 72.
    Accili D, Menghi G, Bonacucina G, Martino PD, Palmieri GF. Mucoadhesion dependence of pharmaceutical polymers on mucosa characteristics. Eur J Pharm Sci. 2004;22(4):225–34.PubMedGoogle Scholar
  73. 73.
    Smart JD, Kellaway IW, Worthington HE. An in-vitro investigation of mucosa-adhesive materials for use in controlled drug delivery. J Pharm Pharmacol. 1984;36(5):295–9.PubMedGoogle Scholar
  74. 74.
    Chen J, Cyr GN. Compositions producing adhesion through hydration. In: Manly RS, editor. Adhesion in biological systems. New York: Academic;1970. pp. 163–81.Google Scholar
  75. 75.
    Nair AB, Kumria R, Harsha S, Attimarad M, Al-Dhubiab BE, Alhaider IA. In vitro techniques to evaluate buccal films. J Control Release. 2013;166(1):10–21.PubMedGoogle Scholar
  76. 76.
    Ch’ng HS, Park H, Kelly P, Robinson JR. Bioadhesive polymers as platforms for oral controlled drug delivery II: synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers. J Pharm Sci. 1985;74(4):399–405.PubMedGoogle Scholar
  77. 77.
    Gandhi RB, Robinson JR. Oral cavity as a site for bioadhesive drug delivery. Adv Drug Deliv Rev. 1994;13(1):43–74.Google Scholar
  78. 78.
    Abruzzo A, Bigucci F, Cerchiara T, Cruciani F, Vitali B, Luppi B. Mucoadhesive chitosan/gelatin films for buccal delivery of propranolol hydrochloride. Carbohydr Polym. 2012;87(1):581–8.Google Scholar
  79. 79.
    Gupta A, Garg S, Khar RK. Measurement of bioadhesion strength of mucoadhesive buccal tablet design of an in vitro assembly. Indian Drugs. 1992;30:152–5.Google Scholar
  80. 80.
    Pendekal MS, Tegginamat PK. Formulation and evaluation of a bioadhesive patch for buccal delivery of tizanidine. Acta Pharm Sin B. 2012;2(3):318–24.Google Scholar
  81. 81.
    Qi H, Chen W, Huang C, Li L, Chen C, Li W, Wu C. Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin. Int J Pharm. 2007;337(1–2):178–87.PubMedGoogle Scholar
  82. 82.
    Choi H-G, Jung J-H, Ryu J-M, Yoon S-J, Oh Y-K, Kim C-K. Development of in situ-gelling and mucoadhesive acetaminophen liquid suppository. Int J Pharm. 1998;165(1):33–44.Google Scholar
  83. 83.
    Hertzog BA, Mathiowitz E. Novel magnetic technique to measure bioadhesion. In: Mathiowitz E, Chickering DE III, Lehr C-M, editor. Bioadhesive drug delivery systems: fundamentals, novel approaches, and development. Boca Raton: CRC Press; 1999. pp. 147–174.Google Scholar
  84. 84.
    Tobyn MJ, Johnson JR, Dettmar PW. Factors affecting in vitro gastric mucoadhesion. I: test conditions and instrumental parameters. Eur J Pharm Biopharm. 1995;41(4):235–41.Google Scholar
  85. 85.
    Jones DS, Woolfson AD, Djokic J. Texture profile analysis of bioadhesive polymeric semisolids mechanical characterization and investigation of interactions between formulation components. J Appl Polym Sci. 1996;61(12):2229–34.Google Scholar
  86. 86.
    Jones DS, Woolfson AD, Djokic J, Coulter WA. Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharm Res. 1996;13(11):1734–8.PubMedGoogle Scholar
  87. 87.
    Jones DS, Woolfson AD, Brown AF. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers. Int J Pharm. 1997;151(2):223–33.Google Scholar
  88. 88.
    Teng C, Ho N. Mechanistic studies in the simultaneous flow and adsorption of polymer-coated latex particles on intestinal mucus I: methods and physical model development. J Control Release. 1987;6(1):133–49.Google Scholar
  89. 89.
    Rao K, Buri P. A novel in situ method to test polymers and coated microparticles for bioadhesion. Int J Pharm. 1989;52(3):265–70.Google Scholar
  90. 90.
    Grabovac V, Guggi D, Bernkop-Schnürch A. Comparison of the mucoadhesive properties of various polymers. Adv Drug Deliv Rev. 2005;57(11):1713–23.PubMedGoogle Scholar
  91. 91.
    Duchê ne D, Ponchel G. Principle and investigation of the bioadhesion mechanism of solid dosage forms. Biomaterials. 1992;13(10):709–14.Google Scholar
  92. 92.
    Kast CE, Bernkop-Schnürch A. Thiolated polymers-thiomers: development and in vitro evaluation of chitosan-thioglycolic acid conjugates. Biomaterials. 2001;22(17):2345–52.PubMedGoogle Scholar
  93. 93.
    Kast CE, Valenta C, Leopold M, Bernkop-Schnürch A. Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole. J Control Release. 2002;81(3):347–54.PubMedGoogle Scholar
  94. 94.
    Nakamura F, Ohta R, Machida Y, Nagai T. In vitro and in vivo nasal mucoadhesion of some water-soluble polymers. Int J Pharm. 1996;134(1):173–81.Google Scholar
  95. 95.
    Bachhav YG, Patravale VB. Microemulsion based vaginal gel of fluconazole: formulation in vitro and in vivo evaluation. Int J Pharm. 2009;365(1–2):175–9.PubMedGoogle Scholar
  96. 96.
    Setnikar I, Fantelli S. Liquefaction time of rectal suppositories. J Pharm Sci. 1962;51:566–71.PubMedGoogle Scholar
  97. 97.
    Alam MA, Ahmad FJ, Khan ZI, Khar RK, Ali M. Development and evaluation of acid-buffering bioadhesive vaginal tablet for mixed vaginal infections. AAPS PharmSciTech. 2007;8(4):E109.Google Scholar
  98. 98.
    Ahmad FJ, Alam MA, Khan ZI, Khar RK, Ali M. Development and in vitro evaluation of an acid buffering bioadhesive vaginal gel for mixed vaginal infections. Acta Pharm. 2008;58(4):407–19.PubMedGoogle Scholar
  99. 99.
    Mahrag Tur K, Ch’ng H-S. Evaluation of possible mechanism(s) of bioadhesion. Int J Pharm. 1998;160(1):61–74.Google Scholar
  100. 100.
    Yu T, Malcolm K, Woolfson D, Jones DS, Andrews GP. Vaginal gel drug delivery systems: understanding rheological characteristics and performance. Expert Opin Drug Deliv. 2011;8(10):1309–22.PubMedGoogle Scholar
  101. 101.
    Cross MM. Rheology of non-Newtonian fluids: a new flow equation for pseudoplastic systems. J Colloid Sci. 1965;20(5):417–37.Google Scholar
  102. 102.
    Bird RB, Dai G, Yarusso BJ. The rheology and flow of viscoplastic materials. Rev Chem Eng. 1983;1(1):1–70.Google Scholar
  103. 103.
    Banerjee R, Bellare JR, Puniyani R. Effect of phospholipid mixtures and surfactant formulations on rheology of polymeric gels, simulating mucus, at shear rates experienced in the tracheobronchial tree. Biochem Eng J. 2001;7(3):195–200.Google Scholar
  104. 104.
    Liu H-H, Li L, Birkholzer J. Unsaturated properties for non-Darcian water flow in clay. J Hydrol. 2012;430:173–8.Google Scholar
  105. 105.
    Barnes HA, Hutton JF, Walters K. An Introduction to Rheology. Amsterdam:Elsevier; 1989.Google Scholar
  106. 106.
    Deem DE. Rheology of dispersed systems. In: Lieberman HA, Rieger MM, Banker GS, editors. Pharmaceutical dosage forms: disperse systems. New York:Marcel Dekker; 1988.Google Scholar
  107. 107.
    Giboreau A, Cuvelier G, Launay B. Rheological behaviour of three biopolymer/water systems, with emphasis on yield stress and viscoelastic properties. J Texture Stud. 1994;25(2):119–38.Google Scholar
  108. 108.
    Jones DS, Bruschi ML, de Freitas O, Gremião MP, Lara EH, Andrews GP. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. Int J Pharm. 2009;372(1–2):49–58.PubMedGoogle Scholar
  109. 109.
    Richardson JL, Whetstone J, Fisher AN, Watts P, Farraj NF, Hinchcliffe M, Benedetti L, Illum L. Gamma-scintigraphy as a novel method to study the distribution and retention of a bioadhesive vaginal delivery system in sheep. J Control Release. 1996;42(2):133–42.Google Scholar
  110. 110.
    Brown J, Hooper G, Kenyon CJ, Haines S, Burt J, Humphries JM, Newman SP, Davis SS, Sparrow RA, Wilding IR. Spreading and retention of vaginal formulations in post-menopausal women as assessed by gamma scintigraphy. Pharm Res. 1997;14(8):1073–8.PubMedGoogle Scholar
  111. 111.
    Witter FR, Barditch-Crovo P, Rocco L, Trapnell CB. Duration of vaginal retention and potential duration of antiviral activity for five nonoxynol-9 containing intravaginal contraceptives. Int J Gynaecol Obstet. 1999;65(2):165–70.PubMedGoogle Scholar
  112. 112.
    Vermani K, Garg S, Zaneveld LJ. Assemblies for in vitro measurement of bioadhesive strength and retention characteristics in simulated vaginal environment. Drug Dev Ind Pharm. 2002;28(9):1133–46.Google Scholar
  113. 113.
    Chatterton BE, Penglis S, Kovacs JC, Presnell B, Hunt B. Retention and distribution of two 99mTc-DTPA labelled vaginal dosage forms. Int J Pharm. 2004;271(1–2):137–43.PubMedGoogle Scholar
  114. 114.
    Albrecht K, Greindl M, Kremser C, Wolf C, Debbage P, Bernkop-Schnürch A. Comparative in vivo mucoadhesion studies of thiomer formulations using magnetic resonance imaging and fluorescence detection. J Control Release. 2006;115(1):78–84.PubMedGoogle Scholar
  115. 115.
    Braga PC, Dal Sasso M, Spallino A, Sturla C, Culici M. Vaginal gel adsorption and retention by human vaginal cells. Visual analysis by means of inorganic and organic markers. Int J Pharm. 2009;373(1–2):10–5.PubMedGoogle Scholar
  116. 116.
    Poelvoorde N, Verstraelen H, Verhelst R, Saerens B, De Backer E, dos Santos SGL, Vervaet C, Vaneechoutte M. De Boeck F, Van Bortel L, Temmerman M, Remon JP. In vivo evaluation of the vaginal distribution and retention of a multi-particulate pellet formulation. Eur J Pharm Biopharm. 2009;73(2):280–4.Google Scholar
  117. 117.
    Mehta S, Verstraelen H, Peremans K, Villeirs G, Vermeire S, De Vos F, Mehuys E, Remon JP, Vervaet C. Vaginal distribution and retention of a multiparticulate drug delivery system, assessed by gamma scintigraphy and magnetic resonance imaging. Int J Pharm. 2012;426(1–2):44–53.PubMedGoogle Scholar
  118. 118.
    das Neves J, Bahia MF. Gels as vaginal drug delivery systems. Int J Pharm. 2006;318(1–2):1–14.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.School of PharmacyThe Queen’s University of BelfastBelfastUK

Personalised recommendations