Skip to main content
SpringerLink
Log in

In Vitro Physical and Imaging Techniques to Evaluate Drug Release Mechanisms from Hydrophilic Matrix Tablets

  • Chapter
  • First Online:
Hydrophilic Matrix Tablets for Oral Controlled Release

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 16))

Abstract

Drug release from hydrophilic tablets is controlled by the physical changes in tablet structure associated with hydration, gelling, swelling and eventual dilution of the drug and polymer within the tablet. The rate-controlling processes are physical rather than chemical and are therefore well suited to being followed using physical and imaging methods. This chapter provides an introduction of how modern imaging and more established in vitro techniques have been applied to the characterisation of hydrophilic matrices. It details how the rapid advances in instrumentation and characterisation technology are increasingly providing pharmaceutical scientists with new opportunities to gain unrivalled information in many aspects of the behaviour of hydrophilic matrices and their related performance characteristics.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Timmins P, Delargy AM, Minchom CM, Howard JR. Influence of some process variables on product properties for a hydrophilic matrix controlled release tablet. Eur J Pharm Biopharm. 1992;38(3):113–8.

    CAS  Google Scholar 

  2. Streubel A, Siepmann J, Dashevsky A, Bodmeier R. pH-independent release of a weakly basic drug from water-insoluble and -soluble matrix tablets. J Control Release. 2000;67:101–10.

    Article  PubMed  CAS  Google Scholar 

  3. Badawy SIF, Hussain MA. Microenvironmental pH modulation in solid dosage forms. J Pharm Sci. 2007;96(5):948–59.

    Article  PubMed  CAS  Google Scholar 

  4. Tatavarti AS, Mehta KA, Augsburger LL, Hoag SW. Influence of methacrylic and acrylic acid polymers on the release performance of weakly basic drugs from sustained release hydrophilic matrices. J Pharm Sci. 2004;93(9):2319–31.

    Article  PubMed  CAS  Google Scholar 

  5. Alderman DA. A review of cellulose ethers in hydrophilic matrices for oral controlled-release dosage forms. Int J Pharm Tech Prod Manuf. 1984;5:1–9.

    CAS  Google Scholar 

  6. Reynolds TD, Gehrke SH, Hussain AS, Shenouda LS. Polymer erosion and drug release characterization of hydroxypropyl methylcellulose matrices. J Pharm Sci. 1998;87(9):1115–23.

    Article  PubMed  CAS  Google Scholar 

  7. Williams HD, Ward R, Hardy IJ, Melia CD. The extended release properties of HPMC matrices in the presence of dietary sugars. J Control Release. 2009;138(3):251–9.

    Article  PubMed  CAS  Google Scholar 

  8. Melia CD. Hydrophilic matrix sustained-release systems based on polysaccharide carriers. Crit Rev Ther Drug Carrier Syst. 1991;8(4):395–421.

    PubMed  CAS  Google Scholar 

  9. Levina M, Palmer D, Rajabi-Siahboomi A. Evaluation of in vitro dissolution methods for the assessment of drug release from hydrophilic extended-release matrices based on polyethylene oxide. Drug Deliv Technol. 2010;10(5):18–23.

    CAS  Google Scholar 

  10. Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci. 1961;50:874–5.

    Article  PubMed  CAS  Google Scholar 

  11. Siepmann J, Peppas NA. Higuchi equation: derivation, applications, use and misuse. Int J Pharm. 2011;418:6–12.

    Article  PubMed  CAS  Google Scholar 

  12. Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropylmethylcellulose. Adv Drug Deliv Rev. 2012;64:163–74.

    Article  Google Scholar 

  13. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35.

    Article  CAS  Google Scholar 

  14. Rinaki E, Valsami G, Machera P. The power law can describe the ‘entire’ drug release curve from HPMC-based matrix tablets: a hypothesis. Int J Pharm. 2003;255:199–207.

    Article  PubMed  CAS  Google Scholar 

  15. Kiil S, Dam-Johansen K. Controlled drug delivery from swellable hydroxypropylmethylcelluslsoe matrices: model-based analysis of observed radial front movements. J Control Release. 2003;90(1):1–21.

    Article  PubMed  CAS  Google Scholar 

  16. Frenning G. Modelling drug release from inert matrix systems: from moving boundary to continuous field descriptions. Int J Pharm. 2011;418:88–99.

    Article  PubMed  CAS  Google Scholar 

  17. Kimber JA, Kazarian SG, Szěpánek F. Modelling of pharmaceutical tablet swelling and dissolution using discrete element method. Chem Eng Sci. 2012;69:394–403.

    Article  CAS  Google Scholar 

  18. Frenning G, Brohede U, Strømme M. Finite element analysis of the release of slowly dissolving drugs from cylindrical matrix systems. J Control Release. 2005;107:320–9.

    Article  PubMed  CAS  Google Scholar 

  19. Lamberti G, Galdi I, Barba AA. Controlled release from hydrogel-based solid matrices. A model accounting for water uptake, swelling and erosion. Int J Pharm. 2011;407:78–86.

    Article  PubMed  CAS  Google Scholar 

  20. Galdi I, Lamberti I. Drug release from matrix systems: analysis by finite element methods. Heat Mass Transfer. 2012;48:519–28.

    Article  CAS  Google Scholar 

  21. Siepmann J, Karout Y, Gehrke M, Penz FK, Siepmann F. Predicting drug release from HPMC/lactose tablets. Int J Pharm. 2013;441:826–34.

    Article  PubMed  CAS  Google Scholar 

  22. Xu Y, Jia Y, Wang Z, Wang Z. Mathematical modeling and finite element simulation of slow release of drugs using hydrogels as carriers with various drug concentration distributions. J Pharm Sci. 2013;102:1532–43.

    Article  PubMed  CAS  Google Scholar 

  23. Desai D, Paruchuri S, Wang J, Ha K, Chen W, Crison J. Quality by Design (QbD) approach in development of a higher strength extended release metformin hydrochloride tablets. Presented at the AAPS annual meeting, Washington, DC. 2011.

    Google Scholar 

  24. Colombo P, Bettini R, Santi P, De Ascentiis A, Peppas N. Analysis of the swelling and release mechanisms from drug delivery systems with emphasis on drug solubility and water transport. J Control Release. 1996;39:231–7.

    Article  CAS  Google Scholar 

  25. Hanley S, Brown J, Timmins P. Investigation into the potential for prodrug hydrolysis within a hydrated HPMC matrix. APS Pharm Sci Meeting, Edinburgh. 2013.

    Google Scholar 

  26. Bonferoni MC, Caramella C, Sangalli ME, Conte U, Hernandez RM, Pedraz JL. Rheological behaviour of hydrophilic polymers and drug release from erodible matrixes. J Control Release. 1992;18:205–12.

    Article  CAS  Google Scholar 

  27. Tahara K, Yamamoto K, Nishihata T. Overall mechanism behind matrix sustained release (SR) tablets prepared with hydroxypropylmethylcellulose 2910. J Control Release. 1995;35:59–66.

    Article  CAS  Google Scholar 

  28. Timmins P, Delargy AM, Howard JR. Optimization and characterization of a pH independent extended-release hydrophilic matrix tablet. Pharm Dev Technol. 1997;2(1):25–31.

    Article  PubMed  CAS  Google Scholar 

  29. Sung KC, Nixon PR, Skoug JW, Ju TR, Gao P, Topp EM, Patel MV. Effect of formulation variables on drug and polymer release from HPMC-based matrix tablets. Int J Pharm. 1996;142(1):53–60.

    Article  CAS  Google Scholar 

  30. Viriden A, Wittgren B, Andersson T, Larsson A. The effect of chemical heterogeneity of HPMC on polymer release from matrix tablets. Eur J Pharm Sci. 2009;36:392–400.

    Article  PubMed  CAS  Google Scholar 

  31. Ghori MU, Ginting G, Smith AM, Conway BR. Simultaneous quantification of drug release and erosion from hypromellose hydrophilic matrices. Int J Pharm. 2014;465:405–12.

    Article  PubMed  CAS  Google Scholar 

  32. Yang L, Johnson B, Fassihi R. Determination of continuous changes in the gel layer thickness of poly(ethylene oxide) and HPMC tablets undergoing hydration: a texture analysis study. Pharm Res. 1998;15(12):1902–6.

    Article  PubMed  CAS  Google Scholar 

  33. Pillay V, Fassihi R. A novel approach for constant rate delivery of highly soluble bioactives from a simple monolithic system. J Control Release. 2000;67:67–78.

    Article  PubMed  CAS  Google Scholar 

  34. Varma MVS, Kaushal AM, Garg S. Influence of micro-environmental pH on gel layer behavior and release of a basic drug from various hydrophilic matrices. J Control Release. 2005;103:499–510.

    Article  PubMed  CAS  Google Scholar 

  35. Baumgartner S, Pavli M, Kristl J. Effect of calcium ions on the gelling and drug release characteristics of xanthan matrix tablets. Eur J Pharm Biopharm. 2008;69:698–707.

    Article  PubMed  CAS  Google Scholar 

  36. Jamzad S, Tutunji L, Fassihi R. Analysis of macromolecular changes and drug release from hydrophilic matrix systems. Int J Pharm. 2005;292:75–85.

    Article  PubMed  CAS  Google Scholar 

  37. Melia CD, Binns JS, Davies MC. Polymer hydration and drug distribution within the gel layer of hydrophilic matrix devices during drug release. J Pharm Pharmacol. 1990;42:125.

    Article  Google Scholar 

  38. Melia CD, Rajabi-Siahboomi AR, Hodsdon AC, Adler J, Mitchell JR. Structure and behaviour of hydrophilic matrix sustained release dosage forms: 1. The origin and mechanism of formation of gas bubbles in the hydrated surface layer. Int J Pharm. 1993;100:263–9.

    Article  CAS  Google Scholar 

  39. Hodsdon AC, Mitchell JR, Davies MC, Melia CD. Structure and behaviour in hydrophilic matrix sustained release dosage forms: 3. The influence of pH on the sustained-release performance and internal gel structure of sodium alginate matrices. J Control Rel. 1995;33:143–52.

    Article  CAS  Google Scholar 

  40. Ashraf M, Iuorno VL, Coffin-Beach D, Anderson Evans C, Augsburger LL. A novel magnetic resonance (NMR) imaging method for measuring the water front penetration rate in hydrophilic polymer matrix capsule plugs and its role in drug release. Pharm Res. 1994;11:733–7.

    Article  PubMed  CAS  Google Scholar 

  41. Gao P, Meury RH. Swelling of hydroxypropyl methylcellulose matrix tablets. 1. Characterization of swelling using a novel optical imaging method. J Pharm Sci. 1996;85:725–31.

    Article  PubMed  CAS  Google Scholar 

  42. Mitchell K, Ford JL, Armstrong DJ, Elliott PNC, Hogan JE, Rostron C. The influence of drugs on the properties of gels and swelling characteristics of matrices containing methylcellulose or hydroxypropylmethylcellulose. Int J Pharm. 1993;100:165–73.

    Article  CAS  Google Scholar 

  43. Conte U, Maggi L. Modulation of the dissolution profiles from Geomatrix(R) multi-layer matrix tablets containing drugs of different solubility. Biomaterials. 1996;17:889.

    Article  PubMed  CAS  Google Scholar 

  44. Konrad R, Christ A, Zessin G, Cobet U. The use of ultrasound and penetrometer to characterize the advancement of swelling and eroding fronts in HPMC matrices. Int J Pharm. 1998;163:123–31.

    Article  CAS  Google Scholar 

  45. Colombo P. Swelling-controlled release in hydrogel matrices for oral route. Adv Drug Deliv Rev. 1993;11:37–57.

    Article  CAS  Google Scholar 

  46. Bettini R, Colombo P, Massimo G, Catellani PL, Vitali T. Swelling and drug release in hydrogel matrices: polymer viscosity and matrix porosity effects. Eur J Pharm Sci. 1994;2:213–9.

    Article  CAS  Google Scholar 

  47. Colombo P, Bettini R, Catellani PL, Santi P, Peppas NA. Drug volume fraction profile in the gel phase and drug release kinetics in hydroxypropylmethyl cellulose materials containing soluble drug. Eur J Pharm Sci. 1999;9:33–40.

    Article  PubMed  CAS  Google Scholar 

  48. Vlachou M, Naseef H, Efentakis M. Image analysis studies of dimensional changes in swellable hydrophilic polymer matrices. Polym Adv Tech. 2004;15:683–9.

    Article  CAS  Google Scholar 

  49. Richardson JC, Bowtell RW, Mader K, Melia CD. Pharmaceutical applications of magnetic resonance imaging (MRI). Adv Drug Deliv Rev. 2005;57(8):1191–209.

    Article  PubMed  CAS  Google Scholar 

  50. Melia CD, Rajabi-Siahboomi AR, Bowtell RW. Magnetic resonance imaging of controlled release pharmaceutical dosage forms. Pharmaceut Sci Tech Today. 1998;1(1):32–9.

    Article  CAS  Google Scholar 

  51. Nott KP. Magnetic resonance imaging of tablet dissolution. Eur J Pharm Biopharm. 2009;74(1):78–83.

    Article  PubMed  Google Scholar 

  52. Bowtell RW, Sharp JC, Peters A, Mansield P, Rajabi-Siahboomi AR, Davies MC, Melia CD. NMR microscopy of hydrating matrix pharmaceutical tablets. Magn Reson Imaging. 1994;12:361–4.

    Article  PubMed  CAS  Google Scholar 

  53. Rajabi-Siahboomi AR, Bowtell RW, Mansfield P, Henderson A, Davies MC, Melia CD. Structure and behaviour in hydrophilic matrix sustained release dosage forms: 2. NMR-imaging studies of dimensional changes in the gel layer and core of HPMC tablets undergoing hydration. J Control Release. 1994;31:124–8.

    Google Scholar 

  54. Rajabi-Siahboomi AR, Bowtell RW, Mansfield P, Davies MC, Melia CD. Structure and behavior in hydrophilic matrix sustained release dosage forms. 4. Studies of water mobility and diffusion coefficients in the gel layer of HPMC tablets using NMR imaging. Pharm Res. 1996;13:376–80.

    Article  PubMed  CAS  Google Scholar 

  55. Fyfe CA, Blazek AI. Investigation of hydrogel formation from hydroxypropylmethylcellulose (HPMC) by NMR spectroscopy and NMR imaging techniques. Macromolecules. 1997;30(20):6230–7.

    Article  CAS  Google Scholar 

  56. Baumgartner S, Lahajnar G, Sepe A, Kristl J. Quantitative evaluation of polymer concentration profile during swelling of hydrophilic matrix tablets using H-1 NMR and MRI methods. Eur J Pharm Biopharm. 2005;59(2):299–306.

    Article  PubMed  CAS  Google Scholar 

  57. Fyfe CA, Blazek-Welsh AI. Quantitative NMR imaging study of the mechanism of drug release from swelling hydroxypropylmethylcellulose tablets. J Control Release. 2000;68(3):313–33.

    Article  PubMed  CAS  Google Scholar 

  58. Chen YY, Hughes LP, Gladden LF, Mantle MD. Quantitative ultra-fast MRI of HPMC swelling and dissolution. J Pharm Sci. 2010;99(8):3462–72.

    Article  PubMed  CAS  Google Scholar 

  59. Kulinowski P, Dorożyński P, Młynarczyk A, Węglarz W. Magnetic resonance imaging and image analysis for assessment of HPMC matrix tablets structural evolution in USP Apparatus 4. Pharm Res. 2011;28:1065–73.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  60. Zhang QL, Gladden L, Avalle P, Mantle M. In vitro quantitative H-1 and F-19 nuclear magnetic resonance spectroscopy and imaging studies of fluvastatin (TM) in Lescol (R) XL tablets in a USP-IV dissolution cell. J Control Release. 2011;156(3):345–54.

    Article  PubMed  CAS  Google Scholar 

  61. Metz H, Mader K. Benchtop-NMR and MRI-A new analytical tool in drug delivery research. Int J Pharm. 2008;364(2):170–5.

    Article  PubMed  CAS  Google Scholar 

  62. Bajwa GS, Hoebler K, Sammon C, Timmins P, Melia CD. Microstructural imaging of early gel layer formation in HPMC matrices. J Pharm Sci. 2006;95(10):2145–57.

    Article  PubMed  CAS  Google Scholar 

  63. Williams HD, Nott KP, Barrett DA, Ward R, Hardy IJ, Melia CD. Drug release from HPMC matrices in milk and fat-rich emulsions. J Pharm Sci. 2011;100(11):4823–35.

    Article  PubMed  CAS  Google Scholar 

  64. Timmins P, Hanley S, Brown J. Mechanistic insights of the effects of process and formulation variables on the performance of hydrophilic matrix tablets using magnetic resonance imaging. Presented at 40th annual meeting and exposition of the Controlled Release Society. 2013.

    Google Scholar 

  65. Melia CD, Marshall P, Stark P, Cunningham S, Kinahan A, Devane J. Investigating in vitro drug release mechanisms inside dosage forms. Monitoring liquid ingress in HPMC hydrophilic matrices using confocal microscopy. In: Young D, editor. In vitro-in vivo correlations. New York, NY: Plenum; 1997.

    Google Scholar 

  66. Pygall SR, Kujawinski S, Timmins P, Melia CD. Mechanisms of drug release in citrate buffered HPMC matrices. Int J Pharm. 2009;370(1–2):110–20.

    Article  PubMed  CAS  Google Scholar 

  67. Williams HD, Ward R, Hardy IJ, Melia CD. The effect of sucrose and salts in combination on the drug release behaviour of an HPMC matrix. Eur J Pharm Biopharm. 2010;76(3):433–6.

    Article  PubMed  CAS  Google Scholar 

  68. Sutch JCD, MacRae RJ, Huatan H, Melia CD. Correlation between drug release and microenvironmental pH measured using ratiometric confocal laser scanning microscopy. Proc. 30th Int. Symp. Control. Release Bioact. Mater. 2003;29:746.

    Google Scholar 

  69. Van der Weerd J, Chan AKL, Kazarian SG. An innovative design of compaction cell for in situ FT-IR imaging of tablet dissolution. Vib Spectros. 2004;35:9–13.

    Article  Google Scholar 

  70. Coutts-Lendon CA, Wright NA, Mieso EV, Koenig JL. The use of FT-IR imaging as an analytical tool for the characterization of drug delivery systems. J Control Release. 2003;93(3):223–48.

    Article  PubMed  CAS  Google Scholar 

  71. Kazarian SG, Chan KLA. “Chemical Photography” of drug release. Macromolecules. 2003;36:9866–72.

    Article  CAS  Google Scholar 

  72. Hardy IJ, Windberg-Baarup A, Neri C, Byway PV, Booth S, Fitzpatrick S. Modulation of drug release kinetics from hydroxypropyl methyl cellulose matrix tablets using polyvinyl pyrrolidone. Int J Pharm. 2007;1–2(7):246–53.

    Article  Google Scholar 

  73. Li W, Woldy A, Araba L, Winstead D. Determination of water penetration and drug concentration profiles in HPMC-based matrix tablets by near infrared chemical imaging. J Pharm Sci. 2010;99(7):3081–8.

    PubMed  CAS  Google Scholar 

  74. Avalle P, Pygall SR, Gower N, Midwinter A. The use of in situ near infrared spectroscopy to provide mechanistic insights into gel layer development in HPMC hydrophilic matrices. Eur J Pharm Sci. 2011;43(5):400–8.

    Article  PubMed  CAS  Google Scholar 

  75. Avalle P, Pygall SR, Pritchard J, Jastrzemska A. Interrogating erosion-based drug liberation phenomena from hydrophilic matrices using near infrared (NIR) spectroscopy. Eur J Pharm Sci. 2013;48(1–2):72–9.

    Article  PubMed  CAS  Google Scholar 

  76. Van der Weerd J, Kazarian SG. Combined approach of FTIR imaging and conventional dissolution tests applied to drug release. J Control Release. 2004;98:295–305.

    Article  PubMed  Google Scholar 

  77. Kazarian SG, van der Weerd J. Simultaneous FTIR spectroscopic imaging and visible photography to monitor tablet dissolution and drug release. Pharm Res. 2008;25(4):853–60.

    Article  PubMed  CAS  Google Scholar 

  78. Laity PR, Cameron RE. Synchotron X-ray microtomographic study of tablet swelling. Eur J Pharm Biopharm. 2010;75(2):263–76.

    Article  PubMed  CAS  Google Scholar 

  79. Laity PR, Mantle MD, Gladden LF, Cameron RE. Magnetic resonance imaging and x-ray microtomography studies of a gel-forming tablet formulation. Eur J Pharm Biopharm. 2010;74(1):109–19.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Drug Product Science and Technology, Bristol-Myers Squibb, Moreton, Merseyside, UK

    Jonathan Brown & Sarah L. Hanley

  2. Commercial Trade Channels, Merck, Sharp and Dohme, Hertford Road, Hoddesdon, Hertfordshire, EN11 9BU, UK

    Samuel R. Pygall

  3. Centre of Material Science and Engineering, Merck, Sharp and Dohme, Schachen, Switzerland

    Paolo Avalle Ph.D.

  4. Pharmaceutical Product Development, Capsugel, Cambridge, MA, USA

    Hywel D. Williams Ph.D.

  5. School of Pharmacy, University of Nottingham, Nottingham, UK

    Colin D. Melia Ph.D.

Authors
  1. Jonathan Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah L. Hanley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Samuel R. Pygall
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paolo Avalle Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hywel D. Williams Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Colin D. Melia Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samuel R. Pygall .

Editor information

Editors and Affiliations

  1. Drug Product Science and Technology, Bristol-Myers Squibb, Moreton, Merseyside, United Kingdom

    Peter Timmins

  2. Commercial Trade Channels, Merck, Sharp and Dohme, Hoddesdon, Hertfordshire, United Kingdom

    Samuel R. Pygall

  3. School of Pharmacy, University of Nottingham, Notthingham, Nottinghamshire, United Kingdom

    Colin D. Melia

Rights and permissions

Reprints and permissions

Copyright information

© 2014 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Brown, J., Hanley, S.L., Pygall, S.R., Avalle, P., Williams, H.D., Melia, C.D. (2014). In Vitro Physical and Imaging Techniques to Evaluate Drug Release Mechanisms from Hydrophilic Matrix Tablets. In: Timmins, P., Pygall, S., Melia, C. (eds) Hydrophilic Matrix Tablets for Oral Controlled Release. AAPS Advances in the Pharmaceutical Sciences Series, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1519-4_7

Download citation

Publish with us

Policies and ethics

Search

Navigation