Skip to main content
SpringerLink
Log in

Visual Monitoring of Disintegration of Solid Oral Dosage Forms in Simulated Gastric Fluids Using Low-Field NMR Imaging

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Compared to traditional drug release monitoring with manual sampling and testing procedures, low-field nuclear magnetic resonance (LF-NMR) imaging is a one-step, visual, non-destructive, and non-invasive measurement method. Here, we reported the application of LF-NMR to image the morphology, component, sub-diffusion, and spatial distribution of a solid oral formulation, Biyankang tablets, during dissolution in vitro. The drug ingredients with characteristic relaxation times were distinguished and localized based on the signal of standards, such as patchouli oil, Xanthium strumarium extract, and starch. The hydration, swelling, disintegration, and sub-diffusion of tablets in simulated gastric fluids (SGF) were visualized statically. All tablets showed similar expansion (37.4–42.0%) along the direction of thickness at 25 min and reached a full disintegration at 145 min, at pH 1.80–6.15, indicating pH-independent swelling and disintegration. Compared to that static immersion within 20 mL SGF, the tablet disintegration time was shortened by ~ 11% in 30 mL SGF. The application of shear reduced the time by ~ 28%, suggesting a major role of hydrodynamic condition in tablet dissolution. The ability to simultaneously visualize, distinguish, and localize drug ingredients using LF-NMR is expected to provide valuable information to develop drug release monitoring systems in vitro and potentially in vivo using small animal studies.

Graphical abstract

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Kulinowski P, et al. Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ-is it possible to detect phenomena related to drug dissolution within the hydrated matrices? Pharm Res. 2014;31(9):2383–92.

    Article  CAS  Google Scholar 

  2. Gajdošová M, et al. Effect of hydrophobic inclusions on polymer swelling kinetics studied by magnetic resonance imaging. Int J Pharm. 2016;500(1):136–43.

    Article  Google Scholar 

  3. Bernin D, et al. Real time MRI to elucidate the functionality of coating films intended for modified release. J Control Release. 2019;311–312:117–24.

    Article  Google Scholar 

  4. Li M, Li B, Zhang W. Rapid and non-invasive detection and imaging of the hydrocolloid-injected prawns with low-field NMR and MRI. Food Chem. 2018;242:16–21.

    Article  CAS  Google Scholar 

  5. Xu F, et al. Investigation on water status and distribution in broccoli and the effects of drying on water status using NMR and MRI methods. Food Res Int. 2017;96:191–7.

    Article  CAS  Google Scholar 

  6. Ding M, Wu P, Chen XD. Investigation of gastric disintegration of carrot during digestion in vitro by a low-field nuclear magnetic resonance device. J Food Eng. 2021;292: 110307.

    Article  CAS  Google Scholar 

  7. Hendrick RE. Tissue relaxation, in breast MRI: fundamentals and technical aspects. 2008, Springer New York: New York, NY. p. 19-29.

  8. Mangrum W et al. Duke review of MRI principles: case review series E-Book. 2018: Elsevier Health Sciences.

  9. Leung H, et al. Water binding of macromolecules determined by pulsed NMR. J Food Sci. 1976;41(2):297–300.

    Article  CAS  Google Scholar 

  10. Nemoto Y, et al. MR appearance of Rathke’s cleft cysts. Neuroradiology. 1988;30(2):155–9.

    Article  CAS  Google Scholar 

  11. Wang Y et al. NMR imaging of chitosan and carboxymethyl starch tablets: swelling and hydration of the polyelectrolyte complex. 2011. 419(1-2), 215-221

  12. Zimny A et al. Intracranial lesions with high signal intensity on T1-weighted MR images–review of pathologies. 2013. 78(4): p. 36.

  13. Tee H et al. SNRo, T1 and T2 characteristics of poly (vinyl) alcohol (PVA) MRI slime phantom with different PVA/borax ratio. in Journal of Physics: Conference Series. 2020. IOP Publishing.

  14. Kempe S, et al. Non-invasive in vivo evaluation of in situ forming PLGA implants by benchtop magnetic resonance imaging (BT-MRI) and EPR spectroscopy. Eur J Pharm Biopharm. 2010;74(1):102–8.

    Article  CAS  Google Scholar 

  15. Minekus M, et al. A standardised static in vitro digestion method suitable for food–an international consensus. Food Funct. 2014;5(6):1113–24.

    Article  CAS  Google Scholar 

  16. Kasim NA, et al. Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol Pharm. 2004;1(1):85–96.

    Article  CAS  Google Scholar 

  17. Swanson-Biearman B. Chlorpheniramine. In: Wexler P, editor. Encyclopedia of Toxicology (Second Edition). New York: Elsevier; 2005. p. 577–8.

    Chapter  Google Scholar 

  18. Schreiner L, et al. Proton NMR spin grouping and exchange in dentin. Biophys J. 1991;59(3):629–39.

    Article  CAS  Google Scholar 

  19. Chinese Pharmacopoeia Committee, Pharmacopoeia of the People’s Republic of China. Vol. 1. 2020: China Medical Science and Technology Press. 1835.

  20. Adebayo SA, Brown-Myrie E, Itiola OA. Comparative disintegrant activities of breadfruit starch and official corn starch. Powder Technol. 2008;181(2):98–103.

    Article  CAS  Google Scholar 

  21. Carriere F, et al. Purification and biochemical characterization of dog gastric lipase. Eur J Biochem. 1991;202(1):75–83.

    Article  CAS  Google Scholar 

  22. Malagelada J-R, Go VL, Summerskill W. Different gastric, pancreatic, and biliary responses to solid-liquid or homogenized meals. Dig Dis Sci. 1979;24(2):101–10.

    Article  CAS  Google Scholar 

  23. van Beek TA, Joulain D. The essential oil of patchouli, Pogostemon cablin: A review. Flavour Fragr J. 2018;33(1):6–51.

    Article  Google Scholar 

  24. Fan W et al. Traditional uses, botany, phytochemistry, pharmacology, pharmacokinetics and toxicology of Xanthium strumarium L.: A Review. Molecules, 2019. 24(2): p. 359.

  25. Zimny A, et al. Intracranial lesions with high signal intensity on T1-weighted MR images–review of pathologies. Pol J Radiol. 2013;78(4):36.

    Article  Google Scholar 

  26. Hedayati S, et al. Physical properties of pregelatinized and granular cold water swelling maize starches at different pH values. Int J Biol Macromol. 2016;91:730–5.

    Article  CAS  Google Scholar 

  27. Zhu Z, Xiao T, Qiu Z. Study on absorbents for lipophilic extract of rhizoma alismatis. Chinese Traditional Patent Medicine, 1992.

  28. Chauhan B, Shimpi S, Paradkar A. Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. Eur J Pharm Sci. 2005;26(2):219–30.

    Article  CAS  Google Scholar 

  29. Wypych G. Fillers–Origin, chemical composition, properties, and morphology. Handbook of Fillers, 2016(4 (266)): p. 13.

  30. Kucharczyk W, et al. The effect of phospholipid vesicles on the NMR relaxation of water: an explanation for the MR appearance of the neurohypophysis? Am J Neuroradiol. 1990;11(4):693–700.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Metzler R, et al. Anomalous diffusion models and their properties: non-stationarity, non-ergodicity, and ageing at the centenary of single particle tracking. Phys Chem Chem Phys. 2014;16(44):24128–64.

    Article  CAS  Google Scholar 

  32. Kahana A, et al. Active transport on disordered microtubule networks: the generalized random velocity model. Phys Rev E. 2008;78(5): 051912.

    Article  Google Scholar 

  33. Banks DS, Fradin C. Anomalous Diffusion of Proteins Due to Molecular Crowding. Biophys J. 2005;89(5):2960–71.

    Article  CAS  Google Scholar 

  34. Moreton RC. Disintegrants in tableting. In: Pharmaceutical Dosage Forms-Tablets. CRC Press; 2008. p. 233–66.

    Google Scholar 

  35. Hellman NN, Boesch TF, Melvin EH. Starch granule swelling in water vapor sorption. J Am Chem Soc. 1952;74(2):348–50.

    Article  CAS  Google Scholar 

  36. Ingram JT, Lowenthal W. Mechanism of action of starch as a tablet disintegrant iii: factors affecting starch grain damage and their effect on swelling of starch grains and disintegration of tablets at 37°. J Pharm Sci. 1968;57(3):393–9.

    Article  CAS  Google Scholar 

  37. Gissinger D, Stamm A. A Comparative evaluation of the properties of some tablet disintegrants. Drug Dev Ind Pharm. 1980;6(5):511–36.

    Article  Google Scholar 

  38. Lowenthal W, Wood JH. Mechanism of action of starch as a tablet disintegrant VI: Location and structure of starch in tablets. J Pharm Sci. 1973;62(2):287–93.

    Article  CAS  Google Scholar 

  39. Rajabi-Siahboomi AR et al. 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. Journal of Controlled Release, 1994. 31(2): p. 121–128.

  40. Jadhav N, et al. Talc: A versatile pharmaceutical excipient. World Journal of Pharmacy and Pharmacutical Sciences. 2013;2:4639–60.

    Google Scholar 

  41. Worsøe J, et al. Gastric transit and small intestinal transit time and motility assessed by a magnet tracking system. BMC Gastroenterol. 2011;11(1):145.

    Article  Google Scholar 

  42. Schulze K. Imaging and modelling of digestion in the stomach and the duodenum. Neurogastroenterol Motil. 2006;18(3):172–83.

    Article  CAS  Google Scholar 

  43. Clifford MN, Kerimi A, Williamson G. Bioavailability and metabolism of chlorogenic acids (acyl-quinic acids) in humans. Comprehensive Reviews in Food Science and Food Safety. 2020;19(4):1299–352.

    Article  CAS  Google Scholar 

  44. Gupta MK, et al. Enhanced drug dissolution and bulk properties of solid dispersions granulated with a surface adsorbent. Pharm Dev Technol. 2001;6(4):563–72.

    Article  CAS  Google Scholar 

  45. Yadav S, Shire SJ, Kalonia DS. Factors affecting the viscosity in high concentration solutions of different monoclonal antibodies. J Pharm Sci. 2010;99(12):4812–29.

    Article  CAS  Google Scholar 

  46. Nedich RL, Kildsig DO. Mechanism of Dissolution I: Mathematical interpretation of concentration gradients developed during dissolution of a solid. J Pharm Sci. 1972;61(2):214–8.

Download references

Funding

This work was financially supported by the Natural Science Foundation of China (22078212).

Author information

Authors and Affiliations

  1. The Life Quality Engineering Interest Group, School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, China

    Qianyu Ye, Meilai Ding, Ping Zhang, Peng Wu & Xiao Dong Chen

  2. School of Chemical Engineering, UNSW Sydney, Sydney, NSW, 2052, Australia

    Qianyu Ye, Yong Wang & Cordelia Selomulya

Authors
  1. Qianyu Ye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meilai Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ping Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cordelia Selomulya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiao Dong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Qianyu Ye: Investigation; data curation; methodology; writing-original draft; writing-review & editing. Meilai Ding: investigation; data curation; methodology. Ping Zhang: Investigation. Peng Wu: formal analysis; writing-original draft; writing-review & editing; supervision. Yong Wang: writing-review & editing. Cordelia Selomulya: supervision; writing-review & editing. Xiao Dong Chen: conceptualization; funding acquisition; project administration; Supervision.

Corresponding authors

Correspondence to Peng Wu or Xiao Dong Chen.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ye, Q., Ding, M., Zhang, P. et al. Visual Monitoring of Disintegration of Solid Oral Dosage Forms in Simulated Gastric Fluids Using Low-Field NMR Imaging. AAPS PharmSciTech 23, 246 (2022). https://doi.org/10.1208/s12249-022-02401-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-022-02401-x

Keywords

Search

Navigation