Skip to main content

Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression

AAPS PharmSciTech volume 18, pages 2055–2066 (2017)Cite this article

ABSTRACT

Orally disintegrating tablets (ODTs) are challenged by the need for simple technology to ensure good mechanical strength coupled with rapid disintegration. The objective of this work was to evaluate microwave-assisted development of ODTs based on simple direct compression tableting technology. Placebo ODTs comprising directly compressible mannitol and lactose as diluents, super disintegrants, and lubricants were prepared by direct compression followed by exposure to >97% relative humidity and then microwave irradiation for 5 min at 490 W. Placebo ODTs with hardness (>5 kg/cm2) and disintegration time (<60 s) were optimized. Palatable ODTs of Lamotrigine (LMG), which exhibited rapid dissolution of LMG, were then developed. The stability of LMG to microwave irradiation (MWI) was confirmed. Solubilization was achieved by complexation with beta-cyclodextrin (β-CD). LMG ODTs with optimal hardness and disintegration time (DT) were optimized by a 23 factorial design using Design Expert software. Taste masking using sweeteners and flavors was confirmed using a potentiometric multisensor-based electronic tongue, coupled with principal component analysis. Placebo ODTs with crospovidone as a superdisintegrant revealed a significant increase in hardness from ∼3 to ∼5 kg/cm2 and a decrease in disintegration time (<60 s) following microwave irradiation. LMG ODTs had hardness >5 kg/cm2, DT < 30s, and rapid dissolution of LMG, and good stability was optimized by DOE and the design space derived. While β-CD complexation enabled rapid dissolution and moderate taste masking, palatability, which was achieved including flavors, was confirmed using an electronic tongue. A simple step of humidification enabled MWI-facilitated development of ODTs by direct compression presenting a practical and scalable advancement in ODT technology.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13

References

  1. Goel H et al. Orally disintegrating systems: innovations in formulation and technology. Recent Patents Drug Deliv Formul. 2008;2(3):258–74.

    CAS  Article  Google Scholar 

  2. Sreenivas S et al. Orodispersible tablets: new-fangled drug delivery system—a review. Indian J Pharmaceut Educ. 2005;39(4):177.

    Google Scholar 

  3. Seager H. Drug‐delivery products and the Zydis fast‐dissolving dosage form*. J Pharm Pharmacol. 1998;50(4):375–82.

    CAS  Article  PubMed  Google Scholar 

  4. Hori H et al. Olanzapine orally disintegrating tablets (Zyprexa ZydisR) rapidly improve excitement components in the acute phase of first-episode schizophrenic patients: an open-label prospective study. World J Biol Psychiatr. 2009;10(4-3):741–5.

    Article  Google Scholar 

  5. Lafon L. Galenic form for oral administration and its method of preparation by lyophilization of an oil-in-water emulsion. 1986, Google Patents.

  6. Gohel M et al. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique. AAPS PharmSciTech. 2004;5(3):10–5.

    Article  PubMed Central  Google Scholar 

  7. Misra TK et al. Fast-dissolving comestible units formed under high-speed/high-pressure conditions. 2000, Google Patents.

  8. Myers GL, Battist GE, Fuisz RC. Process and apparatus for making rapidly dissolving dosage units and product therefrom. 1998, Google Patents.

  9. Sano S et al. Impact of active ingredients on the swelling properties of orally disintegrating tablets prepared by microwave treatment. Int J Pharm. 2014;468(1):234–42.

    CAS  Article  PubMed  Google Scholar 

  10. Sano S et al. Preparation and evaluation of swelling induced-orally disintegrating tablets by microwave irradiation. Int J Pharm. 2011;416(1):252–9.

    CAS  PubMed  Google Scholar 

  11. Sano S et al. Design and evaluation of microwave-treated orally disintegrating tablets containing polymeric disintegrant and mannitol. Int J Pharm. 2013;448(1):132–41.

    CAS  Article  PubMed  Google Scholar 

  12. Bi Y et al. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem Pharm Bull. 1996;44(11):2121–7.

    CAS  Article  PubMed  Google Scholar 

  13. Bi Y, Yonezawa Y, Sunada H. Rapidly disintegrating tablets prepared by the wet compression method: mechanism and optimization. J Pharm Sci. 1999;88(10):1004–10.

    CAS  Article  PubMed  Google Scholar 

  14. Gupta A. Recent trends of fast dissolving tablet-an overview of formulation technology. Int J Pharmaceut Biol Arch. 2010;1(1):1–10.

  15. Iveson SM et al. Nucleation, growth and breakage phenomena in agitated wet granulation processes: a review. Powder Technol. 2001;117(1):3–39.

    CAS  Article  Google Scholar 

  16. Rockland LB. Saturated salt solutions for static control of relative humidity between 5° and 40°C. Anal Chem. 1960;32(10):1375–6.

    CAS  Article  Google Scholar 

  17. Higuchi T, Connors A. Phase-solubility techniques. Adv Chem Instrum. 1965;4:212–217.

  18. Patel H et al. Preparation and characterization of etoricoxib-β-cyclodextrin complexes prepared by the kneading method. Acta Pharma. 2007;57(3):351–9.

    CAS  Article  Google Scholar 

  19. Rudnitskaya A et al. Assessment of bitter taste of pharmaceuticals with multisensor system employing 3 way PLS regression. Anal Chim Acta. 2013;770:45–52.

    CAS  Article  PubMed  Google Scholar 

  20. Esbensen KH. Principal component analysis (PCA)—introduction. In: Esbensen KH, editor. Multivariate data analysis in practice—an introduction to multivariate data analysis and experimental design. 5. Oslo: Camo Software AS; 2001:19–74.

  21. Walter-Levy L. Cristallochimie-sur les variétés cristallines du D-mannitol. CR Acad Sc Paris Ser C. 1968;267:1779–82.

    CAS  Google Scholar 

  22. Augsburger LL et al. Superdisintegrants: characterization and function. Encyclop Pharmaceut Technol. 2007;20:269–90.

    Google Scholar 

  23. Zhao N, Augsburger LL. The influence of swelling capacity of superdisintegrants in different pH media on the dissolution of hydrochlorothiazide from directly compressed tablets. AAPS Pharmscitech. 2005;6(1):E120–6.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gohel MC et al. Preparation and assessment of novel coprocessed superdisintegrant consisting of crospovidone and sodium starch glycolate: a technical note. AAPS PharmSciTech. 2007;8(1):E63–9.

    Article  Google Scholar 

  25. Gryczke A et al. Development and evaluation of orally disintegrating tablets (ODTs) containing ibuprofen granules prepared by hot melt extrusion. Colloids Surf B: Biointerfaces. 2011;86(2):275–84.

    CAS  Article  PubMed  Google Scholar 

  26. Singh J, Garg R, Gupta GD. Enhancement of solubility of Lamotrigine by solid dispersion and development of orally disintegrating tablets using 32 full factorial design. J Pharm (Cairo). 2015;5:828453.

  27. Sharma M, Garg R, Gupta G. Formulation and evaluation of solid dispersion of atorvastatin calcium. J Pharmaceut Sci Innov. 2013;2(4):73–81.

    CAS  Article  Google Scholar 

  28. Shinde VR et al. Enhanced solubility and dissolution rate of Lamotrigine by inclusion complexation and solid dispersion technique. J Pharm Pharmacol. 2008;60(9):1121–9.

    CAS  Article  PubMed  Google Scholar 

  29. Yewale CP et al. Formulation and development of taste masked fast-disintegrating tablets (FDTs) of chlorpheniramine maleate using ion-exchange resins. Pharm Dev Technol. 2013;18(2):367–76.

    CAS  Article  PubMed  Google Scholar 

  30. Bhise K, Shaikh S, Bora D. Taste mask, design and evaluation of an oral formulation using ion exchange resin as drug carrier. AAPS PharmSciTech. 2008;9(2):557–62.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Stojanov M, Wimmer R, Larsen KL. Study of the inclusion complexes formed between cetirizine and α‐, β‐, and γ‐cyclodextrin and evaluation on their taste‐masking properties. J Pharm Sci. 2011;100(8):3177–85.

    CAS  Article  PubMed  Google Scholar 

  32. Goudanavar P, Shah SH, Hiremath D. Development and characterization of lamotrigine orodispersible tablets: inclusion complex with hydroxypropyl B cyclodextrin. Int J Pharm Pharm Sci. 2011;3(3):208–14.

    CAS  Google Scholar 

  33. Bora D, Borude P, Bhise K. Taste masking by spray-drying technique. AAPS PharmSciTech. 2008;9(4):1159–64.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Hu X et al. Preparation and evaluation of orally disintegrating tablets containing taste-masked microcapsules of berberine hydrochloride. AAPS PharmSciTech. 2013;14(1):29–37.

    CAS  Article  PubMed  Google Scholar 

  35. Chen J-C, Bunick FJ, McNally G. Fast dissolving/disintegrating coating compositions. 2013, Google Patents.

  36. Somoza V et al. Method for the identification of bitter tasting compounds and bitter taste modulating compounds. 2015. US Patent 20,150,362,481.

  37. Santi PAD, Nelson DG. Taste masking of phenolics using citrus flavors. 2001, Google Patents.

  38. Skrabanja ATP, Tully RE. Oral liquid antidepressant solution. 2000, Google Patents.

Download references

Acknowledgements

The authors are thankful to the University Grants Commission, Government of India, Department of Science & Technology (DST), Government of India and Russian Foundation for Basic Research (grant INT/RUS/RFBR/P-195 and RFBR no. 15-53-45105), and DST Prime Ministers Fellowship for financial support. Dmitry Kirsanov and Andrey Legin acknowledge partial financial support from Government of Russian Federation (grant 074-U01).

Author information

Affiliations

  1. Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Deemed University, Elite Status and Centre of Excellence (Maharashtra), N.P. Marg, Matunga (E), Mumbai, 400019, Maharashtra, India

    Kishor V. Kande, Darsheen J. Kotak, Mariam S. Degani & Padma V. Devarajan

  2. Institute of Chemistry, St. Petersburg State University, Universitetskaya nab. 7/9, Mendeleev Center, 199034, St. Petersburg, Russia

    Dmitry Kirsanov & Andrey Legin

  3. Laboratory of Artificial Sensory Systems, ITMO University, Kronverkskiy pr., 49, 197101, St. Petersburg, Russia

    Dmitry Kirsanov & Andrey Legin

Authors
  1. Kishor V. Kande
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Darsheen J. Kotak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mariam S. Degani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dmitry Kirsanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrey Legin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Padma V. Devarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Padma V. Devarajan.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Kande, K.V., Kotak, D.J., Degani, M.S. et al. Microwave-Assisted Development of Orally Disintegrating Tablets by Direct Compression. AAPS PharmSciTech 18, 2055–2066 (2017). https://doi.org/10.1208/s12249-016-0683-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-016-0683-z

KEY WORDS

  • Lamotrigine
  • microwave irradiation
  • orally disintegrating tablet
  • taste masking
  • β-cyclodextrin