AAPS PharmSciTech

, Volume 11, Issue 1, pp 356–361 | Cite as

Formulation and Optimization of Orodispersible Tablets of Diazepam

  • Khalid K. Abed
  • Ahmed A. Hussein
  • Mowafaq M. Ghareeb
  • Alaa A. Abdulrasool
Research Article


Diazepam is one of the most prescribed benzodiazepines. The purpose of the present research was to optimize the formulation of orodispersible tablets of diazepam. Orodispersible tablets of diazepam were prepared using different types of superdisintegrants (Ac-Di-Sol, sodium starch glycolate, and crospovidone (CP)) and different types of subliming agents (camphor and ammonium bicarbonate (AB)) at different concentrations and two methods of tablets preparations (wet granulation and direct compression methods). The formulations were evaluated for flow properties, wetting time, hardness, friability, content uniformity, in vivo disintegration time (DT), release profiles, and buccal absorption tests. All formulations showed satisfactory mechanical strength except formula F5 which contains camphor and formula F9 which is prepared by direct compression method. The results revealed that the tablets containing CP as a superdisintegrant have good dissolution profile with shortest DT. The optimized formula F7 is prepared using 10% CP as a superdisintegrant and 20% AB as a subliming agent by wet granulation method which shows the shortest DT and good dissolution profile with acceptable stability. This study helps in revealing the effect of formulation processing variables on tablet properties. It can be concluded that the orodispersible tablets of diazepam with better biopharmaceutical properties than conventional tablets could be obtained using formula F7.

Key words

ammonium bicarbonate crospovidone diazepam orodispersible tablet sublimation 



The authors are thankful to the pharmacists Haider J. Al-Karagully and Hussam H. Tizkam for assistance in HPLC analysis.


  1. 1.
    Seager H. Drug delivery products and the Zydis fast dissolving dosage forms. J Pharm Pharmacol. 1998;50:375–82.PubMedGoogle Scholar
  2. 2.
    Ciper M, Bodmeier R. Modified conventional hard gelatin capsules as fast disintegrating dosage form in the oral cavity. Eur J Pharm Biopharm. 2006;62(2):178–84.CrossRefPubMedGoogle Scholar
  3. 3.
    Suresh B, Rajendar KM, Ramesh G, Yamsani MR. Orodispersible tablets: an overview. Asian J Pharm. 2008;2:2–11.CrossRefGoogle Scholar
  4. 4.
    Dobetti L. Fast-melting tablets: developments and technologies. Pharma Tech. 2001; (Suppl.):44–50.Google Scholar
  5. 5.
    Koizumi K, Watanabe Y, Monita K, Utosuchi N. New method of preparing high porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material. Int J Pharm. 1997;152:127–31.CrossRefGoogle Scholar
  6. 6.
    Fu Y, Yang S, Jeong Sh, Kimura S, Park K. Orally fast disintegrating tablets: developments, technologies, taste-masking and clinical studies. Crit Rev Ther Drug Carrier Sys. 2004;21:433–76.CrossRefGoogle Scholar
  7. 7.
    Sastry SV, Nyshadham JR, Fix JA. Recent technological advances in oral drug delivery: a review. Pharm Sci Technol Today. 2000;3(4):138–45.CrossRefPubMedGoogle Scholar
  8. 8.
    Ahmed IS, Aboul-Einien MH. In vitro and in vivo evaluation of a fast-disintegrating lyophilized dry emulsion tablet containing griseofulvin. Eur J Pharm Sci. 2007;32(1):58–68.CrossRefPubMedGoogle Scholar
  9. 9.
    Biradar SS, Bhagavati ST, Kuppasad IJ. Fast dissolving drug delivery systems: a brief overview. Internet J Pharmacol, 2006; 4(2).Google Scholar
  10. 10.
    Omaima AS, Mohammed AH, Nagia AM, Ahmed SZ. Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion. AAPS PharmSciTech. 2006;7:55.Google Scholar
  11. 11.
    Suresh S, Pandit V, Joshi HP. Preparation and evaluation of mouth dissolving tablets of salbutamol sulphate. Indian J Pharm Sci. 2007;69:467–9.CrossRefGoogle Scholar
  12. 12.
    Bolhuis GK, Zurman K, Wierik GHP. Improvement of dissolution of poorly soluble drug by solid deposition on a super disintegrant. Eur J Pharm Sci. 1997;5:63–9.CrossRefGoogle Scholar
  13. 13.
    Patel M, Patel N, Patel M. Fast-dissolving rofecoxib tablets: formulation development & optimization using factorial design. Drug Del Technol. 2007;7:33–8.Google Scholar
  14. 14.
    Ahmed IS, Fatahalla FA. Pilot study of relative bioavailability of two oral formulations of ketoprofen in healthy subjects, a fast dissolving lyophilized tablet as compared to immediate release tablet. Drug Develop Ind Pharm. 2007;33:505–11.CrossRefGoogle Scholar
  15. 15.
    Gohel M, Patel M, Amin A, Agrawal R, Dave R, Bariya N. Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique. AAPS PharmSciTech. 2004;5:36.CrossRefGoogle Scholar
  16. 16.
    Ahmed IS, Nafadi MM, Fatahalla FA. Formulation of fast dissolving ketoprofen tablet using freeze-drying in blister technique. Drug Develop Ind Pharm. 2006;32:437–42.CrossRefGoogle Scholar
  17. 17.
    Indurwade NH, Rajyaguru TH, Nahat PD. Novel approach in fast dissolving tablets. Indian Drugs. 2002;39(8):405–9.Google Scholar
  18. 18.
    Inada T, Nozaki S, Inagaki A, Furukawa TA. Efficacy of diazepam as an anti-anxiety agent: metaanalysis of double-blind, randomized controlled trials carried out in Japan. Hum Psychopharmacol Clin Exp. 2003;18:483–7.CrossRefGoogle Scholar
  19. 19.
    Kei-ichi K, Yoshiteru W, Kumiko M, Naoki U, Mitsuo M. New method of preparing highporosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material. Int J Pharm. 1997;152:127–31.CrossRefGoogle Scholar
  20. 20.
    British Pharmacopoeia Commission. Powder flow. London: British Pharmacopoeia Commission; 2007 (Appendix XVII N).Google Scholar
  21. 21.
    Hisakadzu S, Yunxia B. Preparation, evaluation and optimization of rapidly disintegrating tablets. Powder Technol. 2002;122:188–98.CrossRefGoogle Scholar
  22. 22.
    Marshall K, Lachman N, Liberman HA. The theory and practice of industrial pharmacy, 3rd ed. Mumbai: Varghese Publishing House; 1987. p. 66–9.Google Scholar
  23. 23.
    Jinichi F, Etsuo Y, Yasuo Y, Katsuhide T. Evaluation of rapidly disintegrating tablets containing glycine and carboxymethylcellulose. Int J Pharm. 2006;310:101–9.CrossRefGoogle Scholar
  24. 24.
    Sharma S, Gupta GD. Formulation and characterization of fast-dissolving tablet of promethazine theocolate. Asian J Pharm. 2008; p. 70–72.Google Scholar
  25. 25.
    Ishikawa et al. Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter-taste-masked granules by the compression method. Chem Pharm Bull. 1999;47(10):1451–4.PubMedGoogle Scholar
  26. 26.
    United States Pharmacopoeia USPXXX, NFXXV. General tests and assays. Rockville: The United State Pharmacopeial Convention, Inc.; 2007.Google Scholar
  27. 27.
    Corveleyn S, Remon JP. Formulation and production of rapidly disintegrating tablets by lyophilization using hydrochlorothiazide as a model drug. Int J Pharm. 1997;152:215–25.CrossRefGoogle Scholar
  28. 28.
    Abdelbary A, Elshafeey AH, Zidan G. Comparative effects of different cellulosic based directly compressed orodispersable tablets on oral bioavailability of famotidine. Carbohydr Polym. 2009;77:799–806.CrossRefGoogle Scholar
  29. 29.
    Setty CM, Prasad DVK, Gupta VRM, SA B. Development of fast dispersible Aceclofenac tablets: effect of functionality of superdisintegrants. Indian J Pharm Sci. 2008;70:180–5.CrossRefPubMedGoogle Scholar
  30. 30.
    Mukesh G, Madhabhai P, Avani A, Ruchi A, Rikita D, Nehal B. Formulation design and optimization of mouth dissolve tablets of Nimesulide using vacuum drying technique. AAPS PharmSciTech. 2004;5(3):1–6.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  • Khalid K. Abed
    • 1
  • Ahmed A. Hussein
    • 1
  • Mowafaq M. Ghareeb
    • 1
  • Alaa A. Abdulrasool
    • 1
  1. 1.Department of Pharmaceutics, College of PharmacyBaghdad UniversityBaghdadIraq

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