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AAPS PharmSciTech

, Volume 10, Issue 2, pp 495–499 | Cite as

Disintegration of Highly Soluble Immediate Release Tablets: A Surrogate for Dissolution

  • Abhay Gupta
  • Robert L. Hunt
  • Rakhi B. Shah
  • Vilayat A. Sayeed
  • Mansoor A. Khan
Research Article

Abstract

The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria.

Key words

disintegration test dissolution test ICH Q6A specification 

Abbreviations

DCP

Dicalcium phosphate dihydrate

HPMC

Hypromellose

ICH

International Conference on Harmonization

LMH

Lactose monohydrate

MCC

Microcrystalline cellulose

NaCMC

Sodium carboxymethyl cellulose

PVP

Polyvinyl pyrollidone

USP

United States Pharmacopeia

VLHX1

Tablets containing LMH, HPMC, without disintegrating agent, and hardness of 6 Kgf

VLHX2

Tablets containing LMH, HPMC, without disintegrating agent, and hardness of 10 Kgf

VLPA1

Tablets containing LMH, PVP, NaCMC, and hardness of 6 Kgf

VLPA2

Tablets containing LMH, PVP, NaCMC, and hardness of 10 Kgf

VLHA1

Tablets containing LMH, HPMC, NaCMC, and hardness of 6 Kgf

VLHA2

Tablets containing LMH, HPMC, NaCMC, and hardness of 10 Kgf

References

  1. 1.
    United States Pharmacopeia 30/National Formulary 25. 2008. The U.S. Pharmacopeial Convention, Inc. Rockville, MD. (www.USP.org).
  2. 2.
    ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances. Available at www.ich.org. Accessed January 24, 2008.
  3. 3.
    Sayeed V. Disintegration test as a surrogate for dissolution: some practical considerations. In: AAPS Workshop on the Role of Dissolution in QbD and Drug Product Life Cycle. Arlington, VA: AAPS Workshop, 2008.Google Scholar
  4. 4.
    Vogelpoel H, Welink J, Amidon GL, Junginger HE, Midha KK, Moller H, et al. Biowaiver monographs for immediate release solid oral dosage forms based on Biopharmaceutics Classification System (BCS) literature data: verapamil hydrochloride, propranolol hydrochloride, and atenolol. J Pharm Sci 2004;93:1945–56.PubMedCrossRefGoogle Scholar
  5. 5.
    Verapamil hydrochloride tablets monograph. United States Pharmacopeia 30/National Formulary 25. 2008. The U.S. Pharmacopeial Convention, Inc. Rockville, MD. (www.USP.org).
  6. 6.
    Chen C. A FDA perspective on Quality by Design. Pharmtech, Dec 5, 2007. Available at http://pharmtech.findpharma.com/pharmtech/Article/A-FDA-Perspective-on-Quality-by-Design/ArticleStandard/Article/detail/469915. Accessed May 15, 2008.

Copyright information

© American Association of Pharmaceutical Scientists 2009

Authors and Affiliations

  • Abhay Gupta
    • 1
  • Robert L. Hunt
    • 1
  • Rakhi B. Shah
    • 1
  • Vilayat A. Sayeed
    • 2
  • Mansoor A. Khan
    • 1
  1. 1.Division of Product Quality Research, Office of Testing and Research, Office of Pharmaceutical ScienceFood and Drug AdministrationSilver SpringUSA
  2. 2.Division of Chemistry III, Office of Generic DrugsFood and Drug AdministrationRockvilleUSA

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