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.
Similar content being viewed by others
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
United States Pharmacopeia 30/National Formulary 25. 2008. The U.S. Pharmacopeial Convention, Inc. Rockville, MD. (www.USP.org).
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.
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.
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.
Verapamil hydrochloride tablets monograph. United States Pharmacopeia 30/National Formulary 25. 2008. The U.S. Pharmacopeial Convention, Inc. Rockville, MD. (www.USP.org).
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.
Author information
Authors and Affiliations
Corresponding author
Additional information
The opinions expressed in this work are only of authors and do not necessarily reflect the policy and statements of the FDA.
Rights and permissions
About this article
Cite this article
Gupta, A., Hunt, R.L., Shah, R.B. et al. Disintegration of Highly Soluble Immediate Release Tablets: A Surrogate for Dissolution. AAPS PharmSciTech 10, 495–499 (2009). https://doi.org/10.1208/s12249-009-9227-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-009-9227-0