Dose dumping - technical perspective
Dose dumping is defined as "Unintended, rapid drug release in a short period of time of the entire amount or a significant fraction of the drug contained in a modified release dosage form1." A sustained/extended/controlled release dosage form is intended to release the drug in desired concentrations for a prolonged period of time. A dosage form is said to be dose dumped when there is an excess release of drug at a particular time interval other than the stated or required amount. This results in higher systemic drug concentrations that may result in toxicity. This toxicity may be more pronounced or significant in case of drugs with narrow therapeutic window (eg: cardiac glycosides). Dose dumping may be due to various reasons like improper product design, drug excipient interactions, due to intake of food or alcohol along with the dosage form2 crushing or chewing by patient 3 . Information on product failures due to dose dumping is limited2. It is necessary to identify the significant factors that may lead to dose dumping. Krajesic and Tucker studied the effect of curing of granules and tablets on drug release. Difference in drug release profile was observed between the granules and tablets without curing and with curing2. Release retardants that are used in formulation of matrix tablets may cause dose dumping due to their alcohol solubility. Other factors like products and composition and solubility of the components used may also lead to dose dumping2. Those factors which may contribute to dose dumping must be identified and controlled in the early product design itself to develop a successful dosage form free from dose dumping.
1. Robert J. Meyer, Ajaz S. Hussain; Awareness Topic: Mitigating the Risks of Ethanol Induced Dose Dumping from Oral Sustained/Controlled Release Dosage Forms U.S.
Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), U.S. Government Printing Office: Washington, DC,
2. http://www.aapspharmaceutica.com/meetings/files/126/khan.pdf accessed on 23/3/2011
3. www.ethypharm.com/typo3conf/ext/in_docs/dl.php?id=329 accessed on 23/2/2011.