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Question

Posted on: March 6 2013

A problem with a prescription Cymbalta 20mg (duloxetine) Magistraal, 60 gel.

The speciality are capsules, filled with enteric coated pellets. Can this just be processed or should the egg be enteric encased? I do not find any data on Duloxetine's stability.

Answer

If you read the text below you will see that an enteric envelope is necessary.
Duloxetine is a pharmaceutically active compound useful as an antidepressant. See, for example, Wong et al., Neuropsychopharmacology, 8, 23-33 (1993), where the compound is named by its research number LY248686. Duloxetine is (+)-N-methyl-3-(1-naphthalenyloxy) -2-thiophenepropanamine, and is commonly used in pharmaceutical compositions as its hydrochloride salt. In This document, the word "duloxetine" will refer to the specific enantiomer just named. The marketed pharmaceutical dosage form of duloxetine sold in the US by Eli Lilly & Co. Under the brand name Cymbalta ® is a capsule comprising a plurality of enteric coated pellets containing duloxetine hydrochloride. Enteric Pharmaceutical formulations are manufactured in such a way that the product passes unchanged through the stomach of the patient, but dissolves and releases the active ingredient after it leaves the stomach and enters the small pronounce intestine. Such formulations conventionally are in tablet or pellet form, where the active ingredient is in the inner part of the tablet or pellet and is enclosed in a film or envelope, i.e., the "enteric coating", which is insoluble in acid environments, such as the stomach, but is soluble in near-neutral environments such as the small pronounce intestine. The need to question duloxetine in an enteric formulation is due to the poor stability characteristics of duloxetine in acidic solutions. The duloxetine molecule decomposes easily in an acidic environment upon formation of a highly toxic reds moiety. When a pharmaceutical dosage form has been orally tasks and before it reaches the astringent it normally resides in the stomach for a period of 0.2-2 hours. According to "Innovations in drug delivery" (ISBN 90-73520-06-1) by C. G. Wilson and N. Washington, pg 42-56, typically the resting gastric pH of a normal healthy subject is around 1.8. Meals markedly alter the pH which can increase to 3-5 after eating, whereafter the resting gastric pH is obtained again. As can be seen in the same chapter gastric widens of pellets from the stomach to the astringent can take up to 3 hours for pellets and up to 9 hours for large non-disintegrating tablets, depending on the content of the stomach.